2nd european conference on brain stimulation in psychiatry...
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2nd European Conference on BrainStimulation in Psychiatry (ECBSP):Individualizing Neuromodulation
12–14 October 2017, Munich, Germany
Hosted by the
Deutsche Gesellschaft fur Hirnstimulation in der
Psychiatrie (DGHP) e.V.
SUPPLEMENT 1 TO VOLUME 267 � 2017
123
In collaboration with
Stimulation Transcranienne en Psy-
chiatrie STEP, and the German Center for Brain
Stimulation (GCBS) funded by the Federal Ministry
of Education and Research (BMBF)
Scientific committee:
Berthold Langguth
Chris Baeken
Emmanuel Poulet
Jerome Brunelin
Djamila Bennabi
Martijn Arns
Local Organizing Committee:
Frank Padberg
Daniel Keeser
Anna-Katharine Brem
Ulrich Palm
Alkomiet Hasan
Oliver Pogarell
ORGANISATION/COMMITTEES
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Symposia and keynote abstracts
KN-01 Individualizing brain stimulation—two perspectives from Boston: A
KN-02 Individualizing brain stimulation: two perspectives from Boston: B
KN-03 Translational research in brain stimulation
KN-04 European guidelines on the therapeutic use of rTMS and tDCS
S-1a Clinical applications 1: tDCS
S-1a-01 Transcranial direct current stimulation for depression: recent findings and perspectives
S-1a-02 tDCS in schizophrenia
S-1a-03 Combining transcranial alternating current stimulation with attention bias modification in tobacco-use
disorder
S-1a-04 Non invasive cortical stimulation in multiple sclerosis: current challenges and future perspectives
S-1b Neuroimaging and closed loop approaches
S-1b-01 State-informed NTBS: perspectives and challenges
S-1b-02 Brain-state dependent brain-stimulation with EEG triggered TMS: demonstration of a new real-time
closed-loop method for individualized therapy
S-1b-03 Brain oscillation synchronized stimulation of the frontal cortex (BOSSFRONT): validation results from a
personalised TMS pilot study with 17 patients with depression
S-1b-04 Using EEG to identify individuals who are likely to benefit from electrical stimulation
S-2a Clinical applications 2: TMS
S-2a-01 rTMS in elderly patients
S-2a-02 rTMS for the treatment of negative symptoms in residual schizophrenia
S-2a-03 Can meta-regression identify the optimal protocols for deep transcranial magnetic stimulation (DTMS)
in studies with neuropsychiatric disorders?
S-2a-04 Effect of repetitive transcranial magnetic stimulation over the left DLPFC on subjective craving,
physiological cue reactivity, and cognitive control in gambling disorder
S-2a-05 Modified deep TMS coils for the treatment of OCD and ADHD: electrophysiological correlates and
prognostic biomarkers
S-2b Brain stimulation with the double cone coil
S-2b-01 Beyond DLPFC-rTMS: more targets, more indications, more remissions
S-2b-02 A literature review on ACDC stimulation targeting the anterior cingulate by double cone coil rTMS
S-2b-03 Comparison of figure-8 and DC coil: physiological and physical data
CONTENTS
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S-3a Clinical applications 3: convulsive therapy and deep brain stimulation
S-3a-01 Stimulation strategies in electroconvulsive therapy
S-3a-02 Resting state networks, brain oscillatory activity and functional connectivity in patients with depression
under electroconvulsive therapy
S-3a-03 Magnetic seizure therapy in psychiatric disorders
S-3a-04 DBS
S-3a-05 Progress and drawbacks in deep brain stimulation for obsessive–compulsive disorder and Tourette
syndrome
S-3b Safety and NIBS across lifespan
S-3b-01 Safety of tES
S-3b-02 Transcranial electrical stimulation in pediatric brain: age or individual differences?
S-3b-03 NIBS in neurodevelopmental disorders
S-3b-04 Transcranial stimulation targeting memory-relevant sleep oscillations as therapeutic approach in aging
and mild cognitive impairment
S-4a Multimodal imaging
S-4a-01 Accounting for interindividual variation in NIBS using computational models
S-4a-02 How to reach deep brain structures: modulation of salience coding of food by rTMS
S-4a-03 Imaging transcranial direct current stimulation: contributions and challenges
S-4a-04 Towards causality: combining non-invasive brain stimulation and neuroimaging to understand
neuroplasticity
SOP-01 Effects of non-invasive neurostimulation on brain activity
SOP-01-01 Modulation of spontaneous and task-related alpha-band oscillations using transcranial alternating
current stimulation (tACS)
SOP-01-02 The effects of frontal tACS on reversal learning
SOP-01-03 The effects of rTMS treatment for auditory verbal hallucinations on inner speech related brain networks
SOP-01-04 Antidepressant effects and change in brain activation of transcranial pulsed electromagnetic fields
for treatment resistant depression
SOP-01-05 Quadri-pulse theta burst stimulation using ultra-high frequency bursts at I-wave periodicity induces
direction dependent bi-directional plasticity in human motor cortex
SOP-02 Clinical applications
SOP-02-01 The Bipolar Depression Electrical Treatment Trial (BETTER): results from a randomized clinical trial
SOP-02-02 Attitudes and educational work regarding rTMS
SOP-02-03 Creating an interventional psychiatry service
S-5a Individualizing treatment
S-5a-01 Understanding and predicting rTMS effect for the treatment of negative symptoms in schizophrenia
S-5a-02 Stimulation genetics: new perspectives for an individualized brain stimulation
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S-5a-03 Individualized treatment of positive symptoms in schizophrenia: potentials and pitfalls
S-5a-04 Computational modelling studies for non-invasive brain stimulation
S-5b Cognition and psychotherapy, state dependency
S-5b-01 Trait rumination moderates the effects of anodal tDCS over the right dorsolateral prefrontal cortex on
cognitive processing of emotional information
S-5b-02 The psychomotor retardation may be a marker of response to rTMS treatment in patients with major
depressive disorder
S-5b-03 Challenging control over emotions in borderline personality disorder with tDCS
S-5b-04 Cognitive and electrophysiological mechanisms of enhancing fluid intelligence
S-5b-05 Towards neurocognitive stimulation to treat affective disorders
S-6a Clinical applications: other
S-6a-01 A multimodal investigation on the biological markers associated with the antidepressant effects of
transcranial direct current stimulation
S-6a-02 The impact of accelerated HF-rTMS on neurochemicals in major depression: insights from 1H MR
spectroscopy
S-6a-03 Transcranial direct current stimulation (tDCS) for obsessive–compulsive disorder
S-6a-04 Cognitive brain stimulation
S-6b NIBS in cells and animals
S-6b-01 Testing neuromodulation avenues in model rats
S-6b-02 Cellular effects of low-dose tDCS: implications for neuroplasticity
S-6b-03 rTMS restores alterations in synaptic excitation/inhibition-balance
S-7a Optimizing NIBS treatment: biomarkers and RDoC approaches
S-7a-01 Matching patient subtypes to neural circuits for novel brain stimulation treatments in affective disorders
S-7a-02 Optimizing TMS treatment for depression using neuro-cardiac guided TMS (NCG TMS)
S-7a-03 Central and plasmatic plasticity markers and response to NIBS
S-7a-04 Personalizing and enhancing rTMS treatment response: EEG predictors, biomarkers and role of
combining interventions
GCBS-1
GCBS-1-01 Neuromodulation in model rats
GCBS-1-02 rTMS animals (WP1B)
GCBS-1-03 Optimizing physiological tDCS effects
GCBS-1-04 Lasting amelioration of deficient cognitive control in depression by transcranial direct current
stimulation (tDCS)-enhanced training
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S-8a Reproducibility of NIBS
S-8a-01 Effects of prefrontal tDCS on resting-state functional connectivity: variability, non-linearity and state-
dependency
S-8a-02 Efficacy and interindividual variability following LTP-like plasticity inducing PAS and anodal tDCS
S-8a-03 What does it tell you when your transcranial electric stimulation experiment failed?
S-8a-04 Reproducibility of tDCS
GCBS-2
GCBS-2-01 Disorder-tailored transcranial direct current stimulation (tDCS) of the prefrontal cortex: goals and
achievements
GCBS-2-02 PsychotherapyPlus: augmentation of cognitive behavioral therapy (CBT) with prefrontal
transcranial direct current stimulation (tDCS) in major depressive disorder: study design and
methodology of a multicenter double-blind randomized placebo controlled trial
GCBS-2-03 Design and methods of an ongoing randomized controlled study of tDCS in major depression: the
DepressionDC Trial
Poster abstracts
P-01 Exploring the parameter space of physiological effects of cathodal transcranial direct current stimulation
over the primary motor cortex
P-02 Electrode montage dependent effects of transcranial direct current stimulation on working memory
P-03 Exploring the effects of transcranial direct current stimulation on cognitive control training
P-04 The effect of transcranial direct current stimulation on cognitive control and emotion regulation in
depressed patients
P-05 General effects of cathodal tDCS on implicit associations
P-06 Brain stimulation over frontopolar cortex enhances motivation to exert effort for reward
P-07 The influence of tDCS on prosocial behaviour when being socially excluded: experimental design
P-08 Prefrontal MRI-compatible tDCS reduces ventromedial cortical perfusion after being criticized
P-09 Does electrode localization in tDCS research matter? A comparison between 10–20 EEG system and
MRI-guided neuronavigation
P-10 Effects of different prefrontal-tDCS electrode-montages on resting-state connectivity and cognitive control
P-11 Neurophysiological impact of a fronto-temporal transcranial direct current stimulation in healthy subjects:
a multimodal PET-MR imaging approach
P-12 Modulation of brain metabolites and resting state functional MRI connectivity by transcranial direct current
stimulation (tDCS) over the left dorsolateral prefrontal cortex in healthy subjects
P-13 Effects of transcranial direct current stimulation (tDCS) on working memory performance in patients with
schizophrenia
P-14 Transcranial direct current stimulation in three patients with Gilles de la Tourette syndrome
P-15 tDCS-enhanced working memory training in subjective cognitive decline
P-16 Transcranial direct current stimulation (tDCS) as treatment for major depression: a prospective
multicenter double blind randomized placebo controlled trial (DepressionDC)—early quality control of
technical data from a blind selection of active tDCS sessions
P-17 Targeting fatigue, mood and cognition in multiple sclerosis using tDCS
P-18 Frontal EEG coherence after beta-tACS during reversal learning
P-19 Online effects of transcranial alternating current stimulation on event-related alpha power modulations: a
concurrent tACS-MEG study
P-20 Long-term effect of 3 daily sessions of transcranial random noise stimulation (tRNS) on inhibitory control
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P-21 Effects of transcranial direct current stimulation applied to the prefrontal cortex on TMS evoked potentials
P-22 Changes in firing properties and synaptic plasticity in different brain regions of schizophrenia model and
control rats after transcranial magnetic stimulation
P-23 Advances in TMS technology: from flexible pulse shape design to high speed individualized biphasic
quadri-pulse stimulation
P-24 The role of the parietal cortex in memory confidence
P-25 Time lapse of individualized rTMS effects on resting state functional connectivity of healthy brains
P-26 The effect of seed determination on functional connectivity analyses to study the effect of transcranial
magnetic stimulation
P-27 The relation between brain morphological factors and efficacy of rTMS treatment in patients with
schizophrenia and auditory verbal hallucinations
P-28 Abnormal brain asymmetry and behavior in ADHD: a TMS-EEG study
P-29 Anxiety symptoms correlates with transcallosal inhibition in patients with multiple sclerosis
P-30 Impaired corticospinal excitability revealed by transcranial magnetic stimulation in patients with major
depressive disorder
P-31 Individualized connectivity between rTMS targets and the subgenual cingulate is unrelated to
antidepressant response
P-32 Imagery guided personalized robotic rTMS in depression: preliminary results of a feasibility study
P-33 A nationwide questionnaire survey on attitudes of Japanese psychiatric specialists toward repetitive
transcranial magnetic stimulation therapy for depression
P-34 Clinical application of deep transcranial magnetic stimulation (DTMS) in neuropsychiatric disorders: a
systematic literature review and meta-analysis
P-35 Acute efficacy of deep transcranial magnetic stimulation (DTMS) in unipolar vs. bipolar major depressive
disorder (MDD): a systematic literature review and meta-analysis
P-36 Predicting deep transcranial magnetic stimulation (dTMS) efficiency in depressed using brain network
activation (BNA) analysis
P-37 Cognitive effects of high-frequency-rTMS in chronic schizophrenic patients
P-38 Transcranial magnetic stimulation has different short-term efficacy on different major depressive disorder
symptoms: a nested prospective cohort study in Croatia
P-39 Efficacy and tolerability of repetitive transcranial magnetic stimulation with and without the Brainsway H1-
coil in treatment of major depressive disorder: presentation of the protocol and interim analysis
P-40 Interaction of serotonin and age is significant predictor of transcranial magnetic stimulation effect on major
depressive disorder: a prospective cohort study in Croatia
P-41 Treatment of pediatric catatonia with ECT: a case series and review
P-42 Adjustment of pulse wave parameters to optimize effective ECT treatment
P-43 Transcranial direct current stimulation (tDCS) replaces electroconvulsive therapy (ECT) in a patient with
corpus callosum agenesis and catatonic schizophrenia: a longitudinal network-metric approach
P-44 Individualized thresholds: calibrating brain stimulation through concurrent TMS/fMRI
P-45 Is hippocampal neurogenesis mediating clinical efficacy and memory outcome after electroconvulsive
therapy in depression?
P-46 Real-time fMRI neurofeedback in patients with alcohol use disorder: craving-related modulations
P-47 LMU scripts • ready-made HPC-applicable pipeline for structural and functional data analyses
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2nd European Conference on Brain Stimulation in Psychiatry(ECBSP): Individualizing Neuromodulation
Symposia and keynote abstracts
KN-01Individualizing brain stimulation—two perspectivesfrom Boston: A
M. D. Fox1,2,3
1Berenson-Allen Center for Noninvasive Brain Stimulation,
Department of Neurology, Harvard Medical School and Beth Israel
Deaconess Medical Center, Boston, USA; 2Department of Neurology,
Massachusetts General Hospital, Harvard Medical School, Boston,
USA; 3Athinoula A. Martinos Center for Biomedical Imaging,
Massachusetts General Hospital, Charlestown, USA
It has become increasingly clear that the therapeutic targets for brain
stimulation are connected brain networks, not isolated brain regions.
Lesions causing the same symptom, but occurring in different loca-
tions, are part of the same connected brain network. Similarly, brain
stimulation sites treating the same symptom, but administered to
different brain locations, are part of the same connected brain net-
work. Brain connectivity with patient-specific stimulation sites can be
used to predict the response of individual patients with depression to
transcranial magnetic stimulation or the response of individual
patients with Parkinson’s disease to deep brain stimulation. As such,
brain connectivity can be used to identify and optimize therapeutic
targets. Because not all patients have the same symptoms or the same
brain connectivity, these principles can be applied towards identifying
individualized patient-specific stimulation sites to optimize thera-
peutic response.
Policy of full disclosure: This work was supported by the NIH
(R21MH099196, K23NS083741 and R21MH098174), by Harvard
Clinical and Translational Science Center/Harvard Catalyst (National
Center for Advancing Translational Sciences, NIH Award
UL1RR025758); Additional assistance came from the Sidney R. Baer
Jr. Foundation, the Dystonia Medical Research Foundation, and the
Nancy Lurie Marks Foundation. MDF is listed as an inventor on
submitted or pending patents using brain imaging to guide brain
stimulation.
KN-02Individualizing brain stimulation: two perspectivesfrom Boston: B
H. Liu1,2
1Harvard Medical School, Boston, USA; 2Laboratory For the Study of
the Brain Basis of Individual Differences, Massachusetts General
Hospital, Boston, USA
A major obstacle for exploring subtle aspects of network organization
and translating insights into clinical applications is the lack of tools
for mapping networks in individual subjects. Until recently, most
studies of human brain organization have focused on averaging data
over many individuals to estimate network properties. However,
marked inter-individual variability has been demonstrated in the
organization of functional systems of the brain, particularly in higher
order association areas. A functional mapping technique with high
sensitivity to the individual’s unique functional organization will
facilitate the discovery of meaningful biomarkers for disease states
and provide personalized therapeutic targets for various neurological
and psychiatric disorders.
We developed a novel brain parcellation approach to accurately
map functional organization at the individual level using resting-state
fMRI. Functional networks mapped by this approach were highly
reproducible within subjects and effectively captured the variability
across subjects. Using the functional regions localized in each indi-
vidual subject, we were able to identify connectivity markers that are
highly predictive of global and dimension-specific symptom severity
in various psychiatric disorders, including psychosis and obsessive–
compulsive disorder (OCD). These individually-identified functional
circuits may lead to novel, personalized targets for neuromodulation
treatments. Finally, I will discuss our data on evaluating the effect of
deep brain stimulation (DBS) on individual patients’ functional
networks.
Policy of full disclosure: The authors do not have disclosures to
report.
KN-03Translational research in brain stimulation
S. H. Lisanby1
1National Institute of Mental Health, Bethesda, USA
No abstract for publication.
KN-04European guidelines on the therapeutic use of rTMS and tDCS
J.-P. Lefaucheur1
1Clinical Neurophysiology, Henri Mondor Hospital, Creteil, France
Since the first therapeutic application of repetitive transcranial mag-
netic stimulation (rTMS) in the mid-1990s and transcranial direct
current stimulation (tDCS) a decade later, many studies showed the
efficacy of these techniques to treat a variety of clinical conditions. A
group of European experts was commissioned to grade the level of
evidence of this therapeutic potential in neurological and psychiatric
diseases1,2. Despite unavoidable methodological heterogeneities, a
level A of evidence (definite efficacy) was found for: (1) the analgesic
effect of high-frequency (HF) rTMS of the primary motor cortex (M1)
contralateral to the pain side and (2) the antidepressant effect of HF-
rTMS of the left dorsolateral prefrontal cortex (DLPFC). A Level B
recommendation (probable efficacy) was found for: (1) the antide-
pressant effect of low-frequency (LF) rTMS of the right DLPFC, (2)
HF-rTMS of the left DLPFC for negative symptoms of schizophrenia,
(3) LF-rTMS of contralesional M1 in chronic motor stroke, (4) anodal
ABSTRACTS
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https://doi.org/10.1007/s00406-017-0856-0
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tDCS of the left M1 (with right orbitofrontal cathode) in fibromyalgia,
(5) anodal tDCS of the left DLPFC (with right orbitofrontal cathode)
in major depressive episodes without drug resistance, (6) anodal tDCS
of the right DLPFC (with left DLPFC cathode) in addiction/craving.
In a number of indications, the effects of rTMS (e.g., LF-rTMS of the
left temporoparietal cortex in tinnitus and auditory hallucinations) or
tDCS (e.g., anodal tDCS of the left M1 in chronic neuropathic pain)
reach level C of evidence (possible efficacy). It remains to determine
how to optimize rTMS and tDCS protocols to give them relevance in
routine clinical practice. Inappropriate applications of these tech-
niques should be avoided by ensuring rigorous training of the
professionals.
References:
1. Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C,
Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder
D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelai-
nen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A,
Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-
Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Zie-
mann U, Paulus W, Garcia-Larrea L (2014) Evidence-based
guidelines on the therapeutic use of repetitive transcranial magnetic
stimulation (rTMS). Clin Neurophysiol 125:2150–2206
2. Lefaucheur JP, Antal A, Ayache SS, Benninger DH, Brunelin J,
Cogiamanian F, Cotelli M, De Ridder D, Ferrucci R, Langguth B,
Marangolo P, Mylius V, Nitsche MA, Padberg F, Palm U, Poulet E,
Priori A, Rossi S, Schecklmann M, Vanneste S, Ziemann U, Garcia-
Larrea L, Paulus W. Evidence-based guidelines on the therapeutic use
of transcranial direct current stimulation (tDCS). Clin Neurophysiol
Policy of full disclosure: The author does not have disclosures to
report.
S-1a Clinical applications 1: tDCS
Chairs: Palm and Brunelin
S-1a-01Transcranial direct current stimulation for depression: recentfindings and perspectives
A. Brunoni1,2
1Service of Interdisciplinary Neuromodulation, Department and
Institute of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil;2Department of Psychiatry and Psychotherapy, LMU Munich,
Munich, Germany
Major depressive disorder is a highly prevalent, disabling condition.
Pharmacological treatments are only moderately effective and asso-
ciated with important adverse effects. These issues reinforce the need
of developing novel treatment alternatives. One of them is transcra-
nial direct current stimulation (tDCS), a non-pharmacological
technique that might be clinically useful as it is easy to use, affordable
and tolerable. TDCS as a treatment for depression has been inten-
sively investigated during the past decade. In this talk, Dr. Brunoni
will discuss the most recent findings, based on the results of ran-
domized clinical trials and meta-analyses. The evidence suggests that
tDCS might be effective in specific groups of depressed patients;
although it is still inferior to pharmacotherapy. Future perspectives on
how to improve tDCS efficacy will be discussed.
Policy of full disclosure: ARB receives a CAPES-Humboldt fellow-
ship for experienced researchers and is a consultant of the Neurocare
(Munich, Germany) group.
S-1a-02tDCS in schizophrenia
U. Palm1
1LMU Munich, Munich, Germany
Transcranial direct current stimulation (tDCS) is an emerging tool in
neuromodulation and has been investigated to treat various
schizophrenia symptoms, e.g. catatonia, auditory verbal hallucina-
tions (AVH), negative symptoms (NS). To date, most evidence is
available for the treatment of AVH with the anode placed over the left
dorsolateral prefrontal cortex (DLPFC) and the cathode placed over
the left temporo-parietal junction (TPJ). Several randomized con-
trolled trials suggest a reduction of AVH and improvement of NS
after a tDCS series. However, overall sample sizes are too small to
draw a final conclusion and at least two failed studies do not show
superiority of active compared to sham stimulation. For the treatment
of NS, two randomized controlled trials and one open label study
showed a decrease of negative symptoms by more than 30% after a
tDCS series of the left DLPFC. Although these results are consistent,
samples sizes are far too small to draw any conclusion. There are
several studies showing an improvement of cognitive performance
after anodal stimulation of the left DLPFC in schizophrenia. There is
no clinical data available for the treatment of schizophrenia in chil-
dren and adolescents. Overall, samples sizes are small, study designs
and samples are heterogeneous and results do not allow a suggestion
of tDCS for regular treatment of schizophrenia symptoms until
stronger evidence from randomized controlled trials becomes
available.
Policy of full disclosure: The authors do not have disclosures to
report.
S-1a-03Combining transcranial alternating current stimulationwith attention bias modification in tobacco-use disorder
M. Mondino1, S. Fecteau1
1Faculte de medecine, Universite Laval, Centre Interdisciplinaire de
Recherche en Readaptation et Integration, Centre CERVO de
l’Institut Universitaire en Sante Mentale de Quebec, Quebec, Canada
Craving is a central feature in tobacco use disorder (TUD). Previous
studies have successfully reduced craving in adults with TUD either
by using an attention bias modification paradigm (ABM)1 or by
applying noninvasive brain stimulation (NIBS) over the dorsolateral
prefrontal cortex (DLPFC)2. Recent work showed that combining
NIBS with ABM lead to greater effects than NIBS alone3. Our
objective was to test whether NIBS applied over the DLPFC com-
bined with ABM might reduce craving intensity in adults with TUD.
We chose to use transcranial alternating current stimulation (tACS), a
NIBS technique that offers the opportunity to modulate brain oscil-
lations in humans.
In a crossover study, 19 subjects with TUD were allocated to
receive one session combining active tACS with ABM and one
combining sham tACS with ABM in a randomized order and sepa-
rated with 1 week. tACS (10 Hz, 2 mA, electrodes applied on F3 and
F4) and ABM (modified dot-probe task) were administered simulta-
neously during 30 min. Craving intensity was assessed after and
before the intervention using the Questionnaire of Smoking Urges.
We also assessed the attentional bias towards smoking cues using an
eye-tracking device during visual scanning of neutral and smoking
cues and decision-making processes using the Delay-Discounting
task.
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Active tACS combined with ABM significantly reduced desire to
smoke, as compared to sham tACS combined with ABM. No sig-
nificant effects were reported on other dimensions of craving. Both
active tACS combined with ABM and sham tACS combined with
ABM reduced the attentional bias for smoking cues. A significant
decrease of impulsive choices at the Delay-Discounting task was
reported after active tACS combined with ABM as compared to sham
tACS combined with ABM.
The combination of active tACS and ABM might reduce desire to
smoke and impulsivity in adults with TUD.
References:
1. Attwood AS, O’Sullivan H, Leonards U, Mackintosh B, Munafo
MR (2008) Attentional bias training and cue reactivity in cigarette
smokers. Addiction 103(11):1875–1882
2. Hone-Blanchet A, Ciraulo DA, Pascual-Leone A, Fecteau S (2015)
Noninvasive brain stimulation to suppress craving in substance use
disorders: review of human evidence and methodological considera-
tions for future work. Neurosci Biobehav Rev 59:184–200
3. Heeren A, Baeken C, Vanderhasselt M-A, Philippot P, de Raedt R
(2015) Impact of anodal and cathodal transcranial direct current
stimulation over the left dorsolateral prefrontal cortex during attention
bias modification: an eye-tracking study. PLoS One 10(4):e0124182
Policy of full disclosure: The authors do not have disclosures to
report.
S-1a-04Non invasive cortical stimulation in multiple sclerosis: currentchallenges and future perspectives
S. S. Ayache1,2,3, J.-P. Lefaucheur1,2, M. A. Chalah1,2
1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-
Est-Creteil, Creteil, France; 2Service de Physiologie-Explorations
Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux
de Paris, Creteil, France; 3Neurology Division, Lebanese American
University Medical Center-Rizk Hospital (LAUMC-RH), Beirut,
Lebanon
Multiple sclerosis (MS) is a chronic inflammatory disease of the
central nervous system. During its course, several invalidating
symptoms take place and might seriously impact the patients’ quality
of life. Among these symptoms, neuropathic pain, spasticity,
sphincter dysfunction, depression, fatigue and cognitive disorders are
difficult to deal with and represent a real challenge for the persons in
charge of this population.
Therefore, noninvasive brain stimulation (NIBS) techniques have
been proposed in this context, with the aim to improve the therapeutic
strategies, limit drug interactions and prevent the accumulation of
side effects1. While repetitive transcranial magnetic stimulation
(rTMS) has been mostly tried to ameliorate spasticity, dexterity and
motor performance; transcranial direct current stimulation (tDCS)
studies have primarily focused on the improvement of fatigue, pain
and cognitive functions. rTMS was applied at high frequency over the
primary motor cortex and led to encouraging results, with a significant
decrease of the Ashworth spasticity scores, and better performance on
the nine hole pegboard task1. Concerning tDCS, this technique was
found to have an interesting impact on chronic neuropathic pain,
fatigue and to a lesser extent on cognitive performance. In fact, anodal
stimulation of the motor or the left prefrontal cortex was able to
reduce pain intensity2. As for fatigue, anodal stimulation of the motor
or sensori-motor cortex was found to be efficacious3. However, some
controversies exist concerning the efficacy of anodal left prefrontal
tDCS on MS fatigue3. Regarding cognition, coupling cognitive tasks
with left prefrontal anodal tDCS could be of particular help. In
addition, vigilance could be ameliorated by the anodal stimulation of
the right parietal cortex.
In conclusion, some promising outcomes have been reported fol-
lowing the application of various NIBS paradigms over different brain
areas. However, the scarcity of the available literature prompts further
investigations of the place of these techniques in the management of
MS symptoms.
References:
1. Palm U, Ayache SS, Padberg F, Lefaucheur JP (2014) Non-inva-
sive brain stimulation therapy in multiple sclerosis: a review of tDCS,
rTMS and ECT results. Brain Stimul 7:849–854
2. Ayache SS, Palm U, Chalah MA, Al-Ani T, Brignol A, Abdellaoui
M, Dimitri D, Sorel M, Creange A, Lefaucheur JP (2016) Prefrontal
tDCS decreases pain in patients with multiple sclerosis. Front Neu-
rosci 10:147
3. Ayache SS, Chalah MA (2017) Fatigue in multiple sclerosis—
insights into evaluation and management. Neurophysiol Clin
47:139–171
Policy of full disclosure: Samar S. Ayache declares having received
grants or compensation from Genzyme, Biogen, Novartis and Roche.
The remaining authors have nothing to disclose.
S-1b Neuroimaging and closed loop approaches
Chairs: Siebner and Zrenner
S-1b-01State-informed NTBS: perspectives and challenges
H.R. Siebner1,2
1Danish Research Centre for Magnetic Resonance, Centre for
Functional and Diagnostic Imaging and Research, Copenhagen
University Hospital Hvidovre, Hvidovre, Denmark; 2Department of
Neurology, Copenhagen University Hospital Bispebjerg,
Copenhagen, Denmark
A wide range of non-invasive transcranial brain stimulation (NTBS)
methods is used as interventional tools to modify human brain
function. While NTBS has shown potential in the treatment of brain
diseases such as depression or stroke, substantial inter-individual
variation in the therapeutic response to NTBS is currently the greatest
obstacle for a more wide-spread therapeutic use of NTBS. This calls
for innovative approaches which fully exploit the potential of NTBS
to shape the architecture of human brain networks. (1) Biophysically
adjusted NTBS: Advanced modelling of the electrical fields that are
induced by NTBS in individual brains can be used to optimally target
the cortical network of interest. (2) State-informed NTBS: Using
electroencephalography (EEG) and functional magnetic resonance
imaging (fMRI) can be used to identify the spatiotemporal signatures
of functional and dysfunctional brain states at an individual level and
to trace the dynamic expression of these ‘‘state signatures’’ during
NTBS. This information will allow for a dynamic adaptation of the
spatiotemporal properties of NTBS to the intrinsically expressed brain
states. Biophysically adjusted State-informed Cortex stimulation
(BaSiCs) has the potential to reinforce the expression of beneficial
brain states and to attenuate the expression of dysfunctional brain
states. This will yield important discoveries regarding the neural
underpinnings of brain (dys)function and push the frontiers of NTBS
as interventional tool to optimize the function of human brain
networks.
Policy of full disclosure: HRS has received honoraria as editor from
Elsevier Publishers, Amsterdam, The Netherlands and Springer
Eur Arch Psychiatry Clin Neurosci
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Publishing, Stuttgart, Germany, and has received a research fund from
Biogen-idec.
S-1b-02Brain-state dependent brain-stimulation with EEG triggeredTMS: demonstration of a new real-time closed-loop methodfor individualized therapy
C. Zrenner1, D. Desideri1, P. Belardinelli1, P. Caldana Gordon1,
U. Ziemann1
1Department of Neurology and Stroke, and Hertie Institute for
Clinical Brain Research, University of Tubingen, Tubingen, Germany
TMS has been shown in numerous studies to be an effective treatment
for a range of neuropsychiatric conditions. However, even when a
clear clinical benefit can be demonstrated at group level, current
stimulation protocols suffer from a vexing inter- and intra-subject
outcome variability and it is difficult to predict whether or not a
particular individual patient will respond to a standardized treatment
protocol (pharmacotherapy, of course, faces the same issue).
Using a custom millisecond-resolution real-time EEG-TMS
closed-loop set-up, we present recent results demonstrating that the
effect of a TMS pulse is determined by the instantaneous brain-state
at the time of the stimulus: Corticospinal excitability fluctuates with
the phase of 10 Hz mu-rhythm oscillations over sensorimotor cortex
with the EEG surface negative peak corresponding to a high-ex-
citability state during which a TMS pulse over the primary motor
cortex evokes larger motor evoked potentials. More importantly,
repetitive stimulation with 200 EEG-triggered 100 Hz triple pulses at
an individually EEG-triggered rate of * 1 Hz, results in LTP-like
effects lasting more than 30 min after stimulation when the bursts are
triggered by the negative peak (high excitability state) vs. no effect
when they are triggered by the positive peak (low excitability state) or
at a random phase of ongoing 10 Hz oscillations.
This result has implications for the development of EEG-guided
individualized therapeutic stimulation protocols: if the goal is to
therapeutically modulate pathological brain network dynamics of a
patient, then this requires individual optimization of both the exact
MRI-guided anatomical locus of stimulation as well as of the precise
EEG-guided time (i.e. during which brain-network state?) when the
application of each pulse will best achieve the desired therapeutic
effect (see Fig. 1).
Policy of full disclosure: The authors do not have disclosures to
report.
S-1b-03Brain oscillation synchronized stimulation of the frontal cortex(BOSSFRONT): validation results from a personalised TMS pilotstudy with 17 patients with depression
B. Zrenner1, P. Gordon1, A. Kempf1, P. Belardinelli1, B. S. Chander2,
C. Plewnia2, S. R. Soekadar2, A. Fallgatter2, C. Zrenner1,
U. Ziemann1, F. Muller-Dahlhaus1,3
1Department of Neurology and Stroke, and Hertie Institute for
Clinical Brain Research, University of Tubingen, Tubingen,
Germany; 2Department of Psychiatry and Psychotherapy, University
Hospital of Tubingen, Tubingen, Germany; 3Department of
Psychiatry and Psychotherapy, Johannes Gutenberg University
Medical Center Mainz, Mainz, Germany
Major depressive disorder (MDD) is characterized by increased alpha
power and reduced cortical excitability in left frontal cortex1. High-
frequency repetitive transcranial magnetic stimulation (TMS) of left
dorsolateral prefrontal cortex (DLPFC) shows definite antidepressant
effects at the group level but its clinical efficacy is limited due to high
inter-individual variability and an average response rate of only 29%2.
Brain-state dependent EEG-triggered TMS, i.e. TMS triggered
dependent on the phase of instantaneous alpha oscillations as detected
by real-time EEG analysis, has been shown to consistently increase
motor cortical excitability3, and may thus be used to personalize TMS
therapy and potentially increase treatment effects in patients with
MDD.
Here, we present a proof-of-principle study of brain-state depen-
dent TMS of left DLPFC in 17 patients with unipolar treatment-
Fig. S-1b-02: A Combination of EEG und TMS using a real-time EEG signal analysis system; B closed-loop EEG-triggered stimulation;
C high-density EEG in combination with individual MRI-segmented anatomy; D real-time source reconstruction; E phase-triggered stimulation.
Eur Arch Psychiatry Clin Neurosci
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resistant MDD to test its feasibility, safety and immediate neuro-
physiological effects. Subjects underwent three separate single
sessions of either (1) brain-state dependent TMS triggered at the
trough of instantaneous alpha oscillations (alpha-trough TMS), (2)
intermittent theta-burst stimulation (iTBS), or (3) a control condition
(replay), in which TMS was applied with the same temporal stimulus
sequence as during alpha-trough TMS (i.e. not phase-locked to the
current oscillatory neural activity during replay). Triggering TMS by
real-time EEG analysis of instantaneous alpha oscillations at the F5
electrode was feasible in all subjects. Side effects reported were
limited to mild discomfort at the site of stimulation. Alpha-trough
TMS selectively reduced resting alpha power at the site of stimulation
as compared to iTBS and replay, which were not significantly dif-
ferent. These findings suggest that brain-state dependent alpha-trough
TMS of left DLPFC can be applied safely and reduces pathological
alpha activity in MDD. Future studies need to test clinical effects of
brain-state dependent TMS in alleviating symptoms of MDD.
References:
1. Jaworska N, Blier P, Fusee W, Knott V (2012) Alpha power, alpha
asymmetry and anterior cingulate cortex activity in depressed males
and females. J Psychiatr Res 46:1483–1491
2. Lefaucheur JP, Andre-Obadia N, Antal A, Ayache S et al (2014)
Evidence-based guidelines on the therapeutic use of repetitive tran-
scranial magnetic stimulation. Clin Neurophysiol 125:2150–2206
3. Zrenner C, Desideri D, Belardinelli P, Ziemann U (2017) Real-time
EEG-defined excitability states determine efficacy of TMS-induced
plasticity in human motor cortex. Under revision
Policy of full disclosure: The authors do not have disclosures to
report.
S-1b-04Using EEG to identify individuals who are likely to benefitfrom electrical stimulation
S. Harty1,2
1University of Oxford, Department of Experimental Psychology,
University of Oxford, Oxford, UK; 2Trinity College Institute of
Neuroscience and School of Psychology, Trinity College Dublin,
Dublin 2, Ireland
Inter-individual variability in responsiveness to interventions poses
great challenges for translational neuroscience, and health care in
general. Reliable and cost-effective screening procedures that can
identify individuals who are more likely to benefit from an inter-
vention could have substantial real-world benefits. In this talk I will
present data from a study wherein we sought to examine the potential
for high-frequency transcranial random noise stimulation (tRNS) to
modulate sustained attention in a manner that was informed by
individual differences in EEG signals. This approach may constitute a
feasible means of using individual differences in neurophysiology to
inform predictions about outcomes from electrical stimulation, and
other targeted cognitive interventions.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2a Clinical applications 2: TMS
Chairs: Langguth and Cordes
S-2a-01rTMS in elderly patients
J. Hoppner1
1Department of Gerontopsychiatry and -psychotherapy, Helios Clinic
Schwerin, Schwerin, Germany
Because of the clinical specific characteristics in elderly depressive
patients, who have greater cognitive and physical impairments, and
who often show inadequate response to antidepressive medication and
more side effects, new innovative non-psychopharmacologic and non-
psychotherapeutic treatments are required. Therefore, especially non-
invasive brain stimulation techniques are required. However, the age
of the patients is one of the most intensive discussed negative pre-
dictor for response to rTMS treatment, the older the patients the
higher the level of non-response. Neurobiological reasons for age-
related non-response to rTMS are cortical atrophy and changes in
myelination, cerebrovascular dysfunctions, and reduction of cortical
excitability. Furthermore, human motor cortex shows age–dependent
reduction of cortical plasticity.
Therefore, only very few studies are available, which directly
compare the antidepressive rTMS effect in association with the age of
the patients. Nevertheless, recent data suggest no deficits in response
to rTMS in the elderly, and no greater risk for side effects.
Because of its shorter stimulation duration time and lower inten-
sity, and because of only very few side effects (low seizure and
adverse event risk) in comparison to rTMS, especially Theta Burst
Stimulation (TBS) could be both effective and well tolerated in older
depressive patients. Our own clinical experiences are in line with this
hypothesis. Clinical randomized and placebo controlled studies
should be of high interest for this subgroup of depressive patients.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2a-02rTMS for the treatment of negative symptoms in residualschizophrenia
J. Cordes1
1Department of Psychiatry and Psychotherapy, Medical Faculty,
Heinrich-Heine-University, Dusseldorf, Germany
Negative symptoms can be divided into those, which derive from
schizophrenia itself (primary symptoms) and those, which are caused
by consequences of the disorder (secondary), such as side effects of
medication. We still have only limited understanding of the patho-
physiological mechanisms underlying negative symptoms and
therefore there is a lack of evidence-based treatments. The treatment
of negative symptoms with non-invasive brain stimulation techniques,
such as rTMS, is a promising new approach, especially because of the
positive side effect profile.
Although there are many encouraging findings, there are several
heterogeneous studies concerning the improvement of negative
symptoms. However, it is still unclear if results patterns are robust,
which stimulation parameters hold the highest efficacy and which
patients benefit most from rTMS. This presentation gives a detailed
overview over recent literature regarding rTMS for the treatment of
Eur Arch Psychiatry Clin Neurosci
123
negative symptoms in schizophrenia patients and derives recom-
mendations for clinical practice.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2a-03Can meta-regression identify the optimal protocols for deeptranscranial magnetic stimulation (DTMS) in studieswith neuropsychiatric disorders?
K. K. Kedzior1
1Institute of Psychology and Transfer, University of Bremen, Bremen,
Germany
Deep transcranial magnetic stimulation (DTMS) with the H-coil
system is an FDA-approved treatment for unipolar major depressive
disorder (MDD). DTMS efficacy in MDD is well-established possibly
due to a consistent protocol utilised in all studies so far, including 20
daily sessions of high-frequency (18–20 Hz) and high-intensity
(120% of the resting motor threshold) stimulation with H1-coil.
Recent studies show that DTMS may also have favourable clinical
outcomes in other neuropsychiatric disorders than MDD. However,
unlike MDD, these studies utilise highly variable stimulation
protocols.
The aim of this talk is to present the clinical outcomes of DTMS in
neuropsychiatric disorders focusing on the stimulation protocols in
studies published until mid 2017. The clinical outcome in each study
is expressed as an effect size (a standardised change in severity of
disorder from baseline to the last daily DTMS session).
According to a multivariate meta-regression analysis (random-
effects with inverse-variance weights) of data from k = 30 studies,
only 13% of variability in effect sizes is explained by the stimulation
protocols (frequency, intensity, and the number of sessions). When
controlling for other predictors in the model, effect sizes improve
with higher frequency of stimulation, with lower intensity, and do not
depend on the number of stimulation sessions. The remaining 87% of
variability in effect sizes could be due to the demographic and the
clinical characteristics of patients as well as other stimulation
parameters (location, number of stimuli).
The results of this meta-regression suggest that efficacy of DTMS
depends on stimulation frequency and that ‘more (intensity)’ may not
necessarily produce ‘better’ outcomes. Future primary and secondary
research should focus on identifying the optimal stimulation protocols
for acute and long-lasting efficacy of DTMS in neuropsychiatric
disorders.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2a-04Effect of repetitive transcranial magnetic stimulation over the leftDLPFC on subjective craving, physiological cue reactivity,and cognitive control in gambling disorder
A. Gay1,2, A. Barcet1, C. Boutet3,4,5, J. Brunelin6,7,8,9,
C. Massoubre1,2
1University Hospital Center of Saint-Etienne, University Department
of Psychiatry and Addiction, Saint-Etienne, France; 2TAPE
Laboratory, EA7423, Jean Monnet University, Saint-Etienne, France;3INSERM, U1059, Saint-Etienne, France; 4University of Lyon, Saint-
Etienne, France; 5Radiology Department, University Hospital, Center
of Saint-Etienne, Saint-Etienne, France; 6INSERM, U1028, CNRS,
UMR5292, Lyon Neuroscience Research Center, WR2 Team, Lyon,
France; 7University of Lyon, Lyon, France; 8Lyon 1 University,
Villeurbanne, France; 9Hospital Center Le Vinatier, Bron, France
Background: Repetitive transcranial magnetic stimulation (rTMS)
over the dorsolateral prefrontal cortex (DLPFC) has alleviated crav-
ing and improved cognition in patients with substance use disorders.
Craving is a key symptom in Gambling Disorder (GD), a common
disabling behavioral addiction with no pharmacological treatment.
We hypothesized that rTMS over the left DLPFC in patients with GD
would reduce gambling craving, automatic cue reactivity and improve
cognitive control. As an exploratory outcome, we investigated if
baseline self-regulation capacity would help identify rTMS
responders.
Methods: In a randomized sham-controlled crossover study, 22
treatment-seeking patients with GD received real or sham treatment
with high frequency rTMS over the left DLPFC and the other treat-
ment a week later. Before and after each rTMS session, participants
performed cognitive tasks (Go/NoGo and Iowa Gambling Task) and
rated their gambling craving before and after viewing a gambling
video used as a cue. We used heart rate variability (HRV) to evaluate
physiological cue-reactivity during viewing. Resting-state HRV was
also used as a marker of self-regulation capacity to subtype partici-
pants and identify potential responders.
Results: Real versus sham rTMS significantly decreased cue-induced
craving but affected neither HRV cue reactivity nor cognitive task
performance. Only patients with low regulation capacity, based on
low resting-state HRV, showed decreased motor impulsivity.
Conclusions: Following one active session of high frequency rTMS
over the left DLPFC, patients with GD reported decreased cue-in-
duced craving with no apparent effect on physiological cue-reactivity.
Despite no overall improvement on cognitive control, subjects with
impaired regulation capacity could be better rTMS responders on this
dimension. Determining the utility of rTMS in GD requires further
large randomized controlled studies with repeated sessions.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2a-05Modified deep TMS coils for the treatment of OCD and ADHD:electrophysiological correlates and prognostic biomarkers
A. Zangen1, U. Alyagon1, L. Carmi12, J. Zohar2
1Department of Life Sciences and the Zlotowski Center for
Neuroscience, Ben-Gurion University of the Negev, Beersheba,
Israel; 2Division of Psychiatry, State of Israel Ministry of Health,
Chaim Sheba Medical Center, Sackler Medical School, Tel-Aviv
University, Tel-Aviv, Israel
Converging evidence suggests that OCD patients suffer from dys-
function of the cortico-striato-thalamo-cortical (CSTC) circuit,
including the medial prefrontal cortex (mPFC) and the anterior cin-
gulate cortex (ACC). Reduced excitability of the right prefrontal
cortex (rPFC) has been implicated in attention deficit/hyperactivity
disorder (ADHD). We have designed different deep TMS coils to
target large volumes of these regions in an attempt to induce lasting
modulations and evaluate potential clinical benefits using various
stimulation parameters.
This lecture will briefly summarize clinical outcomes of treat-
ments using different stimulation parameters in two longitudinal
studies in drug-free ADHD subjects and in medication-resistant OCD
patients. In the ADHD study, EEG recordings were taken before,
during, and after the first and the last days of treatment. In addition,
EEG was recorded during a Stop Signal task (SST), following single
TMS pulses over the rPFC, and during the treatment session itself. In
Eur Arch Psychiatry Clin Neurosci
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the OCD study, EEG recording were performed during a Stroop task
before and after treatment to examine changes in error-related
activity.
In the ADHD study, 20 Hz dTMS (but not focal TMS), to the
rPFC over 3 weeks induced significant clinical improvements and
TMS evoked potential (TEP) in the rPFC was enhanced accordingly.
Moreover, specific EEG bands recorded at rest and during the first
treatment session were highly correlated with the clinical benefit;
yielding a prognostic marker that explains 90% of variance in ther-
apeutic outcome.
In the OCD study, 20 Hz (not 1 Hz) dTMS to the mPFC and ACC
over 6 weeks induced significant improvement in the Yale–Brown-
Obsessive–Compulsive Scale (YBOCS) scores. The clinical results
were replicated in a relatively large (n = 94) double-blind multi-
center study. Notably, the clinical response correlated with increased
Error Related Negativity (ERN) in the Stroop task, an electrophysi-
ological component that is attributed to ACC activity.
These studies demonstrate the value of EEG recordings before and
during rTMS treatment as a tool for predicting response and poten-
tially even tailoring stimulation parameters for individual subjects
based on initial electrophysiological measures before and during the
first treatment session.
Policy of full disclosure: This research is partly supported by grants
from the MAGNET program of the Israeli OCS.
S-2b Brain stimulation with the double cone coil
Chairs: Downar and Schecklmann
S-2b-01Beyond DLPFC-rTMS: more targets, more indications, moreremissions
J. Downar1
1MRI-Guided rTMS Clinic, Toronto Western Hospital, Toronto,
Canada
In clinical practice, the most common use of rTMS is for major
depression, targeting the dorsolateral prefrontal cortex (DLFPC).
However, many other target brain regions and networks are also
accessible to rTMS, particularly using deeper-field coils such as the
double-cone coil. Several of these other prefrontal targets are also
implicated in major depression, and indeed may be involved trans-
diagnostically across a wide variety of Axis I and II disorders. Here
we will review recent evidence that two resting-state functional net-
works, the salience network (SN) and lateral orbitofrontal network
(LOFTN), are involved transdiagnostically across several psychiatric
illnesses including major depression. We will review recent tech-
niques for targeting these networks via double-cone rTMS of the
orbitofrontal cortex (OFC) and dorsomedial prefrontal cortex
(DMPFC). We will review evidence that OFC- and DMPFC-rTMS
may achieve marked improvement not only in major depression but in
other comorbid illnesses, specifically including OCD, bulimia ner-
vosa, PTSD, and borderline personality disorder. Finally, we will
review evidence that a substantial proportion of DLPFC-rTMS non-
responders may achieve remission with DMPFC- or OFC-rTMS, such
that sequential courses of stimulation may achieve aggregate remis-
sion rates approaching or exceeding 50%.
Policy of full disclosure: Research funding from NIH, CIHR, Brain
Canada, Ontario Brain Institute, Klarman Family Foundation, Edge-
stone Foundation, and Toronto General and Western Hospital
Foundation, In-kind equipment support for investigator-initiated trials
from MagVenture, advisory role with equity in BrainCheck.
S-2b-02A literature review on ACDC stimulation targeting the anteriorcingulate by double cone coil rTMS
P. Kreuzer1
1University of Regensburg, Regensburg, Germany
Background: Repetitive transcranial magnetic stimulation (rTMS) has
been shown to modulate the neural activity in the dorsal anterior
cingulate (dACC) by placing a double cone coil (DCC) over the
dorsomedial prefrontal cortex (dmPFC). ACDC-stimulation (anterior-
cingulate stimulation by double cone coil rTMS) has been suggested
as a name for this form of rTMS.
Objective: To provide a systematic and comprehensive review on the
application of ACDC stimulation in different indications.
Methods: We systematically searched the MEDLINE� database (
http://www.ncbi.nlm.nih.gov/pubmed/accession date: 5th of June
2016). Due to the heterogeneous naming of ACDC stimulation a
variety of search terms was applied resulting in a total of 239 hits.
Results: ACDC stimulation has been proven to be safe and feasible in
various psychiatric disorders. Clinical results are encouraging, but
have to be considered as preliminary as data from sham-controlled
clinical trials and knowledge about the neurobiological underpinning
are still scarce.
Conclusion: ACDC stimulation represents a promising approach out
of the fast evolving toolbox of non-invasive brain stimulation tech-
niques allowing the functional modulation of a brain area that is
vitally involved in affect- and salience regulation. This may hold
great potential for both neuroscientific research and clinical applica-
tions in the treatment of psychiatric disorders.
Policy of full disclosure: The authors do not have disclosures to
report.
S-2b-03Comparison of figure-8 and DC coil: physiological and physicaldata
M. Schecklmann1, M. Schmaußer1, F. Klinger2, P. Kreuzer1,
L. Krenkel2, B. Langguth1
1Department of Psychiatry and Psychotherapy, University of
Regensburg, Regensburg, Germany; 2Fakultat Maschinenbau,
Ostbayrische Technische Hochschule, Regensburg, Germany
As indicated by TMS manufacturers and simulation studies stimula-
tion with the double-cone coil is indicated to be able to stimulate
deeper structures of the brain with higher intensity and lower focality
in contrast to a standard figure-of-8 coil. This challenges the clinical
practice of using motor threshold of the hand area as measured with a
standard figure-of-8 coil as stimulation intensity for treatment of the
Anterior Cingulate cortex with Double Cone coil (ACDC). Here, we
present data of 24 healthy subjects whose resting motor thresholds of
the first dorsal interosseous and of the tibialis anterior muscle were
compared by using a standard figure-of-8 and a double cone coil. We
found significant effects for coil type (higher motor threshold for the
figure-of-8 coil), stimulation site (higher motor threshold for the
tibialis anterior muscle), and the interaction coil type by stimulation
site as indicated by higher differences between the coil types for the
tibialis stimulation site. No significant effects were found for stimu-
lation side (left vs. right). Magnetic field measurements affirmed the
physiological data showing higher magnetic field strengths for the
Eur Arch Psychiatry Clin Neurosci
123
double cone coil. These findings concretize the differences in motor
thresholds obtained with different coil types and in different brain
areas.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3a Clinical applications 3: convulsive therapy
and deep brain stimulation
Chairs: Kayser and Schlapfer
S-3a-01Stimulation strategies in electroconvulsive therapy
M. Grozinger1
1Department of Psychiatry, Psychotherapy and Psychosomatics,
RWTH Aachen University, Aachen, Germany
Stimulation strategies in Electroconvulsive Therapy (ECT) vary in
numerous parameters starting with the handling of prior medication,
electrode position, anesthesiologic substances, hyperventilation, and
many others. The initial charge has been determined mainly in two
ways. The first takes advantage of known characteristics of the patient
like age and gender, the second is based on measuring the seizure
threshold by titration. Another aspect of the stimulation strategies
concerns the handling of the anticonvulsive effect. In the past, three
classes of methods were applied: constant high dose, automatic
increase of dosage, and multiple titration.
During the last three decades more and more evidence has
emerged in ECT research that seizures can be differently effective in
improving severe mental illness. Physiological measurements during
the ictal phase like the amplitude of the Electroencephalogram (EEG)
and the pulse rate describing the strength of the seizure have been
shown to be associated with the outcome. This finding can be used to
design a different class of stimulation strategies determining the
stimulus intensity from the quality of the prior seizure and the clinical
status of the patient. This approach aims at continually providing high
quality seizures to optimize the outcome.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3a-02Resting state networks, brain oscillatory activity and functionalconnectivity in patients with depression under electroconvulsivetherapy
O. Pogarell1, S. Karch1, B. Kirsch1, A. Chrobok1, D. Krause1,
A. Berman2, V. Kirsch3, H. Engelbregt1,4, D. Keeser1,2
1Department of Psychiatry and Psychotherapy, University of Munich,
Munich, Germany; 2Institute of Clinical Radiology, University of
Munich, Munich, Germany; 3Department of Neurology, Ludwig-
Maximilians-University, Munich, Germany; 4Hersencentrum,
Amsterdam, The Netherlands
Objectives: Dysfunctions of neuronal circuits, brain oscillatory
activity and functional connectivity have been demonstrated to con-
tribute to the pathophysiology of psychiatric disorders. In patients
with depression, studies showed increased functional MRI and EEG
connectivity. Electroconvulsive therapy (ECT) is highly effective in
patients with depression and there is evidence that ECT impacts on
neuronal networks considered to play an important role in the neu-
robiology of depression.
Methods: Using resting state EEG, we investigated neuronal spec-
trotemporal dynamics and brain functional connectivity in sensor and
source space in a large sample of patients with major depression
(n = 240) compared to gender- and age-matched healthy subjects
(n = 292); a subsample of the subjects (n = 20) was investigated
before and during ECT. Quantitative measures, calculated from
artefact-free EEG recordings, included delta (d), theta (h), alpha (a),beta (b) and gamma (c) power (lV2), hemispheric asymmetry,
coherence, phase and eLORETA current source density (CSD)
analyses.
Results: There was an increase in cortical slow-wave activity in
sensor and source space in patients with depression revealing marked
differences in prefrontal cortical networks. Differences in CSD were
found for d, h, a-bands in the subgenual and the rostral anterior
cingulate cortex (ACC) with increased CSD in the patients. Func-
tional d, h and a- connectivity (coherence and phase) were altered
with a predominance in the left hemisphere. Upon ECT there was an
increased delta and theta power in frontal sensor EEG electrodes,
whereas EEG connectivity significantly decreased in both sensor and
source space.
Conclusions: Dysfunctions of the ACC, together with alterations in
fcEEG may contribute to the pathophysiology of major depression.
ECT is associated with changes in both brain electric activity and
EEG connectivity in frontal brain regions, a key anatomical region in
the pathophysiology of depression. Low frequency power increases
and EEG connectivity decreases may be a neurophysiological corre-
late of the mechanisms of action of ECT.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3a-03Magnetic seizure therapy in psychiatric disorders
Sarah Kayser1
1Department of Psychiatry and Psychotherapy, University Medical
Center of Mainz, Mainz, Germany
Magnetic Seizure Therapy (MST) in Psychiatric Disorders. A failure
to respond to two different antidepressant treatments is defined as
treatment-resistant depression (TRD). Currently, electroconvulsive
therapy (ECT) is recommended in the treatment of TRD. However,
due to its stigma and the fear of cognitive side effects, ECT is often
used only as a treatment of last resort. Through the modulation of
several stimulation parameters cognitive side effects could be
reduced, but even when applying the gold standard, the right unilat-
eral (RUL) electrode placement, in particular, anterograde and
retrograde amnesia occur frequently. The underlying mechanism of
amnesia induced by ECT is an affection of the temporal lobe, the
hippocampus, during treatments. Thus, distinct brain regions may be
associated with cognitive side effects and others with the efficacy of
ECT.
Magnetic seizure therapy (MST) is a further development of the
repetitive transracial magnetic stimulation (rTMS). It generates a
strong focal magnetic field that is robust enough to elicit generalized
tonic–clonic seizures under anaesthesia and muscle relaxation. Unlike
ECT‘s electrical stimulation, the magnetic field crosses the skull and
soft tissue unimpeded to reach brain tissues. In preclinical data, the
focality of the electrical stimulation induced by MST and the superior
cognitive side effect profile compared to electroconvulsive shock
(ECS) were demonstrated. In this symposium, cognitive, clinical and
neuroimaging effects of MST in patients with TRD and other psy-
chiatric disorders were presented and discussed.
Eur Arch Psychiatry Clin Neurosci
123
Policy of full disclosure: The authors do not have disclosures to
report.
S-3a-04DBS
Thomas Schlapfer1
1Division of Interventional Biological Psychiatry, University of
Freiburg, Freiburg, Germany
The recent introduction of Deep Brain Stimulation (DBS) for treat-
ment resistant psychiatric disorders might very well lead to the most
significant development in clinical psychiatry of the last 40 years—
possibly offering a rise of hope for patients to whom medicine had
hitherto little to offer. Furthermore, translational research on neuro-
modulation will allow us to glean something about the underlying
cause of patient’s illnesses before figuring out a treatment that
addresses the source of the problem. Major depression offers perhaps
the best example of the rapid progress being made in understanding
the biology of mental illness. Studies on the underlying neurobiology
of major depression have typically focused on the description of
biological differences between patients and healthy subjects such as
alterations of monoaminergic or endocrine systems. Psychotropic
drugs work by altering neurochemistry to a large extent in widespread
regions of the brain, many of which may be unrelated to depression.
We believe that more focused, targeted treatment approaches that
modulate specific networks in the brain—specifically structures
mediating rewarding responses to emotional stimuli—will prove a
more effective approach to help treatment-resistant patients. In other
words, whereas existing depression treatments approach this disease
as a general brain dysfunction, a more complete and appropriate
treatment will arise from thinking of depression as a dysfunction of
specific brain networks that mediate mood and reward signals. A
better understanding of defined dysfunctions in these networks will
invariably lead to a better understanding of patients afflicted with
depression and perhaps contribute to a de-stigmatization of psychi-
atric patients and the medical specialty treating them.
Policy of full disclosure: This work was partly supported by Med-
tronic Inc. in the framework of an Investigator Initiated Trials. The
authors have no further conflicts of interest.
S-3a-05Progress and drawbacks in deep brain stimulation for obsessive–compulsive disorder and Tourette syndrome
Juan Carlos Baldermann1
1Department of Psychiatry and Psychotherapy, University of Cologne,
Cologne, Germany
After more than 15 years of deep brain stimulation for obsessive
compulsive disorder and Tourette syndrome the field has made major
progress and there is increasing evidence that this neuromodulative
treatment is an effective treatment option for both indications. Still,
there are several drawbacks for research and the clinical application
that need to be addressed.
We highlight key clinical trials, discuss different brain structures
as surgical targets, and summarize recent hypotheses on mechanisms
underlying clinical effects. For obsessive–compulsive disorder, deep
brain stimulation of the ventral striatum has been approved by the
European authorities for severe treatment-refractory patients and
appears to be safe and effective. Whether other brains structures
represent a better alternative or constitute complementary targets
remains open. Deep brain stimulation for Tourette syndrome may
have left its experimental character, but difficulties in designing larger
controlled clinical trials and the numerous targets used by different
centres are relevant obstacles to prove efficacy.
To step forward, researchers must face inconvenient questions and
outperform previous clinical research in this field in terms of cohort
size and experimental design. Relevant topics for future investigations
for both indications include treatment predictors, augmentation
techniques, building up international registries and a better under-
standing of adverse events.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3b Safety and NIBS across lifespan
Chairs: Antal and Moliadze
S-3b-01Safety of tES
A. Antal1
1Department of Clinical Neurophysiology, University Medical
Center, Gottingen, Germany
Given the growing interest in the non-invasive low intensity tran-
scranial electrical stimulation (TES) technologies, the aim of this
session is to summarize safety issues surrounding the use of TES for
the treatment of nervous system disorders as well as for non-thera-
peutic uses, Low intensity TES, encompassing transcranial direct
current (tDCS), transcutaneous spinal Direct Current Stimulation
(tsDCS), transcranial alternating current (tACS), and transcranial
random noise (tRNS) stimulation or their combinations so far appears
to be a safe technique. The prevalence of published AEs is different in
studies specifically assessing AEs vs. those not assessing them.
Nevertheless, the profile of adverse events (AEs) in terms of fre-
quency and type is comparable in healthy and clinical populations.
Typical adverse effects are itching, burning sensations under the
electrode or transient, mild headaches and fatigue. Mild AEs are
mainly skin burns, which can be controlled by improving skin–elec-
trode contact. Very rarely mania or hypomania was induced in
patients with depression. Co-application of neuroimaging electro-
physiological measurements was not associated with further safety
problems. Using AC stimulation fewer AEs were reported compared
to DC. According to recent studies safety is established for low-
intensity TES defined as\ 4 mA, up to 60 min duration per day.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3b-02Transcranial electrical stimulation in pediatric brain: ageor individual differences?
V. Moliadze1
1Department of Medical Psychology and Medical Sociology,
Schleswig-Holstein University Hospital (UK-SH), Christian-
Albrechts-University, Kiel, Germany
Since the developing brain shows a greater capacity of brain plas-
ticity, transcranial electrical brain stimulation (tES) might induce
greater benefits in children. So far, applications of tES in pediatric
studies are not well developed. The talk will give an overview of how
age and individual differences impact tES effects in healthy children
Eur Arch Psychiatry Clin Neurosci
123
and adolescents. Additionally, the research consortium STIPED
(stimulation in pediatrics, European Union’s Horizon 2020, Grant
Agreement No. 731827) will be introduced which aims (1) to char-
acterize interaction between brain development and effects of
transcranial direct current stimulation (tDCS) on neuropsychological
function and (2) to apply individual head modelling and electrical
current estimation to guide individualized treatment with tDCS in
different stages of development.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3b-03NIBS in neurodevelopmental disorders
K. Krauel1
1Department of Child and Adolescent Psychiatry and Psychotherapy,
University of Magdeburg, Magdeburg, Germany
Non-invasive brain stimulation (NIBS) allows inducing changes in
regional cortical excitability, plasticity as well as in functional con-
nectivity of brain networks in healthy and clinical populations.
Recently, the use of NIBS has been also suggested for children and
adolescents with neurodevelopmental disorders such as attention
deficit hyperactivity disorder (ADHD) and autism spectrum disorder
(ASD). In ADHD, particularly the dorsolateral prefrontal cortex and
the inferior frontal gyrus have been used as target regions for tran-
scranial direct current stimulation (tDCS) to improve
neuropsychological and clinical parameters. The current research
consortium STIPED (stimulation in pediatrics, European Union’s
Horizon 2020, Grant Agreement No. 731827) aims to investigate both
the clinical relevance and functional mechanisms of NIBS in ADHD
and ASD, identify predictors of individual responsivity to NIBS, and
develop home-treatment solutions to improve accessibility to NIBS.
Policy of full disclosure: The authors do not have disclosures to
report.
S-3b-04Transcranial stimulation targeting memory-relevant sleeposcillations as therapeutic approach in aging and mild cognitiveimpairment
J. Ladenbauer1,2,3, N. Kulzow1,2, S. Paßmann1, J. Ladenbauer4,5,
A. Floel1,2,3
1Department of Neurology, Charite Universitatsmedizin Berlin,
Berlin, Germany; 2NeuroCure Cluster of Excellence, Charite
Universitatsmedizin Berlin, Berlin, Germany; 3Department of
Neurology, University Medicine Greifswald, Greifswald, Germany;4Department of Software Engineering and Theoretical Computer
Science, Technische Universitat Berlin, Berlin, Germany; 5Bernstein
Center for Computational Neuroscience Berlin, Berlin, Germany
Memory-relevant sleep oscillations, in particular cortical slow oscil-
lations (SO) and thalamo-cortical spindle activity, decrease during
aging, which is accompanied by a decline in declarative memory
consolidation. These changes are profoundly accelerated in Alzhei-
mer’s dementia and its precursor mild cognitive impairment (MCI).
We investigated the potential of slow oscillatory transcranial
direct current stimulation, applied during a daytime nap and night-
time sleep in a brain-state-dependent manner, to modulate these
activity patterns and sleep-related memory consolidation in healthy
elderly and MCI patients.
We consistently found positive immediate effects on SO as well as
fast spindle activity. Stimulation further enhanced the functional
coupling between SO and spindle activity, a mechanistic component
considered crucial for the transfer of memories from hippocampus to
cortical long-term storage networks. Regarding memory performance,
we observed that stimulation during a daytime nap significantly
improved visual recognition performance, while stimulation during
night-time sleep unexpectedly resulted in a negative memory effect.
An explanation for this discrepancy and the relation to other rel-
evant studies will be discussed.
Our findings indicate a well-tolerated therapeutic approach for
disordered sleep physiology and memory deficits and advance our
understanding of offline memory consolidation.
Policy of full disclosure: The authors do not have disclosures to
report.
S-4a Multimodal imaging
Chairs: Stagg and Opitz
S-4a-01Accounting for interindividual variation in NIBS usingcomputational models
A. Opitz1
1University of Minnesota, Minneapolis, USA
The response to non-invasive brain stimulation (NIBS) shows large
variation across individuals. Thus, novel stimulation protocols tai-
loring NIBS to the individual are clearly needed. In this talk, I will
discuss how computational models can be used to account for
interindividual variation in anatomy and function in NIBS. I will
further outline challenges lying ahead such that models can fully
guide individualized NIBS protocols.
Policy of full disclosure: A.O. is an inventor on patents and patent
applications describing methods and devices for noninvasive brain
stimulation.
S-4a-02How to reach deep brain structures: modulation of saliencecoding of food by rTMS
T. Kammer1
1Department of Psychiatry, University of Ulm, Ulm, Germany
In the context of hedonic (over-)eating the ventral tegmental area
(VTA) as a core part of the dopaminergic reward system plays a
central role in coding incentive salience of high-caloric food. Tran-
scranial magnetic stimulation does not directly reach such a deep
structure. Therefore, using seed-based resting-state fMRI with a
functionally defined portion of the VTA serving as seed region we
identified an area in the right mid-ventrolateral prefrontal cortex (mid-
VLPFC) connected to the VTA. In the main experiment we investi-
gated whether theta burst TMS over right mid-VLPFC can induce
modulation of calorie-sensitive brain activation in the VTA. Depen-
dent variables were reaction times as well as BOLD activity profiles.
In a sample of 15 healthy male participants, modulation of calorie-
sensitive VTA activation did not significantly differ between the two
TBS protocols. Comparisons with baseline revealed that both TBS
protocols significantly affected calorie-sensitive neural processing of
the mid-VLPFC in a rather similar way. In the VTA significant
modulation of calorie-sensitive activation was observed after con-
tinuous TBS, whereas the modulatory effect of intermittent TBS was
Eur Arch Psychiatry Clin Neurosci
123
less reliable but also associated with a decrease of activation for high-
caloric food images. Neurostimulation of right mid-VLPFC is sug-
gestive as a main entry point of downstream signal changes for high-
and low-caloric food cues that could enforce a shift in valuating
stimuli of initially different incentive salience.
Policy of full disclosure: The authors do not have disclosures to
report.
S-4a-03Imaging transcranial direct current stimulation: contributionsand challenges
Daniel Keeser1,2, Frank Padberg1
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian
University Munich, Munich, Germany; 2Department of Radiology,
Ludwig Maximilian University Munich, Munich, Germany
Non-invasive transcranial brain stimulation (NIBS) methods (e.g.
transcranial direct current stimulation—tDCS, repetitive transcranial
magnetic stimulation—rTMS and others) provide a unique in vivo
intervention for probing the functional role of regions and hubs in
human neural systems that play a role in the pathophysiology of
psychiatric disorders. Recent research has shown that the individual
human brain functional MRI connectivity (fcMRI) shows distinct
patterns of within- and between-subjects variability1,2,3. Anatomically
targeted analyses of NIBS in neuropsychiatric patients and healthy
subjects have generated promising results5,6,7. Even combining sev-
eral neuroimaging methods (resting state fcMRI, task-based fMRI,
Magnetic Resonance Spectroscopy (MRS)) may be useful to detect
classifiers that can be reliably used to predict NIBS effects. These
neuroimaging methods allow individual brain properties as well as the
evaluation of state-dependency4. By combining neuroimaging and
NIBS (term: imaging stimulation) new functional models are expec-
ted to be developed and compared in different states of health and
pathology, e.g. during the course of psychiatric disorders from pre-
clinical stages to relapsing–remitting or chronic disorders.
References:
1. Mueller S, Wang D, Fox MD et al (2013) Individual variability in
functional connectivity architecture of the human brain. Neuron
77(3):586–595
2. Laumann TO, Gordon EM, Adeyemo B, Snyder AZ, Joo SJ, Chen
MY, Gilmore AW, McDermott KB, Nelson SM, Dosenbach NU,
Schlaggar BL, Mumford JA et al (2015) Functional system and areal
organization of a highly sampled individual human brain. Neuron
5(87):657–670
3. Worsching J, Padberg F, Helbich K et al (2017) Test–retest relia-
bility of prefrontal transcranial Direct Current Stimulation (tDCS)
effects on functional MRI connectivity in healthy subjects. NeuroI-
mage. http://doi.org/10.1016/j.neuroimage.2017.04.052
4. Worsching J, Padberg F, Ertl-Wagner B et al (2016) Imaging
transcranial direct current stimulation (tDCS) of the prefrontal cortex-
correlation or causality in stimulation-mediated effects? Neurosci
Biobehav Rev 69:333–356
5. Fox MD, Buckner RL, White MP et al. Efficacy of transcranial
magnetic stimulation targets for depression is related to intrinsic
functional connectivity with the subgenual cingulate. Biol Psychiatry
72(7):595–603
6. Fox MD, Buckner RL, Liu H et al (2014) Resting-state networks
link invasive and noninvasive brain stimulation across diverse psy-
chiatric and neurological diseases. Proc Natl Acad Sci USA
111(41):E4367–E4375
7. Drysdale AT, Grosenick L, Downar J et al (2017) Resting-state
connectivity biomarkers define neurophysiological subtypes of
depression. Nat Med 23:28–38
Policy of full disclosure: Supported by the Federal Ministry of
Research and Education (‘‘Forschungsnetz fur psychische
Erkrankungen’’, German Center for Brain Stimulation-GCBS-WP5).
F.P. has received speaker’s honorarium from Mag&More GmbH and
the neuroCare Group as well as support with equipment from neu-
roConn GmbH, Ilmenau, Germany, Mag&More GmbH and
Brainsway Inc., Jerusalem, Israel. D.K. does not have disclosures to
report.
S-4a-04Towards causality: combining non-invasive brain stimulationand neuroimaging to understand neuroplasticity
C. Stagg1
1Wellcome Centre for Integrative Neuroimaging (WIN), University of
Oxford, Oxford, UK
Neuroplasticity is of vital importance to how we compensate for, and
recover from, a wide variety of neurological and psychiatric condi-
tions. However, studying these processes in humans is complex and
necessarily indirect. One potentially useful model system for under-
standing the physiological changes that underpin plasticity is the
motor system.
Here, therefore, I will discuss recent studies from our group using
NIBS to study the physiological basis of motor plasticity in vivo, in
combination with MR Imaging, MR Spectroscopy and Magnetoen-
cephalography. These studies provide increasing convergent evidence
that changes in local and network-level inhibitory processing is a key
component in plasticity.
Policy of full disclosure: The authors do not have disclosures to
report.
SOP-01 Effects of non-invasive neurostimulation
on brain activity
Chairs: Aleman and Herrmann
SOP-01-01Modulation of spontaneous and task-related alpha-bandoscillations using transcranial alternating current stimulation(tACS)
F. H. Kasten1, C. S. Herrmann1
1Experimental Psychology Lab, Department of Psychology, European
Medical School, Cluster for Excellence ‘‘Hearing for all’’, Carl von
Ossietzky University, Oldenburg, Germany
Oscillatory activity in the brain has been associated with a variety of
cognitive functions. Likewise, dysfunctional neural oscillations have
been implicated in neurological and psychiatric disorders such as
depression, schizophrenia, Parkinson’s disease, Epilepsy or ADHD.
Traditionally, correlational approaches such as Magneto- or Elec-
troencephalography (M/EEG) have been employed to study these
relationships. In recent years, non-invasive techniques to modulate
brain oscillations receive growing popularity in the scientific com-
munity. These methods now allow to directly probe the causal role of
neural oscillations for cognition and offer potential new treatments for
mental disorders involving dysfunctional oscillations. Especially the
application of alternating currents through the scalp by means of
transcranial alternating current stimulation (tACS) offers a
Eur Arch Psychiatry Clin Neurosci
123
comparatively cheap and easy to apply way to modulate endogenous
brain oscillations, while causing little discomfort for participants.
Here we present recent work from our group showing effects of
single-session tACS applied for 20 min on spontaneous and event-
related alpha oscillations. Increased alpha power after tACS was
observed for up to 70 min after stimulation during resting-state EEG.
Similar effects were elicited when tACS was administered while
participants performed a cognitive task involving frequent event-re-
lated power modulations in the alpha band. In that study, the overall
power increase in the alpha band was accompanied by enhanced
event-related alpha-desynchronization as well as facilitated perfor-
mance in the cognitive task. Subsequent utilization of concurrent
tACS-MEG revealed a similar facilitation of event-related desyn-
chronization in the alpha band already during the continuous
application of tACS. Our results demonstrate that tACS is capable of
eliciting long-lasting, frequency specific effects, which were directly
related to changes in behavioral performance. Further, the continuous
application of tACS during a cognitive task facilitated pre-existed
task-related power modulations in the stimulated frequency band,
rather than overwriting them.
Policy of full disclosure: CSH has filed a patent application on brain
stimulation and received honoraria as editor from Elsevier Publishers,
Amsterdam. FHK declares no competing interests.
SOP-01-02The effects of frontal tACS on reversal learning
M. Wischnewski1, D. Schutter1
1Donders Institute, Donders Centre for Cognition, Radboud
University, Nijmegen, The Netherlands
Reward and punishment learning is associated with increased activity
in the fronto-cortical network1. This frontal network is accompanied
by oscillatory activity in the theta and beta range2. In a previous study
we showed that frontal transcranial alternating current stimulation
(tACS) at the theta range can improve reversal learning performance3.
Here we investigated whether beta tACS has similar effects. Fur-
thermore, we investigated frontal coherence to speculate on the
neurophysiological mechanisms underlying any behavioural effects.
In the present study 108 healthy right-handed volunteers received
1 mA tACS at 20 Hz by applying four electrodes over the frontal
cortex for 12 min. Volunteers were divided into three groups
(n = 36). In the two experimental groups intra-hemispheric tACS was
either in-phase or anti-phase. The third group received sham stimu-
lation. During stimulation a learning task was performed in which
participants had to reverse strategy from a high-risk to a low-risk
option. Before and after the task and stimulation a 4-min resting state
EEG was recorded. Reversal learning performance was investigated
and was correlated to coherence measurements in the beta and theta
range.
Results showed that reversal learning performance was improved
after in-phase tACS compared to sham. Coherence in the theta range
was increased after in-phase stimulation in the left, but not right
frontal cortex. The pretest to posttest change in coherence was posi-
tively correlated with reversal learning performance. Furthermore,
coherence measurements did not depend on the EEG reference
position.
In accordance with previous studies, we here show that frontal
tACS can improve reversal learning performance3. Furthermore, we
show that frontal beta oscillations may affect theta coherence sug-
gesting a relationship between frontal theta and beta oscillatory
activity.
References:
1. Haber SN, Knutson B (2010) The reward circuit: linking primate
anatomy and human imaging. Neuropsychopharmacology 35(1):4–26
2. Fries P (2015) Rhythms for cognition: communication through
coherence. Neuron 88(1):220–235
3. Wischnewski M, Zerr P, Schutter DJLG (2016) Effects of theta
transcranial alternating current stimulation over the frontal cortex on
reversal learning. Brain Stimul 9(5):705–711
Policy of full disclosure: The authors do not have disclosures to
report.
SOP-01-03The effects of rTMS treatment for auditory verbal hallucinationson inner speech related brain networks
L. Bais1,2, E. Liemburg1,2,4, A. Vercammen6, Richard Bruggeman4,5,
R. Knegtering1,2,4, A. Aleman1,3
1Department of Neuroscience, and BCN NeuroImaging Center,
University of Groningen, University Medical Hospital Groningen,
Groningen, The Netherlands; 2Lentis, Psychiatric Institute,
Groningen, The Netherlands; 3Department of Psychology, University
of Groningen, Groningen, The Netherlands; 4University of
Groningen, University Medical Center Groningen, Rob Giel Research
Center, Groningen, The Netherlands; 5Department of Psychiatry,
University of Groningen, University Medical Center Groningen,
Groningen, The Netherlands; 6Independent researcher:
No abstract for publication.
Eur Arch Psychiatry Clin Neurosci
123
SOP-01-04Antidepressant effects and change in brain activationof transcranial pulsed electromagnetic fields for treatmentresistant depression
S. M. van Belkum1,2, E. M. Opmeer2, M. K. de Boer1,
R. A. Schoevers1, A. Aleman2
1Department of Psychiatry, Research School of Behavioral and
Cognitive Neurosciences (BCN), Interdisciplinary Center
Psychopathology of Emotion regulation (ICPE), University of
Groningen, University Medical Center Groningen, Groningen, The
Netherlands; 2Department of Neuroscience, University of Groningen,
University Medical Center Groningen, Groningen, The Netherlands
Noninvasive neurostimulation with transcranial Pulsed Electromag-
netic Fields (tPEMF) is a promising method for the treatment of
treatment resistant depression (TRD). One study has shown remission
of depressive symptoms in patients with TRD but this has not been
replicated yet. We investigated the short- and long-term efficacy of
tPEMF and its effect on brain activation in participants with TRD, as
no evidence on this is available.
We included 55 participants with TRD in a sham-controlled
double-blind multicenter trial. Eligible participants were randomly
assigned to either daily 30 min active tPEMF stimulation or daily
sham stimulation, during 5 weeks. Severity of depression was
assessed directly pre- and post-treatment, and 5 and 15 weeks post-
treatment. We performed a functional MR-scan directly pre- and post-
treatment. Clinical outcome was defined as change on the 17-item
Hamilton depression rating scale (HAMD-17) directly post-treatment.
Participants performed two fMRI-tasks: an emotional processing task
and a reward task.
Of the 55 included participants, 50 completed the treatment pro-
tocol. There was no difference in outcome between the active (pre–
post HAMD-17: 22–16) and the sham group (pre–post HAMD-17:
22–17) on change in depression post-treatment. A small improvement
was observed over time independent of treatment that continued after
the 5-week treatment period until the last follow-up measure. Fur-
thermore, the active treatment group showed decreased activation
during reward processing in the left inferior frontal gyrus and in a
cluster comprising the right lingual gyrus and the posterior part of the
middle temporal gyrus. We did not find an effect of tPEMF on
emotional processing.
In contrast to a previous study using a similar design, our study
showed that treatment with active tPEMF was not superior to sham
treatment in patients with TRD. However, we did observe a small
difference in brain activation during reward processing.
Policy of full disclosure: The authors do not have disclosures to report.
SOP-01-05Quadri-pulse theta burst stimulation using ultra-high frequencybursts at I-wave periodicity induces direction dependent bi-directional plasticity in human motor cortex
N. H. Jung1, B. Gleich2, N. Gattinger2, H. R. Siebner3,4, V. Mall1
1School of Medicine, Technical University of Munich, Social
Pediatrics, Heiglhoftstr. 65, 81377 Munich, Germany; 2Munich
School of BioEngineering (MSB), Technische Universitat Munchen,
Boltzmannstraße 11, 85748 Garching, Germany; 3Danish Research
Center for Magnetic Resonance (DRCMR), Hvidovre Hospital,
Kettegaard Alle 30, 2650 Hvidovre, Denmark; 4Department of
Neurology, Copenhagen University Hospital, Bispebjerg,
Copenhagen, Denmark
Introduction: Patterned transcranial magnetic stimulation (TMS) such
as theta burst stimulation (TBS) or quadri-pulse stimulation (QPS)
can induce long-term potentiation (LTP)-like and long-term depres-
sion (LTD)-like effects in human primary motor cortex (M1). These
mechanisms are considered to be synaptic processes underlying
learning and memory. Impairments are thought to play a pivotal role
in the phenotype of various medical conditions (e.g. bipolar disor-
ders). Here, we aimed to test the plasticity-inducing capabilities of a
novel protocol that merged TBS and QPS at interstimulus intervals
(ISI) that mimic I-wave periodicity (i.e. 1.5 ms/666 Hz) with an
anterior–posterior (AP) and posterior–anterior (PA) directed current
flow in M1.
Methods: We investigated healthy volunteers (n = 12 per protocol)
with 360 bursts of quadri-pulse TBS (qTBS) that was continuously
given to M1 (1440 full-sine pulses). QTBS consisted of repeated
bursts of four biphasic TMS pulses (duration: 160 ls) separated by
ISI of 1.5 ms (666 Hz) and inter-burst intervals of 200 ms. (5 Hz)
TMS was applied by a custom-made magnetic stimulator (MSB,
Munich). Resting motor threshold (rMT), and motor evoked poten-
tials (MEP) with stimulus intensities to target amplitudes of 1mv
(SI1 mV) were measured before (Pre) qTBS, directly after (Post1),
after 15 min (Post2), after 30 min (Post3) and after 60 min (Post4).
Results: PA-qTBS at 666 Hz caused a LTD-like reduction, whereas
AP-qTBS at 666 Hz induced LTP-like increase in mean MEP
amplitude outlasting for approximately 60 min. As expected, baseline
data of rMT prior to qTBS differed significantly, with higher
thresholds in AP direction.
Discussion: Continuous qTBS at 666 Hz can induce lasting changes
in corticospinal excitability. Induced current direction in the brain
appears to be relevant when qTBS targets I-wave periodicity, cor-
roborating that high-fidelity spike timing mechanisms are critical for
inducing bi-directional plasticity in human M1 supporting the need of
individualized non-invasive brain stimulation techniques.
Policy of full disclosure: The authors do not have disclosures to
report.
SOP-02 Clinical applications
Chairs: Schonfeldt-Lecuona and Cordes
SOP-02-01The bipolar depression electrical treatment trial (BETTER):results from a randomized clinical trial
B. de Sampaio Pereira
No abstract for publication.
SOP-02-02Attitudes and educational work regarding rTMS
C. Engelke1
1Department of Psychiatry and Psychotherapy, Medical Faculty,
Heinrich Heine University, Dusseldorf, Germany
Brain stimulation has been shown to be safe and effective, but the use
of brain stimulation techniques still underlies public criticism1,2.
There are several public stigma associated with brain stimulation
techniques for the treatment of depression, but patients who have
received brain stimulation are more favourable to it2. This also affects
the intention of a therapy and treatment compliance3. In this talk, we
Eur Arch Psychiatry Clin Neurosci
123
will present the results of a study examining the attitude towards
rTMS treatment among 122 depressive in-patients and draw conclu-
sions on factors influencing educational work and the handling of
patients.
References:
1. Chakrabarti S, Grover S, Rajagopal R (2010) Electroconvulsive
therapy: a review of knowledge, experience and attitudes of patients
concerning the treatment. World J Biol Psychiatry 11:525–537
2. Walter G, Martin J, Kirkby K, Pridmore S (2001) Transcranial
magnetic stimulation: experience, knowledge and attitudes of recip-
ients. Aust N Z J Psychiatry 35:58–61
3. Vermeire E, Hearnshaw H, Van Royen P, Denekens J (2001)
Patient adherence to treatment: three decades of research. A com-
prehensive review. J Clin Pharm Ther 26:331–342
Robert Ostroff (USA): Creating an interventional psychiatry service.
Policy of full disclosure: The authors do not have disclosures to report.
SOP-02-03Creating an interventional psychiatry service
R. Ostroff1, R. Katz1, S. Wilkinson1, G. Sanacora1
1Yale Department of Psychiatry, Yale Psychiatric Hospital, New
Haven, CT, USA
Interventional psychiatry is an emerging subspecialty that uses vari-
ous procedural neuromodulation techniques to treat mental
dysfunction that views disruption of the normal chemo-electric
functioning of the brain as its proximal cause. Unlike traditional
pharmacologic interventions, the interventions that comprise inter-
ventional psychiatry involve the administration of electrical energy in
a controlled and monitored setting to induce a grand mal seizure, the
use of neurostimulation to increase neuroplasticity through direct
cortical stimulation or vagal nerve stimulation and the use of rapid
acting neuromodulators that can be administered intravenously or
intranasally. The uses of these techniques require special competen-
cies in both administering and monitoring that are beyond those
needed to prescribe a medication. These interventions require special
competency beyond the role of typical psychiatric training. We pre-
sent the Yale Interventional Psychiatry Service as a model for clinical
care, research and training. We will present the necessary steps to
organizing an interventional psychiatry service including required
competencies, staff training, the education of residents, the develop-
ment of a standardized database, research opportunities and ongoing
quality improvement through the use of a tumor board model.
Policy of full disclosure: The authors do not have disclosures to report.
S-5a Individualizing treatment
Chairs: Plewnia and Keeser
S-5a-01Understanding and predicting rTMS effect for the treatmentof negative symptoms in schizophrenia
Alkomiet Hasan, Berthold Langguth, Joachim Cordes, Birgit Kunze,
Nikolaos Koutsouleris, Thomas Wobrock and RESIS Study team
No abstract for publication.
S-5a-02Stimulation genetics: new perspectives for an individualized brainstimulation
C. Plewnia1
1Department of Psychiatry and Psychotherapy, Neurophysiology and
Interventional Neuropsychiatry, University of Tubingen, Tubingen,
Germany
No abstract for publication.
S-5a-03Individualized treatment of positive symptoms in schizophrenia:potentials and pitfalls
S. Winkelbeiner1, Philipp Homan1,2
1Translational Research Center, University Hospital of Psychiatry and
Psychotherapy, University of Bern, Bern, Switzerland; 2Center for
Psychiatric Neuroscience, The Feinstein Institute for Medical
Research, Hofstra Northwell School of Medicine, New York, USA
Individualized treatment of positive symptoms in schizophrenia requires
an understanding of the underlying neurobiological mechanisms of the
specific symptom.We investigated two of the major positive symptoms:
formal thought disorder (FTD) and auditory verbal hallucinations
(AVH). Regarding FTD, we found alterations in white matter integrity,
gray matter thickness, subcortical volume, and perfusion in language-
related areas to be associated with the severity of FTD. These findings
may contribute to a better understanding of involved neurobiological
processes and to the development of specific treatments.
With regard to AVH, we focused on cerebral blood flow (CBF) in
the left superior temporal gyrus (STG) and other language areas
before and after treatment with transcranial magnetic stimulation
(TMS). Treatment-augmentation with brain stimulation techniques is
increasing and has shown promising if mixed results, possibly due to
variability in treatment response. CBF measured with arterial spin
labelling might be a potential predictor of treatment response. Indeed,
we found evidence for higher pre-treatment CBF in the STG in TMS
responders compared to non-responders. This suggests that TMS
might be appropriate only for a clinical sub-population with a high
enough CBF in the left STG.
However, interpreting treatment response is not without pitfalls.
Depending on the study design, factors such as random within-subject
variability and regression to the mean need to be considered. For valid
classification, the difference in variation between treatment and
control have to be calculated, and only if this difference is clinically
meaningful, are subsequent responder analyses indicated.
Taken together, the detection of potential biomarkers of treatment
response has the potential to individualize treatment, but critically
depends on sound statistical modelling.
Policy of full disclosure: The authors do not have disclosures to report.
S-5a-04Computational modelling studies for non-invasive brainstimulation
M. Parazzini1, E. Chiaramello1, S. Fiocchi1, P. Ravazzani1
1Consiglio Nazionale delle Ricerche, Istituto di Elettronica e di
Ingegneria dell’Informazione e delle Telecomunicazioni, IEIIT CNR,
Milan, Italy
Brain neuronal activity can be modulated by non-invasive brain
stimulation (NIBS) techniques, via electric currents induced by an
Eur Arch Psychiatry Clin Neurosci
123
externally generated electric or magnetic field. The possible appli-
cations of NIBS in clinics as a potential non-pharmacologic, non-
invasive, painless and reversible approach to different neurological
disorders, has attracted the interest of many researchers. NIBS is now
considered an elective tool as a treatment option for pain, psychiatric,
neurodegenerative and cognitive disorders, for the neurorehabilitation
from brain injuries and the diagnosis of central motor pathway
damages. One crucial aspect in the development and optimization of
NIBS treatment is the knowledge about the actual distributions of the
electric fields and the current densities induced in the target brain
areas.
Numerical modelling of the interaction between the electromag-
netic fields and the dielectrically inhomogeneous human body
provides a unique way of assessing the resulting spatial distributions
of internal electric fields and currents density. Knowledge of these
parameters is of crucial importance in understanding such interactions
and is a prerequisite when assessing, designing, or optimizing ther-
apeutic or diagnostic medical applications that employ
electromagnetic fields, such as NIBS.
This paper, therefore, aims to address how the use of electro-
magnetic computational techniques can support the development and
optimization of NIBS applications, boosting the translation of com-
putational bio-electromagnetics approaches into valuable information
for therapy and diagnosis.
Policy of full disclosure: The authors do not have disclosures to
report.
S-5b Cognition and psychotherapy, state dependency
Chairs: Brem and Wolkenstein
S-5b-01Trait rumination moderates the effects of anodal tDCSover the right dorsolateral prefrontal cortex on cognitiveprocessing of emotional information
M.-A. Vanderhasselt1,2,3, A. Sanchez 3, H. Josephy 4, C. Baeken1,5,
A. R Brunoni 6, R. De Raedt3
1Department of Psychiatry and Medical Psychology, Ghent
University, Ghent, Belgium; 2Faculty of Medicine and Pharmacy,
Free University Brussels, Brussels, Belgium; 3Department of
Experimental-Clinical and Health Psychology, Ghent University,
Ghent, Belgium; 4Department of Data Analysis, Ghent University,
Ghent, Belgium; 5Department of Psychiatry, Free University
Brussels, Brussels, Belgium; 6Service of Interdisciplinary
Neuromodulation (SIN), Laboratory of Neurosciences (LIM-27),
Department and Institute of Psychiatry, University of Sao Paulo, Sao
Paulo, Brazil
Healthy individuals reporting higher (as compared to lower) levels of
trait rumination recruit more neural activity in dorso-cortical regions
when inhibiting negative information. In the present study, we
investigated whether these latter neural correlates are causally
implicated in cognitive control in these ruminating individuals. We
included a sample of thirty-five healthy volunteers reporting a broad
range of trait rumination levels and the Cued Emotional Control Task,
a measure of cognitive control indexed by cognitive costs for
inhibiting versus providing a habitual response for emotional infor-
mation, was administered. Participants completed the task after
receiving both real and sham-placebo (counterbalanced order) anodal
transcranial Direct Current Stimulation (tDCS) over the right dorso-
lateral prefrontal cortex (DLPFC). Results reveal that the tDCS
induced effects on cognitive costs for emotional information were
associated with individual differences in trait rumination: the higher
the trait rumination level, the less cognitive costs following real
neuromodulation of the right DLPFC. Interestingly, these effects were
observed for both positive and negative stimuli. Overall, the data
suggest that the right DLPFC is causally involved in the alteration of
Fig. 1 S-5b-01: Effect of rumination on the compound scores for cognitive control.
Eur Arch Psychiatry Clin Neurosci
123
cognitive control in healthy individuals who tend to ruminate, pos-
sibly by helping them to disengage from emotional material.
Policy of full disclosure: The authors do not have disclosures to
report.
S-5b-02The psychomotor retardation may be a marker of responseto rTMS treatment in patients with major depressive disorder
A. Sauvaget1, S. Bulteau1,2, T. Deschamps3, V. Thomas-Ollivier3
1CHU de Nantes, Addictology and Liaison Psychiatry Department,
Nantes, France; 2University of Nantes-University of Tours, INSERM,
SPHERE U1246-‘‘methodS for Patients-centered outcomes & HEalth
REsearch’’, Nantes, France; 3Laboratory ‘Movement, Interactions,
Performance’ (EA 4334), Faculty of Sport Sciences, University of
Nantes, Nantes, France
Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic
option often used in routine care plans for patients with major
depressive disorder (MDD).
Cognitive state and state-dependency influence the effectiveness
of rTMS. Based on our recent studies, we therefore assume that
psychomotor retardation (PMR), a core symptom of depression, can
be a marker of response to rTMS. Thus, we aimed at better under-
standing the interaction between the cognitive component of the PMR
and the rTMS in patients with MDD.
First, we investigated the feasibility of a comprehensive battery of
tests assessing PMR in MDD patients after a 3-week protocol of
rTMS. All these measures not only were feasible, free of adverse
effects, and well tolerated by the MDD patients in naturalistic con-
ditions before or after the rTMS protocol. Interestingly, preliminary
insights emerged from improvements in some psychomotor assess-
ments following the intervention, especially in balance performance.
We then examined whether postural control variables, coming from
the analysis of center-of-pressure trajectories recorded by a force
platform, could be a relevant hallmark of depression-related PMR.
We found that the initial postural instability while backward counting
is likely a sound moderator of positive outcomes in MDD patients
after rTMS intervention. The improved dual task performance might
be indicative of improvement in cognitive efficiency. Accordingly,
we explored the cognitive component of PMR through the analysis of
verbal fluency (VF) performance in unipolar and bipolar depression.
We also examined whether rTMS could improve concomitantly the
PMR and VF capacities. Correlations between the Retardation Rating
Scale for Depression and VF performances were found after treat-
ment, showing the cognitive role of psychomotor functioning in
depression. Overall, all these promising results arise the issues of how
to characterize and measure objectively the PMR, and to better
understand the mechanisms of rTMS in depressive disorders.
References:
1. Thomas-Ollivier V, Foyer E, Bulteau S, Pichot A, Valriviere P,
Sauvaget A, Deschamps T (2017) Cognitive component of psy-
chomotor retardation in unipolar and bipolar depression: is verbal
fluency a relevant marker? Impact of repetitive transcranial stimula-
tion. Psychiatry Clin Neurosci 71(9):612–623
2. Deschamps T, Sauvaget A, Pichot A, Valriviere P, Maroulides M,
Bois A, Bulteau S, Thomas-Ollivier V (2016) Posture-cognitive dual-
tasking: a relevant marker of depression-related psychomotor retar-
dation. An illustration of the positive impact of repetitive transcranial
magnetic stimulation in patients with major depressive disorder.
J Psychiatr Res 83:86–93
3. Thomas-Ollivier V, Deschamps T, Bulteau S, Le Gall F, Pichot A,
Valriviere P, Vachon H, Sauvaget A. Effect of Repetitive Transcra-
nial Magnetic Stimulation on Psychomotor Retardation in Major
Depression: A Pilot Feasibility Study. J Neuropsychiatry Clin Neu-
rosci. 2016 Winter;28(1):62-5.
4. Miniussi C, Harris JA, Ruzzoli M (2013) Modelling non-invasive
brain stimulation in cognitive neuroscience. Neurosci Biobehav Rev
37(8):1702–1712
5. Silvanto J, Pascual-Leone A (2008) State-dependency of tran-
scranial magnetic stimulation. Brain Topogr 21(1):1–10
Policy of full disclosure: The authors do not have disclosures to report.
S-5b-03Challenging control over emotions in borderline personalitydisorder with tDCS
L. Wolkenstein1
1LMU, Munich, Germany
No abstract for publication.
S-5b-04Cognitive and electrophysiological mechanisms of enhancing fluidintelligence
A.-K. Brem1,2 on behalf of the Honeywell SHARP Team1Max-Planck Institute of Psychiatry, Munich, Germany; 2Berenson-
Allen Center for Noninvasive Brain Stimulation, Department of
Neurology, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, USA
To date, it is unclear whether fluid intelligence (Gf), an important pre-
dictor for professional success, wealth and health, can be enhanced, and
what the involved mechanisms might be. We investigated this question
in a randomized, controlled, double-blind, multicenter study. 392 par-
ticipants were assigned to receive executive function training combined
with either transcranial electrical stimulation or sham stimulation, or
active control training combined with sham stimulation. The results
show that changes in Gf are achievable as a function of training progress
and subsequent improvement in working memory performance, but not
other executive functions. At the neurophysiological level, the efficacy of
neurostimulation on cognitive training and Gf improvement depended on
frontal midline theta power. We further replicated this effect in an
independent within-subject design study. Understanding the effects of
physiological traits will help us to optimise and individualise interven-
tions using brain stimulation and cognitive training.
Policy of full disclosure: This research is based upon work supported
by the Office of the Director of National Intelligence (ODNI), Intel-
ligence Advanced Research Projects Activity (IARPA), via
2014-13121700007. The views and conclusions contained herein are
those of the authors and should not be interpreted as necessarily
representing the official policies or endorsements, either expressed or
implied, of the ODNI, IARPA, or the U.S. Government. The U.S.
Government is authorized to reproduce and distribute reprints for
Government purposes notwithstanding any copyright annotation
thereon. The speaker has no conflicts of interest.
S-5b-05Towards neurocognitive stimulation to treat affective disorders
J. O’Shea1
1Wellcome Centre for Integrative Neuroimaging, Oxford Centre for
Functional MRI of the Brain (FMRIB), Nuffield Department of
Clinical Neurosciences, University of Oxford, Oxford, UK
Eur Arch Psychiatry Clin Neurosci
123
Cognitive neuropsychological models emphasize a causal role for
negative cognitive biases in susceptibility to anxiety and depression.
Acute administration of antidepressant drugs has been shown to shift
cognitive biases from negative to positive, with variation across
individuals predicting clinical response heterogeneity weeks later.
Thus brain circuits that encode cognitive biases are rational targets for
therapeutic brain stimulation.
While prefrontal TMS is an approved clinical treatment for
depression, tDCS is in development, with growing evidence for its
clinical efficacy. Relatively little is known about the mechanisms by
which prefrontal tDCS could drive affective change. We investigated
this is in a series of experiments.
We found that a single session of bifrontal tDCS reduced threat
vigilance, mimicking the acute cognitive impact of antidepressant
drugs. Next we tested whether this arises by tDCS changing aberrant
fronto-limbic signalling. In a high trait anxious sample, fMRI during
an attentional control task revealed that tDCS suppressed (hyperac-
tive) amygdala threat reactivity, and reduced the behavioural
influence of threatening face distractors. Thus, bifrontal tDCS causes
acute neuro-cognitive changes relevant to anxiety.
Next we asked whether bifrontal tDCS could augment positive
cognitive change induced by training. With attention bias modifica-
tion training in healthy volunteers we found null results. A follow-up
study in a high trait anxious sample also yielded a null effect. In both
studies, there was a null effect of the cognitive training itself. How-
ever, the combination of positive training and tDCS did reduce a
salivary cortisol marker of stress.
Using a reward-guided decision making task, we asked whether
bifrontal tDCS could change healthy volunteers’ learning rates from
probabilistic positive or negative outcomes. Stimulation increased the
influence of positive outcomes on participants’ subsequent instru-
mental choices, increasing approach behaviour. Ongoing research
aims to clarify the neural mediators of this tDCS-induced cognitive
change.
Policy of full disclosure: This work was supported by research
funding from the UK Medical Research Council. The authors have no
conflicts of interest.
S-6a Clinical applications: other
Chairs: Brunoni and Baeken
S-6a-01A multimodal investigation on the biological markers associatedwith the antidepressant effects of transcranial direct currentstimulation
A. Brunoni1,2
1Service of Interdisciplinary Neuromodulation, Department and
Institute of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil;2Department of Psychiatry and Psychotherapy, LMU Munich,
Munich, Germany
Transcranial direct current stimulation (tDCS) has been investigated
as a treatment for major depressive disorder, although results have
been heterogeneous: although some patients improve significantly
after tDCS, others show low response. Investigating predictors of
tDCS antidepressant response can identify patients that would
potentially benefit from tDCS and contribute to a better understanding
on the mechanisms of action of tDCS. In the Escitalopram vs. Electric
Current Therapy for Treating Depression Clinical Study (ELECT-
TDCS) trial, we evaluated the clinical efficacy of tDCS compared to
placebo and escitalopram, finding superiority of escitalopram vs.
tDCS and placebo and superiority of tDCS vs. placebo. In ELECT-
TDCS, we collected potential biomarkers of tDCS antidepressant
response. In this presentation data regarding clinical and neuropsy-
chological variables, heart rate variability, motor cortical excitability,
serum neurotrophin levels and voxel-based morphometry of the brain
in the context of antidepressant prediction will be shown and
discussed.
Policy of full disclosure: ARB receives a CAPES-Humboldt fellow-
ship for experienced researchers and is a consultant of the Neurocare
(Munich, Germany) group.
S-6a-02The impact of accelerated HF-rTMS on neurochemicals in majordepression: insights from 1H MR spectroscopy
C. Baeken1,2,3
1Department of Psychiatry and Medical Psychology, Ghent
University, Ghent, Belgium; 2Department of Psychiatry, Universitair
Ziekenhuis Brussel (UZBrussel), Vrije Universiteit Brussel (VUB),
Brussels, Belgium; 3Ghent Experimental Psychiatry (GHEP) Lab,
Ghent University, Ghent, Belgium
Accelerated repetitive transcranial magnetic stimulation (rTMS)
paradigms are currently used to improve treatment in major depres-
sive disorder (MDD). Although these new treatment algorithms seem
to be able to alleviate mood over a relatively short period of time, no
studies yet examined its cellular effects with regard to clinical out-
come, safety and neural integrity. We recruited eighteen right-handed
antidepressant-free unipolar treatment resistant depressed (TRD)
patients who participated in a 2-week randomized sham-controlled
accelerated high frequency (aHF)-rTMS crossover treatment study,
applied to the left dorsolateral prefrontal cortex (DLPFC). All
underwent 1H MR spectroscopy before and after each week of aHF-
rTMS treatment. We explicitly focused on neurochemical concen-
trations in the bilateral DLPFC and rostral anterior cingulate cortex
(rACC). At baseline, compared to healthy individuals, TRD patients
displayed significant lower glutaminergic concentrations in the left
DLPFC only. Clinical improvement was related to significant GABA
increases also in the left DLPFC only. No influences on neuronal
integrity were observed in any of the predefined regions of interest.
Besides that left DLPFC aHF-rTMS treatment resulted in immediate
GABA increases in the targeted area, this supposed excitatory neu-
rophysiologic stimulation paradigm seems to recruit primarily
inhibitory neurons, without affecting neuronal integrity.
Policy of full disclosure: The authors do not have disclosures to
report.
S-6a-03Transcranial direct current stimulation (tDCS) for obsessive–compulsive disorder
G. D’Urso1, A. R. Brunoni2,3, M. P. Mazzaferro4, A. Anastasia4,
A. de Bartolomeis5, A. Mantovani6,7
1Department of Clinical Neurosciences, Anesthesiology and
Pharmachoutilization, University Hospital of Naples Federico II,
Naples, Italy; 2Service of Interdisciplinary Neuromodulation,
Department and Institute of Psychiatry, University of Sao Paulo, Sao
Paulo, Brazil; 3Department of Psychiatry and Psychotherapy, LMU
Munich, Munich, Germany; 4Department of Public Health, University
of Naples Federico II, Naples, Italy; 5Department of Neurosciences,
Reproductive and Odontostomatological Sciences, University of
Eur Arch Psychiatry Clin Neurosci
123
Naples Federico II, Naples, Italy; 6Department of Physiology,
Pharmacology and Neuroscience, Sophie Davis School of Biomedical
Education, City University of New York, New York, NY, USA;7Division of Experimental Therapeutics, Department of Psychiatry,
Columbia University/New York State Psychiatric Institute, New
York, NY, USA
Introduction: Presupplementary motor area (pre-SMA) hyperactivity
has been detected in obsessive–compulsive disorder (OCD) patients,
but it is not clear whether this is a putative primary cause or a
compensatory mechanism in this disorder pathophysiology. Consid-
ering the polarity-dependent effects on cortical excitability of
transcranial direct current stimulation (tDCS), we applied cathodal
and/or anodal tDCS to the pre-SMA of OCD patients to test which
current polarity might better improve symptoms.
Methods: Twelve treatment resistant OCD patients received in the
first phase of the study either 10 anodal (n = 6) or 10 cathodal
(n = 6) daily consecutive 2 mA/20 min tDCS sessions with the
active electrode placed bilaterally over the pre-SMA. In case of
improvement or no change in symptoms severity, the subjects
underwent 10 more sessions using the same current polarity. In case
of symptoms worsening after the first 10 sessions they were switched
to the other polarity for 10 more sessions to test the hypothesis of a
polarity-dependent effect. Therefore, each subject received 20 tDCS
sessions. The Yale–Brown Obsessive–Compulsive Scale (Y-BOCS)
and the Sheehan Disability Scale (SDS) were administered biweekly
to assess changes in symptoms severity.
Results: After 10 sessions, 50% of patients who initially received
anodal stimulation were switched to cathodal, while 100% of patients
initially assigned to cathodal stimulation continued on the same
polarity. At the end of the study, a statistically significant decrease
was observed in the mean Y-BOCS scores of those patients who
underwent cathodal tDCS, while no pre–post difference was found in
the scores of patients following anodal tDCS.
Discussion: Our results suggest that cathodal but not anodal tDCS
over the pre-SMA might be of help when dealing with treatment
resistant OCD patients.
Fig. 1 S-6a-03
References:
1. D’Urso G, Brunoni A, Mazzaferro M, Anastasia A, de Bartolomeis
A, Mantovani A (2016) Transcranial direct current stimulation for
obsessive–compulsive disorder: a randomized, controlled, partial
crossover trial. Depression Anxiety 33(12):1132–1140
2. Senco N, Huang Y, D’Urso G, Parra L, Bikson M, Mantovani A
et al (2015) Transcranial direct current stimulation in obsessive–
compulsive disorder: emerging clinical evidence and considerations
for optimal montage of electrodes. Expert Rev Med Devices
12(4):381–391
3. D’Urso G, Brunoni A, Anastasia A, Micillo M, de Bartolomeis A,
Mantovani A (2015) Polarity-dependent effects of transcranial direct
current stimulation in obsessive–compulsive disorder. Neurocase
22(1):60–64.
Policy of full disclosure: The authors do not have disclosures to
report.
S-6a-04Cognitive brain stimulation
A. T. Sack1
1Faculty of Psychology and Neuroscience and Maastricht Brain
Imaging Centre, Maastricht University, Maastricht, The Netherlands
Human cognition requires, and is to a large extent based on, our
ability of selectively focusing on certain aspects of our surroundings.
This ability of spatial attention control is often severely impaired after
stroke and in brain diseases including depression or dementia.
Investigating the neurobiological mechanism underlying these cog-
nitive abilities is paramount for understanding the relationship
between brain and cognition as a prerequisite to develop new means
to initiate, guide, and support cognitive enhancement and rehabilita-
tion. Magneto-/electroencephalography research demonstrated that
attention control is related to oscillatory mechanisms in specific lower
frequency-bands (4–20 Hz), especially the alpha frequency (10 Hz).
Directing attention to one visual hemifield lateralizes alpha power in
parietal cortices. We applied transcranial alternating current stimu-
lation (tACS) to modulate alpha lateralization as measured by EEG
and then assessed how such a tACS-induced change in alpha power
lateralization leads to respective changes in behavioral task perfor-
mances in healthy volunteers. Based on these studies, we then applied
this tACS alpha lateralization protocol also in patients suffering from
lateralized spatial attention deficits (hemineglect) in an attempt to
specifically support their cognitive rehabilitation.
Policy of full disclosure: The authors do not have disclosures to
report.
S-6b NIBS in cells and animals
Chairs: Reis and Nitsche
S-6b-01Testing neuromodulation avenues in model rats
R. Hadar1, C. Winter1
1Department of Psychiatry and Psychotherapy, Charite
Universitatsmedizin Berlin, Charite Campus Mitte, Berlin, Germany
The current challenge in the realm of psychiatry afflictions is to
progress from conventional treatments to individualized ones, how-
ever for this the underlying neurobiological mechanisms should be
thoroughly studied in an effort to identify biomarkers used to asso-
ciate symptoms with the underlying neurobiological deficits. To this
end, neuromodulation not only constitutes a promising novel inter-
vention technique, but also provides an excellent investigative tool
into the underlying neuropathologies. Using two different animal
models of psychopathology, a genetic rat model mimicking repetitive
symptoms as in Tourette Syndrome (TS) and the maternal immune
activation (MIA) rodent model of schizophrenia, we were able to
study the potential effects of targeted neuromodulation on disease
progression and manifestation, i.e. as an intervention technique as
well as a prevention measure. More specifically, we were able to
show that invasive deep brain stimulation (DBS) was successful in
Eur Arch Psychiatry Clin Neurosci
123
reducing repetitive behavior and that these therapeutic effects are
mediated via the motor loop of basal ganglia thalamo-cortical circuit.
Further we revealed that non-invasive frontal anodal transcranial
direct current stimulation (tDCS) also yielded beneficial effects on
repetitive behavior, probably via the regulation of striatal parvalbu-
min interneurons. Using the MIA model we were able to show that a
continuous early DBS to the medial prefrontal cortex (mPFC) pre-
vented behavioral, brain structural and neurobiological manifestation
of schizophrenia. The identification of the involvement of the frontal
cortex in disease progression calls for the investigation of non-inva-
sive neuromodulation strategies such as frontal tDCS at an early, non-
symptomatic stage. Altogether our preclinical studies encourage the
testing of tDCS application as an intervention technique for TS
patients. The possibility of preventing or at least delaying symp-
tomatology in schizophrenia via early neuromodulation should be
further elaborated.
Policy of full disclosure: Supported by BMBF 01EW1409 (EraNet
Neuron RD_aDBS) and 01EE1403A (GCBS). The authors do not
have disclosures to report.
S-6b-02Cellular effects of low-dose tDCS: implications for neuroplasticity
B. Fritsch1
1Neuroplasticity and Neuromodulation Lab, Department of
Neurology, University Medical Center Freiburg, Freiburg, Germany
No abstract for publication.
S-6b-03rTMS restores alterations in synaptic excitation/inhibition-balance
A. Vlachos1
1Department of Neuroanatomy, Institute of Anatomy and Cell Biol-
ogy, Faculty of Medicine, University of Freiburg, Freiburg, Germany
Alterations in excitation/inhibition (E/I)-balance and disturbed
cortical homeostasis have been suggested to cause behavioral and
cognitive dysfunction in many brain diseases, such as schizophrenia,
autism and panic disorders. In these disease contexts, the diagnostic
and therapeutic potentials of non-invasive brain stimulation tech-
niques have been extensively studied. Yet, the cellular and molecular
mechanisms of rTMS-mediated neural plasticity and hence rTMS-
based therapies remain incompletely understood. We here tested
whether repetitive magnetic stimulation restores alterations in
synaptic E/I-balance in a preclinical model of maternal immune
activation (MIA). In entorhino-hippocampal slice cultures prepared
from the offspring of the well-established polyinosinic–polycytidylic
acid [Poly(I:C)] MIA model of schizophrenia, whole cell patch-clamp
recordings disclose alterations in E/I-balance of CA1 pyramidal
neurons. Specifically, an increase in inhibitory synaptic strength is
observed, while excitatory neurotransmission is not affected. Indeed,
a 10 Hz stimulation protocol reverses increased inhibitory synaptic
strength in MIA-slice cultures without affecting excitatory synaptic
strength. These results demonstrate that repetitive magnetic stimula-
tion influences the synaptic phenotype in MIA-slice cultures. Thus,
rTMS may assert its positive effects by reversing alterations in
synaptic E/I-balance under pathological conditions.
Policy of full disclosure: Supported by Federal Ministry of Education
and Research, Germany; GCBS-WP1: 01EE1403B.
S-7a Optimizing NIBS treatment: biomarkers
and RDoC approaches
Chairs: Poulet and Arns
S-7a-01Matching patient subtypes to neural circuits for novel brainstimulation treatments in affective disorders
D. Oathes1
1University of Pennsylvania, Philadelphia, USA
The utility of neuroimaging for defining targets in neuromodulation is
becoming increasingly apparent. We have gathered recent evidence
that TMS affects prototypical brain networks even when applied to
only a single brain area1. In our ongoing work, we show evidence that
TMS accessible regions in prefrontal cortex are effective in influ-
encing downstream subcortical brain regions as evidenced by
interleaved single pulse TMS with fMRI recordings. Additionally, our
broader research team has found robust evidence for subtypes of
major depressive disorder patients based on combined symptom and
resting fMRI data (‘biotypes’) that are confirmed in out of sample
cross validation and also predict clinical outcome from TMS2. We
argue that aggregating information from brain network representa-
tions with symptom profiles in patients will generate better, more
individualized targets for neuromodulation.
References:
1. Chen AC, Oathes DJ, Chang C, Bradley T, Zhou ZW, Williams
LM et al (2013) Causal interactions between fronto-parietal central
executive and default-mode networks in humans. Proc Natl Acad Sci
USA 110(49):19944–19949
2. Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F,
Meng Y et al (2017) Resting-state connectivity biomarkers define
neurophysiological subtypes of depression. Nat Med 23(1):28–38
Policy of full disclosure: The authors do not have disclosures to
report.
S-7a-02Optimizing TMS treatment for depression using neuro-cardiacguided TMS (NCG TMS)
T. Iseger1,2, M. Arns1,2,3
1Research Institute Brainclinics, Nijmegen, The Netherlands;2Department of Experimental Psychology, Utrecht University,
Utrecht, The Netherlands; 3neuroCare group, Munich, Germany
The efficacy of rTMS in the treatment of major depressive disorder
(MDD) has been well established in recent years. Most studies to date
have employed the ‘5-cm’ rule for targeting stimulation of the Dor-
solateral Prefrontal Cortex (DLPFC). New variations and
improvements of this targeting technique include the Beam-F3
method or neuronavigated rTMS. Furthermore, it has been proposed
that the efficacy of rTMS in MDD is more related to stimulating the
area that is functionally connected to the subgenual anterior cingulate
cortex (sgACC) rather than to specific cortical anatomical areas.
Therefore, we set-out to develop and test a new method that employs
knowledge about the functional role of the sgACC in parasympathetic
regulation such as heart rate control, to establish in real-time the
cortical area that is functionally connected to the sgACC. Previous
studies have shown that stimulation of both the DLPFC as well as the
sgACC, leads to heart rate deceleration, most likely through down-
stream connectivity with the vagal nerve. In a pilot study, we used
Eur Arch Psychiatry Clin Neurosci
123
electrocardiogram (ECG) R-peak triggered single pulse TMS to
various frontal locations to investigate the location that most con-
sistently resulted in a heart rate deceleration. On group level, F3 and
F4 expressed the largest heart rate deceleration, in line with studies
suggesting these are the best 10–20 sites to target the DLPFC. On the
individual level, 20–40% subjects expressed the largest heart rate
deceleration at FC3 or FC4, indicating individual differences as to the
‘optimal site for stimulation’. The potential implications of this
Neuro-Cardiac-Guided TMS is that this could be the equivalent of the
‘motor threshold’ for the DLPFC, and thereby would be a cost-ef-
fective and reliable method for localizing the most efficient
stimulation target in the treatment of MDD.
Policy of full disclosure: TI has no disclosures to report. MA reports
options from Brain Resource (Sydney, Australia), is director and
owner of Research Institute Brainclinics, a minority shareholder in
neuroCare Group (Munich, Germany); TAI and MA are co-inventor
on a patent application covering NCG-TMS, but do not own the
patent nor receive any proceeds related to this patent; Research
Institute Brainclinics received research funding from Brain Resource
(Sydney, Australia) and neuroCare Group (Munich, Germany);
equipment support from Deymed, neuroConn and Mag-venture,
however data analyses and writing of this manuscript were
unconstrained.
S-7a-03Central and plasmatic plasticity markers and response to NIBS
M. Psomiades1
1Equipe de recherche PsyR2/CRNL/INSERM U1028/CNRS
UMR5292/CH Le Vinatier/UCBL1, Bron, France
Background: Fronto-temporal transcranial direct-current stimulation
(tDCS) with the anode placed over the left prefrontal cortex (PFC)
and the cathode over the left temporoparietal junction (TPJ) has been
proposed as a treatment for auditory verbal hallucinations (AVH) in
patients with schizophrenia1. However the neurophysiological effects
induced by tDCS that might underpin beneficial improvements
remain unclear. In this study, we used proton magnetic resonance
spectroscopy (MRS) to investigate N-acetyl-aspartate (NAA) con-
centration, a marker of brain metabolism, after and before patients
with AVH received ten tDCS sessions. We used ELISA assay to
investigate Brain-Derived Neurotrophic factor (BDNF) levels, a
peripheral marker of neuronal plasticity, after and before one tDCS
session.
We hypothesized that (1) tDCS decreases severity of AVH; (2) tDCS
decreases NAA concentration under the cathode and increases NAA
concentration under the anode; (3) one tDCS session modulates
peripheral BDNF levels.
Methods: In a double blind sham controlled study, 60 patients were
randomly allocated to receive either 10 sessions of real or sham tDCS
(2 sessions/day, 2 mA, 20 min). The severity of AVH was evaluated
by the Auditory Hallucination Rating Scale. 29 patients underwent 2
MRS acquisitions, one before and one after the 10 tDCS sessions.
Voxels were placed in the left TPJ and in the left DLPFC. The
neurotrophic effects of tDCS were evaluated in 27 patients after and
before one tDCS session.
Results: Real tDCS significantly reduced AVH in patients with
schizophrenia [Active group (n = 30): - 26%; sham group (n = 26):
- 12%; F(1,54) = 4.172; p = 0.046; g2 = 0.072]. Active tDCS
significantly decreased NAA concentration in the left TPJ [(n = 14;
- 1.05 ± 1.30; F(1,27) = 4.902; p = 0.035; g2 = 0.154]. One
session of active tDCS significantly decrease peripheral mature
BDNF levels (n = 14; - 24.5 ± 20%; F(1,25) = 5.166; p = 0.032;
g2 = 0.171).
Conclusion: In patients with schizophrenia, tDCS may reduce AVH
and decrease neuronal metabolism in the left TPJ. Also, one tDCS
session may reduce peripheral mature BDNF levels.
Policy of full disclosure: The authors do not have disclosures to
report.
S-7a-04Personalizing and enhancing rTMS treatment response: EEGpredictors, biomarkers and role of combining interventions
M. Arns1,2,3
1Department of Experimental Psychology, Utrecht University,
Utrecht, The Netherlands; 2Research Institute Brainclinics, Nijmegen,
The Netherlands; 3neuroCare group, Munich, Germany
Background: Repetitive transcranial magnetic stimulation (rTMS) is
considered an efficacious non-invasive neuromodulation treatment for
major depressive disorder (MDD). However, little is known about the
clinical outcome of combined rTMS and psychotherapy (rTMS + PT)
and biomarkers to predict treatment response. Through common
neurobiological brain mechanisms, rTMS + PT may exert enhanced
antidepressant effects compared to the respective monotherapies.
Objective: The current naturalistic study aimed to evaluate feasibility
and clinical outcome of rTMS + PT in a large group of MDD
patients. The second aim was to identify predictors of response and
remission.
Methods: A total of 196 patients with MDD were treated with at least
10 sessions of simultaneous rTMS and PT. rTMS was applied over
the DLPFC, either 10 Hz left or 1 Hz right. Psychotherapy was based
on principles of cognitive behavioural therapy (CBT). Symptoms
were measured using the BDI each fifth session until end of treatment
and at 6-month follow-up. Comparisons were made between
responders and non-responders, as well as between the 10 and 1 Hz
protocol. Additionally, baseline variables and early BDI change were
evaluated as predictors of response/remission.
Major findings and conclusions: (1) combining rTMS and PT resulted
in a 66% response and a 56% remission rate at the end of treatment
with 60% sustained remission at follow-up. Compared to previous
findings in RCTs, these rates are relatively high; (2) no differences
were found between the 10 and 1 Hz TMS regarding clinical out-
come; (3) clinical baseline variables were not predictive of treatment
outcomes; (4) early symptom improvement (at session 10) was highly
predictive of response, and may therefore be used to guide
rTMS + PT continuation.
Policy of full disclosure: MA reports options from Brain Resource
(Sydney, Australia); he is director and owner of Research Institute
Brainclinics, a minority shareholder in neuroCare Group (Munich,
Germany), and a co-inventor on 4 patent applications (A61B5/0402;
US2007/0299323, A1; WO2010/139361 A1) related to EEG, neuro-
modulation and psychophysiology, but does not own these nor
receives any proceeds related to these patents; Research Insitute
Brainclinics received funding from Brain Resource (Sydney, Aus-
tralia) and neuroCare Group (Munich, Germany), and equipment
support from Deymed, neuroConn and Magventure, however data
analyses and writing of this manuscript were unconstrained.
Eur Arch Psychiatry Clin Neurosci
123
GCBS-1
Chairs: Nitsche and Winter
GCBS-1-01Neuromodulation in model rats
R. Hadar1, C. Winter1
1Department of Psychiatry and Psychotherapy, Charite
Universitatsmedizin Berlin, Charite Campus Mitte, Berlin, Germany
Non-invasive transcranial direct current stimulation (tDCS) and
invasive deep brain stimulation (DBS) of the prefrontal cortex (PFC)
constitute two stimulation approaches that affect dysfunctional PFC-
associated neural networks, i.e. specific neurobiological states that
underlie the behavioural manifestation of psychiatric syndromes. The
clinical efficacy of the stimulation approach is determined by its
ability to affect the underlying neurobiological states. We here pre-
sent an animal experimental approach that uses two different
previously characterized animal models of psychopathology, a
genetic rat model mimicking repetitive symptoms as in Tourette
Syndrome (TS) and the maternal immune activation (MIA) rodent
model of schizophrenia to study the behavioral and neurobiological
effects of DBS and tDCS on disease progression and manifestation,
i.e. as an intervention technique as well as a prevention measure. DBS
is first used in an effort to normalize pathological behaviors and
further in combination with neurobiological assessments, imaging
techniques and computational modeling such that brain regions for
the application of tDCS are identified. Using the genetic rat model of
TS, we were able to show that DBS was successful in reducing
repetitive behavior and that these therapeutic effects are mediated via
the motor loop of basal ganglia thalamo-cortical circuit. Further we
revealed that frontal anodal tDCS also yielded beneficial effects on
repetitive behavior, probably via the regulation of striatal parvalbu-
min interneurons. Using the MIA model we were able to show that a
continuous early DBS to the medial prefrontal cortex (mPFC) pre-
vented behavioral, brain structural and neurobiological manifestation
of schizophrenia. The identification of the involvement of the frontal
cortex in disease progression also calls for the investigation of non-
invasive frontal neuromodulation at an early, non-symptomatic stage.
In summary we found that non-invasive tDCS and invasive DBS of
the PFC were proven to be effective in normalising aberrant beha-
vioural manifestations along with its underlying neurobiological
states using different pathology models. Altogether, our preclinical
studies encourage the application of tDCS as an intervention tech-
nique and its investigation as a possible preventive strategy in
psychiatry.
Policy of full disclosure: Supported by BMBF 01EW1409 (EraNet
Neuron RD_aDBS) and 01EE1403A (GCBS). The authors do not
have disclosures to report.
GCBS-1-02rTMS animals (WP1B)
K. Funke1
1Department of Neurophysiology, Ruhr-University Bochum, 44780
Bochum, Germany
Project WP1B of the German Center for Brain Stimulation (GCBS)
utilizes rat models to investigate the neural effects of repetitive
transcranial magnetic stimulation (rTMS) at the cellular and beha-
vioural level. Maternal immune stimulation (MIS) is used as a model
system to find cellular counterparts of changes in behavioural phe-
notypes associated with psychiatric states and to test rTMS as a
potential therapeutic intervention. Directly referring is the question if
pathological as well as physiological changes of the status of the
stimulated neuronal network will affect the outcome of rTMS.
Previous studies have shown that high-frequency stimulation
protocols—in particular the intermittent theta-burst stimulation
(iTBS)—induce effects indicative of a disinhibitory actions, evident
as reduced parvalbumin (PV) expression in fast-spiking inhibitory
interneurons (FSI)1, enhanced cortical sensory responses2 and
improved learning performance3. The iTBS effect, however, varies
with the history of exploratory behaviour, age and strain of the rats,
the latter obviously as a consequence of differences in number and
activity of inhibitory elements4.
First results obtained with the MIS model indicate not only altered
sensory gating (pre-pulse inhibition) but also altered expression of PV
and calbindin (another calcium-binding protein expressed in non-FSI)
in subregions of prefrontal cortex (PFC), and altered activity patterns
within the PFC-hippocampal network as verified by the temporal
correlation of theta and gamma rhythms. While effects of iTBS were
not evident at the behavioural level when applied in adulthood, PFC-
hippocampal theta/gamma coupling tended to improve after iTBS.
In vitro studies on CA1 region of the hippocampus showed increased
inhibition and less excitability of pyramidal cells in the MIS model
which could be almost normalized via both acute rTMS treatment
(10 Hz) of hippocampal cultures but also with iTBS of rats prior to
subsequent ex vivo–in vitro analysis. These other findings indicate
possible interventions prior to or during adolescent development.
References:
1. Benali A, Trippe J, Weiler E, Mix A, Petrasch-Parwez E, Girzalsky
W, Eysel UT, Erdmann R, Funke K (2011) Theta-burst transcranial
magnetic stimulation alters cortical inhibition. J Neurosci
31(4):1193–1203. https://doi.org/10.1523/JNEUROSCI.1379-10.2011
2. Thimm A, Funke K (2015) Multiple blocks of intermittent and
continuous theta-burst stimulation applied via transcranial magnetic
stimulation differently affect sensory responses in rat barrel cortex.
J Physiol 593(4):967–985. https://doi.org/10.1113/jphysiol.2014.
282467
3. Mix A, Benali A, Eysel UT, Funke K (2010) Continuous and
intermittent transcranial magnetic theta burst stimulation modify
tactile learning performance and cortical protein expression in the rat
differently. Eur J Neurosci 32(9):1575–1586. https://doi.org/10.1111/
j.1460-9568.2010.07425.x
4. Mix A, Benali A, Funke K (2014) Strain differences in the effect of
rTMS on cortical expression of calcium-binding proteins in rats. Exp
Brain Res 232(2):435–442. https://doi.org/10.1007/s00221-
013-3751-6
Policy of full disclosure: The authors do not have disclosures to
report.
GCBS-1-03Optimizing physiological tDCS effects
M. A. Nitsche1, D. Agboada1, M. Mosayebi1, M.-F. Kuo1
1Department of Psychology and Neurosciences, Leibniz Research
Centre for Working Environment and Human Factors, Leibniz,
Germany
Transcranial direct current stimulation (tDCS) induces neuroplastic
alterations of cortical excitability, which are stimulation-polarity
dependent regarding classical stimulation protocols, where anodal
tDCS enhances, while cathodal tDCS reduces cortical excitability.
For clinical application, stimulation protocols which result in opti-
mized strength of effects are required. Here, the impact of
Eur Arch Psychiatry Clin Neurosci
123
pharmacological interventions as well as specific stimulation dura-
tion, and intensity effects, which have shown to result in non-
linearities of the impact of tDCS on cortical excitability, have to be
taken into account. In two project lines, we (1) explored the impact of
chronic antidepressant application on tDCS effects, and (2) investi-
gated the effects of variation of stimulation duration (15, 20, 30 min),
and intensity (1, 2, and 3 mA) on neuroplastic after-effects of tDCS.
The results show that the SSRI citalopram and the SNRI reboxetine
enhanced the long-term potentiation-like effects of anodal tDCS,
while these pharmacological interventions converted long-term
depression-like effects of cathodal tDCS into facilitation. Moreover,
dependent on stimulation intensity and duration, anodal and cathodal
tDCS exerted complex non-linear effects on cortical excitability. We
thus conclude that combination of tDCS with SSRI and SNRI might
be able to potentiate therapeutic effects of tDCS, if LTP-like plasticity
is warranted, and that furthermore specification of stimulation
intensity and duration might be crucial to obtain optimal effects.
Policy of full disclosure: Member of the Advisory board of
Neuroelectrics.
GCBS-1-04Lasting amelioration of deficient cognitive control in depressionby transcranial direct current stimulation (tDCS)-enhancedtraining
C. Plewnia1
1Department of Psychiatry and Psychotherapy, Neurophysiology and
Interventional Neuropsychiatry, University of Tubingen, Tubingen,
Germany
No abstract for publication.
S-8a Reproducibility of NIBS
Chairs: Kuo and Kammer
S-8a-01Effects of prefrontal tDCS on resting-state functionalconnectivity: variability, non-linearity and state-dependency
J. Worsching1
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-
University, Munich, Germany
Transcranial Direct Current Stimulation (tDCS) is a non-invasive
brain stimulation technique with the potential to modify cortical
excitability. Especially, tDCS over the dorsolateral prefrontal cortex
(DLPFC) may be a promising stimulation target for clinical appli-
cation and in combination with neuroimaging may advance
investigations into plasticity of cognitively relevant neural systems
and circuits. Recently, both the test–retest (TRT) reliability of tDCS
effects as well as the classical anodal-increase and cathodal-decrease
assumptions have been questioned. In addition, inter-individual
variations in and state-dependency of tDCS responses have been
found. Yet, none of these issues have been systematically evaluated
for tDCS-induced modulations in functional magnetic resonance
imaging (fMRI). Therefore, prior to a more extensive use, it is
important to understand the interplay between neural systems and
stimulation protocols requiring basic methodological work. In a first
study, we investigated the TRT reliability of prefrontal tDCS-effects
on functional resting-state (RS) connectivity and found a shift in the
distribution of voxel-wise intra-class-correlations (ICC) towards
lower values in the active tDCS-group as compared to the sham
group. In a second study, we investigated whether tDCS effects are
electrode-montage specific by systematically reversing and changing
the prefrontal electrode-placement within the same subjects. Because
findings, including our TRT results, may be state-dependent, tDCS
effects were monitored using both RS-fMRI and a cognitive task.
Results indicated both montage- and monitoring-level-specific
effects. Altogether, these results support the notion of active tDCS
modulating RS-fMRI connectivity, however point towards a high
intra-individual variability, state-dependency and non-dichotomous
and even non-linear, montage-specific dose–response relations.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 5, grant number: 01EE1403E), funded by the Federal Min-
istry of Education and Research (BMBF).
S-8a-02Efficacy and interindividual variability following LTP-likeplasticity inducing PAS and anodal tDCS
W. Strube1, T. Bunse1, B. Malchow1, A. Hasan1
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian
University (LMU), Munich, Germany
Interindividual response variability to various motor-cortex stimula-
tion protocols has been recently reported. Comparative data of
stimulation protocols with different modes of action is lacking. We
aimed to compare the efficacy and response variability of two LTP-
inducing stimulation protocols in the human motor cortex: anodal
transcranial direct current stimulation (a-tDCS) and paired-associative
stimulation (PAS25). In two experiments 30 subjects received 1 mA
a-tDCS and PAS25. Data analysis focused on motor-cortex
excitability change and response defined as increase in MEP applying
different cut-offs. Furthermore, the predictive pattern of baseline
characteristics was explored. Both protocols induced a significant
increase in motor-cortical excitability. In the PAS25 experiments the
likelihood to develop a MEP response was higher compared to
a-tDCS, whereas for intracortical facilitation (ICF) the likelihood for
a response was higher in the a-tDCS experiments. Baseline ICF
(12 ms) correlated positively with an increase in MEPs only follow-
ing a-tDCS and responders had significantly higher ICF baseline
values. Contrary to recent studies, we showed significant group-level
efficacy following both stimulation protocols confirming older stud-
ies. However, we also observed a remarkable amount of
nonresponders. Our findings highlight the need to define sufficient
physiological read-outs for a given plasticity protocol and to develop
predictive markers for targeted stimulation.
Policy of full disclosure: W.S. has received speaker’s honorarium
from Mag&More GmbH.
S-8a-03What does it tell you when your transcranial electric stimulationexperiment failed?
P. Sauseng1, A. L. Biel1, E. V. C. Friedrich1
1Department of Psychology, LMU Munich, Munich, Germany
Empirical research on electrical brain stimulation in cognition has
been a field where traditionally many experiments are statistically
underpowered. Sample sizes of a couple of participants to approxi-
mately 20 volunteers are common. At the same time it has been
shown that transcranial electrical stimulation leads to fairly small
Eur Arch Psychiatry Clin Neurosci
123
effects on cognition (particularly in young, healthy participants). This
makes it likely that a lot of experiments fail to provide evidence for
the tested alternative hypothesis. But does this mean that these
experiments support the null hypothesis? Here we will discuss what
parameters need to be addressed when planning a transcranial electric
stimulation study, so that the results might be more likely to be
conclusive. And we will propose that under certain circumstances
frequentist statistics (p-statistics) are not suitable for concluding that a
particular effect is not present (i.e. that the null hypothesis is true).
Policy of full disclosure: The authors do not have disclosures to
report.
S-8a-04Reproducibility of tDCS
M.-F. Kuo1, M. A. Nitsche1
1Department of Psychology and Neurosciences, Leibniz Research
Centre for Working Environment and Human Factors, Leibniz,
Germany
Transcranial direct current stimulation has been applied as a tool for
basic neurophysiological research and clinical studies over the past
decades. Despite encouraging results, variability was also observed in
some studies. This presentation will introduce possible sources of
variability, including methodological issues and clinical aspects.
Future directions of research will also be briefly discussed.
Policy of full disclosure: The authors do not have disclosures to
report.
GCBS-2
Chairs: Padberg and Bajbouj
GCBS-2-01Disorder-tailored transcranial direct current stimulation (tDCS)of the prefrontal cortex: goals and achievements
D. Keeser1,2, J. Worsching1, E. Mezger2, F. Padberg1
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian
University Munich, Munich, Germany; 2Department of Radiology,
Ludwig Maximilian University Munich, Munich, Germany
The GCBS consortium aims to better understand non-invasive brain
stimulation methods such as tDCS of the prefrontal brain. In work
package 5 and work package 7, electrical stimulation in healthy
subjects and patients with major depression is investigated using
multimodal Magnetic Resonance Imaging (MRI) techniques. The
overall goal is a better understanding of the effects of transcranial
electrical stimulation in the brain. Are these effects reproducible?
What is the neurophysiological effect of specific prefrontal electrode
montages? Do we need to individually apply imaging to better predict
tDCS outcome? On the basis of finalized studies our approach of
these work packages will be presented and an outlook on (1) basic
research, (2) translation to the clinical application and (3) general-
ization of prefrontal tDCS will be presented and discussed.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 5, Grant number 01EE1403E), funded by the Federal Min-
istry of Education and Research (BMBF).
GCBS-2-02PsychotherapyPlus: augmentation of cognitive behavioraltherapy (CBT) with prefrontal transcranial direct currentstimulation (tDCS) in major depressive disorder: study designand methodology of a multicenter double-blind randomizedplacebo controlled trial
M. Bajbouj1, S. Aust1
1Department of Psychiatry, Charite-Universitatsmedizin Berlin,
Berlin, Germany
Background: Major Depressive Disorder (MDD) is one of the most
prevalent psychiatric disorders worldwide. About 20–30% of patients
do not respond to standard psychopharmacological and/or psy-
chotherapeutic treatment interventions. Mounting evidence from
neuroimaging studies in MDD patients revealed altered activation
patterns in lateral prefrontal brain areas showing that successful
cognitive behavioral therapy (CBT) is associated with a recovery of
these neural alterations. Moreover, it has been demonstrated that
transcranial direct current stimulation (tDCS) is capable of influenc-
ing prefrontal cortex activity and cognitive functions such as working
memory and emotion regulation. Thus, a clinical trial investigating
the effects of an antidepressant intervention combining CBT with
tDCS seems promising. The present study investigates the antide-
pressant efficacy of a combined CBT-tDCS intervention as compared
to CBT with sham-tDCS or CBT alone.
Methods: A total of 192 patients (20–65 years) with MDD (HDRS-
21 C 15) will be recruited at four study sites across Germany (Berlin,
Munich, Tuebingen, Freiburg) and randomly assigned to one of the
following three treatment arms: (1) CBT + active tDCS, (2)
CBT + sham-tDCS, and (3) CBT alone. All participants will attend a
6-week psychotherapeutic intervention comprising twelve sessions of
CBT each lasting 100 min in a closed group setting. tDCS will be
applied during each CBT session with active tDCS including stimu-
lation with an intensity of 2 mA for 30 min with the anode placed
over F3 and the cathode over F4 according to the EEG 10–20 system,
if assigned. The primary outcome measure is the change in Mont-
gomery-Asberg Depression Rating Scale scores from baseline to 6,
18, and 30 weeks after the first session. Participants also undergo pre
and post treatment neuropsychological testing and functional mag-
netic resonance imaging (fMRI) to assess changes in prefrontal
functioning and connectivity.
Discussion: The study investigates whether CBT can be augmented
by non-invasive brain stimulation techniques such as tDCS in the
treatment of MDD. It is designed as a proof-of-principle trial for the
combined tDCS-CBT treatment, but also allows the investigation of
the neurobiological underpinnings of the interaction between both
interventions in MDD.
Policy of full disclosure: The authors do not have disclosures to
report.
GCBS-2-03Design and methods of an ongoing randomized controlled studyof tDCS in major depression: the DepressionDC trial
F. Padberg1, T. Matt1, N. Behler1, L. Wulf1, U. Kumpf1, U. Palm1, S.
Egert2, U. Mansmann3, D. Keeser1, C. Plewnia4, B. Langguth5, J.
Cordes6, C. Normann7, P. Zwanzger8, A. Hasan1, M. Bajbouj9
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian
University Munich, Munich, Germany; 2Munchner Studienzentrum,
Technical University of Munich, Germany; 3Institute for Medical
Information Processing, Biometry and Epidemiology (IBE), Ludwig
Maximilian University Munich, Munich, Germany; 4Department of
Psychiatry and Psychotherapy, University of Tubingen, Tubingen,
Eur Arch Psychiatry Clin Neurosci
123
Germany; 5Department of Psychiatry and Psychotherapy, University
of Regensburg, Regensburg, Germany; 6Department of Psychiatry
and Psychotherapy, Medical Faculty, Heinrich-Heine University,
Dusseldorf, Germany; 7Department of Psychiatry and Psychotherapy,
University Medical Center Freiburg, Freiburg, Germany; 8kbo-Inn-
Salzach-Hospital, Wasserburg am Inn, Germany; 9Department of
Psychiatry and Psychotherapy, Charite-Campus Benjamin Franklin,
Berlin, Germany
The DepressionDC trial is a triple-blind, randomized, placebo-con-
trolled multicenter trial investigating the efficacy and safety of
prefrontal tDCS used as additive treatment in MDD patients who have
not responded to selective serotonin reuptake inhibitors (SSRI). At 7
German sites 152 patients with MDD receive a 6-weeks treatment
with active tDCS (anode F3 and cathode F4, 2 mA intensity,
30 min/day) or sham tDCS add-on to a stable antidepressant medi-
cation with an SSRI. Follow-up visits are at 3 and 6 months after the
last tDCS.
The primary outcome measure is the change of the Montgomery-
Asberg Depression Rating Scale (MADRS) scores at week 6 post-
randomisation compared to baseline. Secondary endpoints also cover
other psychopathological domains, and a comprehensive safety
assessment includes measures of cognition. The study uses an
advanced tDCS technology including recording of technical param-
eters (current, impedance, voltage) in each tDCS session. Here, we
present this novel approach for monitoring technical parameters of
tDCS and further methodological requirements (i.e. current density
modelling, standardized electrode positioning). The DepressionDC
trial aims at answering the clinical question whether prefrontal tDCS
is a safe and effective add-on intervention in patients who have not
sufficiently responded to SSRIs.
Policy of full disclosure: F.P. has received speaker’s honorarium from
Mag&More GmbH and the neuroCare Group as well as support with
equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More
GmbH and Brainsway Inc., Jerusalem, Israel. The other authors do
not have disclosures to report.
Poster abstracts
P-01Exploring the parameter space of physiological effects of cathodaltranscranial direct current stimulation over the primary motorcortex
M. M. Samani1,2, D. Agboada1,3, M.-F. Kuo1, M. A. Nitsche1,4
1Leibniz Research Centre for Working Environment and Human
Factors, Dortmund, Germany; 2Institute of Biomedical Engineering
and Informatics, Ilmenau University of Technology, Ilmenau,
Germany; 3International Graduate School of Neuroscience, IGSN,
Ruhr University Bochum, Bochum, Germany; 4Department of
Neurology, University Hospital Bergmannsheil, Bochum, Germany
Transcranial direct current stimulation (tDCS) can non-invasively
induce polarity-dependent excitability alterations in the human
motor cortex lasting more than an hour after stimulation [1, 2].
Clinical application with encouraging results have been reported in
several pilot studies, but the optimal stimulation protocols remain
to be determined. Recently, it was shown that there is a nonlinear
modulatory effect of stimulation intensity/duration on neuroplas-
ticity [3–5]. In this study, we systemically explored the association
between tDCS parameters (intensity, duration) and induced after-
effects on motor cortex excitability. Cathodal tDCS was applied in
three different intensities (1, 2 and 3 mA) and durations (15, 20
and 30 min) on 16 young healthy subjects and the after-effects
were monitored with TMS-induced motor evoked potentials (MEP)
until the evening after stimulation. The results revealed nonlinear
after-effects, which might be caused by calcium dynamics relevant
for long term depression and potentiation induction. 1 mA (for all
stimulation durations) and 3 mA -20 min induced LTD-like plas-
ticity, while LTP-like plasticity was observed after 2 mA
stimulation for 20 min. Our study thus provides further insights on
the dependency of tDCS-induced neuroplasticity on the stimulation
parameters, and therefore delivers crucial information for future
clinical applications.
References:
1. Nitsche MA, Paulus W (2001) Sustained excitability elevations
induced by transcranial DC motor cortex stimulation in humans.
Neurology 57:1899–1901
2. Nitsche MA, Nitsche MS, Klein CC, Tergau F, Rothwell JC, Paulus
W (2003) Level of action of cathodal DC polarisation induced inhi-
bition of the human motor cortex. Clin Neurophysiol 114:600–604
3. Jamil A, Batsikadze G, Kuo HI, Labruna L, Hasan A, Paulus W
et al (2016) Systematic evaluation of the impact of stimulation
intensity on neuroplastic after-effects induced by transcranial direct
current stimulation. J Physiol 10:1e16
4. Batsikadze G, Moliadze V, Paulus W, Kuo MF, Nitsche MA (2013)
Partially non-linear stimulation intensity-dependent effects of direct
current stimulation on motor cortex excitability in humans. J Physiol
591:1987–2000
5. Monte-Silva K, Kuo M-F, Hessenthaler S, Fresnoza S, Liebetanz
D, Paulus W, Nitsche MA (2013) Induction of late LTP-like plasticity
in the human motor cortex by repeated non-invasive brain stimula-
tion. Brain Stimul 6:424–432
Policy of full disclosure: The authors do not have disclosures to
report.
P-02Electrode montage dependent effects of transcranial directcurrent stimulation on working memory
M. Splittgerber1*, M. Maack1*, H. Brauer2, C. Breitling3,
A. Prehn-Kristensen2, K. Krauel3, P. Miranda4, R. Nowak5,
M. Siniatchkin1*, V. Moliadze1*1Department of Medical Psychology and Medical Sociology,
Schleswig-Holstein University Hospital (UK-SH), Christian-
Albrechts-University, Kiel, Germany; 2Department of Child and
Adolescent Psychiatry, Center for Integrative Psychiatry, Kiel,
Germany; 3Department of Child and Adolescent Psychiatry and
Psychotherapy, Otto-von-Guericke University Magdeburg,
Magdeburg, Germany; 4Fundacao da Faculdade de Ciencias da
Universidade de Lisboa, Lisbon, Portugal; 5Neuroelectrics,
Barcelona, Spain
* These authors have equally contributed to the work
Introduction: Recent studies show that tDCS applied over the left
dorsolateral prefrontal cortex (lDLPFC) can successfully affect
working memory (WM) performance1. The present study investigates
the influences of a classical bipolar and more focal multichannel
tDCS over the lDLPFC on WM performance (2-back task) and con-
tinuous performance task (CPT) as non-target task.
Methods: The study was approved by the Ethic Committee of the
Faculty of Medicine Christian-Albrechts University Kiel. Eighteen
healthy young adults (18–30 years) participated in the study. Partic-
ipants were stimulated 3 times (bipolar, multichannel, sham
stimulation in randomized order) over the lDLPFC for 20 min, min-
imum period between sessions was 7 days. For bipolar stimulation
1 mA was applied by two circular saline-soaked surface sponge
electrodes (25 cm2), with anode positioned over F3 and reference
Eur Arch Psychiatry Clin Neurosci
123
over FP2. For multichannel tDCS we used five 3.14 cm2 circular
PiStim electrodes (Neuroelectrics, Barcelona, Spain), positioned at
AF3 (897uA), AF7 (284uA), F3 (819uA), FP2 (-1000uA) and T7 (-
1000uA). After stimulation EEG at rest (2 min eyes closed, 2 min
eyes open) and during 2-back and CPT performance was recorded.
Results: Preliminary behavioral results show significant improvement
of accuracy in the 2-back task after multichannel and bipolar tDCS
compared to sham stimulation but not for CPT performance. Inci-
dence and intensity of aversive side effects did not differ between
multichannel, bipolar or sham tDCS.
Conclusion: Our behavioral results show that multichannel and
bipolar tDCS over the lDLPFC have the potential of modulating WM
performance, with multifocal stimulation not eliciting greater effects,
which is in contrary to results of motor cortex area stimulation2. Our
results on aversive side effect underline the tolerability of both
multichannel and bipolar tDCS.
References
1. Coffman B; Clark V, Parasuraman R (2014) Battery powered
thought. Enhancement of attention, learning, and memory in healthy
adults using transcranial direct current stimulation. NeuroImage 85(Pt
3):895–908
2. Fischer DB, Fried PJ, Ruffini G, Ripolles O, Salvador R, Banus J
et al (2017) Multifocal tDCS targeting the resting state motor network
increases cortical excitability beyond traditional tDCS targeting uni-
lateral motor cortex. NeuroImage 157:34–44
Policy of full disclosure: This study was conducted as part of the
STIPED program. STIPED has received funding from European
Union’s Horizon 2020 research and innovation programme under
Grant Agreement No. 731827. The authors do not have disclosures to
report.
P-03Exploring the effects of transcranial direct current stimulationon cognitive control training
S. Weller1, C. Plewnia1
1Department of Psychiatry and Psychotherapy Neurophysiology and
Interventional Neuropsychiatry, University Hospital Tubingen,
Tubingen, Germany
The dorsolateral prefrontal cortex (dlPFC) is a brain structure
responsible for working memory performance and cognitive control
(CC) [1]. CC, critically underlying goal-directed behaviour, has been
shown to be impaired in depression and to be associated with reduced
activity of the dlPFC [2]. Transcranial direct current stimulation
(tDCS) of this brain area can modify CC and has already shown to
enable amelioration as well as the impairment of CC [3–5]. Within
this study series we systematically investigate the effects of tDCS on
a CC training in healthy participants by varying stimulation param-
eters regarding intensity, polarity and laterality. Over the course of 8
sessions within 4 weeks participants perform a modified adaptive
paced auditory serial addition task (PASAT) during which they hear a
series of single digit numbers and are instructed to add the most recent
digit to the third to last digit (n + n - 2). Digit presentation speed is
adapted to performance with the goal to challenge CC by inducing
stress and frustration during the experiment. TDCS is applied for
19 min during each training session. The first two test groups receive
stimulation of the left dlPFC with 1 and 2 mA respectively, the third
and fourth group are treated likewise except that stimulation is shifted
to the right dlPFC. Each group is furthermore divided into subjects
receiving either anodal, cathodal or sham tDCS. Within the first study
group, subjects who received anodal stimulation (1 mA) to the left
dlPFC showed significant performance gains in the PASAT compared
to cathodal (1 mA) and sham stimulation, suggesting that
improvement was aided by plasticity enhancement of CC induced by
tDCS. Results for the second group (2 mA, left dlPFC) are currently
being processed, while the third and fourth group (1 and 2 mA, right
dlPFC) will be finished by end of this year.
References
1. Miller EK (2000) The prefrontal cortex and cognitive control. Nat
Rev Neurosci 1(1):59–65
2. Fitzgerald P, Laird A (2008) A meta-analytic study of changes in
brain activation in depression. Hum Brain Mapp [Internet]
29(6):683–695
3. Wolkenstein L, Plewnia C (2013) Amelioration of cognitive con-
trol in depression by transcranial direct current stimulation [Internet].
Biol Psychiatry 73
4. Plewnia C, Schroeder PA, Kunze R, Faehling F, Wolkenstein L
(2015) Keep calm and carry on: Improved frustration tolerance and
processing speed by transcranial direct current stimulation (tDCS).
PLoS One [Internet] 10(4):1–12
5. Plewnia C, Schroeder PA, Wolkenstein L (2015) Targeting the
biased brain: non-invasive brain stimulation to ameliorate cognitive
control. Lancet Psychiatry 2(4):351–356
Policy of full disclosure: The authors do not have disclosures to
report.
P-04The effect of transcranial direct current stimulation on cognitivecontrol and emotion regulation in depressed patients
A. Sommer, S. Max, L. Wolkenstein, C. Plewnia
Department for Neurophysiology and interventional Neuropsychiatry,
University Hospital Tuebingen, Clinic for Psychiatry and
Psychotherapy, Tubingen, Germany
Background: Deficient cognitive control (CC) and the use of dys-
functional emotion regulation strategies (ERS) are both central
characteristics of major depression. Both are associated with reduced
activity of the dorsolateral prefrontal cortex (dlPFC). Transcranial
direct current stimulation (tDCS) is a safe, simple and effective non-
invasive method to modulate the cortical excitability. The goal of our
study is to examine the effect of transcranial direct current stimulation
(tDCS) on the CC and ERS in depressed patients compared to healthy
subjects.
Methods: Overall, this randomized, sham-controlled, double blind
clinical trial will include 44 participants (22 depressed patients and 22
healthy subjects). Each participant will complete a CC task while
receiving sham tDCS in one session and anodal tDCS in the other
session (counterbalanced). Afterwards the ERS ‘rumination’ will be
measured during a 7-min resting phase by means of a questionnaire
and psychophysiological measures (heart rate variability). Overall,
this experiment will provide additional data for the development of
new treatment methods.
Results: As the study is still in preparation preliminary results will be
presented and discussed at the conference. We hypothesize (1) an
amelioration of CC by anodal tDCS and (2) a reduced use of the
dysfunctional emotion regulation strategy ‘rumination’ after anodal
tDCS.
Future prospects: The effect tDCS can outlast the stimulation time
when combined with a training. The next step towards a new treat-
ment method for major depression and also other psychiatric diseases
will be to conduct a tDCS supported CC-training study.
Policy of full disclosure: The authors do not have disclosures to
report.
Eur Arch Psychiatry Clin Neurosci
123
P-05General effects of cathodal tDCS on implicit associations
P. A. Schroeder1, C. Plewnia1
1Department of Psychiatry and Psychotherapy, University of
Tubingen, Tubingen, Germany
In contrast to deliberate decisions, spontaneous human behaviour can
be influenced by implicit cognitive biases. Without direct intention,
and convergent to explicit self-reports, implicit associations are
thought to predict particularly non-reflective behaviours. Neverthe-
less, activation of implicit associations could draw on prefrontal
cortex regions. For example, the implicit spatial association of
number magnitude was reduced during stimulation with cathodal
tDCS to the left prefrontal cortex [1]. In the present study, we tested
the general effect of prefrontal cathodal tDCS on the standardized
insect-flower implicit associations task (IAT). In the task, participants
use two keys to classify four target categories (insects, flowers, pos-
itive, negative). The blocked combinations of insects + negative and
flowers + positive in the compatible IAT condition produced faster
response times than the opposite combinations of insects + positive
and flowers + negative in the incompatible IAT condition. Most
critically, this IAT effect was reduced during cathodal tDCS, as
compared to sham tDCS (see Figure 1). These results indicate gen-
eralizability of our previous findings and exemplify another
potentially beneficial effect of cathodal tDCS [1–3]. Future studies on
modulations of implicit biases with cathodal tDCS are needed to
examine longevity, transfer, and stability in other biases and/or set-
tings. Clinical effectivity should be examined in patient populations
as well.
References:
1. Schroeder PA, Pfister R, Kunde W, Nuerk H-C, Plewnia C (2016)
Counteracting implicit conflicts by electrical inhibition of the pre-
frontal cortex. J Cogn Neurosci 28(11):1737–1748
2. Schroeder PA, Plewnia C (2016) Beneficial effects of cathodal
transcranial direct current stimulation (tDCS) on cognitive perfor-
mance. J Cogn Enhanc 1(1):5–9
3. Zwissler B, Sperber C, Aigeldinger S, Schindler S, Kissler J,
Plewnia C (2014) Shaping memory accuracy by left prefrontal tran-
scranial direct current stimulation. J Neurosci 34(11):4022–4026
Policy of full disclosure: The authors do not have disclosures to
report.
P-06Brain stimulation over frontopolar cortex enhances motivationto exert effort for reward
A. Soutschek1,2, P. Kang1, C. C. Ruff1,2, T. A. Hare1,2,*,
P. N. Tobler1,2,*
1Laboratory for Social and Neural Systems Research, Department of
Economics, University of Zurich, Zurich, Switzerland; 2Neuroscience
Center Zurich, University of Zurich, Swiss Federal Institute of
Technology Zurich, Zurich, Switzerland
*Shared senior authors
Loss of motivation is a characteristic feature of several psychiatric
and neurological disorders. However, the neural mechanisms under-
lying human motivation are far from being understood. Here, we
show that frontopolar cortex (FPC) plays a crucial role in motivating
cognitive and physical effort exertion by computing subjective effort
equivalents. We manipulated neural processing with transcranial
direct current stimulation targeting FPC while participants decided
whether or not to engage in cognitive or physical effort to obtain
rewards. We found that brain stimulation targeting FPC increased the
amount of both types of effort participants were willing to exert for
rewards, while leaving the subjective strain of the required effort
unaffected. Our findings provide important insights into the neural
mechanisms involved in motivating effortful behaviour and suggest
that further exploration of FPC function could facilitate the devel-
opment of treatments for the loss of motivation commonly seen in
psychiatric and other neurological disorders.
Policy of full disclosure: The authors do not have disclosures to
report.
P-07The influence of tDCS on prosocial behaviour when being sociallyexcluded: experimental design
L. Wulf1, J. Dewald-Kaufmann1,2, T. Wustenberg3, B. Barton1, N.
Behler1, J. Worsching1, F. Padberg1
1Department of Psychiatry and Psychotherapy, University Hospital
LMU Munich, Munich, Germany; 2Hochschule Fresenius, University
of Applied Sciences, Munich, Germany; 3Charite-
Universitatsmedizin Berlin, Charite Campus Mitte, Klinik fur
Psychiatrie & Psychotherapie, Berlin, Germany
Background: The Cyberball-Paradigm represents an elegant tool to
investigate psychosocial phenomena such as ostracism, discrimina-
tion and prejudices [1, 2]. A considerable amount of Cyberball-studies
could show that the experience of social exclusion leads to an increase
of negative feelings, aggressive behaviour and the inclination of anti-
social behaviour [3–7]. A new modified version of the Cyberball-
Paradigm allows the simulation of a partial exclusion [8]. The par-
ticipant is excluded by only one player (one includer, one excluder)
which enables a more differentiated data collection regarding beha-
vioural tendencies and cognitions towards the including and
excluding person. For instance, a recent, unpublished study by
Dewald-Kaufmann and colleagues [8] provides evidence that
depressive and borderline patients behave significantly less prosocial
towards the excluder than healthy participants. On this background
the goal of this pilot study is to examine the effect of a brain stim-
ulation targeting emotion regulations areas (rVLPFC, F6) with anodal
tDCS on prosocial behaviour and cognition. In addition, we want to
shed light on potential moderating trait factors like neuroticism val-
ues, self-esteem and resilience. An electrocardiogram (ECG) is
integrated as objective stress measurement to figure out if excluded
participants show a higher stress response than in the inclusion
condition.
Study-design: Double-blind, randomized placebo-controlled 2 9 2
within-subject and between-groups design with 36 healthy partici-
pants. Each participant will play both conditions (inclusion and
exclusion) of the new Cyberball-Paradigm for 12 min. 15 min before
Cyberball starts each participant receives brain stimulation (sham vs.
verum tDCS) of the right ventrolateral prefrontal cortex (F6). The
ECG will record the heart rate in the 12 min period of playing. All
participants will be screened regarding psychological abnormalities in
advance to the first study visit.
Conclusion:With this pilot study we want to gain more insights about
the effects of rVLPFC tDCS on interpersonal behavior and cognition
as well as to figure out potential application areas of tDCS on emotion
regulation and coping with stressful social situations.
References:
1. Williams KD, Jarvis B (2006) Cyberball: a program for use in
research on interpersonal ostracism and acceptance. Behav Res
Methods 38(1):174–180
2. Williams KD, Williams KD, Cheung CK, Choi W (2000)
Cyberostracism: effects of being ignored over the Internet. J Person-
ality Soc Psychol 79(5):748–762
Eur Arch Psychiatry Clin Neurosci
123
3. Riva P, Lauro LJR, DeWall CN, Bushman BJ (2012) Buffer the
pain away stimulating the right ventrolateral prefrontal cortex reduces
pain following social exclusion. Psychol Sci 23(12):1473–1475
4. Riva P, Lauro LJR, DeWall CN, Chester DS, Bushman BJ
(2014) Reducing aggressive responses to social exclusion using
transcranial direct current stimulation (tDCS). Soc Cogn Affect
Neurosci nsu053
5. Riva P, Romero Lauro LJ, Vergallito A, DeWall CN, Bushman BJ
(2015) Electrified emotions: modulatory effects of transcranial direct
stimulation on negative emotional reactions to social exclusion. Soc
Neurosci 10(1):46–54
6. Dambacher F, Schuhmann T, Lobbestael J, Arntz A, Brugman S,
Sack AT (2015) Reducing proactive aggression through non-invasive
brain stimulation. Soc Cogn Affect Neurosci nsv018
7. Eisenberger NI, Lieberman MD, Williams KD (2003) Does
rejection hurt? An fMRI study of social exclusion. Science
302(5643):290–292
8. Dewald-Kaufmann et al., in preparation
Policy of full disclosure: F.P. has received speaker’s honorarium from
Mag&More GmbH and the neuroCare Group as well as support with
equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More
GmbH and Brainsway Inc., Jerusalem, Israel. Linda Wulf is part-time
employee at the neurocare Group.
P-08Prefrontal MRI-compatible tDCS reduces ventromedial corticalperfusion after being criticized
J. Dedoncker1,2, M.-A. Vanderhasselt1,2,3, J. Remue1,3, S. De Witte1,2,
G.-R. Wu4, R. De Raedt3, C. Baeken1,2,5
1Department of Psychiatry and Medical Psychology, University
Hospital (UZ) Ghent, Ghent University, Ghent, Belgium; 2Ghent
Experimental Psychiatry (GHEP) Lab, Ghent, Belgium; 3Department
of Experimental Clinical and Health Psychology, Ghent University,
Ghent, Belgium; 4Key Laboratory of Cognition and Personality,
Faculty of Psychology, Southwest University, Chongqing, China;5Department of Psychiatry, University Hospital (UZ) Brussels,
Brussels, Belgium
Being sensitive to self-referential criticism might be a vulnerability
factor for the development and/or recurrence of mood disorders. We
aimed to explore whether one prefrontal tDCS session is capable of
modulating frontolimbic cortical perfusion in response to criticism,
depending on criticism-sensitivity (low vs. high). In a randomized,
sham-controlled crossover study, 30 healthy females were adminis-
tered one session of left prefrontal MRI-compatible active tDCS (vs.
sham), followed by exposure to verbal criticism recordings in the
scanner. Individual criticism-sensitivity (low vs. high) was evaluated
at baseline. Momentary mood and frontolimbic perfusion (by means
of arterial spin labeling) were assessed in the MRI scanner at three
time points: baseline, directly following tDCS, and after hearing
criticism. Regardless of being sensitive to criticism, and independent
from having had sham or active tDCS, after being criticized young
healthy females felt angrier. Criticism-sensitivity did however influ-
ence tDCS-induced brain perfusion: being criticized following active,
but not sham tDCS was related to a decrease in right ventromedial
prefrontal (pgACC/mPFC) perfusion only in highly criticism-sensi-
tive individuals. Momentary changes in mood following hearing
criticism, specifically increased angriness, were not modulated by
tDCS. Given that active tDCS decreased ventromedial prefrontal
perfusion after being criticized, tDCS may be able to reduce
responsiveness to negative self-referential information in highly
criticism-sensitive young females.
Policy of full disclosure: The authors do not have disclosures to
report.
P-09Does electrode localization in tDCS research matter?A comparison between 10–20 EEG system and MRI-guidedneuronavigation
S. De Witte1,2, D. Klooster3,4,5, J. Dedonckera,b, R. Duprat1,2,
J. Remue1,6, C. Baeken1,2,7
1Department of Psychiatry and Medical Psychology, Ghent
University Hospital, Ghent University, Ghent, Belgium; 2Ghent
Experimental Psychiatry (GHEP) Lab, Ghent, Belgium;3Kempenhaeghe Academic Center for Epileptology, P.O. Box 61,
5590 AB Heeze, The Netherlands; 4Department of Electrical
Engineering, University of Technology Eindhoven, P.O. Box 513,
5600 MB Eindhoven, The Netherlands; 5Department of Neurology,
Ghent University Hospital, Ghent, Belgium; 6Department of
Experimental Clinical and Health Psychology, Ghent University,
Ghent, Belgium; 7Department of Psychiatry, University Hospital
UZBrussel, Brussels, Belgium
Although the 10–20 EEG system is frequently used to locate the
dorsolateral prefrontal cortex (DLPFC) in tDCS research, due to inter-
subject brain variability, this method may have limited target accu-
racy and may result in suboptimal stimulation. To address this issue,
we compared left DLPFC-localization via the 10–20 EEG system to
MRI-guided neuronavigation in forty healthy female participants
within the same age range. Compared to the 10–20 EEG system,
MRI-guided neuronavigation localizes the DLPFC-targeting anode
more latero-posteriorly. Furthermore, tDCS-induced electric fields
(derived from one subject) suggest that these different localization
methods induce different electric fields in distinct brain regions. Our
findings indicate that prefrontal tDCS targeting methods result in
distinct electrode localizations, each of which suggested being asso-
ciated to unique underlying electric field distributions. Considering
the frequent use of tDCS in research, an evaluation and direct com-
parison of the outcome of both targeting methods is therefore
warranted.
Policy of full disclosure: The authors do not have disclosures to
report.
P-10Effects of different prefrontal-tDCS electrode-montageson resting-state connectivity and cognitive control
J. Worsching1*, F.Padberg1*, S. Goerigk1,2, I. Heinz1, C.Bauer1,
C. Plewnia3, A. Hasan1, B. Ertl-Wagner4, Da. Keeser1,4
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-
University, Munich, Germany; 2Department of Psychological
Methodology and Assessment, Ludwig-Maximilians-University,
Munich, Germany; 3Department of Psychiatry and Psychotherapy,
Neurophysiology and Interventional Neuropsychiatry and Werner
Reichardt Centre for Integrative Neuroscience (CIN), University of
Tubingen, Tubingen, Germany; 4Department of Radiology, Ludwig-
Maximilians-University, Munich, Germany
*Both authors contributed equally to this work.
Transcranial direct current stimulation (tDCS) of the prefrontal cortex
has been advocated as an experimental and therapeutic intervention in
various neuropsychiatric disorders. Although computational models
of tDCS induced current density distribution in the brain are avail-
able, there is need for empirical studies investigating
Eur Arch Psychiatry Clin Neurosci
123
neurophysiological effects of prefrontal tDCS and its methodological
underpinnings. We therefore aimed to investigate the influence of
different electrode montages on tDCS-induced neuromodulation.
Within a cross-over design, 32 right-handed healthy male subjects
underwent three active tDCS conditions and sham tDCS in a pseudo-
randomized order. Before and after tDCS a resting-state fMRI (RS
fMRI) was recorded, which was then followed by a cognitive-control
task. RS-fMRI connectivity measures indicated reduced connectivity
within the right frontal gyrus after cathodal tDCS of the left and
concurrent anodal tDCS of the right DLPFC. On a behavioural level,
the expected slowing in reaction times after negative vs. neutral
pictures reversed under anodal tDCS of the left DLPFC with the
cathode placed above the right DLPFC, yet, was intensified when the
cathode was shifted to a more supraorbital position. The current study
provides evidence for electrode-montage specific tDCS-effects and a
complex interaction between passive neurophysiological and active
behavioural outcome measures.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 5, Grant Number 01EE1403E), funded by the Federal Min-
istry of Education and Research (BMBF). F.P. has received speaker’s
honorarium from Mag&More GmbH and the neuroCare Group as
well as support with equipment from neuroConn GmbH, Ilmenau,
Germany, Mag&More GmbH and Brainsway Inc., Jerusalem, Israel.
P-11Neurophysiological impact of a fronto-temporal transcranialdirect current stimulation in healthy subjects: a multimodal PET-MR imaging approach
C. Fonteneau1,2, I. Merida3, J. Redoute3, F. Haesebaert1,2, N. Costesc,
J. Brunelin1,2, M.-F. Suaud-Chagny1,2
1Centre de Recherche en Neurosciences de Lyon, Equipe PSYR2
(INSERM U1028, CNRS UMR5292, UCBL, Universite de Lyon),
Lyon, France; 2Centre Hospitalier Le Vinatier, 69000 Bron, France;3CERMEP-Imagerie du vivant, Lyon, France
Fronto-temporal transcranial direct current stimulation (tDCS), with
anodal stimulation over the left dorsolateral prefrontal cortex and
cathodal stimulation over the left temporo-parietal junction, has been
reported to reduce treatment-resistant symptoms in patients with
schizophrenia. Despite an increasing use in clinical settings, acute and
subsequent effects of fronto-temporal tDCS are far from being
completely understood. The few offline imaging and computational
reports available suggest that fronto-temporal tDCS effects are not
restricted to the brain areas located under the electrodes, but spread
through distributed cortical networks functionally connected with the
targets and reach subcortical areas, such as dopaminergic areas.
However, these effects are currently described at different levels
depending on the imaging technique used and online effects are rarely
inspected. Objectives: The aim of this study is to reveal the combined
acute and subsequent neurobiological effects of a single session of
fronto-temporal tDCS in a unique experiment by developing a
simultaneous multimodal imaging approach (PET-MR).
Methods: 30 healthy subjects randomly received a single-session of
either active (30 min, 1 mA; n = 15) or sham (n = 15) fronto-tem-
poral tDCS during a simultaneous PET-MR scan. The distributed
changes are explored at rest through:
• Specific and localized dopaminergic transmission evaluated by
PET using dopaminergic D2 subtype receptor availability via
[11C]raclopride binding. The tracer was administered intravenous,
using a bolus-plus-continuous-infusion method.
• Brain activity assessed by cerebral blood flow quantitatively and
directly measured by pseudo-continuous arterial spin labelling
(pCASL, three 6 min-scans before, during and after tDCS).
• Spontaneous functional connectivity assessed by resting state
functional MRI (rs-fMRI, three 13 min-scans before, during and
after tDCS).
• Structural connectivity assessed by diffusion tensor imaging (DTI,
two 10 min scans before and after tDCS).
• Perspectives: Our unique combined approach will create a
coherent ensemble, which is a mandatory and critical step to
understand the mechanisms of action of fronto-temporal tDCS.
Policy of full disclosure: The authors do not have disclosures to
report.
P-12Modulation of brain metabolites and resting state functional MRIconnectivity by transcranial direct current stimulation (tDCS)over the left dorsolateral prefrontal cortex in healthy subjects
E. Mezger1, B. Rauchmann1, J. Worsching1, M. Mortazavi1,
A. Brunoni1, B.Ertl-Wagner2, F. Padberg1, D. Keeser1,2
1Department of Psychiatry and Psychotherapy, University Hospital
LMU Munich, Munich, Germany; 2Department of Radiology,
University Hospital LMU Munich, Munich, Germany
Introduction: Magnetic Resonance Spectroscopy (MRS) studies have
shown that transcranial direct current stimulation (tDCS) modulates
the metabolite concentration of GABA in the motor cortex (M1). In a
recent study, Hone-Blanchet et al. (2016) have not observed such
effects for tDCS applied over the dorsolateral prefrontal cortex
(DLPFC), but observed changes in glutamate in the striatum. To
clarify these results, we investigated the effects of tDCS on DLPFC
GABA, N-acetyl-aspartate (NAA), glutamate/glutamine (Glx) and
glutamate concentrations using an online protocol in conjunction with
pre and post fMRI resting state connectivity (fcMRI) measurements.
Methods: Thirty healthy subjects (18 women, mean age 23) were
assigned to active (20 min, 2 mA) and sham tDCS using a double-
blind cross-over design. The anode was positioned over F3 (left
DLPFC), the cathode over F4 (right DLPFC). A MRS MEGA-PRESS
sequence (TE = 68), currently the most widely used technique for
GABA quantification, was acquired before, during and after stimu-
lation. GABA concentrations were quantified using Gannet 2.0.
Repeated measures ANOVA was conducted comparing active and
sham tDCS. Result: Preliminary data of 19 healthy subjects (11
women, mean age 23) showed a statistical significant reduction of
DLPFC glutamate concentrations comparing during to after anodal
tDCS. However, this difference was not significant compared to sham
tDCS. We could not find any effects of anodal tDCS on GABA, NAA
and Glx values. Conclusion: This is the first study reporting a
reduction of glutamate in the left DLPFC due to anodal tDCS stim-
ulation. To our knowledge only the study of Hone-Blanchet and
colleagues (2016) already investigated the change of glutamate con-
centrations in this brain region together with tDCS stimulation. Other
metabolite changes may be also small and only detectable with
increased participant numbers. The effect of tDCS on functional
connectivity will be further analysed.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 5, Grant Number 01EE1403E), funded by the Federal Min-
istry of Education and Research (BMBF). F.P. has received speaker’s
honorarium from Mag&More GmbH and the neuroCare Group as
well as support with equipment from neuroConn GmbH, Ilmenau,
Germany, Mag&More GmbH and Brainsway Inc., Jerusalem, Israel.
Eur Arch Psychiatry Clin Neurosci
123
P-13Effects of transcranial direct current stimulation (tDCS)on working memory performance in patients with schizophrenia
T. Schwippel1, I. Papazova2, W. Strube2, A. Fallgatter1, A. Hasan2, C.
Plewnia1
1Department of Psychiatry and Psychotherapy, Neurophysiology and
Interventional Neuropsychiatry, University of Tubingen, Calwerstr.
14, 72076 Tubingen, Germany; 2Department of Psychiatry and
Psychotherapy, Klinikum der Universitat Munchen, Ludwig-
Maximilians University Munich, Nußbaumstraße 7, 80336 Munich,
Germany
Introduction: Cognitive impairment is a core symptom of
schizophrenia and is in a large part responsible for the poor psy-
chosocial outcome of the disorder. The use of non-invasive brain
stimulations techniques as a therapeutic option is just commencing
and showed a few promising results to ameliorate specific cognitive
domains in impaired patients. In healthy subjects, we have previously
shown that anodal tDCS of the right DLPFC parallel to working
memory training can sustainably enhance performance in a spatial
n-back task (Ruf et al. 2017). As a first translational step, we now
assessed the efficacy of anodal tDCS to the right DLPFC on spatial
working memory performance in patients with schizophrenia.
Methods: 32 patients with the DSM-V diagnosis of schizophrenia
were enrolled in this double-blind, sham controlled cross-over study.
The first experiment was conducted with 1 mA and the second with
2 mA current strength. Both otherwise identical experiments con-
sisted of three experimental sessions, in which a spatial n-back task
was administered. The anode was placed over the right dorsolateral
prefrontal cortex and the cathode over the contralateral deltoid mus-
cle. Calculated baseline corrected d prime was defined as primary
outcome variable.
Results: In experiment 1, no difference between sham and anodal
stimulation was found for corrected d prime. In our preliminary
analysis of experiment 2, the use of 2 mA did result in a significant
difference between sham and anodal tDCS in the most challenging
working memory condition (3-back). With concurrent 2 mA tDCS,
the patients performed better in the 3-back than during sham stimu-
lation. This result is in line with the notion that higher current
intensities are necessary in a patient population and that effects of
stimulation only occur when patients work at their cognitive limit.
Policy of full disclosure: The authors do not have disclosures to
report.
P-14Transcranial direct current stimulation in three patientswith Gilles de la Tourette syndrome
N. Behler1, B. Leitner1, E.Weidinger1, R. Musil1, B. Blum1,2,
B. Kirsch1, L. Wulf1,3, L.Lohrs1, F. Padberg1, U. Palm1,3
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilian
University, Klinikum der Universitat Munchen, 80336 Munich,
Germany; 2Department of Neurology, Ludwig-Maximilian
University, Klinikum der Universitat Munchen, 81377 Munich,
Germany; 3NeuroCare Group, 80331 Munich, Germany
Background: In the treatment of Gilles de la Tourette Syndrome
(GTS) interesting pharmacological options are limited by a lack of
FDA approval, partly unsatisfactory treatment outcomes and often-
times considerable side effects (1). Manualised psychotherapeutic
options are hindered by poor compliance and availability as well as
long application-times (2). In this neuropsychiatric disorder, tics are
caused by alterations in the activity of cortico-striatao-thalamo-
cortical networks with an upregulation of motor-networks and a
downregulation of superordinate control-systems (3). By modifying
cortical activity, non-invasive brain-stimulation appears a viable new
treatment option in GTS. This technique is considered safe, with very
limited side effects. Previous findings suggested high therapeutic
effects of cathodal transcranial direct current stimulation (tDCS) to
pre-SMA both via bilateral or unilateral treatment of the most affected
side (4, 5).
Methods: Hypothesizing that bilateral treatment as well as higher
frequency of treatment and higher current intensity might yield more
pronounced therapeutic effects, we administered 5 days of twice daily
sessions of bilateral cathodal tDCS (30 min, 2 mA) over the pre-SMA
in three patients with severe GTS. Tic severity as well as obsessive–
compulsive disorder (OCD) symptoms and affective scales were rated
before and after 5 days of stimulation.
Result: Only one out of three patients showed any reduction in tic
severity. The two other patients showed an increase in tic severity. All
patients showed a mild increase in positive affect and a reduction in
negative affect.
Conclusion: Our results contradict earlier findings of extensive ther-
apeutic effects of cathodal tDCS on tics in patients with GTS and
show that prediction of stimulation effects on a targeted brain area
remains inaccurate. Thus, we propose a follow-up study to determine
most effective stimulation site, intensity and polarity of tDCS, using a
crossover design in 20 Tourette patients.
Policy of full disclosure: F.P. has received speaker’s honorarium from
Mag&More GmbH and the neuroCare Group as well as support with
equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More
GmbH and Brainsway Inc., Jerusalem, Israel. Linda Wulf is part-time
employee at the neurocare Group. Ulrich Palm has a private practice
with neurocare Group.
P-15tDCS-enhanced working memory training in subjective cognitivedecline
N. Stoynova1, C. Laske1, C. Plewnia1
1University Hospital Tuebingen, Tubingen, Germany
Subjective cognitive decline (SCD) is defined as self-reported cog-
nitive decline before the deficits could be detected by cognitive tests
[1]. SCD increasingly acknowledged as a risk factor for the devel-
opment of Alzheimer’s disease [2] and is therefore considered a stage
particularly accessible for interventional strategies [3]. However,
studies evaluating the efficacy of therapeutic interventions in this
condition are scarce. SCD has been particularly linked with deficient
cognitive control (CC) functions [4]. Anodal transcranial direct cur-
rent stimulation (tDCS) to the left dorsolateral prefrontal cortex
(dlPFC) can significantly enhance CC. Specifically, this has been
demonstrated by means of a challenging and frustrating continuous
performance task (Paced Serial Addition Task; PASAT).
This 2-armed, randomized, sham-controlled study aims at pro-
viding evidence for the efficacy of a tDCS-enhanced cognitive control
training (PASAT) in participants with SCD. 30 participants will take
part in a 4 week training (12 sessions); 50% of them will receive
2 mA anodal tDCS for 20 min applied to the left dlPFC, the other half
will receive sham stimulation. Event-related potentials (ERPs) evoked
by the feedback on the correctness of the response at baseline and
after training will be measured with EEG as neurophysiological sig-
natures of cognitive control. Near and far transfer will be assessed by
a verbal 2-back task and the Trail Making Test A and B. The amount
of worrying regarding the memory impairment will be quantified by
means of a 10-point Likert scale and will serve as the primary mea-
sure outcome. Together with changes of PASAT performance these
Eur Arch Psychiatry Clin Neurosci
123
measures will be obtained before and after the tDCS-enhanced
training. Follow-up assessments 3, 12 and 24 months after training
will investigate the sustainability of the training effects.
This study is designed to provide first proof of principle and
effect-size estimates for larger clinical studies. First results will be
presented at the conference.
References:
1. Molinuevo JL, Rabin LA, Amariglio R et al, Subjective Cognitive
Decline Initiative (SCD-I) Working Group (2016) Implementation of
subjective cognitive decline criteria in research studies. Alzheimers
Dement S1552-5260:33019–9
2. Jessen F, Amariglio RE, Van Boxtel M et al (2014) A conceptual
framework for research on subjective cognitive decline in preclinical
Alzheimer’s disease. Alzheimers Dement 10:844–852
3. Fernandez-Blazquez MA, Avila-Villanueva M, Maestu F, Medina
M (2016) Specific features of subjective cognitive decline predict
faster conversion to mild cognitive impairment. J Alzheimers Dis
52(1):271–281
4. Stogmann E, Moser D, Klug S, Gleiss A, Auff E, Dal-Bianco P,
Pusswald G, Lehrner J (2016) Activities of daily living and depressive
symptoms in patients with subjective cognitive decline, mild cogni-
tive impairment, and Alzheimer’s disease. J Alzheimers Dis
49:1043–1050
Policy of full disclosure: The authors do not have disclosures to
report.
P-16Transcranial direct current stimulation (tDCS) as treatmentfor major depression: a prospective multicenter double blindrandomized placebo controlled trial (DepressionDC)—earlyquality control of technical data from a blind selection of activetDCS sessions
U. Kumpf 1*, T. Nenov-Matt1*, N. Behler1, J. Nolden1, U. Palm1, L.
Wulf1, Be. Kirsch1, J.Worsching1, D. Keeser1, T. Gorlitz1, U.
Mansmann2, M. Bajbouj3, C. Plewnia4, B. Langguth5, P. Zwanzger6,
F. Padberg7
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilian
University, Munich, Germany; 2IBE University of Munich, Munich,
Germany; 3Department of Psychiatry, Charite, Berlin, Germany;4Department of Psychiatry, University Tubingen, Tubingen,
Germany; 5Department of Psychiatry, University Regensburg,
Regensburg, Germany; 6Inn-Salzach-Klinikum, Wasserburg,
Germany
*Both authors equally contributed to this work.
Background: The DepressionDC study investigates efficacy and tol-
erability of prefrontal tDCS used as an additive therapy to an
antidepressant medication (SSRI) as treatment for major depression in
a double-blinded, placebo-controlled multicenter trial. There is a
consensus on parameters like electrical current (1–2 mA) and the
critical impedance values are known from safety-studies, but the
in vivo stability of these technical parameters over the stimulation
period has not been investigated yet. For this study a novel system for
recording and monitoring of technical data has been established.
Here, we present a blind analysis of the technical data of 120 active
tDCS sessions from a single center.
Methods: Patients with MDD receive a 6-weeks treatment with pre-
frontal tDCS (anode: F3, cathode: F4, 5 sessions/week for 4 weeks
followed by 2 sessions/week for 2 weeks, 30 min/day, 2 mA inten-
sity) or sham tDCS (parameters correspondent active tDCS, ramp in
and ramp out periods only without intermittent stimulation) as
adjunctive treatment to a SSRI. Impedance, current and voltage, are
continuously recorded (1800 time points over 30 min). After the
stimulation, data is automatically transferred to a cloud where the data
are stored under the randomization code with maintaining integrity of
blinding.
Results: The descriptive analysis showed a high homogeneity and
stability of the technical parameters over the time of the tDCS session
in 120 active stimulations. Considering only the stimulation time
without ramp in and ramp out periods direct current is stabile between
2008 and 1970 lA, impedance between 6053 and 1454 kX and
voltage between 12,093 and 2902 V. Using a window function the
standard deviation of the measures was analysed. A steady state of
voltage was reached between 46 and 55 measurements, i.e. after
46–55 s, and the impedance reached a steady state after 15–20
measurements i.e. after 15–20 s of stimulation.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 7, Grant Number 01EE1403G), funded by the Federal
Ministry of Education and Research (BMBF).F.P. has received
speaker’s honorarium from Mag&More GmbH and the neuroCare
Group as well as support with equipment from neuroConn GmbH,
Ilmenau, Germany, Mag&More GmbH and Brainsway Inc., Jer-
usalem, Israel. Linda Wulf is part-time employee at the neurocare
Group. Ulrich Palm has a private practice with neurocare Group.
P-17Targeting fatigue, mood and cognition in multiple sclerosis usingtDCS
M. A. Chalah1,2*, J.-P. Lefaucheur1,2, A. Creange1,3, S. S. Ayache1,2,4
1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-
Est-Creteil, Creteil, France; 2Service de Physiologie-Explorations
Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux
de Paris, Creteil, France; 3Service de Neurologie, Hopital Henri
Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France;4Neurology Division, Lebanese American University Medical Center
Rizk Hospital, Beirut, Lebanon
*Corresponding author: Moussa A. Chalah, Service de Physiologie–
Explorations Fonctionnelles, Hopital Henri Mondor, Assistance
Publique–Hopitaux de Paris, 94010 Creteil, France.
Background: Multiple Sclerosis (MS) is a chronic inflammatory and
neurodegenerative disease of the central nervous system, through
which the patients may experience various symptoms such as fatigue,
psychiatric complaints, cognitive deficits, to cite a few [1, 2]. The
current pharmacological treatments are majorly limited by their side
effects profile and modest efficacy. Recently, non-invasive brain
stimulation techniques, particularly transcranial direct current stimu-
lation (tDCS) have proved some benefits in the context of
neurological and psychiatric diseases [2, 3]. The purpose of this work
was to evaluate tDCS effects on fatigue, anxiety and depression
symptoms, and attentional abilities.
Methods: The study adapted a double-blind, sham-controlled and
cross-over design. Each of the 10 MS patients randomly received
three anodal tDCS blocks made each of 5 consecutive daily sessions:
active stimulation over the right posterior parietal cortex (PPC),
active stimulation over the left dorsolateral prefrontal cortex
(DLPFC) or sham stimulation over either site. Each block was made
of 5 consecutive daily sessions. A washout interval of 3 weeks sep-
arated them.
Results: Only right PPC tDCS improved the anxiety and depression
scores. Only left DLPFC tDCS improved fatigue. Neither condition
improved the attentional capacities.
Conclusion: The results of this work highlight the effects of tDCS on
fatigue, anxiety and depression symptoms in the context of MS. This
could be explained by the fact that DLPFC plays a key role in the
Eur Arch Psychiatry Clin Neurosci
123
cortico-striato-thalamo-cortical fatigue loop. In addition, the PPC per
se was previously found to be implicated in the pathophysiology of
anxiety and depressive disorders. Although both cortical sites are
implicated in attentional networks, the lack of tDCS effects on
attention could be partially attributed to the small sample size or the
protocol duration. The current findings merits to be replicated in
large-scale studies aiming to improve MS patients’ quality of life.
References:
1. Chalah MA, Ayache SS (2017) Psychiatric event in multiple
sclerosis: could it be the tip of the iceberg? Rev Bras Psiquiatr.
pii:S1516-44462017005007105.
https://doi.org/10.1590/1516-4446-2016-2105 [Epub ahead of print]
2. Chalah MA, Riachi N, Ahdab R, Creange A, Lefaucheur JP,
Ayache SS (2015) Fatigue in multiple sclerosis: neural correlates and
the role of non-invasive brain stimulation. Front Cell Neurosci 9:460
3. Ayache SS, Chalah MA (2017) Fatigue in multiple sclerosis—
insights into evaluation and management. Neurophysiol Clin
47:139–171
Policy of full disclosure: SSA declares having received travel grants
or compensation from Genzyme, Biogen, Novartis and Roche. AC
gave expert testimony for CSL Behring, Novartis, received grants
from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and
gave lectures for Genzyme. JPL and MAC: Nothing to disclose.
P-18Frontal EEG coherence after beta-tACS during reversal learning
M. Wischnewski, D. Schutter
Donders Institute, Donders Centre for Cognition, Radboud
University, Nijmegen, The Netherlands
No abstract for publication.
P-19Online effects of transcranial alternating current stimulationon event-related alpha power modulations: a concurrent tACS-MEG study
F. H. Kasten1,2, B. Maess3, C. S. Herrmann1,2,4
1Experimental Psychology Lab, Department of Psychology, European
Medical School, Cluster for Excellence ‘‘Hearing for All’’, Carl von
Ossietzky University, Oldenburg, Germany; 2Neuroimaging Center,
European Medical School, Carl von Ossietzky University, Oldenburg,
Germany; 3MEG and Cortical Networks Group, Max Planck Institute
for Human Cognitive and Brain Sciences, Leipzig, Germany;4Research Center Neurosensory Science, Carl von Ossietzky
University, Oldenburg, Germany
Transcranial alternating current stimulation (tACS) is receiving
increasing popularity as a non-invasive approach to modulate oscil-
latory activity in the brain. Besides allowing to study causal
relationships between brain oscillations and cognition, tACS might
offer promising new therapeutic applications for a variety of neuro-
logical and psychiatric conditions in which dysfunctional brain
oscillations are implied. However, so far, only little is known about
effects of tACS during stimulation, due to a massive stimulation
artifact at the targeted frequency. Especially, it is not clear how
continuous tACS application during a cognitive task changes event-
related oscillatory activity. TACS might either enhance event-related
changes in oscillatory activity or overwrite the existing pattern of
perturbations. Knowledge about the direction of tACS effects on
event-related oscillations is crucial to understand and predict the
outcome of solely behavioral experiments or clinical trials.
Here, a recently proposed procedure to suppress tACS artifacts by
projecting MEG data into source space using a linearly constrained
minimum variance beamformer was utilized to reveal the effect of tACS
on event-related power modulations in the alpha band during a cognitive
task. Twenty volunteers performed a mental rotation task, while MEG
was continuously recorded. After 10 min of baseline measurement, they
received either 20 min of tACS at individual alpha frequency or sham
stimulation. Another 40 min of MEG were acquired thereafter.
Results revealed a strong facilitation of event-related power
modulations in the alpha band during tACS. Data provide first direct
evidence that tACS does not counteract top–down suppression of
intrinsic oscillations, but rather enhances pre-existent power modu-
lations within the range of the individual alpha (=stimulation)
frequency. Furthermore, the study provides a framework to analyze
event-related oscillatory dynamics during tACS in the presence of
residual artefacts. Thus, it contributes to further understand mecha-
nisms of tACS, paving the way for future therapeutic applications.
Policy of full disclosure: CSH has filed a patent application on brain
stimulation and received honoraria as an editor from Elsevier Pub-
lishers, Amsterdam. FHK and BM declare no competing interests.
P-20Long-term effect of 3 daily sessions of transcranial random noisestimulation (tRNS) on inhibitory control
C. Brevet-Aeby1,2,3, M. Mondino1,2, E. Poulet1,2,3,4, J. Brunelin1,2,4
1Inserm, U1028; Cnrs, Umr5292; Lyon Neuroscience Research
Center, WR2 Team, 69000 Lyon, France; 2University Lyon 1, 69000
Villeurbanne, France; 3Emergency Psychiatry, Edouard Herriot
Hospital, Hospices Civils de Lyon, Lyon, France; 4Centre Hospitalier
Le Vinatier, 69678 Bron, France
Introduction: Deficits in inhibitory control, a key feature of impul-
sivity, was reported in numerous neuropsychiatric conditions. These
deficits may lead to inappropriate behaviours such as suicidal attempt.
Noninvasive brain stimulation technique applied over the dorsolateral
prefrontal cortex (DLPFC) may enhance inhibitory control but little is
known regarding the duration of these beneficial effects.
Objective: To investigate the duration of the effect of 1 and of 3
sessions of transcranial random noise stimulation (tRNS) applied over
the DLPFC on inhibitory control as compared with sham. The effect
of stimulation was measured immediately after tRNS, 1 day (D1) and
1 week (D8) after the end of the sessions.
Method: In a double blind sham-controlled study, 32 healthy subjects
were randomly allocated to receive 1 active and 2 placebo (1A2P,
n = 10), 3 active (3A, n = 11) or 3 placebo (3P, n = 11) tRNS
sessions. One session lasted 20 min at 2 mA and each tRNS sessions
were separated by 30 min. The anode was placed over the right
DLPFC and the cathode over the left. Inhibitory control was measured
by reaction time at the Go/No Go test.
Results: Repeated measures ANOVA revealed a significant interac-
tion between time and group (p = 0.03, g2 = 0.14). After tRNS,
there was a significant difference between 3P (0.00 ± 0.03%) and 3A
(- 8.51 ± 0.03%; p = 0.04), 3P and 1A2P (- 8.75 ± 0.02%;
p = 0.01) but no difference between 3A and 1A2P groups. At D1,
there was a significant difference between 3P (- 3.33 ± 0.03%) and
3A (- 14.2 ± 0.02%; p\ 0.01), 3P and 1A2P (- 10.55 ± 0.02%;
p = 0.04) groups but no difference between 3A and 1A2P groups. At
D8, only the 3P (- 4.42 ± 0.03%) and 3A (- 13.54 ± 0.02%)
groups were significantly different (p = 0.03).
Conclusion: Compared with sham and with 1 session of tRNS, 3
sessions of tRNS over the DLPFC have a longer beneficial duration
on inhibitory control.
Eur Arch Psychiatry Clin Neurosci
123
Policy of full disclosure: The authors do not have disclosures to
report.
P-21Effects of transcranial direct current stimulation appliedto the prefrontal cortex on TMS evoked potentials
P. C. Gordon1,2, C. Zrenner1, D. Desideri1, P. Belardinelli1,
B. Zrenner1, A. Brunoni2, U. Ziemann1
1Department of Neurology and Stroke, and Hertie Institute for
Clinical Brain Research, University of Tubingen, Tubingen,
Germany; 2Department of Psychiatry, University of Sao Paulo, Sao
Paulo, Brazil
Transcranial direct current stimulation (tDCS) of prefrontal cortex
(PFC) is considered a possible therapy for various psychiatric con-
ditions1. However, current models of tDCS mechanism of action are
largely based on studies targeting human motor cortex, where
excitability can be quantified through motor evoked potentials, but
where reported effects are also variable, partially due to differences in
stimulation parameters2. A recent study has shown a significant
change in TMS evoked potentials (TEPs) over PFC following tDCS3.
In the present study, we further investigate the effects of tDCS on
TEPs over PFC in response to different tDCS parameters.
22 healthy subjects underwent 5 different tDCS interventions in a
randomized double-blind study design with the following parameters:
(1) 1.5 mA, anode left-PFC, cathode right-PFC, (2) 1.5 mA, cathode
left-PFC, anode right-PFC, (3) 0.5 mA, anode left-PFC, cathode
right-PFC, (4) 1.5 mA, anode left-PFC, cathode deltoid muscle, (5)
sham. Stimulation was delivered by tDCS electrodes integrated
between the EEG sensors of a standard 64 channel EEG cap, centred
around the dorsolateral PFC and having a total area of 3 cm2 over
each hemisphere. 160 TEPs were recorded before and after the tDCS
intervention. A cluster based analysis was performed as well as an
analysis of TEP peaks in a predefined region of interest (ROI) con-
sisting of 10 EEG channels over left PFC and within the following
times of interest (TOI): 25–55 ms (N40), 45–75 ms (P60), 85–145 ms
(N100) and 170–230 ms (P200).
Cluster based statistics revealed a negative cluster over the pari-
eto-occipital region (p = 0.003) at the N100 in condition 1 only. No
other cluster was shown to be statistically significant in any other
condition. A repeated measures ANOVA failed to identify any sta-
tistically significant effect of time (pre and post tDCS) or condition in
the TEPs amplitude of the ROI.
Policy of full disclosure: The authors do not have disclosures to
report.
P-22Changes in firing properties and synaptic plasticity in differentbrain regions of schizophrenia model and control ratsafter transcranial magnetic stimulation
G. Barmashenko1, K. Funke1
1Department of Neurophysiology, Medical Faculty University
Bochum, Bochum, Germany
In former experiments repetitive transcranial magnetic stimulation
(rTMS) seems to change functional properties of brain inhibitory
systems. In our study we compare rats with schizophrenia model
resulting from maternal immune activation (MIA) and control rats
after rTMS and sham rTMS treatment. Firing properties in four brain
regions (prefrontal cortex (PrL), nucleus accumbens (NAc), ventral
tegmental area (VTA) and ventral hippocampus) in vivo show the
significantly different changes between the animal groups after high
frequency stimulation (130 Hz) and after theta burst stimulation.
In vitro experiments in prefrontal cortex and hippocampal slices show
the alteration in short term (paired pulse facilitation) and long term
(LTP) synaptic plasticity.
Policy of full disclosure: The authors do not have disclosures to
report.
P-23Advances in TMS technology: from flexible pulse shape designto high speed individualized biphasic quadri-pulse stimulation
N. Gattinger1, A. Heidsieck1, N. Jung2, V. Mall2, B. Gleich1
1Technische Universitat Munchen, Munich School of BioEngineering
(MSB), Boltzmannstraße 11, 85748 Garching, Germany; 2Technical
University of Munich, School of Medicine, Social Pediatrics,
Heiglhoftstr. 65, 81377 Munich, Germany
Transcranial magnetic stimulation (TMS) is able to noninvasively
excite neuronal populations due to brief magnetic field pulses. The
efficiency and the characteristics of stimulation pulse shapes, repeti-
tion rate and pulse length influence the physiological effect of TMS.
However, commercial devices mostly allow only a minimum of
control of different pulse shapes. Basically, only sinusoidal and
monophasic pulse shapes with fixed pulse widths are available. Only
few research groups are working on TMS devices with controllable
pulse parameters such as pulse shape or pulse width. We describe
three novel TMS devices based on our IGBT technology. The flexible
flexTMS device can generate magnetic pulses, which can be adjusted
with respect to pulse shape, pulse width, polarity, and intensity with
repetition rates up to 30 pulses per second (pps), or, respectively, up
to 100 pps in theta burst mode. The QPS device allows the application
of quadri-pulses with biphasic and polyphasic pulse currents,
respectively. ISI as short as 1.5 ms with a repetition rate of up to 100
pulses per second are possible. The experiment also shows that both,
biphasic as well as polyphasic, QPS given at a sub-threshold level
were able to modulate brain activity. The IQPS device is an
enhancement of the QPS stimulator. It allows the user to individualize
the ISI with respect to the subjects I-wave latency even within in a
quadri-pulse burst. The device can be fully controlled by a computer
and is usable for closed-loop applications with the possibility of
triggering each individual stimulus within the protocol.
References:
1. Jung NH, Gleich B, Gattinger N, Hoess C, Haug C, Siebner HR,
Mall V (2016) Quadri-pulse theta burst stimulation using ultra-high
frequency bursts—a new protocol to induce changes in cortico spinal
excitability in human motor cortex. PLoS One 11:e0168410
2. Gattinger N, Moessnang G, Gleich B (2012) flexTMS—a novel
repetitive transcranial magnetic stimulation device with freely pro-
grammable stimulus currents. IEEE Trans Biomed Eng 59:1962–1970
Policy of full disclosure: The authors do not have disclosures to
report.
P-24The role of the parietal cortex in memory confidence
S. C. Wynn1, M. P. H. Hendriks1,2, S. M. Daselaar1, R. P. C. Kessels1,
D. J. L. G. Schutter1
1Donders Institute for Brain, Cognition and Behaviour, Radboud
University, Nijmegen, The Netherlands; 2Academic Centre of
Epileptology, Kempenhaeghe, Heeze, The Netherlands
No abstract for publication.
Eur Arch Psychiatry Clin Neurosci
123
P-25Time lapse of individualized rTMS effects on resting statefunctional connectivity of healthy brains
A. Singh1*, T. Erwin-Grabner1*, G. Sutcliffe1, S. Wolter1, R. Goya
Maldonado1
1Systems Neuroscience and Imaging in Psychiatry, Clinic for
Psychiatry and Psychotherapy, University Medical Center, Gottingen,
Germany
*Equal contribution
Numerous studies have suggested that a single session of repetitive
transcranial magnetic stimulation (rTMS) is effective at manipulating
the brain’s functional connectivity [1]. While it is possible to
manipulate functional connectivity by stimulating at several acces-
sible cortical targets, the DLPFC as an rTMS target is of particular
importance due to its therapeutic use in the alleviation of depressive
symptoms. To detect differences in rTMS induced effects related to
time lapsed after stimulation targeted at the left DLPFC in healthy
brains, we recruited healthy volunteers for three experimental ses-
sions. In the initial session, the resting state (rs)-fMRI scan is utilized
to select the strongest node within the overlap of two components, one
spanning the DLPFC (positive correlation), and the other the anterior
cingulate cortex (negative correlation), which then becomes the target
for individualized rTMS intervention [2]. The next two sessions, at
least a week apart, involve either real or sham rTMS intervention
delivered using real time neuronavigation. A pre-rTMS rs-fMRI
session and three subsequent post-rTMS sessions are acquired upon
completion of rTMS. The data is analyzed for differences in func-
tional connectivity during resting state, both within the three rs-fMRI
scans acquired post-rTMS and between the pre-rTMS and post-rTMS
resting state scans, to answer how long the rTMS effects are sustained
and which resting state networks are involved over time, also com-
plimenting the work by Tik et al. 2017 [3]. Additionally, we also aim
to utilize the rs-fMRI scan from the first session and the two pre-
rTMS rs-fMRI scans from next two sessions to test the stationarity of
target selection across sessions [4].
References:
1. Fox M, Halko M, Eldaief M, Pascual-Leone A (2012) Measuring
and manipulating brain connectivity with resting state functional
connectivity magnetic resonance imaging (fcMRI) and transcranial
magnetic stimulation (TMS). NeuroImage 62(4):2232–2243
2. Fox M, Buckner R, White M, Greicius M, Pascual-Leone A (2012)
Efficacy of transcranial magnetic stimulation targets for depression is
related to intrinsic functional connectivity with the subgenual cin-
gulate. Biol Psychiatry 72(7):595–603
3. Tik M (2017) Towards understanding rTMS mechanism of action:
stimulation of the DLPFC causes network-specific increase in func-
tional connectivity. NeuroImage 162:289–596
4. Fox M, Liu H, Pascual-Leone A (2013) Identification of repro-
ducible individualized targets for treatment of depression with TMS
based on intrinsic connectivity. NeuroImage 66:151–160
Policy of full disclosure: The authors do not have disclosures to
report.
P-26The effect of seed determination on functional connectivityanalyses to study the effect of transcranial magnetic stimulation
D. C. W. Klooster1,2,3, R. M. H. Besseling1,2,3, A. P. Aldenkamp1,2,3,4,
M. D. Fox5,6, C. Baeken3,7
1Academic Center for Epileptology Kempenhaeghe, Heeze, The
Netherlands; 2Eindhoven University of Technology, Eindhoven, The
Netherlands; 3Ghent University Hospital, Ghent, Belgium;
4Maastricht University Hospital, Maastricht, The Netherlands;5Berenson-Allen Center for Noninvasive Brain Stimulation, Boston,
USA; 6Harvard Medical School, Boston, USA; 7University Hospital
Brussel, Brussels, Belgium
Functional connectivity (FC) studies have shown insight into the
mechanism of action of transcranial magnetic stimulation (TMS).
However, the choice of the seed, representing the stimulated area, is
ambiguous. The aim of this study is to investigate the effect of the
choice of the seed region.
Baseline anatomical and resting-state functional MRI (rs-fMRI)
data were collected from 50 depression patients who were stimulated
at the left DLPFC. The rs-fMRI scans were realigned, motion- and
slice-time-corrected, smoothed and normalized. Motion parameters,
including their first derivatives, white matter signal, cerebrospinal
fluid signal, and a linear and quadratic trend were used as con-
founders. Time-series were bandpass filtered between 0.01 and 0.1 Hz
[1].
Three different seeding methods were implemented. The first two
seeds were derived from electric field simulations (Simnibs [2]). A
weighted regressor (RegEfield_bin-weighted) was calculated as a weighted
average of time-series within the gray matter voxels, using the electric
field strengths as weights. A binary-weighted regressor (RegEfield_bin-
weighted) was defined as the weighted time-series of the gray matter
voxels where the electric field exceeds a patient-specific threshold
(50% of the maximum field strength in gray matter [3]). Third, a
simpler cone model [4] was implemented (RegCone).
Regressors resulting from the different seeding methods were
correlated with each other. High correlations were found:
mean = 0.84, std = 0.14 for RegEfield_bin-weighted versus RegEfield_bin-
weighted, mean = 0.79, std = 0.22 for RegCone versus RegEfield_bin-
weighted, and mean = 0.81, std = 0.13 for RegCone versus RegEfield_bin-
weighted. Zooming in on the effects of stimulation on the specific
connection between the left DLPFC and the sgACC did not show any
effect, for either type of regressor. This indicates that the relatively
simple cone model can be used to derive a representative TMS
regressor for FC analyses.
References:
1. Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F,
Meng Y, Fetcho RN, Zebley B, Oathes D, Etkin A, Schatzberg AF,
Sudheimer K, Keller J, Mayberg HS, Gunning FM, Alexopoulos GS,
Fox MD, Pascual-Leone A, Voss HU, Casey BJ, Dubin MJ, Liston C
(2016) Resting-state connectivity biomarkers define neurophysiolog-
ical subtypes of depression. Nat Med 23(1):28–38
2. Thielscher A, Antunes A, Saturnino GB (2015) Field modeling
for transcranial magnetic stimulation: a useful tool to understand
the physiological effects of TMS? IEEE EMBS 2015, Milano,
Italy
3. Opitz A, Fox MD, Craddock CR, Colcombe S, Milham MP (2016)
An integrated framework for targeting functional networks via tran-
scranial magnetic stimulation. NeuroImage 127:86–96
4. Fox MD, Liu H, Pascual-Leone A (2013) Identification of repro-
ducible individualized targets for treatment of depression with TMS
based intrinsic connectivity. NeuroImage 1:151–160
Policy of full disclosure: The authors do not have disclosures to
report.
P-27The relation between brain morphological factors and efficacyof rTMS treatment in patients with schizophrenia and auditoryverbal hallucinations
L. Bais1, C. Kos1, J.-B. Marsman1, S. Koops2,3, J. Dlabac-de Lange1,5,
He. Knegtering4,5, I. E. Sommer2,3, M.-J. van Tol1, A. Aleman1,5,6
Eur Arch Psychiatry Clin Neurosci
123
1Department of Neuroscience, University Medical Center Groningen,
University of Groningen, Antonius Deusinglaan 2, 9713 AW
Groningen, The Netherlands; 2Department of Psychiatry, University
Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The
Netherlands; 3UMC Utrecht Brain Center Rudolf Magnus,
Universiteitsweg 100 Utrecht, 3584 CG Utrecht, The Netherlands;4Lentis Research, Lentis Center for Mental Health Care, Hereweg 80,
9725 AG Groningen, The Netherlands; 5Rob Giel Research Center,
University Medical Center Groningen, University of Groningen,
Hanzeplein 1, 9713 GZ Groningen, The Netherlands; 6Department of
Psychology, University of Groningen, Grote Kruisstraat 2/1, 9712 TS
Groningen, The Netherlands
Background: Repetitive Transcranial Magnetic Stimulation (rTMS)
has been studied as a treatment option for auditory verbal halluci-
nations in patients with schizophrenia. However, meta-analyses on the
efficacy of rTMS treatment are inconclusive [4]. Inter-individual
differences in response to treatment have been observed, which
indicates that patient-specific characteristics might play a role [1]. In
this study, it was assessed whether morphological factors, including
scalp-to-cortex distance (SCD) and gray matter density (GMD) of the
stimulated brain region could predict response to rTMS treatment in
patients suffering from auditory verbal hallucinations (AVH).
Methods: Data from four clinical trials were combined, leading to the
inclusion of 54 patients. All patients received inhibitory rTMS of the
temporo-parietal junction (TPJ), and underwent Magnetic Resonance
Imaging before the start of the treatment. Correlation coefficient
calculations and hierarchical linear regression models were applied to
investigate the relationship between treatment efficacy and SCD and
GMD of the stimulated brain region.
Results: Shorter SCD and higher GMD of the TPJ were associated
with greater AVH improvement after rTMS treatment.
Conclusion: SCD and GMD possibly predict the efficacy of rTMS
treatment for AVH. When these associations are proved to be robust
in future studies, rTMS treatment efficacy might benefit from indi-
vidual-specific protocols.
References:
1. Bais L, Vercammen A, Stewart R, van Es F, Visser B, Aleman A
(2014) Short and long term effects of left and bilateral repetitive
transcranial magnetic stimulation in schizophrenia patients with
auditory verbal hallucinations: a randomized controlled trial. PLoS
One 9:e108828
2. Dlabac-de Lange JJ, Knegtering R, Aleman A (2010) Repetitive
transcranial magnetic stimulation for negative symptoms of
schizophrenia: review and meta-analysis. J Clin Psychiatry
71:411–418
3. Freitas C, Fregni F, Pascual-Leone A (2009) Meta-analysis of the
effects of repetitive transcranial magnetic stimulation (rTMS) on
negative and positive symptoms in schizophrenia. Schizophr Res
108:11–24
4. Slotema CW, Aleman A, Daskalakis ZJ, Sommer IE (2012) Meta-
analysis of repetitive transcranial magnetic stimulation in the treat-
ment of auditory verbal hallucinations: update and effects after
1 month. Schizophr Res 142:40–45
Policy of full disclosure: The authors do not have disclosures to
report.
P-28Abnormal brain asymmetry and behavior in ADHD: a TMS-EEGstudy
A. Avnit1, U. Alyagon1, S. Zibman1, A. Zangen1
1Department of Life Sciences and Zlotowski Center for Neuroscience,
Ben-Gurion University of the Negev, Beersheba, Israel
Background: ADHD is characterized by abnormal hemispheric
asymmetry, which may result from compromised inter-hemispheric
connectivity, and by deficient response inhibition. Here, we investi-
gated the relations between these factors in ADHD and their
relevance to its symptomology. For this purpose, we examined the
hemispheric asymmetry of the stop-signal N200 event-related
potential (ERP) component, which is related to response inhibition,
TMS-evoked potential (TEP) in the right frontal hemisphere, and
frontal right-to-left interhemispheric signal propagation (ISP).
Methods: ERPs of 52 ADHD and 43 non-clinical adult participants
were measured during performance of a visual stop-signal task. N200
right-asymmetry was calculated for each group in posterior and
anterior regions of interest (ROIs). Concurrent TMS and EEG were
used to measure TEP and ISP during rest.
Results: The ADHD group demonstrated greater N200 right-asym-
metry in the posterior ROI specifically for successful stop trials. In the
anterior ROI, this group exhibited reduced N200 right-asymmetry,
which was positively correlated with response inhibition performance
(for successful stop trials) and with symptoms severity (for unsuc-
cessful stop trials). ISP was stronger in the ADHD group, while TEP
was reduced and positively correlated with anterior N200 asymmetry
(for successful stop trials) in this group only.
Discussion: Compromised anterior asymmetry is related to sympto-
mology, as well as to cognitive and neurophysiological deficits in
ADHD, and may constitute an endophenotype of this disorder. The
observation that TEP, but not ISP, correlated with anterior N200
asymmetry suggests that this abnormal asymmetry is not the resultant
of compromised inter-hemispheric connectivity, but of reduced ability
of the right hemisphere to activate inhibitory interneurons in the left
hemisphere.
Policy of full disclosure: The authors do not have disclosures to
report.
P-29Anxiety symptoms correlates with transcallosal inhibitionin patients with multiple sclerosis
M. A. Chalah1,2, J.-P. Lefaucheur1,2, A. Creange1,3,
S. S. Ayache1,2,4,*1EA 4391, Excitabilite Nerveuse et Therapeutique, Universite Paris-
Est-Creteil, Creteil, France; 2Service de Physiologie-Explorations
Fonctionnelles, Hopital Henri Mondor, Assistance Publique-Hopitaux
de Paris, Creteil, France; 3Service de Neurologie, Hopital Henri
Mondor, Assistance Publique-Hopitaux de Paris, Creteil, France;4Neurology Division, Lebanese American University Medical Center
Rizk Hospital, Beirut, Lebanon
*Corresponding author: Samar S. Ayache, Service de Physiologie-
Explorations Fonctionnelles, Hopital Henri Mondor, Assistance
Publique-Hopitaux de Paris, 94010 Creteil, France.
Objectives: Psychiatric symptoms, particularly anxiety and depres-
sion, are commonly reported during the course of multiple sclerosis
(MS) [1]. Despite their drastic impact on the patients’ quality of life,
their neurophysiological correlates were not previously assessed. This
work addresses the relationship between cortical excitability measures
and each of anxiety and depression.
Methods: Patients were included if they were aged between 18 and
75 years, with a confirmed diagnosis of MS according to the 2010
revised McDonald criteria, and not taking any medication that might
alter cortical excitability measures. The Hospital Anxiety and
Depression Scale was employed. Socio-demographic and clinical data
were obtained. Transcranial magnetic stimulation was used to assess
the following cortical excitability measures: resting motor threshold,
motor evoked potentials amplitudes and latencies, contralateral silent
Eur Arch Psychiatry Clin Neurosci
123
period, short-interval intracortical inhibition, intracortical facilitation
and interhemispheric inhibition [2]. Correlation analysis was per-
formed to evaluate the association between psychiatric scores
(HADS) and cortical excitability measures.
Results: Fifty consecutive MS patients completed the protocol (24
women; mean age: 51.82 ± 12.72 years; mean expanded disability
status score: 5.52 ± 1.64; mean duration of illness:
11.88 ± 6.03 years). Their mean depression and anxiety scores were
respectively 6.08 ± 3.66 (range 0–14) and 5.82 ± 3.42 (range 1–15).
Correlation analysis revealed a significant positive correlation
between anxiety scores and interhemispheric inhibition mean
(r = 0.43, p = 0.003) and maximal values (r = 0.35, 0.017).
Depression did not correlate with any neurophysiological measure.
Conclusion: A direct relationship between anxiety and callosal
transfer was previously reported in one study [3]. Our results could be
interpreted in the light of the latter findings, in a way that MS patients
with higher anxiety scores may have relatively more efficient callosal
transfer compared to those with low anxiety scores.
References:
1. Chalah MA, Ayache SS (2017) Psychiatric event in multiple
sclerosis: could it be the tip of the iceberg? Rev Bras Psiquiatr.
pii:S1516-44462017005007105.
https://doi.org/10.1590/1516-4446-2016-2105 [Epub ahead of print]
2. Ayache SS, Creange A, Farhat WH, Zouari HG, Mylius V, Ahdab
R et al (2014) Relapses in multiple sclerosis: effects of high-dose
steroids on cortical excitability. Eur J Neurol 21:630–636
3. Leavengood A, Weekes NY (2000) The association between stress,
hemispheric specialization, and callosal interactions. Brain Cogn
43:306–310
Policy of full disclosure: SSA declares having received travel grants
or compensation from Genzyme, Biogen, Novartis and Roche. AC
gave expert testimony for CSL Behring, Novartis, received grants
from Biogen, Novartis, CSL Behring, GE Neuro, Octapharma, and
gave lectures for Genzyme. JPL and MAC: Nothing to disclose.
P-30Impaired corticospinal excitability revealed by transcranialmagnetic stimulation in patients with major depressive disorder
P. Vignaud1, E. Poulet1,2, M.-F. Suaud-Chagny1, J. Brunelin 1
1INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research
Center, PsyR2 Team, Centre Hospitalier Le Vinatier, University
Lyon, 69000 Lyon, France; University Lyon 1, 69000 Villeurbanne,
France; 2Department of Psychiatric Emergency, Hopital Edouard
Herriot, Lyon, France
Background: Growing evidence suggests that neuroplasticity is
impaired in patients with Major Depressive Disorder (MDD). The
modulation of corticospinal excitability induced by Transcranial
Magnetic Stimulation (TMS) might be an index of neuroplasticity
measured in the living Human. In the last years, several studies
reported impaired neuroplasticity induced by TMS protocol in
patients with psychiatric disorders such as autism spectrum disorder.
We hypothesized that TMS would revealed impaired neuroplasticity
in patients with MDD.
Methods: Eight right-handed patients with DSM 5 unipolar MDD free
for any other axis I disorder and 6 matched healthy controls were
included. Participants were free for any psychotropic drugs.
In a crossover study, participants received 2 sessions of theta-burst
stimulation (TBS) protocols separated by a least 2 days: one session
of intermittent TBS (iTBS) and one sessions of continuous TBS
(cTBS). TBS was applied over the left primary motor cortex (M1).
Motor evoked potentials (MEPs) were recorded before TBS ses-
sions and each 10 min during 2 hs after the TBS sessions.
Results: Effect of iTBS induced a significant increase of MEPs
amplitude in both patients with MDD and healthy controls. iTBS
induced a significant lower effect (p = 0.003) in depressed patients
(+ 537.4 mV ± 329.3) as compared with healthy volunteers
(+ 1581.4 mV ± 728.9) Effect of cTBS induced a significant
decrease of MEPs amplitude in both depressed patients and controls.
There was no difference (p = 0.2) between the cTBS induced
decrease of MEPs amplitude in healthy volunteers (- 389.2 ± 308.8)
and in depressed patients (- 811.8 ± 513.4; p = 0.2).
Conclusion: iTBS revealed impaired corticospinal excitability in
patients with MDD. Response to cTBS seems preserved in patients as
compared to controls. These results suggest that LTP-like plasticity is
impaired in MDD but not LTD-like plasticity.
Policy of full disclosure: The authors do not have disclosures to
report.
P-31Individualized connectivity between rTMS targetsand the subgenual cingulate is unrelated to antidepressantresponse
S. H. Siddiqi1,2,3, A. T. Weigand4,5, A. Pascual-Leone5, M. D. Fox2,5
1Department of Neurology, McLean Hospital, Belmont, MA, USA;2Department of Neurology, Massachusetts General Hospital, Boston,
MA, USA; 3Department of Psychiatry, Washington University School
of Medicine, St. Louis, MO, USA; 4Berlin School of Mind and Brain,
Humboldt-Universitat zu Berlin, Berlin, Germany; 5Berenson-Allen
Center for Noninvasive Brain Stimulation, Beth Israel Deaconess
Medical Center, Boston, MA, USA
Background: Antidepressant efficacy of rTMS targets for depression
has been related to resting-state functional connectivity (FC) between
each target and the subgenual anterior cingulate cortex (sgACC) [1,
2]. However, this prior work utilized connectome data from a large
group of normal subjects, ignoring individual differences in func-
tional connectivity that may better predict antidepressant response [3].
Methods: 25 patients with medication-refractory depression under-
went resting-state fMRI scans (3T GE scanner, 28 min of FC data per
patient) before a course of clinical rTMS. Functional data were pro-
cessed following Power et al. 2014 [4]. Each patient’s stimulation site
was identified using the standard 5.5 cm approach and recorded using
neuronavigation. Individualized FC between this site and an a priori
region of interest (ROI) in the sgACC was computed and compared to
antidepressant response (percent change in Beck Depression Inven-
tory). Given known problems with signal to noise ratio (SNR) in the
sgACC, several approaches were used to optimize this ROI: (1) a
‘‘seed map’’ approach previously shown to improve reproducibility of
sgACC connectivity estimates [3], (2) a sgACC ROI weighted by
individualized SNR maps, (3) an individualized subgenual ROI based
on connectivity to the above seed map, and (4) an individualized
subgenual ROI based on an individualized cortical parcellation
algorithm [5].
Results: Antidepressant response was unrelated to individualized FC
between the stimulation site and the sgACC (r = 0.04). All patients
showed extremely poor SNR in the area of the sgACC. Approaches
for optimizing the subgenual ROI improved the reproducibility of
individualized FC estimates, but did not improve the association with
antidepressant response (- 0.06\ r\0.20).
Conclusions: Antidepressant efficacy of rTMS is unrelated to indi-
vidualized connectivity between the stimulation site and the sgACC.
Our results do not support the use of subject-specific FC with the
sgACC for selecting individualized rTMS targets for depression.
Eur Arch Psychiatry Clin Neurosci
123
References:
1. Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A
(2012) Efficacy of transcranial magnetic stimulation targets for
depression is related to intrinsic functional connectivity with the
subgenual cingulate. Biol Psychiatry 72(7):595–603
2. Fox MD, Buckner RL, Liu H, Chakravarty MM, Lozano AM,
Pascual-Leone A (2014) Resting-state networks link invasive and
noninvasive brain stimulation across diverse psychiatric and neuro-
logical diseases. Proc Natl Acad Sci USA 111(41):E4367–E4375
3. Fox MD, Liu H, Pascual-Leone A (2013) Identification of repro-
ducible individualized targets for treatment of depression with TMS
based on intrinsic connectivity. Neuroimage 66:151–160
4. Power JD, Mitra A, Laumann TO, Snyder AZ, Schlaggar BL,
Petersen SE (2014) Methods to detect, characterize, and remove
motion artifact in resting state fMRI. Neuroimage 84:320–341
5. Hacker CD, Laumann TO, Szrama NP, Baldassarre A, Snyder AZ,
Leuthardt EC et al (2013) Resting state network estimation in indi-
vidual subjects. Neuroimage. 82:616–633
Policy of full disclosure: The authors do not have disclosures to
report.
P-32Imagery guided personalized robotic rTMS in depression:preliminary results of a feasibility study
J. R. Foucher*1,2, O. A. Mainberger1,2, S. Weibel3,4, G. Bertschy3,4
1ICube-CNRS UMR 7357, Neurophysiology, FMTS, University of
Strasbourg, Strasbourg, France; 2CEMNIS-Noninvasive
Neuromodulation Center, University Hospital Strasbourg, Strasbourg,
France; 3Physiopathologie et Psychopathologie Cognitive de la
Schizophrenie-INSERM 1114, FMTS, University of Strasbourg,
Strasbourg, France; 4Pole de Psychiatrie, Sante Mentale et
Addictologie, University Hospital Strasbourg, Strasbourg, France
Introduction: The iADAPT study - Imagery guided Anti-Depressive
Adaptive Personalized TMS (Clinicaltrials NCT02863380)—is a
double-blind randomized cross-over study designed to assess the
feasibility and efficiency of personalizing rTMS protocol, based on
the functional imaging of single subjects, relative to classical HF-
rTMS and tDCS. Each patient undergone two sessions per day for
10 days.
Method: Brain imaging included two kinds of ASL sequences, con-
verted in rCBF, repeated in three different sessions, using different
functional paradigms and contrasted to thirty-six normal controls. The
tDCS protocol used an F3 anodal positioning, cathode upon the right
upper arm, 20 min sessions at 2 mA DC. Classical HF-rTMS on F3,
delivering 3000 pulses per session (120%, 10 Hz, 4 s trains, 26 ISI).
Last personalized rTMS was designed to correct the rCBF anomalies.
Thirty targets were planned to cover at best reachable parts of the
complex regions with abnormal perfusion. Coil positioning used a
robotic neuronavigated device.
Results: We report on the first 11 patients. All patients had significant
rCBF changes with two main patterns: one with a bilateral fronto-
parietal hypo-perfusion (n = 9, figure 1a), and one with a bilateral
frontal hyper-perfusion (n = 2, figure 1b). The classical target, the
L-DLPFC, was hypo-perfused in only half of the patients, hyper-
perfused in one case. Three patients improved under tDCS, six under
classical rTMS and seven under personalized rTMS. Patient’s rating
showed an average of 10, 30 and 40% symptomatic improvement
respectively for tDCS (blue), classical rTMS (green) and personalized
rTMS (red, figure 1c).
Conclusion: Getting reliable single subject functional results to guide
rTMS treatment was possible. The robotic settings allowed to design
and execute complex personalized protocols which permitted a good
coverage of perfusion anomalies. More subjects are needed to draw
conclusion on the therapeutic efficacy of each arm.
Fig. 1 P-32
Policy of full disclosure: The authors do not have disclosures to
report.
P-33A nationwide questionnaire survey on attitudes of Japanesepsychiatric specialists toward repetitive transcranial magneticstimulation therapy for depression
S. Takahashi1,2, S. Kito3,4, M. Nakamura5,6, K. Shinosaki2,7
1Clinic for Psychiatry and Psychotherapy, Ludwig-Maximilians
University Munchen, Munich, Germany; 2Department of
Neuropsychiatry, Wakayama Medical University, Wakayama, Japan;3Department of Psychiatry and Advanced Medical Technology,
National Center Hospital, National Center of Neurology and
Psychiatry, Tokyo, Japan; 4Department of Neuropsychiatry, Kyorin
University School of Medicine, Tokyo, Japan; 5Kanagawa Psychiatric
Center, Yokohama, Japan; 6 Medical Institute of Developmental
Disabilities Research, Showa University, Tokyo, Japan; 7Asakayama
General Hospital, Sakai, Japan
Introduction: Repetitive transcranial magnetic stimulation (rTMS)
was developed as a non-invasive neuromodulation therapy for treat-
ment-resistant depression, but it has not been approved in the clinical
use in Japan. The aim of this study was to reveal the opinions of
psychiatric specialists on the introduction of rTMS therapy for
depression to the clinical setting in Japan.
Methods: This questionnaire survey was designed by the ECT and
rTMS Review Committee of the Japanese Society of Psychiatry and
Neurology (JSPN). Questionnaires were distributed nationwide to
1318 Japanese psychiatric specialist training facilities, and data from
711 facilities were analysed in 2015. The questionnaire inquired about
agreement with the introduction of rTMS therapy for depression to
the clinical setting and recognized problems with its introduction.
Results: In Japan, 60.3% of the responding facilities needed the
introduction of rTMS therapy for depression to the clinical setting.
Conversely, over half of the responding facilities reported insufficient
evidence for the therapeutic benefit of rTMS, uncertainty of the
Eur Arch Psychiatry Clin Neurosci
123
differences in indications between rTMS and other existing therapies,
and insufficient information about rTMS therapy systems. Addition-
ally, 90.0% of the responding facilities indicated that academic
societies should issue treatment guidelines for rTMS; 63.2% of the
responding facilities wanted a training seminar on rTMS operation.
Conclusion: This questionnaire survey suggested that the majority of
psychiatric specialists needed the introduction of rTMS therapy for
depression to the clinical setting in Japan; they also recognized sev-
eral problems with its introduction. Additionally, treatment guidelines
and training seminars for rTMS therapy were deemed necessary.
After this survey, on July 2017, Ministry of Health, Labor and
Welfare in Japan commissioned academic working group to formu-
late guideline for clinical application of rTMS in treatment of
depression.
Policy of full disclosure: This survey was conducted and sponsored by
the Japanese Society of Psychiatry and Neurology. All authors have
no conflict of interest in relation to this survey.
P-34Clinical application of deep transcranial magnetic stimulation(DTMS) in neuropsychiatric disorders: a systematic literaturereview and meta-analysis
K. K. Kedzior1, H. M. Gellersen2
1Institute of Psychology and Transfer, University of Bremen, Bremen,
Germany; 2Department of Psychology, University of Cambridge,
Cambridge, UK
Introduction: Deep transcranial magnetic stimulation (DTMS) with
the H-coil is a non-invasive method of stimulating the entire cortex
and presumably deeper neural structures. The aim of the current study
was to evaluate the acute clinical outcomes of daily DTMS treatment
in neuropsychiatric disorders using a systematic review and meta-
analysis.
Methods: Following a systematic literature search of PsycInfo and
Medline (up to 28.04.2017), k = 35 studies (k = 24 open-label and
k = 11 double-blind randomised controlled trials, RCT, with inactive
sham groups) were included in the current study. The clinical out-
comes were assessed with standardised scales at baseline and after
daily DTMS and expressed as standardised change scores (Hedges’
g). Effect sizes were pooled using a random-effects meta-analysis
with inverse-variance weights.
Results: Symptom severity significantly decreased after DTMS rela-
tive to baseline (large pooled g = 1.23, 95% confidence interval CI
0.97–1.49; k = 35 studies with 560 patients who received active
treatment). The largest reductions in symptom severity were observed
in studies with unipolar major depression (MDD; k = 11), bipolar
MDD (k = 4), neuropathy (k = 2), and substance use disorders
(SUD; k = 6). High-frequency (18–20 Hz) and high-intensity (120%
of the resting motor threshold, %RMT) protocols produced signifi-
cantly better outcomes relative to lower frequency/intensity (\ 18 Hz/
\ 120% RMT) protocols. DTMS also produced significant reductions
in symptom severity relative to sham (moderate pooled g = 0.53,
95% CI 0.24–0.82; k = 11 RCTs with 383 patients).
Discussion: DTMS produces acceptable clinical outcomes in various
neuropsychiatric disorders, especially in MDD and SUD. Future
research is required to understand the influence of stimulation pro-
tocols on the clinical outcomes.
Policy of full disclosure: The authors do not have disclosures to
report.
P-35Acute efficacy of deep transcranial magnetic stimulation (DTMS)in unipolar vs. bipolar major depressive disorder (MDD):a systematic literature review and meta-analysis
H. M Gellersen1, K. K Kedzior2
1Department of Psychology, University of Cambridge, Cambridge,
UK; 2Institute of Psychology and Transfer, University of Bremen,
Bremen, Germany
Introduction: Deep transcranial magnetic stimulation (DTMS) with
the H-coil is a non-invasive treatment alternative for pharmaco-re-
sistant major depression (MDD) as it stimulates widespread cortical
and presumably subcortical regions to normalise brain activity. The
method has been FDA-approved for unipolar MDD. The aim of the
current study was to determine the efficacy of DTMS for bipolar
compared to unipolar MDD using a systematic review and meta-
analysis.
Methods: A systematic literature search of PubMed and PsycInfo
identified k = 4 studies that used the H-coil to treat bipolar MDD
(one randomised-controlled trial [RCT], three open-label) and k = 11
studies with unipolar MDD (one RCT, ten open-label). Clinical out-
comes were the standardised change in depression severity
(baseline—after last daily DTMS session) according to standardised
scales and expressed as Hedges’ g (effect size), and response and
remission rates. A random-effects meta-analysis with inverse-vari-
ance weights was carried out to pool the effects.
Results: The meta-analysis revealed a large acute antidepressant
effect in k = 4 studies with n = 65 bipolar patients (g = 1.81, 95%
confidence interval CI 0.90–2.72). Pooled response and remission
rates were 62 and 29%, respectively. The antidepressant effect in
n = 282 unipolar patients was similarly large (g = 1.51, 95% CI
1.23–1.79), with pooled response and remission rates of 51 and 29%,
respectively. Most of k = 15 studies used stimulation parameters of
18–20 Hz frequency at 120% motor threshold with 1680 or 1980
stimuli (42 or 55 trains per session) across 20 daily sessions. The
majority of patients in both groups were on concurrent
stable antidepressants.
Discussion: The acute antidepressant outcomes for unipolar and
bipolar MDD are of similar magnitude and suggest acceptable clinical
relevance of DTMS. However, effects in bipolar patients were more
variable. Results are limited by the use of mostly open-label studies
with medicated patients. Nonetheless, they show that DTMS is a
promising acute treatment for bipolar MDD.
Policy of full disclosure: The authors do not have disclosures to
report.
P-36Predicting deep transcranial magnetic stimulation (dTMS)efficiency in depressed using brain network activation (BNA)analysis
C. Baumeister1, R. Shani-Hershkovich1, A. Amit1, Z. Peremen1, Y.
Levkovitz2,3, A. Geva1,4
1ElmindA Ltd, Hertsliya, Israel; 2Tel Aviv University, Tel Aviv,
Israel; 3Beer Yaakov-Ness Ziona Mental Health Center, Be’er
Ya’akov, Israel; 4Ben Gurion University, Beersheba, Israel
No abstract for publication.
Eur Arch Psychiatry Clin Neurosci
123
P-37Cognitive effects of high-frequency-rTMS in chronicschizophrenic patients
S. J. Kim1, E. Meuthen1, J.Cordes1
1Department of Psychiatry and Psychotherapy, LVR-Klinikum
Dusseldorf, University Hospital HHU Dusseldorf, Dusseldorf,
Germany
Introduction: To assess positive as well as negative cognitive effects
of high-frequency-rTMS we examined cognitive changes in n = 32
chronic schizophrenic in-patients with predominant negative symp-
toms. Furthermore we explored both whether cognitive rTMS-effects
were correlated with baseline psychopathology and whether rTMS-
effects on psychopathology were associated with baseline cognitive
performance.
Methods: Patients on stable antipsychotic treatment were randomly
assigned to verum- or sham-condition. In the verum-group patients
received ten sessions of 10 Hz-rTMS over the left dorsolateral pre-
frontal cortex (DLPFC) at 110%-motor-threshold over 2 weeks. The
sham-group received sham-stimulation. RTMS-effects on cognitive
performance were assessed with a neurocognitive test-battery con-
sisting of the trail making test A and B (TMT), Wisconsin card sorting
test (WCST), D2 attention task and the ‘‘shortest for general intelli-
gence’’ (KAI). Psychopathology and global-functioning were
measured by the Clinical Global Impression scale (CGI), Global
Assessment of Functioning Scale (GAF) and Positive and Negative
Symptom Scale (PANSS).
Results: No statistically significant differences in cognitive rTMS-
effects between groups with small to moderate effect sizes were
shown, the effects were partly contradictory. In the verum-group a
poor performance in executive-functions at baseline was associated
with an improvement in psychopathology, especially in negative
symptoms, after rTMS-treatment. Whereas in the sham-group a
favourable status in executive-functions at baseline was associated
with an improvement in clinical global impression after sham-
stimulation.
Discussion: Our results show no significant change in cognitive
performance after 10 Hz-rTMS-treatment. Thus they indicate good
tolerability in regard to negative cognitive side-effects, but they also
failed to show consistent favourable effects on cognitive performance.
Moreover they suggest, that the effects of high-frequency-rTMS on
psychopathology and cognitive performance could be associated with
baseline cognitive performance or baseline psychopathology respec-
tively. The absence of significant effects might be due to low
stimulation-parameters, short stimulation-periods and a small sample-
size (n = 32).
Policy of full disclosure: The authors do not have disclosures to
report.
P-38Transcranial magnetic stimulation has different short-termefficacy on different major depressive disorder symptoms:a nested prospective cohort study in Croatia
T. Gajsak1, I. Filipcic1,2,3, Z. Milovac1, S. Sucic1, S. Zecevic Penic1,
E. Ivezic1, Z. Bajic4
1Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb, Croatia; 2Faculty of
Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,
Croatia; 3School of Medicine, University of Zagreb, Zagreb, Croatia;4Biometrika Healthcare Research, Zagreb, Croatia
Introduction: This presentation will describe the protocol and interim
analysis of 12-month study with rTMS/dTMS and standard therapy
control in patients with moderate/severe MDD. The study objective is
to explore the short and long-term efficacy/tolerability, and to create
and validate the treatment outcomes multivariate prediction model.
Methods: In this, randomized, active-controlled, prospective study
4-weeks sessions are conducted with rTMS, five times weekly, at
10 pulses/s, 120% of motor threshold, 3000 pulses/session, and with
dTMS by Brainsway protocol. Primary outcomes are the changes in
HAM-D17, PSQ9, MADRS, BDI-II results and remission rates.
Secondary outcomes are changes in WHOQOL, EQ-5D-5L, GAF.
Sleep quality is evaluated with EPWORTH and Pittsburgh scales.
Tolerability assessment included all adverse events (AEs). Personality
traits measured by IPIP, plasma serotonin, BDNF and other clinical
variables will be used in the derivation of a prediction model.
Results: By May 2017, 162 patients were enrolled (54 randomized in
each group). After adjustment for baseline HAM-D17 and con-
founders, TMS groups were significantly different from the control
group (p\ 0.001). Mean HAM-D17 score was lowered for 69% in
dTMS, 59% in rTMS and 28% in control group. The difference
between dTMS and rTMS was not significant (p = 0.070). After
4-weeks, 63% of patients treated with dTMS achieved remission, 52%
in rTMS and 19% in control group. The difference between TMS and
control was significant (p\ 0.001), but not between the two TMS
groups (p = 0.243). We did not observe significant changes in quality
of life. TMS was well tolerated with a no dropout for AEs.
Conclusion: Preliminary data indicate that augmentative rTMS or
dTMS are more effective in MDD treatment than standard therapy.
dTMS with H1-coil is more effective than rTMS, but not statistically
significant. Both treatments are well tolerated.
Policy of full disclosure: The authors do not have disclosures to
report.
P-39Efficacy and tolerability of repetitive transcranial magneticstimulation with and without the Brainsway H1-coil in treatmentof major depressive disorder: presentation of the protocoland interim analysis
I. Filipcic1,2,3, I. S. Filipcic4, T. Gajsak1, S. Sucic1, Z. Milovac1,
S. Zecevic Penic1, E. Ivezic1, I. Orgulan1, N. Tunjic Vukadinovic1,
Z. Bajic5
1Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb, Croatia; 2Faculty of
Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,
Croatia; 3School of Medicine, University of Zagreb, Zagreb, Croatia;4Department of Psychological Medicine, University Hospital Center
Zagreb, Zagreb, Croatia; 5Biometrika Healthcare Research, Zagreb,
Croatia
Introduction: This presentation will describe the protocol and interim
analysis of 12-month study with rTMS/dTMS and standard therapy
control in patients with moderate/severe MDD. The study objective is
to explore the short and long-term efficacy/tolerability, and to create
and validate the treatment outcomes multivariate prediction model.
Methods: In this, randomized, active-controlled, prospective study
4-weeks sessions are conducted with rTMS, five times weekly, at
10 pulses/s, 120% of motor threshold, 3000 pulses/session, and with
dTMS by Brainsway protocol. Primary outcomes are the changes in
HAM-D17, PSQ9, MADRS, BDI-II results and remission rates.
Secondary outcomes are changes in WHOQOL, EQ-5D-5L, GAF.
Sleep quality is evaluated with EPWORTH and Pittsburgh scales.
Tolerability assessment included all adverse events (AEs). Personality
traits measured by IPIP, plasma serotonin, BDNF and other clinical
variables will be used in the derivation of a prediction model.
Results: By May 2017, 162 patients were enrolled (54 randomized in
each group). After adjustment for baseline HAM-D17 and
Eur Arch Psychiatry Clin Neurosci
123
confounders, TMS groups were significantly different from the con-
trol group (p\ 0.001). Mean HAM-D17 score was lowered for 69%
in dTMS, 59% in rTMS and 28% in control group. The difference
between dTMS and rTMS was not significant (p = 0.070). After
4-weeks, 63% of patients treated with dTMS achieved remission, 52%
in rTMS and 19% in control group. The difference between TMS and
control was significant (p\ 0.001), but not between the two TMS
groups (p = 0.243). We did not observe significant changes in quality
of life. TMS was well tolerated with a no dropout for AEs.
Conclusion: Preliminary data indicate that augmentative rTMS or
dTMS are more effective in MDD treatment than standard therapy.
dTMS with H1-coil is more effective than rTMS, but not statistically
significant. Both treatments are well tolerated.
Policy of full disclosure: The authors do not have disclosures to
report.
P-40Interaction of serotonin and age is significant predictorof transcranial magnetic stimulation effect on major depressivedisorder: a prospective cohort study in Croatia
I. Simunovic Filipcic1, T. Gajsak2, S. Sucic2, Z. Milovac2, S. Zecevic
Penic2, E. Ivezic2, N.Ruljancic2, Z. Bajic3, I.Filipcic2,4,5
1Department of psychological medicine, University Hospital Center
Zagreb, Zagreb, Croatia; 2Psychiatric Hospital ‘‘Sveti Ivan’’, Zagreb,
Croatia; 3Biometrika Healthcare Research, Zagreb, Croatia; 4Faculty
of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek,
Croatia; 5School of Medicine, University of Zagreb, Zagreb, Croatia
Introduction: Serotonin plays an important role in mood control. It is
one of the two primary antidepressants’ targets. However, previous
studies have not found the baseline serotonin level to be a significant
predictor of TMS effects on major depressive disorder (MDD). One
of the explanations was that plasma concentrations may have limited
validity for the brain serotonin levels.
Objective: We hypothesized that previous studies failed to detect
serotonin predictive value because they missed to analyze some
important moderators or control the effect of some important con-
founders. We hypothesized that such moderators may be: age, sex,
duration and severity of MDD.
Methods: This cohort study was conducted at Psychiatric Hospital
Sveti Ivan, Zagreb, Croatia during 2016/2017, on the sample of
patients diagnosed with MDD. The outcome was Beck Depression
Inventory-II (BDI-II) result after 4-week treatment with TMS,
adjusted for BDI-II baseline result. Moderators values defining
Johnson–Neyman significance regions were analyzed in PROCESS
Release 1.16.2, written by Andrew F. Hayes.
Results: We enrolled the sample of 37 patients. The overall model
including age, serotonin, and their interaction significantly predicted
BDI-II change (R2 = 0.52; p = 0.006). Interaction of baseline sero-
tonin concentration and age was significant predictor by itself
(R2 = 0.29; p = 0.003). Serotonin was a significant predictor of TMS
effects in patients younger than 35, and older than 51. In younger
patients, higher baseline serotonin levels were associated with higher
BDI-II results at fourth week indicating lower efficacy of TMS
treatment. In older patients, this effect was reversed. Interactions of
serotonin and other hypothesized moderators were not significant
predictors of BDI-II change.
Conclusion: Baseline serotonin level prediction value for TMS effects
on MDD is moderated by patients’ age. If serotonin is analyzed alone,
it is not significantly associated with TMS treatment outcome, as its
effects in lower and higher age groups are reversed and they mutter.
Policy of full disclosure: The authors do not have disclosures to
report.
P-41Treatment of pediatric catatonia with ECT: a case seriesand review
R. Katz1, M. Toprak1, Z. Qayyum1, C. Wilson1, R. Ostroff1
1Yale Psychiatric Hospital, Yale Department of Psychiatry, New
Haven, CT, USA
Catatonia is an under-recognized illness commonly associated with
mood disorders, psychotic disorders and medical illness, for which the
gold standard curative treatment is Electroconvulsive Therapy (ECT).
Morbidity and mortality in this state are significant, especially in
malignant catatonic states with autonomic instability, and warrants
urgent and aggressive care. We discuss six cases of pediatric patients
presenting with catatonia, all of whom were successfully treated with
ECT on our Interventional Psychiatry Service. Notably, two of these
patients had no history of psychiatric illness. We will review the
literature on pediatric catatonic states and the history of and evidence
for treating this condition. We will also address the legal issues sur-
rounding consent for ECT in a pediatric population.
Policy of full disclosure: The authors do not have disclosures to
report.
P-42Adjustment of pulse wave parameters to optimize effective ECTtreatment
R. Ostroff1, R. Katz1, J. Cahill1
1Yale Psychiatric Hospital, Yale Department of Psychiatry, New
Haven, CT, USA
The sine qua non for a therapeutic effect of ECT is the induction of a
generalized grand mal seizure achieved by administering a dose of
energy above the patient’s seizure threshold (ST). The seizure
threshold (ST) at any given ECT treatment may vary depending on
both patient characteristics and treatment specific factors. Conven-
tionally, ST is estimated as the total energy (in Joules, J) or charge (in
milliCoulombs, mC) required to induce a seizure at titration. At times
patients with exceptionally high STs exceed the maximum allowed
stimulus energy that can be administered with a pulse wave apparatus
particularly on subsequent treatments which call for a five- to sixfold
increase in right ultra brief pulse unilateral treatment and 50%
increase in bilateral treatment courses. Recent evidence however,
points to a complex interaction between the pulse wave parameters
and ST. This may result in an apparent ‘super-saturation’ of the sei-
zure threshold in patients requiring high-energy stimulations. This
case series presents examples where an excessively high stimulus
frequency appears to negate seizure initiation at a comparatively high
energy (an example of ‘stimulus-crowding’). A reduction in fre-
quency and the overall energy produced a seizure. Focus only on the
total quantity of energy delivered during a pulse wave stimulation, in
lieu of adjusting other pulse wave parameters, may result in sub-
threshold stimulations, unnecessary side effects and a non-therapeutic
treatment session. An extension in the range of available stimulus
parameters, specifically duration, should result in the practitioner’s
ability to keep the frequency setting within physiological parameters
and still obtain an adequate energy level to induce a seizure.
Policy of full disclosure: The authors do not have disclosures to
report.
Eur Arch Psychiatry Clin Neurosci
123
P-43Transcranial direct current stimulation (tDCS) replaceselectroconvulsive therapy (ECT) in a patient with corpuscallosum agenesis and catatonic schizophrenia: a longitudinalnetwork-metric approach
D. Keeser 1,2, O. Pogarell1, U. Palm1, E.Weidinger1, V. Kirsch3, A.
Hasan1, B. Kirsch1, T. Karali1,2, J. Worsching1, S. Karch1, Ma.
Paolini2, B. Ertl-Wagner2, F. Padberg1
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian
University, Munich, Germany; 2Institute of Clinical Radiology,
Ludwig Maximilian University, Munich, Germany; 3Department of
Neurology, Ludwig Maximilian University, Munich, Germany
Introduction: Here, we report about a single case of catatonic
schizophrenia, which has been treated with prefrontal tDCS for
almost 4 years. Based on excessive stimulation sessions, clinical
ratings, multimodal MRI measurements, and EEG recordings, we
show the relationship between clinical improvement and macroscale
brain activity changes.
Methods: The 44-year-old male patient with known complete corpus
callosum agenesis CCA had shown severe catatonic symptoms since
adolescence and been treated with weekly electroconvulsive therapy
(ECT) for almost 6 years, because drug treatment was ineffective.
After obtaining approval from the local ethics committee and
informed consent from the patient and his relatives, tDCS was started
with the following stimulation settings: Anode over the left dorso-
lateral prefrontal cortex (F3) and cathode over the right (F4); 2 mA
for 2 9 20 min/day (90-min interval), 39/week for 2 weeks, once to
twice weekly thereafter with the same parameter settings. Concomi-
tant medication (clozapine 600 mg/day, aripiprazole 10 mg/day,
pirenzepine 50 mg/day, lorazepam 3 mg/day) was continued. A
weekly clinical assessment was conducted that included the Bush-
Francis Catatonia Rating Scale. Functional magnetic resonance
imaging was performed at baseline and after 70, and 140 tDCS ses-
sions to assess resting-state functional connectivity (rs-FC), structural
brain volumes (T1-MPRAGE, T2-FLAIR) and Diffusion Tensor
Imaging (DTI). EEG was recorded at baseline and after 70, 140 and
300 tDCS sessions. To obtain a reference to healthy age-matched
male subjects, 26 volunteers were measured at the same time with a
rehearsal session using resting state EEG and fMRI.
Results: The patient overall received about 330 tDCS sessions
between August 2013 and June 2017. ECT was needed only once
after a 10-day hospitalization for pneumonia in September 2013,
during which time tDCS had been suspended. The patient showed
fewer catatonic symptoms ([ 50% of BCRS reduction in average)
during tDCS treatment than during ECT treatment (BCRS scores:
20–27/69 during ECT, 4–12/69 during tDCS with one outlier of a
BCRS score of 18 at September 9, 2015. His speech fluency, personal
hygiene, and attendance at a sheltered workshop improved. Seed-
based functional connectivity in the right insula and the frontal brain
showed increased connectivity after 140 tDCS sessions compared to
baseline. Low-frequency EEG activity (1–12 Hz) decreased over the
course of the tES sessions in the frontal and insula cortex, whereas
high-frequency EEG activity (12–50 Hz) increased. The BCRS scores
were negatively correlated with left frontal (- 0.74, p = 0.002), right
frontal (r = - 0.62, p = 0.01) and right insular cortex (r = - 0.867,
p\ 0.001) rs-FC. There was no correlation to the left insular cortex
(r = - 0.09, p = 0.75). The BCRS scores were positively correlated
to the low-frequency in right frontal (r = r = 0.63, p = 0.03) and left
insular cortex (r = r = 0.78, p = 0.003) and negatively correlated
with the right insular cortex (r = - 0.87, p\ 0.001). EEG and rs-FC
changes developed in the direction of the healthy cohort, but still
remained deviated after over 300 tDCS sessions.
Discussion: The findings of this study increase our knowledge of
longitudinal non-invasive brain stimulation in a case of catatonic
schizophrenia with CCA. We show that network activity changes in
the frontal brain are associated with clinical improvement, which
might have been induced by tES. The results illustrate the utility of
high temporal resolution and high spatial resolution to monitor
experimental therapy intervention. The negative correlation between
BCRS scores and the number of activated seed-based left, right
frontal, and right insular cortices in the resting fMRI and the positive
correlation between BCRS scores in the left, right frontal, and left
insular cortices (negative correlation in the right insular cortex) and
low-frequency EEG indicate network based mechanism of clinical
improvement. Finally, by providing repeated assessments of network
metrics, this approach could help to track individual patients longi-
tudinally, and also assess their neural responses to therapeutic
interventions.
Policy of full disclosure: This work was supported by the German
Center for Brain Stimulation (GCBS) research consortium (Work
Package 5, Grant Number 01EE1403E), funded by the Federal Min-
istry of Education and Research (BMBF). F.P. has received speaker’s
honorarium from Mag&More GmbH and the neuroCare Group as
well as support with equipment from neuroConn GmbH, Ilmenau,
Germany, Mag&More GmbH and Brainsway Inc., Jerusalem, Israel.
P-44Individualized thresholds: calibrating brain stimulation throughconcurrent TMS/fMRI
M. Tik1, M. Woletz1, A. Hummer1, N. Geissberger1,
C. Windischberger1
1fMRI.at, Center for Medical Physics and Biomedical Engineering,
Medical University of Vienna, Vienna, Austria
Introduction: Current TMS applications are adjusted in relation to
individual motor thresholds (MT), however there is no consensus on
how to define this threshold (1) and if determined MT is applicable to
other cortical targets (2). We have developed a setup for high-reso-
lution image acquisition and unimpeded simultaneous TMS based on
a dedicated TMS/fMRI multi-channel receive (RF) array. This has
been shown to allow mapping of intensity-dependent TMS effects in
the primary motor cortex, m1(3). Here we go beyond m1 to exploit
this high sensitivity setup combined with advanced imaging and
neuronavigation methods to map intensity-related TMS effects over
left DLPFC.
Methods: The study was performed on a 3T Prisma (Siemens,
Erlangen, Germany). TMS/fMRI setup included a MagProX100
stimulator (Magventure, Farum, Denmark), MRi-B91 MR-compatible
TMS coil mounted on dedicated RF-coil, MR-compatible neuronav-
igation and MR-visible fiducial markers installed in the RF-coil to
allow coil-localisation during imaging. Five right-handed female
subjects (age 24.9 ± 3.2 years) participated in the experiment.
Functional images were acquired using EPI sequence with TR/
TE = 1000/33 ms, 28 slices, 1.5 9 1.5 9 3 mm3. FMRI data anal-
yses were performed using SPM12. The design matrix comprised four
regressors representing different stimulation amplitudes of 10 Hz
rTMS over left DLPFC.
Results: 10 Hz TMS led to intensity-dependent local and remote
activation changes. The stimulated target (left DLPFC) and its con-
tralateral homologue (right DLPFC) showed proportional direct
intensity related changes, while ACC manifested a more complex
response pattern. Tracking of fiducial markers unraveled subject-
drifts of more than 4 mm to render stimulation ineffective.
Discussion: We demonstrate acute local and network effects of TMS
over the left DLPFC on an individual level, i.e. intensity-dependent
BOLD increase at the stimulation site and in interconnected network
nodes. This allows setting a framework for optimal individualized
Eur Arch Psychiatry Clin Neurosci
123
stimulation, based on parameters that evoke exactly the desired local
or network effect/response, without having to rely on MT.
Policy of full disclosure: The authors do not have disclosures to
report.
P-45Is hippocampal neurogenesis mediating clinical efficacyand memory outcome after electroconvulsive therapyin depression?
D. Attali1,2, A. Cachia3, P. Abdel-Ahad1,2, C. Oppenheim3, P. Gori3,
M. O. Krebs1,2, R. Gaillard1,2, M. Plaze1,2
1Pathophysiology of Psychiatric Disorders: Development and
Vulnerability, Center of Psychiatry and Neurosciences, INSERM
UMR 894, University Paris Descartes, Sorbonne Paris Cite, Paris,
France; 2Centre Hospitalier Sainte-Anne, Service Hospitalo-
Universitaire, Paris, France; 3Biomarkers of Brain Development and
Disorders, Center of Psychiatry and Neurosciences, INSERM
UMR894, University Paris Descartes, Sorbonne Paris Cite, Paris,
France
Background: Electroconvulsive therapy (ECT) is the most effective
treatment for treatment-resistant depression (TRD) but its use is partly
restricted due to its cognitive side effects (1). Animal models have
linked hippocampal neurogenesis to both ECT response (2) and
memory function, suggesting that increasing hippocampal neurogen-
esis weakens existing memories (3, 4). The aim of this study was to
investigate the effect of ECT on hippocampal volume and its relation
to clinical and memory outcome in depression.
Method: 10 patients with TRD, referred for ECT by their psychiatrist,
were recruited at Sainte-Anne Hospital in Paris. Patients were treated
twice weekly with bi-temporal ECT until remission on the MADRS
was achieved. Clinical and cognitive outcomes were investigated with
a neuropsychological test battery focused on retrograde amnesia for
autobiographical information (CUAMI-SF) and retrograde episodic
memory loss (mWMS-IV). Patients underwent 1.5 T structural MRI
at both time points. We used the CAT12 toolbox in SPM12 to study
whole brain voxel-wise longitudinal grey matter changes and FSL 5.0
to measure hippocampal volumes.
Results: Both left and right hippocampal volumes increased signifi-
cantly following ECT (5.06 ± 0.85%, p\ 0.001). Retrograde
memory was altered with significant autobiographical and pre-exist-
ing episodic memory loss (p\ 0.01). Positive correlations were
observed between increase in total hippocampal volume and (1)
treatment efficacy (p = 0.008) and (2) retrograde episodic memory
loss (p = 0.002).
Conclusion: Patients with TRD showed specific bilateral hippocampal
volume increases following ECT. Total hippocampal volume increase
was associated with (1) treatment efficacy and (2) retrograde episodic
memory loss. These findings suggest that ECT clinical efficacy and its
cognitive side-effects could be underpinned by common neurobio-
logical mechanisms, such as neurogenesis, gliogenesis,
synaptogenesis or angiogenesis. Larger sample sizes, control groups,
functional imaging and peripheral biomarkers could provide a better
coverage of biological substrates that contribute to ECT-induced
clinical improvement and cognitive side-effects.
References:
1. UK ECT Review Group (2003) Efficacy and safety of electro-
convulsive therapy in depressive disorders: a systematic review and
meta-analysis. Lancet Lond Engl 361(9360):799–808
2. Schloesser RJ, Orvoen S, Jimenez DV, Hardy NF, Maynard KR,
Sukumar M et al (2015) Antidepressant-like effects of electrocon-
vulsive seizures require adult neurogenesis in a neuroendocrine model
of depression. Brain Stimul 8(5):862–867
3. Epp JR, Silva Mera R, Kohler S, Josselyn SA, Frankland PW
(2016) Neurogenesis-mediated forgetting minimizes proactive inter-
ference. Nat Commun 7:10838
4. Akers KG, Martinez-Canabal A, Restivo L, Yiu AP, De Cristofaro
A, Hsiang H-LL et al (2014) Hippocampal neurogenesis regulates
forgetting during adulthood and infancy. Science 344(6184):598–602
Policy of full disclosure: This study was supported by the Fondation
Pierre Deniker. The authors declare no conflict of interest.
P-46Real-time fMRI neurofeedback in patients with alcohol usedisorder: craving-related modulations
K. Lehnert1, J. Konrad1, D. Haller1, S. Gschwendtner1, H. Jeanty1,
A. Reckenfelderbaumer1, O. Yaseen1, M. Paolini2, D. Keeser1,2,
G. Koller1, B. Ertl-Wagner2, O. Pogarell1, S. Karch1
1Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-
University Munich, Munich, Germany; 2Institute of Clinical
Radiology; Ludwig-Maximilians-University Munich, Munich,
Germany
Background: About 1.7 million persons in Germany suffer from
alcohol use disorder, 10.4 million persons show a risky alcohol
consumption [2]. Hartwell and colleagues [1] demonstrated that the
modulation of neuronal activity using real-time fMRI neurofeedback
(rtfMRI NF) is a promising therapeutic approach for patients with
alcohol use disorder.
Aim: Aim of the present study was to examine if patients with alcohol
use disorder are able to learn the modulation of craving-related
neuronal responses using rtfMRI NF and to reduce craving.
Methods: 52 patients with alcohol use disorder participated in the
study. All patients were recruited in a ward specialised for the
treatment of alcohol use disorders. The rtfMRI NF training was an
add-on to the standard treatment. Patients were randomised to a real
and sham condition. During the fMRI session, alcohol-associated and
neutral pictures were presented. Subjects were instructed to reduce
their neuronal responses during the presentation of alcohol cues in the
individual region of interest (ROI: anterior cingulate cortex, insula or
dorsolateral prefrontal cortex). Directly before and after the rtfMRI
session individual craving (Obsessive Compulsive Drinking Scale;
Mann & Ackermann, 2000) as well as emotional responses (Beck
Depression Inventory [BDI]; Barrett Impulsiveness Scale [BIS]) were
assessed.
Results and discussion: The relapse rate was lower in the real group
compared to the sham group. A significant reduction auf neuronal
responses in the target regions (especially frontal areas/prefrontal
cortex, insula) was demonstrated. In addition, BOLD responses in
brain regions which are associated with emotion processing (e.g.
limbic regions) decreased.
The comparison of BOLD responses of patients that remained
abstinent 3 months after the rtfMRI NF training and patients with a
relapse 3 month after the fMRI measurements revealed a pronounced
reduction of frontal responses during NF training in patients that
remained abstinent. Overall, the rtfMRI NF training may be useful as
an add-on to the standard treatment. Further studies should address
questions about subgroups as well as rtfMRI parameters to enhance
the effect of the training.
References:
1. Hartwell KJ et al (2013) Real-time fMRI in the treatment of
nicotine dependence: a conceptual review and pilot studies. Psychol
Addict Behav US 27:501–509
Eur Arch Psychiatry Clin Neurosci
123
2. Singer MV, Teyssen S, Schneider A (2005) Alkohol und Alko-
holfolgekrankheiten: Grundlagen-Diagnostik-Therapie. Springer,
Berlin
Policy of full disclosure: The authors do not have disclosures to
report.
P-47LMU scripts • ready-made HPC-applicable pipelinefor structural and functional data analyses
T. Karali1, V. Kirsch2, F. Padberg3, B. Ertl-Wagner4, D. Keeser1
1Department of Psychiatry, Institute of Clinical Radiology, Ludwig-
Maximilians University, Munich, Germany; 2Department of
Neurology, Ludwig-Maximilians University, Munich, Germany;3Department of Psychiatry and Psychotherapy, Ludwig-Maximilians
University, Munich, Germany; 4Institute of Clinical Radiology,
Ludwig-Maximilians University, Munich, Germany
Introduction: Basic requirements in imaging research are changing
rapidly due to the growing size of datasets and multimodal approa-
ches with increasingly complex, time consuming, diverse, and fast-
altering standards. LMU Scripts offers a ready-made, free and open-
source (FOSS) high-performance-computing (HPC) applicable pipe-
line for state-of-the-art structural and functional data analyses that
utilize parallel processing.
Methods: LMU Scripts depends on the software libraries listed below.
FSL [1], AFNI [2], R [3], including the packages car [4], gplots [5],
grDevices [3], graphics [3], nlme [6], multcomp [7], Python [8],
including the package rpy2.
LMU Scripts is compatible with Linux-based operating systems. For a
dataset with n[ 1, parallel processing is supported using SLURM on
a HPC cluster, and using a Python multiprocessing pool on a local
computer. This procedure is elaborated below.
Results: LMU Scripts follows a three-step workflow, as illustrated
below.
The starter script checks whether all required files are available and
valid, sets up the folder structure for output files, and spawns sub-
processes in an efficient way. Multiple instances of the pre-processing
script(s) calculate and permanently store the ‘‘subject-level’’ data
(voxel counts, T1/T2 anatomical data, connectivity matrices, etc.).
Finally, the post-processing script accesses the data that was created
by the instances of the pre-processing script(s), and processes it into
the ‘‘group-and-study-level’’ data (overviews, plots, statistical calcu-
lations, etc.).
Examples to output data—as mentioned—are illustrated below.
• Structural preprocessing (FLTR: skull strip, CSF/WM/GM seg-
mentation, brain mask, individual brain parcellation).
• Functional preprocessing (time series, registration, motion cor-
rection, z-scores).
• Quality control (FoV, motion, SNR)
• Anatomical region finding using autoaq and automatic generation
of publication-ready tables.
Conclusion: In future, HPC applicable pipelines will be a requirement
for any imaging lab. LMU Scripts offers a ready-made, cost-free, and
open source alternative. A publication, along with a release of the
source code tree, is currently in preparation.
References:
1. Jenkinson M et al (2012) FSL. NeuroImage 62:782–790
2. Cox R (1996) AFNI: software for analysis and visualization of
functional magnetic resonance neuroimages. Comput Biomed Res
29:162–173
3. R Core Team (2016) R: a language and environment for statistical
computing. R Foundation for Statistical Computing, Vienna, Austria.
https://www.R-project.org/
4. Fox J et al (2011) An R companion to applied regression, 2nd edn.
Sage, Thousand Oaks
5. Warnes G et al (2016) gplots: Various R programming tools for
plotting data. R package version 3.0.1. https://CRAN.R-project.
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Policy of full disclosure: F.P. has received speaker’s honorarium from
Mag&More GmbH and the neuroCare Group as well as support with
equipment from neuroConn GmbH, Ilmenau, Germany, Mag&More
GmbH and Brainsway Inc., Jerusalem, Israel.
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