selective impairment of the conflict network in patients

Selective impairment of the conflict network in patients with frontal lesions

Von der Medizinischen Fakultät

der Rheinisch-Westfälischen Technischen Hochschule Aachen zur Erlangung des akademischen Grades

einer Doktorin der Medizin genehmigte Dissertation

vorgelegt von

Eva-Maria Meier

aus

Paderborn

Berichter: Herr Universitätsprofessor Dr.phil. Dipl.-Psych. Siegfried Gauggel Herr Universitätsprofessor Dr.rer.nat. Klaus Willmes-von Hinckeldey Tag der mündlichen Prüfung: 12. Juli 2011 Diese Dissertation ist auf den Internetseiten der Hochschulbibliothek online verfügbar.

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Table of contents

ABBREVIATIONS ..................................................................................... 1

1. INTRODUCTION ................................................................................... 2

2. METHODS............................................................................................. 6

2.1 Participants.................................................................................................................. 6

2.2 Background neuropsychological assessment ........................................................ 7

2.3. Attention Network Test (ANT)................................................................................... 8

2.4. Procedure ................................................................................................................. 10

2.5. Lesion analysis ........................................................................................................ 11

2.6 Statistical analysis.................................................................................................... 11

3. RESULTS............................................................................................ 13

3.1 Background neuropsychological assessment ...................................................... 13

3.2 Performance in the ANT ........................................................................................... 13

4. DISCUSSION ...................................................................................... 18

5. SUMMARIES....................................................................................... 22

5.1. English summary ..................................................................................................... 22

5.2. Deutsche Zusammenfassung ................................................................................. 23

6. REFERENCES .................................................................................... 24

7. APPENDIX .......................................................................................... 31

7.1. List of tables ............................................................................................................. 31

7.2. List of figures ........................................................................................................... 32

7.3. Supplementary material .......................................................................................... 33

8. ERKLÄRUNG § 5 ABS. 1 ZUR DATENAUFBEWAHRUNG .............. 43

9. CURRICULUM VITAE......................................................................... 45

Eva-Maria Meier


1

Abbreviations

ACC anterior cingulate cortex

ADHD attention-deficit/hyperactivity disorder

ANOVA analysis of variance

ANT Attention Network Test

bi bilateral

CG control group

CT computer tomography

DLPFC dorsolateral prefrontal cortex

ES effect size

ESC elementary school

FG frontal group

fMRI functional magnetic resonance imaging

GS grammar school

l left

LPS Leistungs-Prüf-System

MRI magnetic resonance imaging

m mean

n number

NFG non-frontal group

r right

RAE relative alerting effect

RCE relative conflict effect

ROE relative orienting effect

RT reaction time

SD standard deviation

SGS secondary general school

SMS secondary modern school

TMS transcranial magnetic stimulation

TMT Trail Making Test

VLMT Verbaler Lern- und Merkfähigkeitstes

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1. Introduction

Executive functions play an important role in daily living, due to the fact

that they enable us to handle situations in which routine or automatic

processes are incommensurate. That is why patients with lesions in

responsible brain areas are impaired in performing several actions as

planning, decision making or attentional control. Because of the enormous

importance of executive functions, there exist many theories about this

issue (for example Posner & Rothbart, 1998; Norman & Shallice, 1986;

Berger & Posner, 2000).

One important aspect of executive control is monitoring and resolving

conflict. Miller & Cohen (2001) illustrate the occurrence of conflict as a

situation in which two trains want to cross tracks at the same time. In daily

life conflict occurs when competing responses or information are present

(Durston et al., 2003), for example the doorbell rings while someone is

talking on the phone. Ullsperger & von Cramon (2004) defined the term

“pre-response conflict” which arises when more than one response

tendencies induced by the same goal are activated simultaneously and

when these response tendencies are in conflict. Especially during

perceptual representation, stimulus categorization, response selection and

task representation a high degree of response conflict can be triggered

(Botvinick et al., 2004). Response conflict manifests itself in uncertainness

in handling such situations and an increased incidence of errors. Only

task-appropriate stimuli and responses have to be allocated and

distracting stimuli and thoughts have to be ignored. For this reason there is

a need for “cognitive control” which is described as the ability to generate,

maintain and adjust sets of goal-directed processing strategies (Egner,

2008).

Botvinick et al. (1999) established the conflict monitoring hypothesis with

the following considerations:

1) Specific subsystems in the human brain monitor the occurrence of

conflict in information processing.

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2) The occurrence of conflict triggers strategic adjustments in cognitive

control, which serve to prevent conflict in subsequent performance.

3) Conflict monitoring might represent one aspect of a more general

monitoring function, which detects internal states signalling a need

to intensify or redirect attention or control.

These cognitive control processes have top-down influences on other

brain areas involved in motor and sensory converting, whereas simple and

automatic behaviour rely on stereotyped reactions and bottom-up

processing (guided activation theory by Miller & Cohen, 2001).

The investigation of responsible brain areas for accomplishing these

cognitive processes has grown in popularity over the last years. Studies

using different methods which will be subsequently explained in greater

detail indicate that especially frontal brain areas are important for resolving

response conflict. Several functional magnetic resonance imaging (fMRI)

studies in healthy subjects have implicated a network of brain areas which

are activated during flanker task performance: the anterior cingulate cortex

(ACC; Botvinick et al., 1999; Bunge et al., 2002; Casey et al., 2000;

Durston et al., 2003; Fan et al., 2003, 2005, 2007, 2008; Hazeltine et al.,

2003; Lau et al., 2006; Luks et al., 2007; McNab et al., 2008; Ochsner et

al., 2009; van Veen et al., 2001; Wager et al., 2005), the dorsolateral

prefrontal cortex (DLPFC; Casey et al., 2000; Durston et al. 2003; Fan et

al., 2007; Luks et al., 2007; van Veen et al., 2001) and parietal regions

(Bunge et al., 2002; Casey et al., 2000; Durston et al., 2003; Fan et al.,

2007; Hazeltine et al., 2000; Luks et al., 2007; van Veen et al. 2001;

Wager et al., 2005; Wang et al., 2010). Table 4 in the appendix gives a

detailed review over all of these studies.

Similar regions were also activated in studies using the Stroop task, which

is a further tool for measuring conflict (Barch et al., 2001; Carter et al.,

2000; Haupt et al., 2009; Kerns et al., 2004; MacDonald et al., 2000;

Roberts et al., 2008; Zysset et al., 2001). Studies of Stroop task using

fMRI in healthy controls are listed in table 5 in the appendix.

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Figure 1. Frontal brain areas play an important role in handling with the

occurrence of conflict: frontal lobe and anterior cingulate cortex

(BrainVoyager Brain Tutor, Version 2.0).

Another way to localize relevant brain areas is transcranial magnetic

stimulation (TMS). Using TMS, Taylor et al. (2007) simulated a lesion in

the dorsal medial frontal cortex in 16 subjects during performance of the

flanker task. Their results indicate that dorsal medial frontal cortex

resolves conflict by exerting top-down control.

Given that many neuroimaging studies already addressed the allocation of

these processes, lesion studies complement their results by indicating if

different brain regions are essential for resolving response conflict. Only

few studies have so far investigated the performance of brain-damaged

patients in the flanker task (Beck et al., 2008; Rafal et al., 1996; Snow &

Mattingley, 2006), the Stroop task (Baird et al., 2006; Cohen et al., 1999;

Fellows & Farah, 2005; Stuss et al., 2001; Swick & Turken, 2002; Swick &

Jovanovic, 2002; Vendrell et al., 1995) and the Simon task (di Pelligrino et

al., 2007), most of them demonstrating that lesions in the ACC are

associated with impaired performance. In comparison to this study neither

used the ANT to measure response conflict, nor did they compare the

results of the patients with those of a healthy control group. Further studies

with neurological and psychiatric patients revealed that Chorea Huntington

(Beste et al., 2008), Morbus Parkinson (Wylie et al., 2005), attention-

deficit/hyperactivity disorder (ADHD; Bush et al., 1999), schizophrenia

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(Carter et al., 1997) and depression (Holmes et al., 2008) are associated

with an impairment in monitoring and resolving response conflict.

As mentioned above, in many neuropsychological studies response

conflict was triggered within different paradigms: flanker task (Bunge et al.,

2002), Stroop task (Carter et al., 2000), Simon task (Wühr et al., 2008)

and go/no-go paradigm (Casey et al., 1997). In the present study the

Attention Network Test (ANT) developed by Fan and colleagues was used,

to operationalize a conflict situation. The ANT is a combination of the

flanker task (Eriksen & Eriksen, 1974) and the cued reaction time

paradigm(Posner, 1980) and determines the three attentional networks:

alerting, orienting and executive attention. The ANT was used amongst

others to investigate the independence and heritability of the three

different attentional networks (Fan et al., 2001; 2002), in functional

magnetic resonance imaging (fMRI) studies with children and adults

(Konrad et al., 2005; Fan et al., 2003, 2005, 2007, 2008) and in patients

with schizophrenia (Gooding et al., 2006) or borderline personality disorder

(Posner et al., 2002). Up to now only Beck et al. (2008) applied the ANT in

neurological patients with stroke or traumatic brain injury indicating the

clinical usefulness of this test. Most notably mean reaction time was the

best predictor for attention deficits. However, they neither compared the

results of the patients with a group of healthy controls, nor did they

separate the patients on the basis of their lesion localization into different

groups.

On account of this, the present study deals with performance on the ANT

in neurological patients with frontal and non-frontal brain lesions, turning

attention to the conflict effect. The hypothesis of this study is that patients

with frontal brain areas show a selective impairment in the conflict effect of

the ANT and normal performance in orienting, alerting and the background

neuropsychological assessment as compared to patients with non-frontal

brain lesions.

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2. Methods

2.1 Participants

The 22 neurological patients were a consecutive sample and were

selected during their inpatient stay in the neurological department of the

university hospital of the RWTH Aachen according to the location and

etiology of their brain lesion. Only patients with ischaemic stroke or tumor

were asked to participate in the study and were tested in the subacute

state. Exclusion criteria were aphasia with comprehension difficulties,

massive intellectual deficits, degenerative neurological disorders, visual

disorders, neglect and German not as first language. On the basis of

neuroradiological findings in computer tomography (CT) or magnetic

resonance imaging (MRI) the patients were divided into two groups: the

frontal group (FG) containing 11 patients with lesion located predominantly

in the frontal lobe and the non-frontal group (NFG) containing 11 patients

with lesion outside the frontal lobe. The two groups did not differ as to age.

Details of patient characteristics are summarized in table 2. For a review of

the lesion localizations of the patients see table 6 in the appendix.

Additionally, 11 age and education matched healthy controls were tested

to compare their performance with those of the patients. All participants

reported normal or corrected to normal vision. Written informed consent

was obtained from all participants after complete description of the study

before the session. Participants participated voluntarily and received no

payment for study participation. The project was approved by the local

Ethics Committee of the Medical Faculty of the RWTH Aachen.

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Table 1. Demographic and clinical data of patients with frontal lesions

(FG), patients with non-frontal lesions (NFG) and healthy controls (CG).

FG NFG CG

(n=9) (n=11) (n=11)

Sex: (male/female) 4/5 8/3 5/6

Age (M, SD) 56 (16) 57 (17) 58 (14)

Graduation (ESC/SGS/SMS/GS)1 3/1/3/2 1/4/2/4 2/2/3/4

Handedness premorbid (r/l/bi)2** 9/0/0 9/2/0

Handedness at testing date (r/l/bi) 8/1/0 9/2/0 11/0/0

Etiology (stroke/tumor) 7/2 11/0

Days since onset (M, SD) 11.7 (5.3) 7.2 (2.9)

1 ESC = elementary school, SGS = secondary general school, SMS = secondary modern school, GS = grammar school; 2 r = right, l = left, bi = bilateral

2.2 Background neuropsychological assessment

To examine whether the participants showed comparable performance in

other cognitive functions, three different neuropsychological tests were

used:

VLMT (Verbaler Lern- und Merkfähigkeitstest, Auditory Verbal Learning

Test) by Helmstaedter, Lendt & Lux, 2001

The VLMT is a German version of the Auditory Verbal Learning Test and

measures verbal learning and memory. A learning list of 15 words is read

out to the patient in five successive trials, each one of them is followed by

a free recall, and after the fifth trial an interference list is read which also

has to be recalled. Finally a free recall of the learning list is accomplished.

The following specific values were engaged: sum of reproduced correct

words in trial 1 to trial 5 (learning efficiency), difference of named correct

words between trial 6 and trial 5 (performance of demand), false positive

words, number of perseverations and named words that belong to the

other list of words. Results are reported in scores of counted words.

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TMT (Trail Making Test) by Reitan, 1955

The TMT consists of 2 different parts: part A analyses speed of information

processing whereas part B investigates cognitive flexibility. While in part A

the participant’s task is to connect numbers from 1 to 25 on a paper in

ascending order (TMT-A), in part B the 25 numbers and letters he has to

connect are in alternating order (TMT-B). Both tasks were timed by the

tester. Results are reported in ms.

LPS (Leistungs-Prüf-System, Achievement Measure System) by Horn,

1983: Subtest 4

The LPS (Achievement Measure System) tests abstract logical thinking

and reasoning respectively. Subtest 4 implies 40 items containing eight

digits and letters. The elements of each line are sorted according to

different rules. Within eight minutes the participant has to identify one

element in each line, which does not fit the rule. Results are reported in T-

values.

2.3. Attention Network Test (ANT)

The Attention Network Test (ANT), a choice reaction time task, was

originally developed by Jin Fan and colleagues (Sackler Institute, Cornell

University New York) and represents a combination of the cued reaction

time (Posner et al., 1980) and the flanker task (Eriksen & Eriksen, 1974).

We used Version 1.3.0 modified by Siegfried Gauggel and Maren Böcker

(Institute of Medical Psychology and Medical Sociology, RWTH Aachen) in

which four cue conditions (no cue, center cue, double cue, spatial cue, see

Figure 3) and three target conditions (congruent, incongruent, neutral, see

Figure 2) are integrated to investigate the efficacy of the following three

attentional networks: orienting, alertness and executive control. This study

concentrates on the executive control system which is operationalized

within the flanker paradigm. The stimuli consist of a row of 5 horizontal

black arrows. However, the participants are instructed to respond only to

the central one (target). Depending on the arrows direction they have to

press the left or the right button with the instruction to respond as fast and

as accurate as possible. The subjects are guided to look steadily at a

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fixation cross in the middle of the computer screen, which is presented

before the arrows appear. In order to integrate a conflict condition, the

target is flanked by two arrows on each side, pointing to the same direction

(congruent condition) or the opposite direction (incongruent condition) of

the target. In a neutral condition the flankers consist of four lines without

information of direction (Figure 2). The difference between mean reaction

time (RT) of the incongruent and the congruent condition represents the

conflict effect.

Figure 2. Target conditions of the ANT.

The alertness component is introduced by the double cue condition, where

two stars, positioned above and below the fixation cross, precede the

stimuli. These cues do not give the subjects any information of direction,

but they tell the subject that the stimuli will immediately be presented. The

difference between no cue and double cue condition represents the

alerting effect (see Figure 3).

In the orienting condition a spatial cue gives the information where the

target will appear. Therefore a star is presented above or below the

fixation cross according to the location of the target. In order to introduce a

control condition, a center cue is released at the position of the fixation

cross. The orienting effect is estimated by the difference between the RT

of the center cue and the spatial cue condition.

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Figure 3. Cue conditions of the ANT.

In Figure 3 the course of the ANT is presented. In each trial a fixation

cross appears until a cue condition is presented a variable time later (F1 =

400 - 1600 ms). After 100 ms the cue disappears and 400 ms (F2) later

the target stimuli appear as long as the participant responds with a button

press, but for no longer than 1700 ms. Having responded, the fixation

cross reappears for a variable duration (F3 = 3500 ms - RT – F1 ms).

Figure 4. Schema of the ANT.

2.4. Procedure

Participants were tested in a separate test room or their sickroom,

depending on their condition. First they performed the ANT, approximately

50 cm in front of a laptop. The test consisted of an instruction, a practice

block with 24 trials and three test blocks, each containing 96 trials. All trials

were randomized and each test block lasted 5 minutes, so that the entire

test took approximately 20 minutes. Afterwards the subjects received

feedback on their performance, which included the conflict, orienting and

alerting effect (in ms), mean RT (in ms) and accuracy (in percent).

Subsequently they accomplished the VLMT, LPS and TMT and also

obtained the results of these tests. Finally, in order to get more information

about the subject’s background, they filled out a demographic

questionnaire.

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2.5. Lesion analysis

Available brain images of the patients were collected, preferably magnetic

resonance imaging (MRI). Computer tomography images were only used

in case of no MRI picture. Identifiable lesions were marked for each patient

in MRIcron (Rorden et al. 2007; for download see

http://www.sph.sc.edu/comd/rorden/mricron/). On the basis of these

pictures lesion localizations were determined (see Appendix table 6). The

method is demonstrated exemplary in figure 5.

Figure 5. In MRIcron marked lesion.

2.6 Statistical analysis

Behavioural data

For the statistical analysis the SPSS-Program Version 15 was used. First

all data were screened for deviation from normality, outliers and

homogeneity of variance. In a next step all dependent variables underwent

analyses of variance (ANOVA). In doing so, the three different groups

(frontal group, non-frontal group, healthy controls) were first compared

with respond to their performance in the background neuropsychological

assessment in order to reveal potential performance differences. For the

ANT, the standard parameters were compared between the three groups:

mean RT, mean accuracy, conflict effect, alerting effect and orienting

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effect. Beside the absolute effects of the latter three dependent variables,

the relative effects were also compared, due to the fact that they account

for general differences of speed. The relative effects were computed by

means of the following formulas:

1) Conflict effect: Conflict effect * 100 / Median RTincongruent

2) Alerting effect: Alerting effect * 100 / Median RTno cue

3) Orienting effect: Orienting effect * 100 / Median RTcentral cue

They state the percental variance oriented on the baseline. Additionally,

effect sizes were calculated for the ANT parameters as effect sizes are

sample size independent and allow an estimation of the magnitude of the

difference between the investigated groups.

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3. Results

3.1 Background neuropsychological assessment

One patient of the frontal group was not considered for the statistical

analysis of the TMT part A because his mean reaction time differed over

three standard deviations from the others so that he produced great

intergroup-differences.

Results of the background neuropsychological assessment are presented

in table 2.

Table 2. Neuropsychological data of patients with frontal lesions (FG),

patients with non-frontal lesions (NFG) and controls (CG).

FG NFG CG p F (k-1, n-k)

(M, SD, n) (M, SD, n) (M, SD, n)

VLMT Dg 1-5 42 (17) 8 42 (10) 10 45 (12) 11 0.76 0.3 (2, 26)

VLMT Dg 5 – 6 1 (2) 8 2 (2) 10 2 (2) 11 0.41 0.9 (2, 26)

VLMT FP 2 (5) 8 2 (2) 10 1 (3) 11 0.73 0.5 (2, 26)

VLMT P 4 (2) 8 3 (4) 10 4 (4) 11 0.90 0.1 (2, 26)

VLMT In 0.5 (0.6) 8 0.2 (0.4) 10 0.1 (0.3) 11 0.22 1.6 (2, 26)

TMT Part A (ms) 46 (28) 6 35 (11) 9 28 (8) 11 0.09 2.7 (2, 23)

TMT Part B (ms) 92 (61) 7 98 (46) 9 64 (30) 11 0.22 1.6 (2, 24)

LPS (T-score) 53 (11) 7 45 (11) 10 56 (9) 5 0.14 2.2 (2, 19)

VLMT = Verbal Learning and Memory Test, TMT = Trail Making Test, LPS = Achievement Measure System

No significant differences were found in the Verbal Learning and Memory

Test (VLMT), the Trail Making Test (TMT) and the Achievement Measure

System (LPS).

3.2 Performance in the ANT

Two patients of the frontal group were not considered for further analysis

in order to not distort the results. One of them was an outlier in the

accuracy, he differed over ten standard deviations from the others. The

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test-results of the other one could not be utilized by the ANT for calculating

the variables, due to the fact that his reaction times were longer than

1700ms. Results of the ANT are presented in table 3 and in figures 6 to

10.

Table 3. Results of the ANT of patients with frontal lesions (FG), patients

with non-frontal lesions (NFG) and controls (CG).

FG (n=9) NFG (n=11) CG (n=11) p F (k-1, n-k)

(M, SD) (M, SD) (M, SD)

Mean RT (ms) 660 (152) 673 (99) 560 (73) 0.05 3.47 (2, 28)

Accuracy (%) 96.7 (4.4) 96.9 (3.4) 98.6 (0.8) 0.31 1.22 (2, 28)

Conflict e. (ms) 113 (50) 91 (39) 57 (26) 0.01 5.47 (2, 28)

RCE (%) 14.9 (3.7) 12.5 (4.9) 9.4 (4.1) 0.03 4.17 (2, 28)

Alerting e. (ms) 31 (32) 39 (20) 25 (13) 0.35 1.09 (2, 28)

RAE (%) 4.6 (4.1) 5.4 (2.3) 4.4 (2.4) 0.71 0.34 (2, 28)

Orienting e. (ms) 28 (32) 22 (28) 32 (18) 0.68 0.40 (2, 28)

ROE (%) 4.7 (4.6) 3.3 (4.0) 5.6 (3.0) 0.42 0.90 (2, 28)

RT = reaction time, e. = effect, RCE = relative conflict effect, RAE = relative

alerting effect, ROE = relative orienting effect

The oneway ANOVA showed significant differences between the three

groups in mean reaction time (F (2, 28) = 3.47, p = 0.05), the conflict effect

(F (2, 28) = 5.47, p = 0.01) and the relative conflict effect (F (2, 28) = 4.17,

p = 0.03). In accuracy (F (2, 28) = 1.22, p = 0.31), alerting effect (F (2, 28)

= 1.09, p = 0.35), relative alerting effect (F (2, 28) = 0.34, p = 0.71),

orienting effect (F (2, 28) = 0.40, p = 0.68) and relative orienting effect (F

(2, 28) = 0.90, p = 0.42) there were no significant differences between the

three groups.

Effect sizes (ES) for conflict effect (FG - NFG = 0.50, FG – CG = 1.46,

NFG – CG = 1.04) and relative conflict effect (FG – NFG = 0.54, FG – CG

= 1.40, NFG – CG = 0.68) showed a difference between frontal group and

non-frontal group of medium size and a great difference between patients

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and controls indicating the greatest problems in resolving conflict in the

patients with frontal brain lesions. The large effect size for conflict effect

between the non-frontal group and the control group should be seen in

context with the general slowing of patients in mean reaction time. This is

reflected in the medium effect size for relative conflict effect between the

non-frontal group and the control group (NFG – CG = 0.69) and the great

difference between frontal group and control group (FG – CG = 1.59).

There were only small effects for mean reaction time and accuracy

between the patient groups, but as mentioned above obvious differences

between patients and control group indicating slower reaction times for the

patient groups (FG – CG = 0.88, NFG – CG = 1.30). Concerning the

accuracy, effect sizes of medium size were found for the differences

between the patients groups and the control group with the healthy

controls reacting more accurately than the patients (FG – CG = -0.61,

NFG – CG = -0.70). Alerting effect, relative alerting effect, orienting effect

and relative alerting effect showed only small effect sizes between the

patient groups and between patients and controls (see figures 6 to 10).

0

100

200

300

400

500

600

700

800

900

FG NFG CG

Indication

Mea

nre

acti

on

tim

e (m

s)

0

100

200

300

400

500

600

700

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FG NFG CG

Indication

Mea

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on

tim

e (m

s)

Figure 6. Mean reaction time of patients with frontal lesions (FG), patients


ES = 1.30

ES = 0.88

ES = -0.10

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86

88

90

92

94

96

98

100

102

FG NFG CG

Indication

Ac

cu

racy

(%)

86

88

90

92

94

96

98

100

102

FG NFG CG

Indication

Ac

cu

racy

(%)

Figure 7. Accuracy of patients with frontal lesions (FG), patients with non-

frontal lesions (NFG) and controls (CG).

0

20

40

60

80

100

120

140

160

180

FG NFG CG

Indication

Co

nfl

ict

eff

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t(m

s)

0

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FG NFG CG

Indication

Co

nfl

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eff

ec

t(m

s)

Figure 8. Conflict effect of patients with frontal lesions (FG), patients with

non-frontal lesions (NFG) and controls (CG).

ES = -0.70

ES = -0.65

ES = -0.05

ES = 1.04

ES = 1.46

ES = 0.50

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-20

0

20

40

60

80

100

120

140

160

180

FG NFG CG

Indication

Ale

rtin

gef

fect

(ms)

-20

0

20

40

60

80

100

120

140

160

180

FG NFG CG

Indication

Ale

rtin

gef

fect

(ms)

Figure 9. Alerting effect of patients with frontal lesions (FG), patients with

non-frontal lesions (NFG) and controls (CG).

-20

0

20

40

60

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100

120

140

160

180

FG NFG CG

Indication

Ori

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-20

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FG NFG CG

Indication

Ori

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ffec

t(m

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Figure 10. Orienting effect of patients with frontal lesions (FG), patients


ES = 0.83

ES = -0.31

ES = 0.26

ES = -0.42

ES = -0.14

ES = 0.21

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4. Discussion

The aim of the present study was to investigate whether neurological patients

with lesions in frontal brain areas show impairment in detecting and resolving

conflict in comparison to patients with lesions in other brain areas and

healthy controls. The three groups performed the ANT and further

neuropsychological tests to distinguish if other cognitive control functions are

also affected. Given that many neuroimaging studies already identified

certain frontal brain areas that are involved in the detection and resolution of

conflict, this study also gives an answer to the question if these brain regions

are actually essential for this executive function.

Summarizing the most important results there are no significant differences in

the background neuropsychological assessment between the frontal group,

the non-frontal group and the control group. Relating to the ANT, there were

no appreciable differences comparing the frontal group with the non-frontal

group except for the conflict effect which argues for a strong dissociation.

The fact that patients were generally slower and less accurate in contrast to

healthy controls indicates a deficit in speed of information processing of brain

injured patients. This effect of general slowing in neurological patients was

found in other neuropsychological studies as well (Hochstenbach et al., 1998;

Ponsford et al., 1992; Zahn et al., 1999, Beck et al., 2008). Only Beck et al.

(2008) investigated the ANT performance of neurological patients with stroke

or traumatic brain injury, but they did not compare the results with those of a

healthy control group. Their patients showed longer mean reaction times than

our patient groups and our control group (M = 703 ms, SD = 169 ms). The

results of accuracy are similar with those of both patient groups, the patients

were less accurate than our control group (M = 97%, SD = 3%).

Investigating the responsible brain areas for resolving conflict, several

neuroimaging studies using the ANT (Fan et al., 2003, 2005, 2007, 2008),

other flanker tasks (Botvinick et al., 1999; Bunge et al., 2002; Casey et al.,

2000; Durston et al., 2003; Hazeltine et al., 2000, 2003; Lau et al., 2005;

Luks et al., 2007; McNab et al., 2008; Ochsner et al., 2009; van Veen et al.,

2001; Wager et al., 2005; Wang et al., 2009) and the Stroop task (Barch et

Eva-Maria Meier


19

al., 2001; Carter et al., 2000; Haupt et al., 2009; Kerns et al., 2004;

MacDonald et al., 2000; Roberts et al., 2008; Zysset et al., 2001)

demonstrated that frontal brain areas like DLPFC and ACC were activated

during response conflict. However, imaging studies can not answer the

question whether these brain areas are essential.

Therefore lesion studies are very important in further research simply

because they have the possibility to complement the results of neuroimaging

studies by indicating that certain brain areas are necessary for performing a

task. Until now only few studies engage in the performance of flanker task in

brain damaged patients, and some of the results are consistent with our

findings (Rafal et al., 1996; Snow & Mattingley, 2006). Rafal et al. (1996)

compared the performance of a flanker task of patients with lesions involving

inferior lateral prefrontal cortex with those of neurological control patients.

Their lesion patients also showed longer reaction times for incompatible trials

indicating a deficit in response channel activation. Snow and Mattingley

(2006) tested patients with lesions in the right hemisphere not differentiating

between frontal and non-frontal regions. In comparison to a healthy control

group, the patients showed longer mean reaction times and longer reaction

times for incompatible flankers. This is consistent with our conclusion of

generally slowing in neurological patients. In addition to lesion studies TMS

was used during flanker tasks to verify the necessity of frontal brain regions

in response conflict. Taylor et al. (2007) applied TMS to left dorsal medial

frontal cortex demonstrating that this area modulates primary motor cortical

activity during conflict. In summary, neuroimaging and lesions studies

underline the hypothesis that frontal brain areas play an important role in

monitoring and resolving conflict.

Due to the fact that the present study was a clinical study, several

methodological limitations were given. Only a small number of patients could

participate in the study because most of the neurological patients did not

conform to the selection criteria. Due to this circumstance, the patient group

was very heterogeneous with respect to age and affected hemisphere, they

also showed different lesion localizations. Furthermore, some of the patients

with frontal lesions showed additional lesions in other brain areas, with the

Eva-Maria Meier


20

most affected part allocated in the frontal lobe. With regard to the

neuroradiological data some patients got an MRI scan during their stay in the

neurological clinic, while others only got a CT. On account of these limitations

further lesion studies should emply a larger and more homogeneous group of

patients with identical neuroradiological image technique and lesions

allocated in those brain areas which are associated with the determined

function. Bates et al. (2003) developed a new method called ´Voxel-based

lesion-symptom mapping´ (VLSM). As in functional neuroimaging studies, the

relationship between tissue damage and behaviour is investigated on a

voxel-by-voxel basis. The outcome of this is continuous behavioural and

lesion information without any loss of information. For this method a greater

sample size of patients is very important.

Neuroimaging studies using time-resolved fMRI (Richter et al., 1999) or TMS

could help to decide between two prominent theories. According to the

conflict monitoring hypothesis (Botvinick et al., 1999), the ACC monitors the

occurrence of conflict between two competing responses and triggers

strategic adjustments in cognitive control to the DLPFC. The DLPFC then

has the executive function to resolve the conflict situation by exerting top-

down influences to other brain regions involved in sensory and motor

processing (Miller & Cohen, 2001). One of these brain areas is located in the

parietal cortex which is thought to be involved in activating appropriate motor

responses (Bunge et al., 2002). In contrast, the selection for action

hypothesis of Posner & diGirolamo (1998) suggests that the ACC and other

midfrontal areas are responsible for top-down attentional influences and

therefore for resolving conflict. The results of this study cannot disprove any

of these hypotheses. They do, however, underline that frontal brain areas are

a necessary part of the conflict network.

In conclusion, patients with lesions in frontal brain areas showed in

comparison to patients with non-frontal brain lesions and healthy controls a

significantly larger conflict effect in the ANT and normal performance in other

functions of cognitive functions. This dissociation is consistent with previous

findings in other lesion studies and several neuroimaging studies. The

controversially disputed function of ACC in response conflict (conflict

Eva-Maria Meier


21

monitoring hypothesis by Botvinick et al., 1999 versus the selection for action

hypothesis of Posner & diGirolamo, 1998) can neither be verified nor can it

be disproved. However, we can deduce from the results that a frontal brain

network is necessary for the executive function of monitoring and resolving

conflict. Further studies with larger sample size and methods like VLSM or

time-resolved fMRI have to distinguish in particular which brain areas are

responsible for the specific process units during response competition.

Eva-Maria Meier


22

5. Summaries

5.1. English summary

Many neuroimaging studies investigated the role of frontal brain areas in

monitoring and resolving conflict, but until now there exist only few lesion

studies. In order to reassess the necessity of frontal brain areas for

accomplishing this executive function, we used a lesion study design to

compare 11 neurological patients with frontal brain lesions with 11 patients

with non-frontal brain lesions and 11 healthy controls with regard to their

performance in the Attention Network Test (ANT), especially in the conflict

effect. Besides a general slowing effect in both patient groups indicated by a

slower overall mean reaction time as compared to the healthy controls, a

significant difference between the three groups was given for the conflict

effect and the relative conflict effect. In doing so medium effect sizes were

found for the conflict effect and relative conflict effect between the frontal

group and non-frontal group and great effect sizes between patients and

healthy controls indicating greater difficulties of resolving conflict in the

patients with frontal brain lesions. As no differences were found for other

cognitive functions, these results indicate that patients with frontal lesions are

selectively impaired in the conflict effect of the ANT. This dissociation

complements the results of functional magnetic resonance imaging (fMRI)

studies (Fan et al., 2002, 2005, 2007, 2008) proving the necessity of these

brain areas for this executive function.

Eva-Maria Meier


23

5.2. Deutsche Zusammenfassung

Viele bildgebende Studien haben sich in den letzten Jahren mit dem

Zusammenhang zwischen frontalen Hirnarealen und dem Erkennen und

Lösen einer Konfliktsituation beschäftigt, jedoch gibt es bisher kaum

Läsionsstudien, die dieses Thema untersucht haben. Um die Notwendigkeit

frontaler Hirnareale im Hinblick auf die Verarbeitung von Konflikt zu

überprüfen, wurden in dieser Studie 11 Patienten mit frontalen

Hirnschädigungen mit 11 weiteren Patienten mit nicht-frontalen

Hirnschädigungen und 11 gesunden Kontrollpersonen hinsichtlich ihrer

Ergebnisse im Aufmerksamkeits-Netzwerk-Test (ANT), insbesondere im

Konflikteffekt, und in verschiedenen anderen neuropsychologischen Tests

verglichen. Signifikante Unterschiede zwischen den drei Gruppen fanden

sich im Konflikteffekt, im relativen Konflikteffekt sowie in der

durchschnittlichen Reaktionsgeschwindigkeit. Im Konflikteffekt und im

relativen Konflikteffekt ergaben sich mittlere Effektstärken im Vergleich der

frontalen Gruppe mit der nicht-frontalen Gruppe und große Effektstärken im

Vergleich der Patientengruppen mit der gesunden Kontrollgruppe. Diese

Ergebnisse deuten auf eine allgemeine Verlangsamung neurologischer

Patienten und Schwierigkeiten in Konfliktsituationen hin, welche allerdings

besonders bei Patienten mit frontalen Hirnschädigungen ausgeprägt sind.

Diese Dissoziation ergänzt die Ergebnisse von funktionellen

Magnetresonanztomographie (fMRT) -Studien (Fan et al., 2002, 2005, 2007,

2008) und beweist die Notwendigkeit dieser Hirnregionen für diese exekutive

Funktion.

Eva-Maria Meier


24

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7. Appendix

7.1. List of tables

Table 1: Demographic and clinical data of patients with frontal lesions (FG),

patients with non-frontal lesions (NFG) and healthy controls (CG). ............... 7

Table 2: Neuropsychological data of patients with frontal lesions (FG),

patients with non-frontal lesions (NFG) and controls (CG). ………………....13

Table 3: Results of the ANT of patients with frontal lesions (FG), patients

with non-frontal lesions (NFG) and controls (CG). …………………………....14

Table 4: fMRI studies of the flanker task in healthy controls. …………….....33

Table 5: fMRI studies of the Stroop task in healthy controls. ……………….37

Table 6: Patients lesion localization. …………………………………………..39

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7.2. List of figures

Figure 1: Brain areas that play an important role in handling with the

occurrence of conflict: frontal lobe (especially anterior cingulate gyrus and

dorsolateral prefrontal cortex) and parietal cortex (BrainVoyager Brain Tutor,

Version 2.0) ....................................................................................................4

Figure 2: Target conditions ............................................................................9

Figure 3: Cue conditions ................................................................................9

Figure 4: Schema of the ANT ......................................................................10

Figure 5: In MRIcron marked lesion. ............................................................11

Figure 6: Mean reaction time of patients with frontal lesions (FG), patients

with non-frontal lesions (NFG) and controls (CG). ........................................15

Figure 7: Accuracy of patients with frontal lesions (FG), patients with non-

frontal lesions (NFG) and controls (CG). ......................................................16

Figure 8: Conflict effect of patients with frontal lesions (FG), patients with

non-frontal lesions (NFG) and controls (CG). ...............................................16

Figure 9: Alerting effect of patients with frontal lesions (FG), patients with


Figure 10: Orienting effect of patients with frontal lesions (FG), patients with


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rior

parie

tal l

obul

e, l

ST

G, r

cer

ebel

lum

Dur

ston

et a

l. , 2

003

9 E

R

bi

-lt A

CC

, l M

FG

, r S

FG

, bi-l

t sup

erio

r pa

rieta

l lob

e, r

intr

apar

ieta

l sul

cus,

l fu

sifo

rm

gyru

s

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

34

Aut

hor

n D

esig

n R

esul

ts

Fan

et a

l. , 2

003

12

E

R

bi

-lt c

ingu

late

gyr

us, r

pos

tcen

tral

gyr

us, l

MF

G, b

i-lt l

ingu

al g

yrus

, l p

rece

ntra

l gyr

us, r

infe

rior

parie

tal l

obul

e, l

post

cent

ral g

yrus

, bi-l

t SF

G, b

i-lt I

TG

, l S

TG

, r p

recu

neus

Fan

et a

l. , 2

005

12

E

R

r

AC

C, T

hala

mus

, l S

FG

, bi-l

t IF

G, b

i-lt f

usifo

rm g

yrus

, cer

ebel

lar

verm

is, r

MF

G

Fan

et a

l., 2

007

20

E

R

l A

CC

, bi-l

t MF

G, l

sup

erio

r pa

rieta

l lob

ule,

r p

recu

neus

, r M

FG

, r p

arac

entr

al lo

bule

Fan

et a

l. , 2

008

16

E

R

l A

CC

, r IF

G, r

sup

erio

r pa

rieta

l lob

ule,

l fu

sifo

rm g

yrus

, l in

sula

, l p

ostc

entr

al g

yrus

, r

thal

amus

(pu

lvin

ar)

Haz

eltin

e et

al.

, 200

0 8

B

r

infe

rior

pref

ront

al c

orte

x, l

supp

lem

enta

ry m

otor

cor

tex,

l su

perio

r pa

rieta

l cor

tex,

l

infe

rior

ante

rior

parie

tal c

orte

x

Haz

eltin

e et

al.

, 200

3 10

E

R

r

AC

C, r

IFG

, r M

FG

, r S

FG

, bi-l

t pre

mot

or c

orte

x, l

prec

entr

al

cort

ex, r

infe

rior

parie

tal c

orte

x

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

35

Aut

hor

n D

esig

n R

esul

ts

Lau

et a

l. , 2

005

16

B

AC

C

Luks

et a

l. , 2

007

11

E

R

bi

-lt A

CC

, bi-l

t pre

SM

A, b

i-lt I

PS

, r D

LPF

C, b

i-lt v

entr

olat

eral

PF

C, b

i-lt o

rbito

fron

tal

cort

ex

McN

ab e

t al.

, 200

8

14

B

l A

CC

, l c

orpu

s ca

llosu

m, r

infe

rior

parie

tal c

orte

x, r

sup

erio

r pa

rieta

l cor

tex

Och

sner

et a

l. , 2

009

16

B

bi

-lt M

FG

, r in

sula

, bi-l

t IF

G, b

i-lt p

rece

ntra

l gyr

us, l

cin

gula

te g

yrus

, l s

uper

ior

parie

tal l

obul

e, l

para

hipp

ocam

pal g

yrus

, bi-l

t pre

cune

us, l

SF

G, r

ST

G, r

cau

date

Van

Vee

n et

al.

, 200

1 12

E

R

A

CC

, l IF

C, b

i-lt D

LPF

C, r

par

ieta

l cor

tex,

l pr

ecun

eus,

pos

terio

r ci

ngul

ate

gyru

s, l

pola

r

fron

tal c

orte

x

Wag

er e

t al,

2005

14

ER

l par

ieta

l cor

tex,

bi-l

t ant

erio

r pr

efro

ntal

cor

tex,

l in

sula

, r A

CC

, bi-l

t cau

date

, bi-l

t

Put

amen

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

36

Aut

hor

n D

esig

n R

esul

ts

Wan

g et

al.

, 201

0

18

B

bi

-lt A

CC

, r m

iddl

e ci

ngul

ate

cort

ex, r

pos

tcen

tral

gyr

us, r

SF

G, r

MF

G, l

thal

amus

, l

IFG

, l p

rece

ntra

l gyr

us, l

infe

rior

parie

tal g

yrus

ER

= e

vent

-rel

ated

des

ign;

B =

blo

ck d

esig

n; l

= le

ft; r

= r

ight

; bi-l

t = b

ilate

ral

AC

C =

ant

erio

r ci

ngul

ate

cort

ex,

PC

C =

po

ster

ior

cing

ulat

e co

rtex

, M

FG

= m

edia

l fr

onta

l gy

rus;

IF

G =

inf

erio

r fr

onta

l gy

rus;

SF

G =

supe

rior

fron

tal

gyru

s; I

PS

= i

nfer

ior

parie

tal

sulc

us;

PC

S =

pos

tcen

tral

sul

cus;

ST

G =

sup

erio

r te

mpo

ral

gyru

s; I

TG

= i

nfer

ior

tem

pora

l

gyru

s; D

LPF

C =

dor

sola

tera

l pre

fron

tal c

orte

x; S

MA

= s

uppl

emen

tary

mot

or a

rea

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

37

Tab

le 5

. fM

RI s

tudi

es o

f th

e S

troo

p ta

sk in

hea

lthy

cont

rols

.

Aut

hor

n

Des

ign

R

esul

ts

Bar

ch e

t al.,

200

1

13

E

R

l AC

C, S

MA

, pre

-SM

A

Car

ter

et a

l., 2

000

12

ER

A

CC

, l IP

C, b

i-lt I

FC

, ext

rast

riate

vis

ual c

orte

x

H

aupt

et a

l., 2

009

29

B

bi-lt

DLP

FC

, l in

sula

, l c

ingu

late

gyr

us, l

lent

iform

nuc

leus

, l M

FG

, l

Tha

lam

us, l

AC

C, p

re-S

MA

, SF

G

Ker

ns e

t al.,

200

4

23

E

R

AC

C, l

fro

ntal

cor

tex,

r IP

C, b

i-lt M

FG

, r p

arie

tal c

orte

x, l

ST

G,

r

puta

men

, l M

TG

, l th

alam

us, b

i-lt I

FG

Mac

Don

ald

et a

l., 2

000

12

E

R

AC

C, l

DLP

FC

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

38

Aut

hor

n D

esig

n R

esul

ts

Rob

erts

et a

l., 2

008

16

B

bi-lt

late

ral P

FC

, AC

C, l

eft p

rem

otor

cor

tex,

l su

perio

r pa

rieta

l lob

ule,

l

infe

rior

parie

tal l

obul

e, p

recu

neus

, r IF

G, r

ant

erio

r in

sula

cor

tex

Zys

set e

t al.,

200

1

9

B

l pos

terio

r in

ferio

r fr

onta

l sul

cus,

bi-l

t occ

ipito

tem

pora

l gyr

us, l

cun

eus

ER

= e

vent

-rel

ated

des

ign;

B =

blo

ck d

esig

n; l

= le

ft; r

= r

ight

; bi-l

t = b

ilate

ral

AC

C =

ant

erio

r ci

ngul

ate

cort

ex, I

PC

= in

ferio

r pa

rieta

l cor

tex,

MF

G =

med

ial f

ront

al g

yrus

, ST

G =

sup

erio

r te

mpo

ral g

yrus

, MT

G =

med

ial t

empo

ral

gyru

s, D

LPF

C =

dor

sola

tera

l pre

fron

tal c

orte

x, S

MA

= s

uppl

emen

tary

mot

or a

rea,

PF

C =

pre

fron

tal c

orte

x, IF

G =

infe

rior

fron

tal g

yrus

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

39

Tab

le 6

. Pat

ient

s le

sion

loca

lizat

ion

in th

e pr

esen

t stu

dy.

Pat

ient

G

roup

E

tiolo

gy

Le

sion

loca

lizat

ion

Le

sion

siz

e

H

emis

pher

e

Reg

ion

(cc)

91

F

G

st

roke

left

Gyr

us p

raec

entr

alis

0.3

98

F

G

tu

mor

right

G

yrus

fro

ntal

is s

uper

ior

33

.74

le

ft

pa

ram

edia

n ce

ntra

l reg

ion

Gyr

us f

ront

alis

sup

erio

r

Gyr

i occ

ipita

les

155

F

G

tu

mor

left

Gyr

us f

ront

alis

infe

rior

78

.41

199

F

G

st

roke

right

fr

onta

l Ope

rcul

um, d

iffer

ent p

arts

of

90

.64

the

fron

tal c

orte

x

315

F

G

st

roke

left

Gyr

us p

ostc

entr

alis

up

to p

arie

tal

24

.88

and

fron

tal O

perc

ulum

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

40

Pat

ient

G

roup

E

tiolo

gy

Le

sion

loca

lizat

ion

Le

sion

siz

e

H

emis

pher

e

Reg

ion

(cc)

330

F

G

st

roke

left

fron

tal a

nd p

arie

tal O

perc

ulum

12

.55

346

F

G

st

roke

left

med

ulla

ry c

ente

r

3.

3

369

F

G

st

roke

left

ante

rior

terr

itoria

l str

oke

10.2

5

with

par

t of

the

Gyr

us fr

onta

lis s

uper

ior

423

F

G

st

roke

left

Cen

trum

sem

iova

le

1.

31

Str

iatu

m

117

N

FG

stro

ke

rig

ht

Cel

la m

edia

of

the

right

7.42

side

ven

tric

le u

p to

cor

tex

267

N

FG

stro

ke

le

ft

m

ultip

le d

isse

min

atin

g in

farc

ts in

the

2.15

terr

itory

of

the

mid

dle

cere

bral

art

ery

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

41

Pat

ient

G

roup

E

tiolo

gy

Le

sion

loca

lizat

ion

Le

sion

siz

e

H

emis

pher

e

Reg

ion

(cc)

313

N

FG

stro

ke

le

ft

pa

rieto

occi

pita

l

0.

62

336

N

FG

stro

ke

le

ft

m

edia

l occ

ipita

l lob

e

6.15

342

N

FG

stro

ke

le

ft

T

rigon

um

345

N

FG

stro

ke

rig

ht

Gyr

us p

ostc

entr

alis

2.3

347

N

FG

stro

ke

rig

ht

mar

row

bed

1.64

Tha

lam

us, P

utam

en

mes

ence

phal

348

N

FG

stro

ke

rig

ht

tem

poro

-par

ieta

l

31

.84

Ev

a-M

aria

Me

ier

Se

lec

tive

im

pa

irm

en

ts o

f th

e c

on

flic

t n

etw

ork

in

pa

tie

nts

with

fro

nta

l le

sio

ns

42

Pat

ient

G

roup

E

tiolo

gy

Le

sion

loca

lizat

ion

Le

sion

siz

e

H

emis

pher

e

Reg

ion

(cc)

349

N

FG

stro

ke

rig

ht

Put

amen

0.27

post

erio

r cr

us o

f th

e in

tern

al c

apsu

le

subi

nsul

e co

rtex

med

ial t

empo

ral l

obe

(with

Hip

poca

mpu

s)

350

N

FG

stro

ke

le

ft

C

entr

um s

emio

vale

368

N

FG

stro

ke

le

ft

m

arro

w b

ed

0.

68

FG

= f

ront

al g

roup

, NF

G =

non

-fro

ntal

gro

up, c

c =

cub

ic c

entim

etre

Eva-Maria Meier

Selective impairments of the conflict network in patients with frontal

lesions

43

9. Danksagung

Mein Dank gilt allen, die das Entstehen meiner Dissertation gefördert

haben, insbesondere meinem Betreuer Prof. Dr. Siegfried Gauggel. Ein

großer Dank geht auch an Frau Dr. Maren Böcker für ihre fachliche und

tatkräftige Unterstützung, insbesondere bei der Einarbeitung in das

Statistikprogramm SPSS. Außerdem danke ich Dr. Mario Städtgen für die

Einarbeitung in das Programm MRIcron, sowie der neurologischen Klinik

des Uniklinikums Aachen für die Bereitstellung der Patienten.

Eva-Maria Meier


lesions

44

8. Erklärung § 5 Abs. 1 zur Datenaufbewahrung

Hiermit erkläre ich, dass die dieser Dissertation zu Grunde liegenden

Originaldaten im

Institut für Medizinische Psychologie und Medizinische Soziologie,

Universitätsklinikum der RWTH Aachen,

Pauwelsstraße 30, 52074 Aachen

hinterlegt sind.

Eva-Maria Meier


lesions

45

9. Curriculum vitae Name: Eva-Maria Meier

Geburtsdatum: 14.02.1985

Geburtsort: Paderborn

Nationalität: deutsch

Familienstand: ledig

Email: [email protected]

Schulischer Werdegang:

1991 – 1995 Grundschule Delbrück-Ostenland

1995 – 2004 Gymnasium Schloß-Neuhaus

2004: Allgemeine Hochschulriefe (Note: 1,5)

06 – 08/2002 Auslandaufenthalt in Chile:

Gastschülerin an der Deutschen Schule in Santiago

de Chile

Hochschule:

WS 2004/2005 bis Studium der Humanmedizin an der RWTH Aachen

WS 2010/2011

09/2007 Ärztliche Basisprüfung (Note: Gut)

11/2010 Zweiter Abschnitt der Ärztlichen Prüfung (Note:

Sehr gut )

selective impairment of the conflict network in patients

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