Novel Brain Stimulation Strategies – Obesity, Pain, AddictionsMark S. George, MDDistinguished Professor of Psychiatry, Neurology and Radiology, Medical University of South Carolina

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Acknowledgments - – Foundations - NARSAD, Stanley, Dana, Hope– NIMH, NINDS, NIDA, NIAAA, NASA, DARPA, DOD, VA– Industry grants (last 20 yrs) – Brainsway, Cadwell, Cortex, Cyberonics,

Dantec, Darpharma, Electrocore, Glaxo Smith Kline, Jazz, MagStim, MECTA, Medtronic, Neostim, Neosync, Neuronetics, Neotonus, St. Jude Medical.

Disclosures - – No equity in any device or pharma company– 2 combinational patents pending– Speakers fees from industry (none in past 3 years)– Past Paid Consultant - GSK, Cyberonics, NeuroPace, Jazz– Unpaid Consultant – Brainsway, Neuronetics, Neostim, Neosync– Paid Consultant – Puretech Ventures– Editor-in-Chief, Brain Stimulation, Elsevier

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Electricity is the Currency of the BrainElectricity is the Currency of the Brain

All of synaptic pharmacology simply serves to All of synaptic pharmacology simply serves to transmit electrical signals to the next neurontransmit electrical signals to the next neuron

The Brain is an The Brain is an ElectroElectrochemical chemical OrganOrgan

US FDA Approved ECT - Electroconvulsive Therapy

– FEAST rTMS - repeated Transcranial

Magnetic Stimulation– Neuronetics, Magstim, Brainsway,

Neuralieve, Neostim, Neosync DBS - Deep Brain Stimulation -

PD– RST - Responsive Stimulation

Therapy– Epidural Cortical Stimulation

VNS - Vagus Nerve Stimulation – Epilepsy and Depression

Not FDA Approved MST - Magnetic Seizure

Therapy tDCS - transcranial Direct

Current Stimulation TENS - transcutaneous

Electrical Nerve Stimulation– Cranial Electrical Stimulation

(CES) Alpha-stim

EPI-fMRI - echoplanar fMRI Transcranial pulsed ultrasound

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02/05/15 RiverMend Health, LLC 5George MS. Sci Am. 2003;289:66-73.

Craving is certainly modifiable with cortical TMS– Lab induced craving, knockout– Small clinical trials

Smoking Brainsway has unpublished pilot study,

ongoing FDA RCT

Unclear if tDCS has enough power to be clinically useful

DBS may work, no large studies underway or planned

VNS can modulate, likely too costly

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Gyral morphology differs radically, even in identical twins

Functional location varies even more, especially for complicated tasks.

50%

RestSmoking

CuesNeutral

Cues Rest

A) B)

Group AverageCraving minus neutral

Individual PeaksCraving minus neutral

What is the right task, imaging modality, for each application or disease?

• Acute Lab pain is certainly modifiable with cortical TMS• Opiate dependent, blocked with morphine• Numerous studies have found post-op TMS able to reduce post

surgical opiate use• Some evidence of effectiveness in chronic pain, fibromyalgia

• tDCS also works, perhaps 2-3 times smaller effect size. • DBS of thalamus may work, cortical stim works, • VNS can also modulate

• VNS, particularly of gastric fibers, can reduce eating • Pigs, dogs, one small human trial

• No real work with TMS or tDCS• DBS of hypothalamus