Brain Stimulation for The Treatment Of Epilepsy

Associate Professor of Neurology and BioengineeringUniversity of Pennsylvania

Brian Litt, MD

Disclosure

Why devices to treat epilepsy ?

60 million people

No Effective Rx in 25%

Entree: intelligent BCI

treat disease

Other Applications

Movement Disorders

Schizophrenia

Depression

Stroke, TBI

NeuroPace Responsive Stimulator

Stimulating Electrode, 4 contactsElectrode (4 contacts)

Anthony Murro, M.D.Medical College of Georgia

Stimulated Temporal Lobe Epileptiform Activity

Stimulation

Courtesy of NeuroPace Inc.

eRNS Sample Data

Seizure

-5 -4 -3

-2 0-1-6Hours

0 hrs: Seizure

- 2 hrs: “Chirps” start & build

Accumulated Energy 50 min epochs

Raw EEG: 6 sec burst

Energy Accumulates

- 1 hour

EEG: 10 sec shown

- 8 hrs: bursts increase

Raw EEG: 15 min epoch

Energy over time to Seizure Onset

(A)

(B)(C)

(D)

Gamma Precursors in Neocortical Epilepsy

~85 Hz

Sz onset (in red)

Worrell, et al., Brain, in press

50 V

100 ms

~70-100 Hz oscillation

Interictal HFEO: Seizure Precusors?

Worrell et al., 2004

Ictal Recording/ Mapping Defining the Network

Dysplasia (stealth)

Ictal onset zone

Rapid Sz spread

Epileptogenic Zone

Brocca’s area

HFEOs

Hippocampal InterneuronsDiversity & characteristic anatomy

Images reproduced from Freund TF, Buzsaki G: Interneurons of the Hippocampus. Hippocampus 1996, 6(4):345-470.

Hippocampal NeuromodulationIntrinsic and subcortical sources

Neuromodulator ReceptorSourceGlutamate mGluR IntrinsicGABA GABAB IntrinsicAcetylcholine m1 Medial septal nucleus

m2 Diagonal band of Brocam3m4

Serotonin 5HT-3 Median raphé nucleus5HT-2 Dorsal raphé nucleus5HT-1A

Norepinephrine 1 Locus coeruleus2

1

Dopamine D1 Ventral tegmental area

D2Histamine H2Tuberomamillary nucleusAdenosine IntrinsicSomatostatin IntrinsicNPY IntrinsicCRF Hypothalamus

Where we’re going….. Sensor: Arrays, harmless, network, units, fields,

single cell to function system

MHz throughput

Gigabytes storage

Wireless, on net

In the head

“MRI-able” small

UpgradableLogic: Learns “on the fly”

Long battery life

Where we’re going…..

Logic: Learns “on the fly”

Anticipates activity (AI)

Rapid processing and response

Stimulation: Multiplexed, microsecond resolution

Neuroscience: neuro-encoding, decoding

Bio

Brian Litt received the A.B. degree in engineering and applied science from Harvard University in 1982 and the M.D. degree from Johns Hopkins University in 1986. Residency in Neurology, Johns Hopkins University, 1988–1991. Neurology Faculty, Johns Hopkins Hospital, 1991–1996. Neurology/Biomedical Engineering Faculty, Emory University/Georgia Institute of Technology 1997–1999. Dr. Litt is an Associate Professor of Neurology; Associate Professor of Bioengineering, and Director, EEG Laboratory at the Hospital of the University of Pennsylvania. His scientific research is focused on his clinical work as a Neurologist specializing in the care and treatment of individuals with epilepsy. It encompasses a number of related projects: 1) automated implantable devices for the treatment of epilepsy, 2) seizure prediction: developing an engineering model of how seizures are generated and spread in human epilepsy, 3) localization of seizures in extratemporal epilepsy, 5) Translation of computational neuroscience into clinical application, and 4) minimally invasive tools for acquisition and display of high fidelity electrophysiologic recording.