2. Brain Stimulation for The Treatment Of Epilepsy Associate Professor of Neurology and Bioengineering University of Pennsylvania Brian Litt, MD Disclosure

3. Why devices to treat epilepsy ?  60 million people  No Effective Rx in 25%  Entree: intelligent BCI treat disease

4. Other Applications  Movement Disorders  Schizophrenia  Depression  Stroke, TBI

7. NeuroPace Responsive Stimulator

8. Stimulating Electrode, 4 contacts Electrode (4 contacts )

9. Anthony Murro, M.D. Medical College of Georgia

10. Stimulated Temporal Lobe Epileptiform Activity Stimulation Courtesy of NeuroPace Inc.

11. eRNS Sample Data

12. Seizure -5-4-3-20 -6 Hours 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)

13. Gamma Precursors in Neocortical Epilepsy ~85 Hz Sz onset (in red) Worrell, et al., Brain, in press

14. 50  V 100 ms ~70-100 Hz oscillation Interictal HFEO: Seizure Precusors? Worrell et al., 2004

15. Ictal Recording/ Mapping Defining the Network Dysplasia (stealth) Ictal onset zone Rapid Sz spread Epileptogenic Zone Brocca’s area HFEOs

16. Hippocampal Interneurons Diversity & characteristic anatomy Images reproduced from Freund TF, Buzsaki G: Interneurons of the Hippocampus. Hippocampus 1996, 6(4):345-470.

18. Hippocampal Neuromodulation Intrinsic and subcortical sources NeuromodulatorReceptorSource GlutamatemGluRIntrinsic GABAGABA B Intrinsic Acetylcholinem1Medial septal nucleus m2Diagonal band of Broca m3 m4 Serotonin5HT-3Median raphé nucleus 5HT-2Dorsal raphé nucleus 5HT-1A Norepinephrine  1 Locus coeruleus  2  1 Dopamine D1Ventral tegmental area D2 Histamine H2Tuberomamillary nucleus AdenosineIntrinsic SomatostatinIntrinsic NPYIntrinsic CRFHypothalamus

20. 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

21. Where we’re going….. Logic: Learns “on the fly” Anticipates activity (AI) Rapid processing and response  Stimulation: Multiplexed, microsecond resolution  Neuroscience: neuro-encoding, decoding

23. 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.