Brain Stimulation for The Treatment Of Epilepsy Brian Litt, MD Associate Professor of Neurology and Bioengineering University of Pennsylvania 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
Neuro. Pace Responsive Stimulator
Stimulating Electrode, 4 contacts Electrode (4 contacts)
Anthony Murro, M. D. Medical College of Georgia
Stimulated Temporal Lobe Epileptiform Activity Stimulation Courtesy of Neuro. Pace Inc.
e. RNS Sample Data
Energy over time to Seizure Onset Seizure Energy Accumulates - 1 hour (A) - 8 hrs: bursts increase (D) Raw EEG: 15 min epoch Accumulated Energy 50 min epochs 0 hrs: Seizure (C) (B) - 2 hrs: “Chirps” start & build Raw EEG: 6 sec burst EEG: 10 sec shown Hours -6 -5 -4 -3 -2 -1 0
Gamma Precursors in Neocortical Epilepsy ~85 Hz Sz onset (in red) Worrell, et al. , Brain, in press
Interictal HFEO: Seizure Precusors? ~70 -100 Hz oscillation 50 m. V 100 ms 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 Interneurons Diversity & characteristic anatomy Images reproduced from Freund TF, Buzsaki G: Interneurons of the Hippocampus 1996, 6(4): 345 -470.
Hippocampal Neuromodulation Intrinsic and subcortical sources Neuromodulator Receptor Source Glutamate GABA Acetylcholine m. Glu. R GABAB m 1 m 2 m 3 m 4 5 HT-3 5 HT-2 5 HT-1 A a 1 a 2 b 1 D 2 H 2 Intrinsic Medial septal nucleus Diagonal band of Broca Serotonin Norepinephrine Dopamine Histamine Adenosine Somatostatin NPY CRF Median raphé nucleus Dorsal raphé nucleus Locus coeruleus Ventral tegmental area Tuberomamillary nucleus Intrinsic Hypothalamus
Where we’re going…. . n Sensor: Arrays, harmless, network, units, fields, single cell to function system MHz throughput Gigabytes storage Wireless, on net In the head “MRI-able” small Upgradable. Logic: Learns “on the fly” Long battery life
Where we’re going…. . n 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.
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