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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.