Developing New Drugs for Intractable Epilepsy and for Preventing Epilepsy

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Brain Stimulation for The Treatment Of Epilepsy
Brian Litt, MD
Associate Professor of Neurology and
Bioengineering University of Pennsylvania
Disclosure
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Why devices to treat epilepsy ?

• 60 million people
• No Effective Rx in 25
• Entree intelligent BCI
• treat disease

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Other Applications

• Movement Disorders
• Schizophrenia
• Depression
• Stroke, TBI

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NeuroPace Responsive Stimulator
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Electrode (4 contacts)
Stimulating Electrode, 4 contacts
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Anthony Murro, M.D. Medical College of Georgia
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Stimulated Temporal Lobe Epileptiform Activity
Stimulation
Courtesy of NeuroPace Inc.
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eRNS Sample Data
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Energy over time to Seizure Onset
Seizure
Energy Accumulates
(A)
- 1 hour
- 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
-5
-4
-3
-2
0
-1
-6
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Gamma Precursors in Neocortical Epilepsy
85 Hz
Sz onset (in red)
Worrell, et al., Brain, in press
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Interictal HFEO Seizure Precusors?
Worrell et al., 2004
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Ictal Recording/ Mapping
Defining the Network
Dysplasia (stealth)
Ictal onset zone
Rapid Sz spread
Epileptogenic Zone
Broccas area
HFEOs
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Hippocampal InterneuronsDiversity
characteristic anatomy
Images reproduced from Freund TF, Buzsaki G
Interneurons of the Hippocampus. Hippocampus
1996, 6(4)345-470.
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Hippocampal NeuromodulationIntrinsic and
subcortical sources
Neuromodulator Receptor Source Glutamate mGluR In
trinsic GABA GABAB Intrinsic Acetylcholine m1 Med
ial septal nucleus m2 Diagonal band of
Broca m3 m4 Serotonin 5HT-3 Median raphé
nucleus 5HT-2 Dorsal raphé nucleus 5HT-1A Nore
pinephrine a1 Locus coeruleus a2 b1 Dopamine
D1 Ventral tegmental area D2 Histamine
H2 Tuberomamillary nucleus Adenosine Intrinsic
Somatostatin Intrinsic NPY Intrinsic CRF H
ypothalamus
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Where were 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

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Where were going..

• Logic Learns on the fly
• Anticipates activity (AI)
• Rapid processing and response
• Stimulation Multiplexed, microsecond resolution
• Neuroscience neuro-encoding, decoding

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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, 19881991.
  Neurology Faculty, Johns Hopkins Hospital,
  19911996. Neurology/Biomedical Engineering
  Faculty, Emory University/Georgia Institute of
  Technology 19971999. 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.