Flexible, Multi-Scale, Brain-Computer
Interfaces for Treating Epilepsy December 2, 2011
Brian Litt, MD
Associate Professor of Biology and Bioengineering
University of Pennsylvania
Philadelphia, PA
American Epilepsy Society | Annual Meeting
Disclosure
Name of Commercial
Interest
NeuroVista, Inc.
MC10
NeuroPace, Inc.
Type of Financial
Relationship
SAB, Consultant
SAB, Co-Founder (Medical Division)
Shareholder (from Licensed IP)
American Epilepsy Society | Annual Meeting
Learning Objectives
To understand:
• The need for high resolution recording and intervention in epilepsy
• Flexible, active electronic devices
• New high resolution findings in neocortical epilepsy, in-vivo
American Epilepsy Society | Annual Meeting
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What is a seizure?
Basic epileptic unit?
Topology, architecture, scale?
How to intervene?
Fundamental Questions
Multiple Approaches
Hardware
Algorithms
Human studies
Animal electrophysiology
Computational Modeling
New Devices
The International Database
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HFOs increased in SOZ vs. non-SOZ
Worrell et al. Brain, 2008
And Spatially…
•8 cm x 8 cm
•Individually wired
•Large volume increases morbidity
1 cm
12 Million Neurons 1 Electrode
1 cm
Collaborators
John A. Rogers Ph.D. Materials Science, UIUC
Cherie R. Kagan, Ph.D. ESE, UPenn
Diego Contreras M.D., Ph.D. Neuroscience, UPenn
David J. Callans, M.D. Cardiology, UPHS
Dae-Hyeong Kim, Ph.D. Materials Science, Soeul National Univ University
Jan Van der Spiegel Ph.D. ESE, UPenn
Jonathan Viventi Ph.D. ECE/Neuroscienc, NYU-Poly
Yale Cohen, Ph.D. Otorhinolaryngology, UPenn
High Density Neural Sensor
Viventi, J., Kim, D-H. et al. Unpublished.
• 360 Electrodes • 20 x 18
• 500 µm spacing
• 10 x 9mm
• 39 wires
Seizures
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Viventi, J., Kim, D-H. et al. Nature Neuroscience, 12 2011.
Spike
500 ms
2 m
V
1. Spike Detection
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25 ms
2 m
V
2. Delay Calculation
3 mV
-3 mV
0 mV
Movie of a Spike
38 ms
0 ms
19 ms
Resulting Delay Map
Automated Analysis Method II 4. PCA
5. Clustering
J.A. Blanco, M. Stead, A. Krieger, J. Viventi et al. Journal of neurophysiology 2900-2912 (2010).
3. Zero-Mean RMS
1.8 mV
0.4 mV
1.1 mV
http://www.cs.cornell.edu/courses/cs322/2008sp/images/thumb_PCA.
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6. Gap Statistic
Tibshirani, R., Walther, G. & Hastie, T. Journal of the Royal Statistical Society: Series B 63, 411-423 (2001).
0 ms 24 ms
Plane
Wave
Clockwise
Spiral
0 ms 90 ms
Plane
Wave
0 ms 38 ms
Counter
Clockwise
Spiral
0 ms 165 ms
Plane
Wave
0 ms 39 ms
Plane
Wave
0 ms 38 ms
Waves within a seizure
500 ms
2 m
V
Viventi, J., Kim, D-H. et al. Nature Neuroscience, 12 2011.
Spike Clusters
0 ms 29 ms
0 ms 38 ms
0 ms 39 ms
0 ms 24 ms
0 ms 38 ms
40 ms
2 m
V
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0 ms 21 ms
Spike Patterns
•Cluster relationship to:
–Seizure initiation
–Seizure propagation
–Seizure termination
•Does this inform therapy?
–New electrode designs with multiplexed stimulation
–Closed-loop, wave microstimulation
Support
NINDS (R01-NS041811-04, RO1-NS48598-01,
U24NS063930-01A1)
CURE
The Dr. Michel and Mrs. Anna Mirowski Discovery Fund