flexible, multi-scale, brain-computer interfaces for...
TRANSCRIPT
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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Courtesy of Gordon Baltuch, M.D., Ph.D., UPenn
Stacey and Litt, Nature Clinical Neurology, 2010
Antiepileptic Devices
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
Worrell et al.
Brain, 2008
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HFOs increased in SOZ vs. non-SOZ
Worrell et al. Brain, 2008
Justin Blanco
* * *
*
*
September, 2010
Stead et al., Brain, 2010
Lead to Sz
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
Flexible and Stretchable Silicon Electronics
Kim, D-H. et al. Science 320, 507-11(2008).
Fabrication Steps
Viventi, J., Kim, D-H. et al. Science Translational Medicine 2, 24ra22 (2010).
Cross-Section
Flexible, Scalable BCI for Epilepsy
Flexible, Scalable BCI for Epilepsy
Catheter Delivery
1.5 mm
0.5 mm
hole
Science Translational Medicine, March 2010
720 Channel Array on Brain
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 Unpublished.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
Improved Conformability
76 m 2.8 m
Mesh
0.3 cm
0.2 cm
Visual Cortex
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Induced Seizure Recorded
Viventi, J., Kim, D-H. et al. Unpublished.
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.
png
6. Gap Statistic
Tibshirani, R., Walther, G. & Hastie, T. Journal of the Royal Statistical Society: Series B 63, 411-423 (2001).
Cluster Homogeneity
0 ms 27 ms
Cluster Homogeneity
0 ms 22 ms
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
40 ms
2 m
V
40 ms
2 m
V
40 ms
2 m
V
40 ms
2 m
V
40 ms
2 m
V
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
