treating epilepsy via adaptive neurostimulation
DESCRIPTION
Treating Epilepsy via Adaptive Neurostimulation. Joelle Pineau, PhD School of Computer Science, McGill University Congress of the Canadian Neurological Sciences Foundation June 9, 2010. Learning objectives. Review the neurostimulation hypothesis for treating epilepsy. - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/1.jpg)
Treating Epilepsy via Adaptive Neurostimulation
Joelle Pineau, PhD
School of Computer Science, McGill University
Congress of the Canadian Neurological Sciences Foundation
June 9, 2010
![Page 2: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/2.jpg)
Adaptive Neurostimulation 2 Joelle Pineau
Learning objectives
• Review the neurostimulation hypothesis for treating epilepsy.
• Understand the basic principles of adaptive neurostimulation.
• Study a mathematical framework for optimizing the choice of neurostimulation parameters.
• Observe results from applying adaptive neurostimulation in vitro.
![Page 3: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/3.jpg)
Adaptive Neurostimulation 3 Joelle Pineau
Disclosure statement
This research was supported by the Natural Sciences and
Engineering Research Council of Canada and the Canadian
Institutes of Health Research.
This is joint work with Massimo Avoli, MD, PhD; Keith Bush, PhD;
Arthur Guez; Gabriella Panuccio, MD, PhD; and Robert Vincent.
![Page 4: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/4.jpg)
Adaptive Neurostimulation 4 Joelle Pineau
Epilepsy
• Epilepsy is a neurological disorder marked by spontaneous seizures.
– Affects ~1% of world's population.
– Up to 20-25% of those do not benefit from standard treatments (anti-convulsants, surgery).
• Causes are varied (pre-disposition, head
trauma, fever, tumor, etc.)
• What is a seizure?
– Abnormal electrical activity in the brain,
may produce physical convulsions, or
other symptoms.
www.chse.louisville.edu/graphics/epilepsy07.jpg
![Page 5: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/5.jpg)
Adaptive Neurostimulation 5 Joelle Pineau
Anatomy of a seizure (in vitro)
![Page 6: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/6.jpg)
Adaptive Neurostimulation 6 Joelle Pineau
Neurostimulation hypothesis
External perturbation of an epileptic neural system can
alter dynamics away from excitability.
![Page 7: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/7.jpg)
Adaptive Neurostimulation 7 Joelle Pineau
Deep brain stimulation (DBS)
• Implanted electrodes electrically stimulate brain tissue.
• Recent clinical trials of DBS:
– Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy (SANTÉ)
» 157 people; 17 sites in US; 2003-2008; sponsored by MedtronicNeuro
– Randomized Controlled Trial of Hippocampal Stimulation for Temporal Lobe Epilepsy (METTLE)
» 90 people; 1 site in Canada; 2008-2011; sponsored by U. of Calgary
– RNSTM System Long-Term Treatment Clinical Investigation:» 280 people; 28 sites in US; 2006-2013; sponsored by NeuroPace
» Closed-loop stimulation “detect-then-stimulate”
Many parameters to control: stimulation site,
stimulation frequency/intensity, stimulation pattern, …
www.medgadget.com
www.onemedplace.com
![Page 8: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/8.jpg)
Adaptive Neurostimulation 8 Joelle Pineau
Electrophysiology results from in vitro model
The literature repeatedly shows 1Hz, 10-200A, fixed stimulation successfully suppresses seizures in vitro. [D’Arcangelo et al., Neurob of Disease. 2005].
![Page 9: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/9.jpg)
Adaptive Neurostimulation 9 Joelle Pineau
A few interesting open questions
• What parameter settings (stimulation site, frequency,
intensity, pattern) achieve maximal suppression?
• Can we reduce the number and/or intensity of stimulations,
while maintaining suppression efficacy?
• How can we customize parameters for different subjects?
![Page 10: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/10.jpg)
Adaptive Neurostimulation 10 Joelle Pineau
Adaptive neurostimulation paradigm
Objective: create a stimulation device which is
1. Optimal: maximize seizure reduction + minimize stimulation.
2. Responsive: strategy evolves as a function of the observation.
3. Automatic: stimulation strategy learned from data.
![Page 11: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/11.jpg)
Adaptive Neurostimulation 11 Joelle Pineau
Adaptive neurostimulation example
![Page 12: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/12.jpg)
Adaptive Neurostimulation 12 Joelle Pineau
Methods: Data collection in vitro
• Electrophysiological recording in the Entorhinal Cortex (B), with stimulation at fixed frequencies in the Subiculum (A).
QuickTime™ and a decompressor
are needed to see this picture.
QuickTime™ and a decompressor
are needed to see this picture.
![Page 13: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/13.jpg)
Adaptive Neurostimulation 13 Joelle Pineau
Methods: Data collection and labeling
Experimental protocol:
• Control (min. 3 seizures)
• Periodic pacing at 0.2Hz (min. 20 minutes).
• Recovery (until interval between ictal events stabilizes).
• Etc. with 0.5Hz, 1.0Hz, 2.0Hz.
Then, manually identify:
• Seizure occurrences
• Neurostimulation parameters:
{0Hz, 0.2Hz, 0.5Hz, 1.0Hz, 2.0Hz}
QuickTime™ and a decompressor
are needed to see this picture.
![Page 14: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/14.jpg)
Adaptive Neurostimulation 14 Joelle Pineau
Methods: Signal processing
• Select decision window duration: 1 sec.
• Select observation window duration: 13 sec.
• Extract observation features using signal processing techniques:
– Range, energy, multi-scale Fourier transform
QuickTime™ and a decompressor
are needed to see this picture.
![Page 15: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/15.jpg)
Adaptive Neurostimulation 15 Joelle Pineau
Methods: Training data
• Form an input vector, xt, for each decision window, t :
xt = {zt, at, ct, zt+1}
where zt = observation features at t
at = neurostimulation parameters at t
ct = cost function at t
• The cost function depends on the occurrence of seizures and stimulation delivered:
ct = ctseizure + ct
stim
where ctseizure = {1 if seizure occurred at time t, 0 otherwise}
ctstim = {1 if stimulation occurred at time t, 0
otherwise} is a free parameter.
![Page 16: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/16.jpg)
Adaptive Neurostimulation 16 Joelle Pineau
Methods: Minimizing the cost function
• The objective is to select actions such as to minimize the expected cumulative cost:
E [ ct + ct+1 + ct+2 + … + cT | zt ]
• Use regression analysis to estimate the cost for different action choices from the training data:
Qk(zt, at) = ct + maxaA Qk-1(zt+1, a)
• Select the action which minimizes the expected cost:
at := argmaxaA Qk(zt, a)
![Page 17: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/17.jpg)
Adaptive Neurostimulation 17 Joelle Pineau
Experimental protocol for validation
1. Control period (min. 3 seizures).
2. Periodic pacing at 1.0 Hz (min. 20 minutes).
3. Recovery period.
4. Adaptive stimulation strategy (min. 20 minutes).
5. Recovery period, no stimulation.
6. Periodic pacing at effective frequency f = ns/T
where ns=# stimulations during adaptive protocol
T=duration of adaptive protocol
![Page 18: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/18.jpg)
Adaptive Neurostimulation 18 Joelle Pineau
Proportion of time spent in seizure
• Proportion of time spent in seizure, averaged over N=11 slices.
QuickTime™ and a decompressor
are needed to see this picture.
* = statistically significant at p=0.05
![Page 19: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/19.jpg)
Adaptive Neurostimulation 19 Joelle Pineau
Effective frequency of the adaptive protocol
![Page 20: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/20.jpg)
Adaptive Neurostimulation 20 Joelle Pineau
Suppression efficacy for slices with eff > 1Hz
QuickTime™ and a decompressor
are needed to see this picture.
* = statistically significant at p=0.1
*
N=11 N=4
![Page 21: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/21.jpg)
Adaptive Neurostimulation 21 Joelle Pineau
Adaptive protocol example #1
QuickTime™ and a decompressor
are needed to see this picture.
(a) Adaptive controller suppresses a seizure by increasing the frequency of stimulation.
![Page 22: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/22.jpg)
Adaptive Neurostimulation 22 Joelle Pineau
Adaptive protocol example #2
QuickTime™ and a decompressor
are needed to see this picture.
(a) Adaptive controller suppresses a seizure by increasing the frequency of stimulation.
(b) A short seizure develops, stimulation is applied to shorten its duration.
![Page 23: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/23.jpg)
Adaptive Neurostimulation 23 Joelle Pineau
Adaptive protocol example #3
QuickTime™ and a decompressor
are needed to see this picture.
(a) Adaptive controller suppresses a seizure by increasing the frequency of stimulation.
(b) A short seizure develops, stimulation is applied to shorten its duration.
(c) Adaptive controller increases frequency to suppress seizure, then decreases frequency.
![Page 24: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/24.jpg)
Adaptive Neurostimulation 24 Joelle Pineau
In vivo: Challenges
Limited slice-to-slice variation.
Short lifespan.
In vitro model has known periodic
pacing strategy.
Restricted parameter space.
Larger variance between subjects.
Longer lifetime; disease can
evolve over time.
No known open-loop strategies.
Higher-dimensional action space
(more electrodes, intensity
settings, etc.)
In vitro model In vivo model
![Page 25: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/25.jpg)
Adaptive Neurostimulation 25 Joelle Pineau
Discussion
• Animal models of epilepsy provide a rich framework for investigating adaptive neurostimulation strategies.
• Most adaptive neurostimulation approaches adopt a “detect-then-stimulate” paradigm.
• Our work leverages techniques from the control literature.
– Goal is to directly minimize a cost function.
– Explicit seizure prediction (or detection) is not required.
• Results show good suppression in vitro, in some cases using significantly less stimulation than periodic pacing.
• Preliminary evidence suggests that neurostimulation can be used to probe the excitability of the system.
![Page 26: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/26.jpg)
Adaptive Neurostimulation 26 Joelle Pineau
References
• J. Pineau, A. Guez, R. Vincent, G. Panuccio & M. Avoli, Treating epilepsy via adaptive neurostimulation: A reinforcement learning approach. Int. J. of Neural Systems. 19(4). 2009.
• M. Avoli, M. D’Antuono, J. Louvel, R. Kohling, G. Biagini, R. Pumain, G. D’Arcangelo, & V. Tancredi, Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic systems in vitro. Prog. Neurobiol. 68(3). 2002.
• G. D’Arcangelo, G. Panuccio, B. Tancredi, M. Avoli. Repetitive low-frequency stimulation reduces epileptiform synchronization in limbic neuronal networks. Neurobiology of Disease. 19(1-2). 2005.
• A. Guez, R. Vincent, M. Avoli, J. Pineau. Adaptive treatment of epilepsy via batch-mode reinforcement learning. Innovative applications of Artificial Intelligence. 2008.
![Page 27: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/27.jpg)
Adaptive Neurostimulation 27 Joelle Pineau
Contrasting approaches to adaptive neurostimulation
1. Use observation window to
detect seizures; when a
seizure is detected, start
neurostimulation.
2. Use observation window to characterize state of the system; apply neurostimulation as necessary to minimize seizure occurrence.
![Page 28: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/28.jpg)
Adaptive Neurostimulation 28 Joelle Pineau
Results: Proportion of decision windows with seizures
![Page 29: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/29.jpg)
Adaptive Neurostimulation 29 Joelle Pineau
Results: Proportion of decision windows with stimulation
![Page 30: Treating Epilepsy via Adaptive Neurostimulation](https://reader035.vdocuments.mx/reader035/viewer/2022062806/56814f59550346895dbd0828/html5/thumbnails/30.jpg)
Adaptive Neurostimulation 30 Joelle Pineau
Adaptive neurostimulation deployed in vitro