Bidirectional electrical interfacewith neurones: a proof ...leti.congres-scientifique.com/annualreview2009/AnnualReview/AR09... · 1 2007 Annual review 2009 R. Guillemaud 23/06/2009

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Annual review 2009 R. Guillemaud 23/06/2009

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is prohibited without the prior written consent of CEA

Bidirectional electrical

interface with neurones:

a proof of concept of closed-loop

from recording to stimulation

RRRRéééégis Guillemaudgis Guillemaudgis Guillemaudgis Guillemaud

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Outline

Introduction : challenges for brain stimulation

BioMEA development from LETI

Proof of concept for closed-loop stimulation on rat model

Conclusion

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Heart electrical wave management

External recording : ECG

Implanted stimulation : pace-maker

Stimulation

With a few electrodes

Recording

Closed-loopstimulation basedon heart model

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Brain electrical wave management

External recording : EEG

Implanted stimulation :

.

http://www.cerebromente.org.br/n03/tecnologia/eeg.htm http://neurocog.psy.tufts.edu/courses/images/eeg_tracing.htm

Stimulation


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Implantable devices for neurostimulation

Deep Brain Stimulation : Parkinson disease (Pr A.L. Benabid)

Vagus Nerve Stimulation : epilepsy, depression

Pain stimulation on spinal cord

Cochlear implant

Medtronic

Boston Scientific

Cyberonics

MXM/Neurelec

Stimulation of very large neural structureswith a limited number of macro electrodes

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Brain electrical wave management

External recording : EEG

Implanted stimulation :

No recording, no closed-loop, limited brain model

http://www.cerebromente.org.br/n03/tecnologia/eeg.htm http://neurocog.psy.tufts.edu/courses/images/eeg_tracing.htm

Stimulation


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New challenges for neurostimulation

Technical challenges

Neurosciences challenges

stimu lation

Implantable electronics

InnovationInnovation : implantable recording

Record

RF

Applications :Applications :• Transmission RF : diagnosis, BCI• Closed loop : epilepsy, Parkinson, …

2 functions :

1. RF transmission RF of signal

2. Closed loop for stimulation

Need for development of brain model for neurostimulation

- Which signal must be recorded ?

- Localization of stimulation, stimulation pattern ?

Action Potentialone neurone

Local Field Potential(LFP) network activity)

Brain oscillationAlpha, Beta, Gamma …

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Outline


BioMEA development from LETI Proof of concept for closed-loop stimulation on

rat model

Conclusion

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In vitro studies with Micro-Electrode Array

Extracellular neuronal bioeletrical activity recording with MEA

Microelectrode Array (MEA)

Ayanda MEAµ-electrode 10-100 µm

Ionic and capacitive currents through the

membrane (Im) Biopotential

Microelectrodes

Im

+

Reference-

Action Potentialone neurone

Local Field Potential(LFP) network activity)

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Objectives of the NEUROCOM project

BioMEABioMEA TMTM systemsystem

Partners of the Neurocom project :

Funded by ANR

New tool for in vitro neurosciences

Needs for : High number of electrodes Better spatial resolution Recording & Stimulation capabilities on each electrode

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ASIC AGNES : Asic for General Neurons Electrical Study

11.2 mm

Voltage MeasurementVariable-gain: 1, 10, 75, or 750Low frequency cut-off : 0.1 Hz (cut the DC baseline)High frequency cut-off : 3.5 kHz (anti-aliasing filter)Input referred noise : 3.3 µVRMSInput impedance > 1012 Ω

Current StimulationRange +/- 400 µA max, time resolution < 1µsEight voltage-controlled current patterns available for each channel at any time

ASIC general characteristics• 64 measurement channels • 64 current stimulation channels with a choice of 8 voltage controlled patterns• Analog sampled output with a snapshot style sample & hold• Maximum Sampling Frequency: 50 kHz/channel• Total layout area = 26.5 mm2 (2.4 mm*11.2 mm)• Power supply : VSS / VDD=VSS+5V (floating)• Max power consumption : 125 mW• CMOS 0.35 µm

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BioMEA System set-up

ASIC 64ASIC 64

ASIC 64 ASIC 64

User interface

Recording and Stimulation Electronic

Control

ASIC 64

BioMEA 256256 Channels (4 ASICs) – High density MEA 256

BioMEA 64 64 Channels – MEA 60

High density MEAMEA 60 (MCS compatible)

Or

Innovations :

• MEA : (ESIEE) 3-D tips, 256 channels

• Recording & stimulation on each electrode

• 64-channel ASIC : Electronicintegration of the frontendstage (amplifier, stimulation, multiplexing)

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BioMEA : Results from LNR (CNRS Bordeaux)

Model for study from B. Yvert : Spontaneous neurone activity of spinal cord of mouse embryo

2D neurone activity mapping

Recording and stimulation of specific zones

64 élec. 256 élec.

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Outline


BioMEA development from LETI

Proof of concept for closed-loop stimulation on rat model

Conclusion

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In vivo test plateform with BioMEA

Rat withimplantedelectrodes

Experimental set-up

MatLabInterface

on PC

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Epileptic model : GAERS rat

Team

Epilepsy seizure recordedon GAERS rat :

Local Field Potential signals

• GIN - INSERM U 836 Equipe : Dynamique des Réseaux Synchrones épileptiques : A. Depaulis, C. Deransart, S. Saillet, A. Asfour, O. David,

recording


CXS1

Striatum

Thalamus

Temps [sec]

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Proof of concept : on-line closed loop recording/stimulationto stop epilepsy seizure


Experimental set-up Team

Epilepsy seizure recordingon GAERS rat :

Local Field Potential signals

• GIN - INSERM U 836 Equipe : Dynamique des Réseaux Synchrones épileptiques : A. Depaulis, C. Deransart, S. Saillet, A. Asfour, O. David,

0 .0 0 1 0 0

0 .0 0 0 7 5

0 .0 0 0 5 0

0 .0 0 0 2 5

0 .0 0 0 0 0

-0 .0 0 0 2 5

-0 .0 0 0 5 0

-0 .0 0 0 7 5

Vo

lts

E2

(ch

an

3

0 .0 0 1 0

0 .0 0 0 5

0 .0 0 0 0

-0 .0 0 0 5

-0 .0 0 1 0

Vo

lts

E1

(ch

an

2

0 .0 0 0 5

0 .0 0 0 0

-0 .0 0 0 5

-0 .0 0 1 0

-0 .0 0 1 5

Vo

lts

E0

(ch

an

1

1 4 5 1 4 6 1 4 7 1 4 8 1 4 9 1 5 0 1 5 1 1 5 2 1 5 3 1 5 4 1 5 5 1 5 6 1 5 7 1 5 8 1 5 9 1 6 0 1 6 1 1 6 2 1 6 3

Current bipolar stimulation stop epilepsy seizure

Matlab : on-line epilepsy

seizure detection

on-line closed loop recording/stimulation

CXS1

Striatum

Thalamus

Temps [sec]

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Conclusion

We have developped the system BioMEAto record and stimulate neurone networks

in vitro and in vivo.This system is becoming a product for Neurosciences

This is a tool to address new challenges of neurostimulations : recording and closed-loopstimulation .

We are working closely with clinical teams to address challenges of brain model and knowledge : ex proof of concept on rat model for epilepsy seizure management with closed-loop stimulation.

In parallel we are working on next generation of low power ASIC for recording and signal processing, towards brain implant.

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145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163

BioLogic

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Acknowledgments

LETI DTBS :

A. Bourgerette, G. Charvet, S. Gharbi, J.F. Bêche, C. Moulin, R. Escola, P. Pham, A. Defontaine, T. Levi S. Bonnet, F. Sauter, O. Bibari, P. Caillat, ,

DCIS : O. Billoint, JP Rostaing, C. Condemine

CNIC : ESIEE, MEMSCAP B. Yvert, P. Meyrand L. Rousseau,S. Spirkovitch

Biologic : F. Goy, T. Kaufman

GIN A. Dépaulis, O. David, S. Saillet

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Innovation

for industry

Documents

Bidirectional electrical interfacewith neurones: a proof ...leti.congres-scientifique.com/annualreview2009/AnnualReview/AR09... · 1 2007 Annual review 2009 R. Guillemaud 23/06/2009