Biophysics of Neural Stimulation electrical stimulation ... · Biophysics of Neural Stimulation and...

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Biophysics of Neural Stimulation and Recording Warren M. Grill Department of Biomedical Engineering Duke University Durham NC USA [email protected] electrical stimulation: introduce information into the nervous system exert external control (e.g., muscle contraction) restoration of function = neural prosthesis electrical recording: extract information from the nervous system determine internal state provides potential command or feedback signal © 2006 Warren M. Grill Information Exchange with the Nervous System Information Representation within the Nervous System communication through rate and pattern of impulses, called action potentials © 2006 Warren M. Grill © 2006 Warren M. Grill Information Exchange at Multiple Levels . . . Soma (cell body) Dendrites (input) Axon (output) ~human hair NEURONS: the cells of the nervous system © 2006 Warren M. Grill “recent discovery of electricity and other kindred mysteries of Nature seemed to open paths into the region of miracle” Nathaniel Hawthorne The Birthmark No… fundamentals are well understood, can, to some extent be controlled, and have important implications for therapies © 2006 Warren M. Grill

Transcript of Biophysics of Neural Stimulation electrical stimulation ... · Biophysics of Neural Stimulation and...

Biophysics ofNeural Stimulation

and Recording

Warren M. Grill

Department of Biomedical EngineeringDuke University

Durham NC USA

[email protected]

electrical stimulation:introduce information into the nervous systemexert external control (e.g., muscle contraction)restoration of function = neural prosthesis

electrical recording:extract information from the nervous systemdetermine internal stateprovides potential command or feedback signal

© 2006 Warren M. Grill

Information Exchange with the Nervous System

Information Representation within the Nervous System

communication through rate and pattern of impulses, called action potentials

© 2006 Warren M. Grill © 2006 Warren M. Grill

Information Exchange at Multiple Levels

. . .

Soma (cell body)

Dendrites (input)

Axon (output)

~human hair

NEURONS: the cells of the nervous system

© 2006 Warren M. Grill

“recent discovery of electricity and other kindred mysteriesof Nature seemed to open paths into the region of miracle”

Nathaniel Hawthorne The Birthmark

No… fundamentals are well understood, can, to some extentbe controlled, and have important implications for therapies

© 2006 Warren M. Grill

electrical stimulation:introduce information into the nervous systemexert external control (e.g., muscle contraction)restoration of function = neural prosthesis

© 2006 Warren M. Grill

Information Exchange with the Nervous System

electrical recording:extract information from the nervous systemdetermine internal stateprovides potential command or feedback signal

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

Fundamental Principal

© 2006 Warren M. Grill

neurotransmitterrelease

Fundamental Principal

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

© 2006 Warren M. Grill © 2006 Warren M. Grill

neurotransmitterrelease

Fundamental Principal

bindingpost-synaptic action(e.g., muscle contraction)

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

Response to Electrical Stimulation is the Same

© 2006 Warren M. Grill

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

neurotransmitterrelease

Response to Electrical Stimulation is the Same

© 2006 Warren M. Grill

nerve terminal(presynaptic)

nerve cell or muscle(postynaptic)

neurotransmitterrelease

Response to Electrical Stimulation is the Same

bindingpost-synaptic action (e.g., muscle contraction)

© 2006 Warren M. Grill © 2006 Warren M. Grill

Peripheral Nerve Stimulation

Vagus Nerve Stimulation:EpilepsyDepression Pudendal Nerve Stimulation:

Incontinence

Pudendal Nerve

BION

Grill et al. (2002)

© 2006 Warren M. Grill

Peripheral Nerve Stimulation

50 µm

Nerves are bundlesof axons

How do applied currents excite nerves ?

© 2006 Warren M. Grill

Structure of Individual Myelinated Axons

1 µm© 2006 Warren M. Grill

Molecular Structure of Myelinated Axons

Channels (pores) that pass specfic (K+, Na+) ions© 2006 Warren M. Grill

t=0

t=1 ms

t=2 ms

t=4 ms

0 5 10 15

time (ms)

OUT

Ionic current

IN

Sodium CurrentPotassium Current

Na+

K+

Na+

outside

inside

K+

© 2006 Warren M. Grill

0.01

0.1

1

10

100

0 1 2 3 4 5

Point SourceCylinder (DBS)Disk

Distance (mm)

Generation of Voltages in Tissue (~v=iR)

Volta

ge (V

)

© 2006 Warren M. Grill

50 mV1 ms

Istim<threshold

Istim>threshold

20 mV2 ms

Artificial Generation of Action Potentials

© 2006 Warren M. Grill

Properties of Peripheral Nerve Stimulation

• effect of nerve fiber diameter

• effect of electrode to fiber distance

© 2006 Warren M. Grill

Small Diameter Fibers

Large Diameter Fibers

Transmem

brane Potential

Stimulation of Peripheral Axons:Current-Diameter Relationship

© 2006 Warren M. Grill

Distant Fibers

Close Fibers

Transmem

brane Potential

Stimulation of Peripheral Axons:Current-Distance Relationship

© 2006 Warren M. Grill

Stimulation of Peripheral Axons:Origin of Sigmoidal Input-Output Curve

© 2006 Warren M. Grill

Stimulation of Muscles:

Functional Neuromuscular Stimulation

Retraining in Stroke

Retraining in SCI

© 2006 Warren M. Grill

STIM

MeasureForce

Stim -> Force = F

Apply curare - OR - Botox

Stim -> Force = F’

F’/F = 0.04

Crago et al. (1974)

Muscle Stimulation:What is stimulated by Muscle-Based Electrodes?

© 2006 Warren M. Grill

Ca++

acetylcholine release

neuromuscular junction

nerve terminal(presynaptic)

muscle fiber(postynaptic)

acetylcholine binding

acetylcholine bindingNa+

muscle contraction

NeuromuscularTransmission

© 2006 Warren M. Grill

Ca++

curare

NO acetylcholine binding

NO muscle contraction

BlockingNeuromuscularTransmission

Competitive antagonist

© 2006 Warren M. Grill

Stim -> Force = F

Apply curare - OR - botox

Stim -> Force = F’

F’/F = 0.04

Crago et al. (1974)

Conclude that nerve is stimulated, not muscle

Therefore, all principles of nerve stimulation translate to muscle “stimulation”

STIM

MeasureForce

Muscle Stimulation:What is stimulated by Muscle-Based Electrodes?

© 2006 Warren M. Grill

© 2006 Warren M. Grill

Applications of Central Stimulation

Deep Brain Stimulation Movement Disorders

• Parkinson’s Disease• Essential Tremor• Dystonia

Epilepsy (AN Trial) Depression Pain Obsessive Compulsive Disorder

from Nature Neuroscience

Epidural Cortical Stimulation Parkinson’s Disease Epilepsy Stroke Rehabilitation Pain

© 2006 Warren M. Grill

Epidural Spinal Cord Stimulation Pain

from Technology Review

Electrodes are placed in heterogeneouspopulations of neural elements

(spaghetti and meatballs)

Multiple elements can be activated

Results can be substantially more complex

Brain (CNS) Stimulation:

© 2006 Warren M. Grill Dostrovsky et al. (2000)

Electrode-to-Neuron Distance (mm)

2.0

1.5

1.0

0.5

00 0.5 1.0 1.5 2.0

Presynaptic Terminal

McIntyre and Grill, unpublished

Stim

ulus

Am

plitu

de (V

) Neuron

Example: “Indirect” Effects of Stimulation

Direct

© 2006 Warren M. Grill

Inhibition of Ongoing Neuronal Activity

electrical stimulation:introduce information into the nervous systemexert external control (e.g., muscle contraction)restoration of function = neural prosthesis

© 2006 Warren M. Grill

Information Exchange with the Nervous System

electrical recording:extract information from the nervous systemdetermine internal stateprovides potential command or feedback signal

© 2006 Warren M. Grill

Information Exchange at Multiple Levels

© 2006 Warren M. Grill

Transmembrane Currents are Source of Recorded Voltage

2.0 nA0.2 ms

2.0 µV0.2 ms

Electromyogram

- electrical signal in contracting skeletal muscle- 100µV - 10 mV- 10 Hz - 1 kHz

- recorded with surface or implanted electrodes

- multiple channels for control© 2006 Warren M. Grill

Electroneurogram- aggregate electrical activity in peripheral nerve- 0.1 µV - 5 µV (very low SNR)- 500 Hz - 5 kHz- recorded with implanted electrodes

60

0

cmH20

10

0

-10

µV

1.6

1.0

µV

time (min)

bladder pressure

pudendal electroneurogram

rectified, integrated neurogram

0 1 2 3 4 5 6

© 2006 Warren M. Grill

10-100µV

© 2006 Warren M. Grill

Multiple Approaches to Direct Brain Interfaces

Wolpaw et al. 2005

Electroencephalogram

- aggregate electrical activity of populations of neurons- 10-100µV- recorded with surface (or epidural) electrodes

© 2006 Warren M. Grill

• can be voluntarily controlled

Single Neuron Recording

© 2006 Warren M. Grill

Data from Drake et al. 1988 and Cham et al. 2005

© 2006 Warren M. Grill

Requires Close Proximity to Neurons

Vetter et al. 2004

© 2006 Warren M. Grill

Vetter et al. 2004

Suner et al. 2005

Long-term Recordings of Multiple Single-Units

Num

ber o

f Ele

ctro

des

with

Goo

d or

Fai

r Sig

nals

Wolpaw et al. 2000

© 2006 Warren M. Grill

}(Wolpaw et al., 2002)EEG

}(Taylor et al., 2003)multiple single units

Information Requirements vs. Approximate Throughput

Fundamental Principals of Stimulation and Recording are Well Understood

“recent discovery of electricity and other kindred mysteriesof Nature seemed to open paths into the region of miracle”

Nathaniel Hawthorne The Birthmark

Reliable and Stable Long-Term Interface RemainsA Challenge

© 2006 Warren M. Grill

Biophysics ofNeural Stimulation

and Recording

Warren M. Grill

Department of Biomedical EngineeringDuke University

Durham NC USA

[email protected]