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