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ECE 795: Quantitative Electrophysiology Notes for Lecture #10 Wednesday, November 22, 2006

EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Page 1: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

ECE 795:

Quantitative ElectrophysiologyNotes for Lecture #10

Wednesday, November 22, 2006

Page 2: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES)

We will look at:Design issues for FESSubthreshold response to extracellular stimulationSuprathreshold response to extracellular stimulationNerve excitationRecruitment

Page 3: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Design of functional electrical stimulation:In functional electrical stimulation (FES), nerve stimulation is achieved by passing current between two or more electrodes implanted in the body.In order for this system to produce functionalnerve activation, the appropriate spatial and temporal patterns of stimulation must be determined for the desired stimulus response. This requires an understanding of both the stimulus properties and the resulting nerve response properties.

Page 4: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Design of FES (cont.):Stimulus design considerations include electrode properties such as:

number and positions of electrodes,material,size,shape, and

stimulating current properties such as:strength, andwaveform.

Page 5: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Design of FES (cont.):A crucial point in understanding FES is the difference between intracellular and extracellular stimulation.

(Rattay, Neurosci. 1999)

Page 6: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus:Consider thesource-fibergeometryshown to theright.

Page 7: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus (cont.):The resulting extracellular field is:

where I0 is the current strength, σe is the conductivity of the extracellular medium, and r is the distance from the source to an arbitrary field point.Note that the effect of the fiber on the field is typically ignored.

Page 8: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus (cont.):Reformulating Eqn. (6.25) gives:

where z now defines the axial (longitudinal) coordinate.The transmembrane current im must also equal the intrinsic ionic plus capacitive current of the membrane.

Page 9: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus (cont.):Replacing φi by vm + φe and im by iion + cm∂vm/∂t in Eqn. (7.71) gives:

At rest, vm = 0 for all z⇒ ∂2vm/∂z2 = 0 and iion = vm/rm = 0. Consequently, when the stimulus is first applied:

Page 10: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus (cont.):

Thus, the region where excitation is possible is where ∂2φe/∂z2 is positive, because this will make ∂vm/∂t initially positive.

Conversely, regions where ∂2φe/∂z2 is negative will hyperpolarize, because this will make ∂vm/∂t initially negative.

Consequently, the function ∂2φe/∂z2 has been named the activating function.

Page 11: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Subthreshold response to an external point current stimulus (cont.):

Page 12: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Suprathreshold response to an external point stimulus:A space-clamped patch of membrane subjected to an external point stimulus has a threshold potential that is relatively independent of the stimulus duration.In contrast, a fiber has higher threshold potentials for shorter stimuli, an effect that is strongest when the source is very close to the fiber and grows weaker as the source is moved away from the fiber.

Page 13: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Suprathreshold response to an external point stimulus (cont.):

Page 14: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Suprathreshold response to an external point stimulus (cont.):

Page 15: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Suprathreshold response to an external point stimulus (cont.):

Page 16: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Suprathreshold response to an external point stimulus (cont.):The effect of stimulus duration and distance from the fiber on the threshold potential results from the hyperpolarized regions that flank the depolarized region. The membrane potential decay is accelerated by the flow of current from the depolarized region into the surrounding hyperpolarized regions. As the source is moved away from the fiber, the hyperpolarized regions move away from the depolarized region, diminishing the effect.

Page 17: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation:To evaluate the pattern of nerve activation that is produced by a particular electrode configuration, we must consider:

the geometry of the electrode(s) and nerve fibers,the conductivities of the medium in which the electrode(s) and nerve fibers lie, andthe properties of the nerve fiber membrane, either subthreshold (i.e., linear) or suprathreshold (i.e., nonlinear).

Page 18: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Consider the linear-core-conductor model of a myelinated fiber being stimulated by a bipolarelectrode pair (i.e., delivering equal and opposite current).

Page 19: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):For this configuration, excitation will occur below the cathode if the stimulating current is large enough.The strength-duration behaviour can be described as:

where IR is the rheobase current and K is an experimentally-determined constant that depends on the electrode geometry, medium conductivities, etc., as well as the membrane properties.

Page 20: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):A result of this strength-duration behaviour is that charge is wasted in stimulating a nerve fiber if the duration of the pulse is much larger than the chronaxie, which is defined in this case as:

Note that we wish to minimize the total charge delivered in order to avoid electrochemical reactions at the electrode-electrolyte interface.

Page 21: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Thus, short pulse durations are highly desirable based on this criterion.

Page 22: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Example stimulus waveform shapes:

monophasic,biphasic,chopped,triphasic, and asymmetric,

and parameters:pulse amplitude,pulse width,interphase gap, andpulse rate.

(From Shepherd & Javel, Hear. Res. 1999)

Page 23: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):The injected primary current pulse is designed to achieve nerve activation.The secondary pulse in a biphasic current waveform is introduced to mitigate a build up of charge at the electrode-tissue interface.However, this secondary pulse will be hyperpolarizing, and consequently it may suppress action potential generation. Adding an inter-phase delay can avoid this problem.

Page 24: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):The effect of inter-phase delay on action potential generation is illustrated below.

Page 25: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Another important factor is the electrode-fiber geometry.Consider stimulation of the peripheral nerve via a cuff electrode as shown below.

Page 26: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Modelling cuff-electrode stimulation using the equivalent circuit illustrated below gives rise to the activation pattern shown on the next slide.

Page 27: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):

Page 28: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):Stimulation using a surface electrode produces the activation pattern shown on the next slide if the neuron is normal to the surface.

Page 29: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):

Page 30: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):In contrast, the activation pattern is quite different if the electrode is adjacent to the fiber.In this case, the flanking hyperpolarized regions may block action potential generation.

Page 31: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):

Page 32: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):When modelling the response of myelinated fibers, it may be sufficient to just included active (nonlinear) membrane properties in the node closest to the electrode.

Page 33: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerve excitation (cont.):However, if the electrode is more distant from the fiber, or close to the soma or dendrites, then more complicated excitation patterns can result.

(Rattay, IEEE Trans. Biomed. Eng. 1998)

Page 34: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Nerveexcitation(cont.):

(Rattay, IEEE Trans. Biomed. Eng. 1998)

Page 35: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment:Control of both the pulse width and the pulse ratecan be utilized to affect which fibers are recruited.

Page 36: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):In myelinated nerve, the fiber diameter d can have a strong effect on the threshold current Ith.The diameter has a direct effect through the axoplasmic resistance per unit length ri.An indirect effect of the diameter results from the fact that the internodal segment length (i.e., the distance between nodes of Ranvier) is proportional to the fiber diameter.

Page 37: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):Ith versus fiber diameter and electrode-fiber distance.

Page 38: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):Ith versus fiber diameter and pulse duration.

Page 39: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):Ith versus pulse duration for nerve and muscle.

Page 40: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):Considering the results of the simulations and experimental data shown in the previous three slides, large diameter fibers tend to be recruitedbefore small diameter fibers.However, under physiological conditions for motor units, small diameter fibers innervating slow oxidative (SO) muscle fibers tend to be recruited before larger diameter fibers innervating fast glycolytic (FG) muscle fibers.Thus, the natural order of recruitment is reversed in FES.

Page 41: EE3BB3: Cellular Bioelectricity€¦ · Notes for Lecture #10 Wednesday, November 22, 2006. 2 14. FUNDAMENTALS OF FUNCTIONAL ELECTRICAL STIMULATION (FES) We will look at: ¾Design

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Recruitment (cont.):One approach to combat this recruitment-order problem is to utilize two electrodes.The first electrode supplies a large depolarizing current that excites fibers with a large range of diameters.The second electrode supplies a small hyperpolarizing current that prevents action potential propagation on the large diameter fibersexcited by the first electrode.The hyperpolarizing pulse must be designed with a ramp that prevents anode-break excitation.