U.S. patent application number 14/440874 was filed with the patent office on 2015-10-08 for method and system for controlling electrical conditions of tissue ii.
This patent application is currently assigned to Saluda Medical Pty Ltd. The applicant listed for this patent is SALUDA MEDICAL PTY LTD. Invention is credited to Peter Scott Vallack Single.
Application Number | 20150282725 14/440874 |
Document ID | / |
Family ID | 50683823 |
Filed Date | 2015-10-08 |
United States Patent
Application |
20150282725 |
Kind Code |
A1 |
Single; Peter Scott
Vallack |
October 8, 2015 |
Method and System for Controlling Electrical Conditions of Tissue
II
Abstract
A method for controlling electrical conditions of tissue in
relation to a current stimulus. A first current produced by a first
current source is delivered to the tissue via a current injection
electrode. A second current drawn by a second current source is
extracted from the tissue via a current extraction electrode. The
second current source is matched with the first current source so
as to balance the first current and the second current. A ground
electrode which is proximal to the current injection electrode and
the current extraction electrode is grounded, to provide a ground
path for any mismatch current between the first current and second
current. A response of the tissue to the current stimulus is
measured via at least one measurement electrode.
Inventors: |
Single; Peter Scott Vallack;
(Artarmon, AU) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SALUDA MEDICAL PTY LTD |
Artarmon, |
|
AU |
|
|
Assignee: |
Saluda Medical Pty Ltd
Artarmon
AU
|
Family ID: |
50683823 |
Appl. No.: |
14/440874 |
Filed: |
November 6, 2013 |
PCT Filed: |
November 6, 2013 |
PCT NO: |
PCT/AU2013/001280 |
371 Date: |
May 5, 2015 |
Current U.S.
Class: |
600/393 |
Current CPC
Class: |
A61N 1/36125 20130101;
A61B 5/04001 20130101; A61B 5/0428 20130101; A61B 5/04004 20130101;
A61B 5/7217 20130101; A61N 1/36142 20130101 |
International
Class: |
A61B 5/04 20060101
A61B005/04 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 6, 2012 |
AU |
2012904838 |
Claims
1. A method for controlling electrical conditions of tissue in
relation to a current stimulus, the method comprising: delivering
to the tissue via a current injection electrode a first current
produced by a first current source; extracting from the tissue via
a current extraction electrode a second current drawn by a second
current source, the second current source being matched with the
first current source so as to balance the first current and the
second current; grounding a ground electrode which is proximal to
the current injection electrode and the current extraction
electrode, to provide a ground path for any mismatch current
between the first current and second current; and measuring via at
least one measurement electrode a response of the tissue to the
current stimulus.
2. The method of claim 1 wherein the ground electrode is connected
to ground throughout application of a stimulus by the first and
second current sources.
3. The method of claim 1 wherein the ground electrode is
disconnected, or floating, during some or all of the application of
the stimulus.
4. The method of claim 1 wherein the ground electrode and the
measurement electrode are located outside a dipole formed by the
current injection electrode and the current extraction
electrode.
5. The method of claim 1 wherein the ground electrode is grounded
to a distal patient ground electrode.
6. An implantable device for controlling electrical conditions of
tissue in relation to a current stimulus, the device comprising: a
plurality of electrodes including at least one nominal current
injection electrode, at least one nominal current extraction
electrode, at least one nominal ground electrode which is proximal
to the current injection electrode and the current extraction
electrode, and at least one nominal measurement electrode, the
electrodes being configured to be positioned proximal to the tissue
to make electrical contact with the tissue; a first current source
for producing a first current to be delivered to the tissue by the
current injection electrode; a second current source for producing
a second current to be extracted from the tissue via the current
extraction electrode, the second current source being matched with
the first current source so as to balance the first current and the
second current; an electrical ground for grounding the ground
electrode, to provide a ground path for any mismatch current
between the first current and second current; and measurement
circuitry for measuring via the at least one measurement electrode
a response of the tissue to the current stimulus.
7. The implantable device of claim 6 wherein the ground electrode
and the measurement electrode are located outside a dipole formed
by the current injection electrode and the current extraction
electrode.
8. The implantable device of claim 6 wherein the ground electrode
is grounded to a distal patient ground electrode.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of Australian
Provisional Patent Application No. 2012904838 filed 6 Nov. 2012,
which is incorporated herein by reference.
TECHNICAL FIELD
[0002] The present invention relates to controlling the electrical
conditions of tissue, for example for use in suppressing artefact
to enable improved measurement of a response to a stimulus, such as
measurement of a compound action potential by using one or more
electrodes implanted proximal to a neural pathway.
BACKGROUND OF THE INVENTION
[0003] Neuromodulation is used to treat a variety of disorders
including chronic pain, Parkinson's disease, and migraine. A
neuromodulation system applies an electrical pulse to tissue in
order to generate a therapeutic effect. When used to relieve
chronic pain, the electrical pulse is applied to the dorsal column
(DC) of the spinal cord or dorsal root ganglion (DRG). Such a
system typically comprises an implanted electrical pulse generator,
and a power source such as a battery that may be rechargeable by
transcutaneous inductive transfer. An electrode array is connected
to the pulse generator, and is positioned in the dorsal epidural
space above the dorsal column. An electrical pulse applied to the
dorsal column by an electrode causes the depolarisation of neurons,
and generation of propagating action potentials. The fibres being
stimulated in this way inhibit the transmission of pain from that
segment in the spinal cord to the brain.
[0004] While the clinical effect of spinal cord stimulation (SCS)
is well established, the precise mechanisms involved are poorly
understood. The DC is the target of the electrical stimulation, as
it contains the afferent A.beta. fibres of interest. A.beta. fibres
mediate sensations of touch, vibration and pressure from the skin.
The prevailing view is that SCS stimulates only a small number of
A.beta. fibres in the DC. The pain relief mechanisms of SCS are
thought to include evoked antidromic activity of A.beta. fibres
having an inhibitory effect, and evoked orthodromic activity of
A.beta. fibres playing a role in pain suppression. It is also
thought that SCS recruits A.beta. nerve fibres primarily in the DC,
with antidromic propagation of the evoked response from the DC into
the dorsal horn thought to synapse to wide dynamic range neurons in
an inhibitory manner.
[0005] Neuromodulation may also be used to stimulate efferent
fibres, for example to induce motor functions. In general, the
electrical stimulus generated in a neuromodulation system triggers
a neural action potential which then has either an inhibitory or
excitatory effect. Inhibitory effects can be used to modulate an
undesired process such as the transmission of pain, or to cause a
desired effect such as the contraction of a muscle.
[0006] The action potentials generated among a large number of
fibres sum to form a compound action potential (CAP). The CAP is
the sum of responses from a large number of single fibre action
potentials. The CAP recorded is the result of a large number of
different fibres depolarising. The propagation velocity is
determined largely by the fibre diameter and for large myelinated
fibres as found in the dorsal root entry zone (DREZ) and nearby
dorsal column the velocity can be over 60 ms.sup.-1. The CAP
generated from the firing of a group of similar fibres is measured
as a positive peak potential P1, then a negative peak N1, followed
by a second positive peak P2. This is caused by the region of
activation passing the recording electrode as the action potentials
propagate along the individual fibres.
[0007] To better understand the effects of neuromodulation and/or
other neural stimuli, it is desirable to record a CAP resulting
from the stimulus. However, this can be a difficult task as an
observed CAP signal will typically have a maximum amplitude in the
range of microvolts, whereas a stimulus applied to evoke the CAP is
typically several volts. Electrode artefact usually results from
the stimulus, and manifests as a decaying output of several
millivolts throughout the time that the CAP occurs, presenting a
significant obstacle to isolating the CAP of interest. Some
neuromodulators use monophasic pulses and have capacitors to ensure
there is no DC flow to the tissue. In such a design, current flows
through the electrodes at all times, either stimulation current or
equilibration current, hindering spinal cord potential (SCP)
measurement attempts. The capacitor recovers charge at the highest
rate immediately after the stimulus, undesirably causing greatest
artefact at the same time that the evoked response occurs.
[0008] To resolve a 10 uV SCP with 1 uV resolution in the presence
of an input 5V stimulus, for example, requires an amplifier with a
dynamic range of 134 dB, which is impractical in implant systems.
As the neural response can be contemporaneous with the stimulus
and/or the stimulus artefact, CAP measurements present a difficult
challenge of amplifier design. In practice, many non-ideal aspects
of a circuit lead to artefact, and as these mostly have a decaying
exponential appearance that can be of positive or negative
polarity, their identification and elimination can be
laborious.
[0009] A number of approaches have been proposed for recording a
CAP. King (U.S. Pat. No. 5,913,882) measures the spinal cord
potential (SCP) using electrodes which are physically spaced apart
from the stimulus site. To avoid amplifier saturation during the
stimulus artefact period, recording starts at least 1-2.5 ms after
the stimulus. At typical neural conduction velocities, this
requires that the measurement electrodes be spaced around 10 cm or
more away from the stimulus site, which is undesirable as the
measurement then necessarily occurs in a different spinal segment
and may be of reduced amplitude.
[0010] Nygard (U.S. Pat. No. 5,785,651) measures the evoked CAP
upon an auditory nerve in the cochlea, and aims to deal with
artefacts by a sequence which comprises: (1) equilibrating
electrodes by short circuiting stimulus electrodes and a sense
electrode to each other; (2) applying a stimulus via the stimulus
electrodes, with the sense electrode being open circuited from both
the stimulus electrodes and from the measurement circuitry; (3) a
delay, in which the stimulus electrodes are switched to open
circuit and the sense electrode remains open circuited; and (4)
measuring, by switching the sense electrode into the measurement
circuitry. Nygard also teaches a method of nulling the amplifier
following the stimulus. This sets a bias point for the amplifier
during the period following stimulus, when the electrode is not in
equilibrium. As the bias point is reset each cycle, it is
susceptible to noise. The Nygard measurement amplifier is a
differentiator during the nulling phase which makes it susceptible
to pickup from noise and input transients when a non-ideal
amplifier with finite gain and bandwidth is used for
implementation.
[0011] Daly (US Patent Application No. 2007/0225767) utilizes a
biphasic stimulus plus a third phase "compensatory" stimulus which
is refined via feedback to counter stimulus artefact. As for
Nygard, Daly's focus is the cochlea. Daly's measurement sequence
comprises (1) a quiescent phase where stimulus and sense electrodes
are switched to Vdd; (2) applying the stimulus and then the
compensatory phase, while the sense electrodes are open circuited
from both the stimulus electrodes and from the measurement
circuitry; (3) a load settling phase of about 1 .mu.s in which the
stimulus electrodes and sense electrodes are shorted to Vdd; and
(4) measurement, with stimulus electrodes open circuited from Vdd
and from the current source, and with sense electrodes switched to
the measurement circuitry. However a 1 .mu.s load settling period
is too short for equilibration of electrodes which typically have a
time constant of around 100 .mu.s. Further, connecting the sense
electrodes to Vdd pushes charge onto the sense electrodes,
exacerbating the very problem the circuit is designed to
address.
[0012] Evoked responses are less difficult to detect when they
appear later in time than the artefact, or when the signal-to-noise
ratio is sufficiently high. The artefact is often restricted to a
time of 1-2 ms after the stimulus and so, provided the neural
response is detected after this time window, data can be obtained.
This is the case in surgical monitoring where there are large
distances between the stimulating and recording electrodes so that
the propagation time from the stimulus site to the recording
electrodes exceeds 2 ms.
[0013] Because of the unique anatomy and tighter coupling in the
cochlea, cochlear implants use small stimulation currents relative
to the tens of mA sometimes required for SCS, and thus measured
signals in cochlear systems present a relatively lower artefact. To
characterize the responses from the dorsal columns, high
stimulation currents and close proximity between electrodes are
required. Moreover, when using closely spaced electrodes both for
stimulus and for measurement the measurement process must overcome
artefact directly, in contrast to existing "surgical monitoring"
techniques involving measurement electrode(s) which are relatively
distant from the stimulus electrode(s).
[0014] Any discussion of documents, acts, materials, devices,
articles or the like which has been included in the present
specification is solely for the purpose of providing a context for
the present invention. It is not to be taken as an admission that
any or all of these matters form part of the prior art base or were
common general knowledge in the field relevant to the present
invention as it existed before the priority date of each claim of
this application.
[0015] Throughout this specification the word "comprise", or
variations such as "comprises" or "comprising", will be understood
to imply the inclusion of a stated element, integer or step, or
group of elements, integers or steps, but not the exclusion of any
other element, integer or step, or group of elements, integers or
steps.
[0016] In this specification, a statement that an element may be
"at least one of" a list of options is to be understood that the
element may be any one of the listed options, or may be any
combination of two or more of the listed options.
SUMMARY OF THE INVENTION
[0017] According to a first aspect the present invention provides a
method for controlling electrical conditions of tissue in relation
to a current stimulus, the method comprising:
[0018] delivering to the tissue via a current injection electrode a
first current produced by a first current source;
[0019] extracting from the tissue via a current extraction
electrode a second current drawn by a second current source, the
second current source being matched with the first current source
so as to balance the first current and the second current;
[0020] grounding a ground electrode which is proximal to the
current injection electrode and the current extraction electrode,
to provide a ground path for any mismatch current between the first
current and second current; and
[0021] measuring via at least one measurement electrode a response
of the tissue to the current stimulus.
[0022] According to a second aspect the present invention provides
an implantable device for controlling electrical conditions of
tissue in relation to a current stimulus, the device
comprising:
[0023] a plurality of electrodes including at least one nominal
current injection electrode, at least one nominal current
extraction electrode, at least one nominal ground electrode which
is proximal to the current injection electrode and the current
extraction electrode, and at least one nominal measurement
electrode, the electrodes being configured to be positioned
proximal to the tissue to make electrical contact with the
tissue;
[0024] a first current source for producing a first current to be
delivered to the tissue by the current injection electrode;
[0025] a second current source for producing a second current to be
extracted from the tissue via the current extraction electrode, the
second current source being matched with the first current source
so as to balance the first current and the second current;
[0026] an electrical ground for grounding the ground electrode, to
provide a ground path for any mismatch current between the first
current and second current; and
[0027] measurement circuitry for measuring via the at least one
measurement electrode a response of the tissue to the current
stimulus.
[0028] In preferred embodiments of the invention the ground
electrode is connected to ground throughout application of a
stimulus by the first and second current sources. Alternatively, in
some embodiments of the invention the ground electrode may be
disconnected, or floating, during some or all of the application of
the stimulus.
[0029] In preferred embodiments, the ground electrode and the
measurement electrode are located outside the dipole formed by the
current injection electrode and the current extraction electrode.
In such embodiments the operation of the ground electrode acts to
spatially shield the measurement electrode from the stimulus field,
noting that the voltage at points between the poles of a dipole is
comparable to the voltage on the electrodes, whereas outside the
dipole the voltage drops with the square of distance.
[0030] Preferred embodiments of the invention may thus reduce
artefact by reducing interaction between the stimulus and the
measurement recording via a measurement amplifier input
capacitance.
[0031] Some embodiments of the invention may utilise a blanking
circuit for blanking the measurement amplifier during and/or close
in time to the application of a stimulus. However, alternative
embodiments may utilise an unblanked measurement amplifier, which
connects a measurement electrode to an analog-to-digital circuit,
significantly reducing complexity in the measurement signal
chain.
[0032] The electrical ground may be referenced to a patient ground
electrode distal from the array such as a device body electrode, or
to a device ground. Driving the ground electrode to electrical
ground will thus act to counteract any non-zero stimulus artefact
produced by mismatched currents during application of the
stimulus.
[0033] The electrodes are preferably part of a single electrode
array, and are physically substantially identical whereby any
electrode of the array may serve as any one of the nominal
electrodes at a given time. Alternatively the electrodes may be
separately formed, and not in a single array, while being
individually positioned proximal to the tissue of interest.
[0034] In preferred embodiments of the invention, the ground
electrode, current injection electrode, current extraction
electrode and measurement electrode are selected from an implanted
electrode array. The electrode array may for example comprise a
linear array of electrodes arranged in a single column along the
array. Alternatively the electrode array may comprise a two
dimensional array having two or more columns of electrodes arranged
along the array. Preferably, each electrode of the electrode array
is provided with an associated measurement amplifier, to avoid the
need to switch the sense electrode(s) to a shared measurement
amplifier, as such switching can add to measurement artefact.
Providing a dedicated measurement amplifier for each sense
electrode is further advantageous in permitting recordings to be
obtained from multiple sense electrodes simultaneously.
[0035] In the first and second aspects of the invention, the
measurement may be a single-ended measurement obtained by passing a
signal from a single sense electrode to a single-ended amplifier.
Alternatively, the measurement may be a differential measurement
obtained by passing signals from two measurement electrodes to a
differential amplifier. In some embodiments three stimulus
electrodes may be used to apply a tripolar stimulus for example by
using one current injection electrode and two current extraction
electrodes driven by respective extraction current sources which
together are balanced to the injection current source. The stimulus
may be monophasic, biphasic, or otherwise.
[0036] Embodiments of the invention may prove beneficial in
obtaining a CAP measurement which has lower dynamic range and
simpler morphology as compared to systems more susceptible to
artefact. Such embodiments of the present invention may thus reduce
the dynamic range requirements of implanted amplifiers, and may
avoid or reduce the complexity of signal processing systems for
feature extraction, simplifying and miniaturizing an implanted
integrated circuit. Such embodiments may thus be particularly
applicable for an automated implanted evoked response feedback
system for stimulus control.
[0037] According to another aspect the present invention provides a
computer program product comprising computer program code means to
make an implanted processor execute a procedure for controlling
electrical conditions of neural tissue, the computer program
product comprising computer program code means for carrying out the
method of the first aspect.
[0038] According to a further aspect the present invention provides
a computer readable storage medium, excluding signals, loaded with
computer program code means to make an implanted processor execute
a procedure for controlling electrical conditions of neural tissue,
the computer readable storage medium loaded with computer program
code means for carrying out the method of the first aspect.
[0039] The present invention recognises that when considering
spinal cord stimulation, obtaining information about the activity
within the spinal segment where stimulation is occurring is highly
desirable. Observing the activity and extent of propagation both
above (rostrally of) and below (caudally of) the level of
stimulation is also highly desirable. The present invention
recognises that in order to record the evoked activity within the
same spinal segment as the stimulus requires an evoked potential
recording system which is capable of recording an SCP within
approximately 3 cm of its source, i.e. within approximately 0.3 ms
of the stimulus, and further recognises that in order to record the
evoked activity using the same electrode array as applied the
stimulus requires an evoked potential recording system which is
capable of recording an SCP within approximately 7 cm of its
source, i.e. within approximately 0.7 ms of the stimulus.
[0040] In some embodiments the method of the present invention may
be applied to measurement of other bioelectrical signals, such as
muscle potentials. The method of the present invention may be
applicable to any measurement of any voltage within tissue during
or after stimulation, and where the stimulation may obscure the
voltage being measured. Such situations include the measurement of
evoked spinal cord potentials, potentials evoked local to an
electrode during deep brain stimulation (DBS), the measurement of
EEGs during deep brain stimulation (where the source of the
potential is distant from the stimulating electrodes), the
measurement of signals in the heart (ECGs) by a pacemaker, the
measurement of voltages in stimulated muscles (EMGs), and the
measurement of EMGs triggered by the stimulation of distant and
controlling nervous tissue.
BRIEF DESCRIPTION OF THE DRAWINGS
[0041] An example of the invention will now be described with
reference to the accompanying drawings, in which:
[0042] FIG. 1 illustrates an implantable device suitable for
implementing the present invention;
[0043] FIG. 2 illustrates currents and voltages which can
contribute to SCP measurements;
[0044] FIG. 3 illustrates the equivalent circuit of a typical
system for applying a neural stimulus and attempting to measure a
neural response;
[0045] FIG. 4 is an equivalent circuit modelling the
tissue/electrode interface and electrode loading;
[0046] FIG. 5 illustrates a circuit having the problem of
mismatched current sources;
[0047] FIG. 6 illustrates another embodiment of the present
invention;
[0048] FIGS. 7a and 7b plot the electrode voltages arising during
stimulation in the circuits of FIGS. 3 and 6 respectively, while
FIGS. 7c and 7d respectively plot the artefact on the sense
electrodes during such stimuli; and
[0049] FIG. 8a plots the measurements from an electrode array in
response to a stimulus delivered by the array to a sheep dorsal
column, while FIG. 8b is a superimposed plot of similar data,
demonstrating timing of respective signal features.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0050] FIG. 1 illustrates an implantable device 100 suitable for
implementing the present invention. Device 100 comprises an
implanted control unit 110, which controls application of a
sequence of neural stimuli. In this embodiment the unit 110 is also
configured to control a measurement process for obtaining a
measurement of a neural response evoked by a single stimulus
delivered by one or more of the electrodes 122. Device 100 further
comprises an electrode array 120 consisting of a three by eight
array of electrodes 122, each of which may be selectively used as
the stimulus electrode, sense electrode, compensation electrode or
sense electrode.
[0051] FIG. 2 shows the currents and voltages that contribute to
spinal cord potential (SCP) measurements in a typical system of the
type shown in FIG. 3. These signals include the stimulus current
202 applied by two stimulus electrodes, which is a charge-balanced
biphasic pulse to avoid net charge transfer to or from the tissue
and to provide low artefact. Alternative embodiments may instead
use three electrodes to apply a tripolar charge balanced stimulus
for example where a central electrode. In the case of spinal cord
stimulation, the stimulus currents 202 used to provide paraesthesia
and pain relief typically consist of pulses in the range of 3-30 mA
amplitude, with pulse width typically in the range of 100-400
.mu.s, or alternatively may be paraesthesia-free such as neuro or
escalator style stimuli. The stimuli can comprise monophasic or
biphasic pulses.
[0052] The stimulus 202 induces a voltage on adjacent electrodes,
referred to as stimulus crosstalk 204. Where the stimuli 202 are
SCP stimuli they typically induce a voltage 204 in the range of
about 1-5 V on a SCP sense electrode.
[0053] The stimulus 202 also induces electrode artefact. The
mechanism of artefact production can be considered as follows. The
stimulus crosstalk can be modelled as a voltage, with an equivalent
output impedance. In a human spinal cord, this impedance is
typically around 500 ohms per electrode, but will be larger or
smaller in different applications. This resistance has little
effect in the circuit, but is included for completeness. The
stimulus crosstalk drives the measurement amplifiers through the
electrode/tissue interface. This interface is shown in FIG. 4 as a
set of series capacitance/resistance pairs, modelling a component
referred to in the literature as a "Warburg element". The RC pairs
model the complex diffusion behaviour at the electrode surface, and
have time constants from micro-seconds to seconds. The cables from
the electrode to the amplifier add capacitance which loads the
electrode, along with the resistive input impedance of the
amplifier itself. Typical loading would be 200 pF of capacitance
and 1 megohms of resistance. Following this is an ideal amplifier
in this equivalent circuit of FIG. 4.
[0054] The electrode artefact is the response of the
electrode/tissue interface, when driven by the stimulus crosstalk
and loaded by the capacitance and resistance at the amplifier
input. It can be observed, either with a circuit simulator or in a
laboratory. It can also be observed that the sign of the artefact
is opposite for capacitive and resistive loading. Electrical
artefact usually also arises from the behaviour of the amplifier
circuitry in response to these particular circumstances.
[0055] It is possible to reduce artefact by reducing the loading on
the electrode, however in practical situations there are limits to
how low this capacitance can be made. Increasing the electrode
surface area also decreases artefact but again in practical
situations there will be limits to the electrode size. Artefact can
also be reduced by adding resistance or capacitance to the
amplifier input relying on the opposite sign of the artefact
produced by these terms. However, this only works to a limited
extent, and changing the size of the electrode changes the size of
the required compensation components which makes it difficult to
make a general purpose amplifier that can be connected to a range
of electrodes. One can also reduce artefact by reducing the size of
the stimulus crosstalk, and this is the aim of the embodiment of
this invention shown in FIG. 6, which relates to evoking and
measuring a neural response.
[0056] Referring again to FIGS. 2 and 3, an appropriate electrical
stimulus 202 will induce nerves to fire, and thereby produces an
evoked neural response 206. In the spinal cord, the neural response
206 can have two major components: a fast response lasting .about.2
ms and a slow response lasting .about.15 ms. The slow response only
appears at stimulation amplitudes which are larger than the minimum
stimulus required to elicit a fast response. Many therapeutic
stimuli paradigms seek to evoke fast responses only, and to avoid
evoking any slow response. Thus, the neural response of interest
for neural response measurements concludes within about 2 ms. The
amplitude of the evoked response seen by epidural electrodes is
typically no more than hundreds of microvolts, but in some clinical
situations can be only tens of microvolts.
[0057] In practical implementation a measurement amplifier used to
measure the evoked response does not have infinite bandwidth, and
will normally have infinite impulse response filter poles, and so
the stimulus crosstalk 204 will produce an output 208 during the
evoked response 206, this output being referred to as electrical
artefact.
[0058] Electrical artefact can be in the hundreds of millivolts as
compared to a SCP of interest in the tens of microvolts. Electrical
artefact can however be somewhat reduced by suitable choice of a
high-pass filter pole frequency.
[0059] The measurement amplifier output 210 will therefore contain
the sum of these various contributions 202-208. Separating the
evoked response of interest (206) from the artefacts 204 and 208 is
a significant technical challenge. For example, to resolve a 10
.mu.V SCP with 1 .mu.V resolution, and have at the input a 5V
stimulus, requires an amplifier with a dynamic range of 134 dB. As
the response can overlap the stimulus this represents a difficult
challenge of amplifier design.
[0060] FIG. 5 illustrates a problem of mismatched current sources,
and FIG. 6 illustrates an embodiment in accordance with the present
invention. In FIG. 5, a first current source injects a current
stimulus (+I) to the tissue via an injection electrode. A second
current source extracts an extraction current (-I) via an
extraction electrode. However, some slight mismatch between the
first and second current sources is inevitable, so that a mismatch
current (dI) will leak via stray impedances Z, giving rise to some
unknown mismatch voltage in the tissue, corrupting measurements of
evoked responses. Since the current into the amplifier output
exactly matches the current from the current source, one could
consider using two matched current sources. However, with non-ideal
sources the current sources do not match. We call the error in the
current match "dI". The mismatch is driven into the impedance from
bulk tissue to ground Z. This is usually large, so the electrodes
are exposed to a large voltage dI.Z. This voltage can be close to
the full supply voltage--if (say) the positive current source
outputs more current than the negative source, the tissue will be
driven positive until the positive current source saturates, and
the current between the two sources is exactly balanced.
[0061] In contrast, FIG. 6 illustrates an embodiment in accordance
with the present invention, in which an error sink electrode, or
ground electrode, is provided and is interposed between the
stimulus electrodes and the measurement electrodes. Thus, by adding
an additional electrode connected to ground, this mismatch current
has a place to go. The voltage on the bulk tissue is dI.R, the
current source mismatch multiplied by the tissue impedance R. This
will be small relative to dI.Z. This therefore reduces the
electrode crosstalk to a small value. In alternative embodiments,
the error sink electrode could be driven by "active ground"
circuitry which uses feedback to seek to drive the tissue
electrical conditions to ground. A suitable active ground circuit
concept is disclosed in Australian provisional patent application
no. 2012904836 entitled "Method and System for Controlling
Electrical Conditions of Tissue", by the present applicant.
[0062] The plots of FIG. 7 show the electrode voltages in a 100 ohm
star load at 5 mA stimulus current and 360 us interphase gap. Trace
712 is from the stimulus electrode and trace 714 is from the ground
electrode, while traces 716 and 718 are from two nominal sense
electrodes, respectively. In FIG. 7a the stimulation configuration
of FIG. 3 was used, namely a stimulating electrode was driven by a
current source and a nearby electrode was grounded to provide a
path for current flow. The biphasic stimulus evident in trace 712
was applied to a 1/10 PBS saline solution. As can be seen in traces
716 and 718 considerable crosstalk artefact arises on the sense
electrodes when using such a stimulus configuration.
[0063] In contrast to FIG. 7a, FIG. 7b shows the result when
matched current sources and a ground electrode are used, in
accordance with one embodiment of the present invention. In FIG.
7b, the same biphasic stimulus is applied via a first stimulus
electrode to give rise to trace 722 on that electrode, while the
matched negative current source gives rise to voltage 724 on an
adjacent second stimulus electrode. A third electrode near the
current sources is grounded in accordance with the present
invention (voltage trace not shown in FIG. 7b). Traces 726 and 728
were obtained from two sense electrodes, and show that the stimulus
crosstalk has been significantly reduced. These traces show that
the technique of FIG. 6 produces low artefact in traces 726 and
728.
[0064] FIGS. 7c and 7d illustrate the artefact on the same two
sense electrodes, denoted electrodes 4 (solid) and 5 (dashed),
during normal stimulation as reflected in FIG. 7a. FIG. 7d shows
the artefact on the same electrodes 4 and 5 during the stimulation
reflected by FIG. 7b. As can be seen, the artefact has been reduced
from about 450 .mu.V to about 100 .mu.V by use of the present
embodiment of the present invention.
[0065] FIG. 8a shows the evoked response in a sheep dorsal column.
In particular, FIG. 8a plots the measurements obtained
simultaneously from 22 electrodes of a 24 electrode array in
response to a stimulus delivered by two adjacent electrodes
positioned centrally in the array. As can be seen, evoked responses
propagate simultaneously both caudally and rostrally from the
central stimulus site. The current required to evoke such a
response in a sheep is much lower than in humans, and the evoked
response signals are higher, so artefact is less of a problem. In
other regards the sheep signals are similar to the human case. In
FIG. 8a the amplifiers are unblanked at approximately 0.75 msec and
the response finishes within another 0.75 ms. FIG. 8b is a
superimposed plot of similar data, demonstrating timing of
respective signal features when measuring on multiple electrodes at
increasing distance from the stimulus site. FIGS. 8a and 8b
illustrate the importance of reducing artefact during the period
immediately after stimulation.
[0066] It will be appreciated by persons skilled in the art that
numerous variations and/or modifications may be made to the
invention as shown in the specific embodiments without departing
from the spirit or scope of the invention as broadly described. For
example while application of the method to neural stimulation is
described, it is to be appreciated that the techniques described in
this patent apply in other situations involving measurement of a
voltage within tissue during or after stimulation.
[0067] The present embodiments are, therefore, to be considered in
all respects as illustrative and not restrictive.
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