U.S. patent application number 17/234678 was filed with the patent office on 2021-10-07 for neural stimulation dosing.
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 John Louis Parker.
Application Number | 20210308449 17/234678 |
Document ID | / |
Family ID | 1000005653099 |
Filed Date | 2021-10-07 |
United States Patent
Application |
20210308449 |
Kind Code |
A1 |
Parker; John Louis |
October 7, 2021 |
Neural Stimulation Dosing
Abstract
Applying therapeutic neural stimuli involves monitoring for at
least one of sensory input and movement of a user. In response to
detection of sensory input or user movement, an increased stimulus
dosage is delivered within a period of time corresponding to a
duration of time for which the detected sensory input or user
movement gives rise to masking, the increased stimulus dosage being
configured to give rise to increased neural recruitment.
Inventors: |
Parker; John Louis;
(Artarmon, AU) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Saluda Medical Pty Ltd |
Artarmon |
|
AU |
|
|
Assignee: |
Saluda Medical Pty Ltd
Artarmon
AU
|
Family ID: |
1000005653099 |
Appl. No.: |
17/234678 |
Filed: |
April 19, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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16823296 |
Mar 18, 2020 |
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17234678 |
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15327981 |
Jan 20, 2017 |
10632307 |
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PCT/AU2015/050422 |
Jul 27, 2015 |
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16823296 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/36171 20130101;
A61N 1/36071 20130101; A61N 1/36185 20130101; A61N 1/36178
20130101; A61N 1/36175 20130101; A61N 1/37247 20130101; A61N 1/0551
20130101; A61N 1/36021 20130101; A61N 1/06 20130101; A61N 1/3605
20130101; A61N 1/36146 20130101; A61N 1/05 20130101 |
International
Class: |
A61N 1/05 20060101
A61N001/05; A61N 1/36 20060101 A61N001/36; A61N 1/06 20060101
A61N001/06; A61N 1/372 20060101 A61N001/372 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 25, 2014 |
AU |
2014902897 |
Mar 13, 2015 |
AU |
2015900912 |
Claims
1. A method of applying therapeutic neural stimuli, the method
comprising: monitoring for at least one of sensory input and
movement of a user; and in response to detection of at least one of
sensory input and a user movement, delivering an increased stimulus
dosage within a period of time corresponding to a duration of time
for which the detected sensory input or user movement gives rise to
masking, the increased stimulus dosage being configured to give
rise to increased neural recruitment.
2. The method of claim 1, wherein the increased stimulus dosage is
effected by increasing one or more of the stimulus amplitude, the
stimulus pulse width and/or the stimulus frequency.
3. The method of claim 2, wherein the increased stimulus dosage
comprises a burst of high frequency stimuli.
4. The method of claim 1 wherein at times when neither sensory
input nor movement is detected stimuli are delivered at a reduced
dosage.
5. The method of claim 1 wherein at times when neither sensory
input nor movement is detected no stimuli are delivered.
6. The method of claim 1 further comprising monitoring a cumulative
stimulus dosage delivered to the user, and using the cumulative
stimulus dosage as a basis to define a required stimulus regime
either during or between movements in order to seek to deliver a
desired total stimulus dosage.
7. The method of claim 1 wherein at least one of sensory input and
movement of the user is detected by measuring neural activity upon
the neural pathway.
8. The method of claim 7 wherein the measured neural activity
comprises evoked neural responses resulting from electrical stimuli
applied to the neural pathway.
9. The method of claim 8 wherein movement is detected when a change
is detected in the neural response evoked from a given
stimulus.
10. The method of claim 7 wherein the measured neural activity
comprises non-evoked neural activity.
11. The method of claim 1 wherein movement of the user is detected
by an accelerometer.
12. The method of claim 1 wherein the period of time within which
the increased stimulus dosage is delivered is a predefined
approximation of the duration of a typical human movement.
13. The method of claim 1 wherein the period of time for which the
increased stimulus dosage is delivered is adaptively determined by
performing the further step of detecting a cessation of sensory
input or movement by the user, and in turn ceasing the delivery of
the increased stimulus dosage.
14. The method of claim 1 wherein the increased stimulus dosage is
delivered at select moments within the period of time.
15. A device for applying therapeutic neural stimuli, the device
comprising: at least one electrode configured to be positioned
alongside a neural pathway of a user; and a control unit configured
to monitor for at least one of sensory input and movement of the
user, and configured to deliver an increased stimulus dosage via
the at least one electrode within a period of time corresponding to
a duration of time for which the detected sensory input or user
movement gives rise to masking, the increased stimulus dosage being
configured to give rise to increased neural recruitment.
16. A method for effecting a neural blockade, the method
comprising: delivering a sequence of electrical stimuli to neural
tissue, each stimulus configured at a level whereby at least at a
given relative position of a stimulus electrode to the neural
tissue a first stimulus of the sequence generates an action
potential and whereby each subsequent stimulus alters a membrane
potential of the neural tissue without causing depolarisation of
the neural tissue nor evoking an action potential, each subsequent
stimulus being delivered prior to recovery of the membrane
potential of the neural tissue from a preceding stimulus such that
the sequence of stimuli maintains the membrane potential in an
altered range in which conduction of action potentials is hindered
or prevented.
17. The method of claim 16, wherein the blockade is effected by
applying a sequence of supra-threshold stimuli, the first of which
will evoke an action potential.
18. The method of claim 16 wherein the blockade is effected by
applying a sequence of stimuli which are sub-threshold in a first
posture, but which become supra-threshold at times when the user
moves to a second posture.
19. The method of claim 16 wherein the sequence of stimuli is
delivered at a frequency greater than 500 Hz.
20. The method of claim 19 wherein the sequence of stimuli is
delivered at a frequency greater than 1 kHz.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The current application is a continuation of U.S. patent
application Ser. No. 16/823,296, entitled "Neural Stimulation
Dosing" to John Louis Parker, filed Mar. 18, 2020, which
application is a continuation of U.S. patent application Ser. No.
15/327,981, entitled "Neural Stimulation Dosing" to John Louis
Parker, filed Jan. 20, 2017 and issued on Apr. 28, 2020 as U.S.
Pat. No. 10,632,307, which application is a 35 U.S.C. .sctn. 371
National Stage Patent Application of PCT Patent Application Serial
No. PCT/AU2015/050422 entitled "Neural Stimulation Dosing" to John
Louis Parker, filed Jul. 27, 2015, which application claims
priority to Australian Patent Application Serial No. 2014902897,
filed Jul. 25, 2014 and Australian Patent Application Serial No.
2015900912, filed Mar. 13, 2015. The disclosures of Australian
Patent Application Serial Nos. 2014902897 and 2015900912 are hereby
incorporated by reference in their entirety.
TECHNICAL FIELD
[0002] The present invention relates to the application of
therapeutic neural stimuli, and in particular relates to applying a
desired dose of stimuli by using one or more electrodes implanted
proximal to the neural pathway in a variable manner to minimise
adverse effects.
BACKGROUND OF THE INVENTION
[0003] There are a range of situations in which it is desirable to
apply neural stimuli in order to give rise to a compound action
potential (CAP). For example, neuromodulation is used to treat a
variety of disorders including chronic neuropathic pain,
Parkinson's disease, and migraine. A neuromodulation system applies
an electrical pulse to tissue in order to generate a therapeutic
effect.
[0004] When used to relieve neuropathic pain originating in the
trunk and limbs, the electrical pulse is applied to the dorsal
column (DC) of the spinal cord. 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 the 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. To sustain the pain relief effects,
stimuli are applied substantially continuously, for example at a
frequency in the range of 30 Hz-100 Hz.
[0005] 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.
[0006] For effective and comfortable operation, it is necessary to
maintain stimuli amplitude or delivered charge above a recruitment
threshold. Stimuli below the recruitment threshold will fail to
recruit any action potentials. It is also necessary to apply
stimuli which are below a comfort threshold, above which
uncomfortable or painful percepts arise due to increasing
recruitment of A.beta. fibres which when recruitment is too large
produce uncomfortable sensations and at high stimulation levels may
even recruit sensory nerve fibres associated with acute pain, cold
and pressure sensation. In almost all neuromodulation applications,
a single class of fibre response is desired, but the stimulus
waveforms employed can recruit other classes of fibres which cause
unwanted side effects, such as muscle contraction if afferent or
efferent motor fibres are recruited. The task of maintaining
appropriate neural recruitment is made more difficult by electrode
migration and/or postural changes of the implant recipient, either
of which can significantly alter the neural recruitment arising
from a given stimulus, depending on whether the stimulus is applied
before or after the change in electrode position or user posture.
There is room in the epidural space for the electrode array to
move, and such array movement alters the electrode-to-fibre
distance and thus the recruitment efficacy of a given stimulus.
Moreover the spinal cord itself can move within the cerebrospinal
fluid (CSF) with respect to the dura. During postural changes the
amount of CSF and the distance between the spinal cord and the
electrode can change significantly. This effect is so large that
postural changes alone can cause a previously comfortable and
effective stimulus regime to become either ineffectual or
painful.
[0007] 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.
[0008] 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.
[0009] 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
[0010] According to a first aspect the present invention provides a
method of applying therapeutic neural stimuli, the method
comprising:
[0011] monitoring for at least one of sensory input and movement of
a user; and
[0012] in response to detection of at least one of sensory input
and a user movement, delivering an increased stimulus dosage within
a period of time corresponding to a duration of time for which the
detected sensory input or user movement gives rise to masking, the
increased stimulus dosage being configured to give rise to
increased neural recruitment.
[0013] According to a second aspect the present invention provides
a device for applying therapeutic neural stimuli, the device
comprising:
[0014] at least one electrode configured to be positioned alongside
a neural pathway of a user; and
[0015] a control unit configured to monitor for at least one of
sensory input and movement of the user, and configured to deliver,
in response to detection of at least one of sensory input and a
user movement, an increased stimulus dosage via the at least one
electrode within a period of time corresponding to a duration of
time for which the detected sensory input or user movement gives
rise to masking, the increased stimulus dosage being configured to
give rise to increased neural recruitment.
[0016] The first and second aspects of the present invention
recognise that during movement or sensory input the psychophysics
of perception can result in the individual perceiving a reduced
sensation from a given stimulus as compared to when the same
stimulus is applied while the individual is not moving nor
receiving sensory input. However, the benefits of delivering a
large dosage of stimuli remain for a period of time after
conclusion of the stimuli. The first and second aspects of the
present invention thus recognise that periods of time during which
the user is moving or receiving sensory input present an
opportunity to deliver an increased dosage of stimulation.
[0017] In some embodiments of the first and second aspects of the
invention, the increased stimulus dosage may be effected by
increasing one or more of the stimulus amplitude, the stimulus
pulse width and/or the stimulus frequency. The increased stimulus
dosage may for example comprise a burst of high frequency stimuli,
for example stimuli at 10 kHz, 40 .mu.s pulse width and 2 mA
amplitude. At times when neither sensory input nor movement is
detected stimuli may be delivered at a reduced dosage, for example
at 20 or 30 Hz, or even not at all.
[0018] In some embodiments, a cumulative stimulus dosage delivered
to the user may be monitored, and may be used as a basis to define
a required stimulus regime during periods of sensory input or
movement, and/or during periods of no sensory input and no
movement, in order to seek to deliver a desired total stimulus
dosage over the course of a dosage period such as an hour or a
day.
[0019] In some embodiments, sensory input or movement of the user
is detected by measuring neural activity upon the neural pathway.
The measured neural activity may comprise evoked neural responses
resulting from electrical stimuli applied to the neural pathway,
and for example sensory input or movement may be detected when a
change is detected in the neural response evoked from a given
stimulus. The measured neural activity may additionally or
alternatively comprise non-evoked neural activity, being the neural
activity present on the neural pathway for reasons other than the
application of electrical stimuli by the device. Such embodiments
recognise that non-evoked neural activity rises significantly
during periods of sensory input or user movement, so that an
observed increase or alteration in non-evoked neural activity can
be taken to indicate sensory input or user movement.
[0020] In other embodiments, movement of the user may be detected
by an accelerometer or other movement detector.
[0021] The period of time within which the increased stimulus
dosage is delivered may be predefined as an approximation of the
duration of a typical human movement, and for example may be
predefined to be of the order of one second in duration.
Additionally or alternatively, the period of time for which the
increased stimulus dosage is delivered may be adaptively determined
by performing the further step of detecting a cessation of sensory
input or movement of the user, and in turn ceasing the delivery of
the increased stimulus dosage.
[0022] Additionally or alternatively, the period of time for which
the increased stimulus dosage is delivered may be predefined or
adaptively determined to take a value corresponding to the typical
duration of non-evoked neural activity. For example, in some
embodiments the period of time for which the increased stimulus
dosage is delivered may be in the range 10-100 ms, or more
preferably 20-40 ms, more preferably around 30 ms. In such
embodiments the increase in stimulus dosage may involve imposing an
increased frequency of stimulation, for example by increasing a
frequency of stimulation from 60 Hz to 1 kHz in order to deliver
around 30 stimuli during a 30 ms window of non-evoked neural
activity rather than delivering only about 2 stimuli as would occur
at 60 Hz.
[0023] Additionally or alternatively, the period of time for which
the increased stimulus dosage is delivered and/or a stimulus
strength of the increased stimulus dosage may be adaptively
determined by performing the further step of measuring a strength
of the movement or sensory input, and determining the period of
time and/or the stimulus strength from the movement strength, for
example the period of time and/or the stimulus strength may be made
to be proportional to the movement strength. The movement or
sensory strength may for example comprise a magnitude or power of
the detected movement or sensory input, or other strength measure
of the detected movement or sensory input. In such embodiments the
stimulus strength may be controlled to remain below a threshold for
sensation by a certain amount or fraction, over time as the
threshold for sensation varies with movement or sensory input, to
thereby avoid or minimise the stimuli causing a paraesthesia
sensation while maintaining a therapeutic dose of the stimuli.
[0024] The increased stimulus dosage may be delivered throughout
the period of time or at select moments within the period of time
such as only at the commencement and/or cessation of the sensory
input or movement or the period of time.
[0025] According to a third aspect the present invention provides a
method for effecting a neural blockade, the method comprising:
[0026] delivering a sequence of electrical stimuli to neural
tissue, each stimulus configured at a level whereby at least at a
given relative position of a stimulus electrode to the neural
tissue a first stimulus of the sequence generates an action
potential and whereby each subsequent stimulus alters a membrane
potential of the neural tissue without causing depolarisation of
the neural tissue nor evoking an action potential, each subsequent
stimulus being delivered prior to recovery of the membrane
potential of the neural tissue from a preceding stimulus such that
the sequence of stimuli maintains the membrane potential in an
altered range in which conduction of action potentials is hindered
or prevented.
[0027] According to a fourth aspect the present invention provides
a device for effecting a neural blockade, the device
comprising:
[0028] at least one electrode configured to be positioned alongside
a neural pathway of a user; and
[0029] a control unit configured to deliver a sequence of
electrical stimuli to neural tissue, each stimulus configured at a
level whereby at least at a given relative position of the
electrode to the neural tissue a first stimulus of the sequence
generates an action potential and whereby each subsequent stimulus
alters a membrane potential of the neural tissue without causing
depolarisation of the neural tissue nor evoking an action
potential, each subsequent stimulus being delivered prior to
recovery of the membrane potential of the neural tissue from a
preceding stimulus such that the sequence of stimuli maintains the
membrane potential in an altered range in which conduction of
action potentials is hindered or prevented.
[0030] Embodiments of the third and fourth aspects of the invention
thus apply a sequence of stimuli which at first produce an action
potential and which then create a blockade, the blockade arising
during the period in which the sequence of stimuli maintains the
membrane potential in an altered range in which conduction of
action potentials is hindered or prevented. In some embodiments a
blockade may be effected by applying a sequence of supra-threshold
stimuli, the first of which will evoke an action potential.
Additional or alternative embodiments may effect a blockade by
applying a sequence of stimuli which are sub-threshold in a first
posture, but which become supra-threshold at times when the user
moves to a second posture. In such embodiments, the first stimulus
delivered after the stimulus threshold falls below the stimulus
amplitude will evoke an action potential. Blockading is beneficial
because the stimuli delivered during the blockade evoke few or no
action potentials at the stimulus site and will thus give rise to a
significantly reduced effect of, or even a complete absence of,
paresthesia.
[0031] In some embodiments of the third and fourth aspects of the
invention, the sequence of stimuli may be delivered at a frequency,
or an average frequency, which is greater than 500 Hz, more
preferably greater than 1 kHz, and for example may be in the range
of 5-15 kHz. In some embodiments the frequency may be defined by
determining an average refractory period of the subject, such as by
using the techniques of International Patent Application
Publication No. WO2012155189, the contents of which are
incorporated herein by reference. The frequency of the delivered
stimuli may then be set so that the inter-stimulus time is less
than the determined refractory period, or is a suitable fraction or
multiple thereof
[0032] In some embodiments of the third and fourth aspects of the
invention, the nominal sub-threshold level may be predetermined for
example by a clinician at a time of fitting of an implanted
stimulator for the user. The nominal sub-threshold level is in some
embodiments set at a level which is a large fraction of a stimulus
threshold in a given posture, for example being 50%, 75% or 90% as
large as the stimulus threshold in that posture. The nominal
sub-threshold level may be adaptively determined, for example by
repeatedly determining a recruitment threshold of the neural tissue
from time to time, such as by measuring neural responses evoked by
stimuli, and re-setting the nominal sub-threshold level by
reference to a most recent determined threshold level. The
recruitment threshold of the neural tissue is in some embodiments
determined at time intervals which are substantially greater than
the duration of a typical human movement so as to allow the neural
blockade to be established during a movement.
[0033] Some embodiments of the invention may implement blockading
in accordance with the third aspect of the invention only at times
of detected sensory input or movement, in accordance with the first
aspect of the invention. In such embodiments, the detection of
sensory input or movement may be effected by delivering the
blockade stimuli continuously at the nominal sub-threshold level,
whereby the blockade stimuli come into effect only during sensory
input or movements which cause the momentary recruitment threshold
to fall below the nominal sub-threshold level. Alternatively, in
such embodiments the blockading may be commenced in response to
detection of sensory input or movement so that the action potential
generated by the first stimulus of the sequence is masked by the
sensory input or movement.
[0034] According to a fifth aspect the present invention provides a
computer program product comprising computer program code means to
make a computer execute a procedure for applying therapeutic neural
stimuli, the computer program product comprising:
[0035] computer program code means for monitoring for at least one
of sensory input and movement of a user; and
[0036] computer program code means for, in response to detection of
at least one of sensory input and a user movement, delivering an
increased stimulus dosage within a period of time corresponding to
a duration of time for which the detected sensory input or user
movement gives rise to masking, the increased stimulus dosage being
configured to give rise to increased neural recruitment.
[0037] According to a sixth aspect the present invention provides a
computer program product comprising computer program code means to
make a computer execute a procedure for effecting a neural
blockade, the computer program product comprising:
[0038] computer program code means for delivering a sequence of
electrical stimuli to neural tissue, each stimulus configured at a
level whereby at least at a given relative position of a stimulus
electrode to the neural tissue a first stimulus of the sequence
generates an action potential and whereby each subsequent stimulus
alters a membrane potential of the neural tissue without causing
depolarisation of the neural tissue nor evoking an action
potential, each subsequent stimulus being delivered prior to
recovery of the membrane potential of the neural tissue from a
preceding stimulus such that the sequence of stimuli maintains the
membrane potential in an altered range in which conduction of
action potentials is hindered or prevented.
[0039] In some embodiments of the fifth and sixth aspects of the
invention, the computer program product comprises a non-transitory
computer readable medium comprising instructions for execution by
one or more processors.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] An example of the invention will now be described with
reference to the accompanying drawings, in which:
[0041] FIG. 1 schematically illustrates an implanted spinal cord
stimulator;
[0042] FIG. 2 is a block diagram of the implanted
neurostimulator;
[0043] FIG. 3 is a schematic illustrating interaction of the
implanted stimulator with a nerve;
[0044] FIG. 4 illustrates the strength duration curve followed by
the threshold for action potential generation in an axon;
[0045] FIG. 5 illustrates the effect on the strength duration curve
of delivering a high frequency pulse train;
[0046] FIG. 6 shows the amplitude growth curves for an individual
at a number of different postures;
[0047] FIG. 7 shows the strength duration curve corresponding to
the activation of the dorsal columns;
[0048] FIG. 8 illustrates monitoring of a stimulation current
required to maintain a constant ECAP response;
[0049] FIG. 9 show examples of ECAP recordings with a patient at
rest;
[0050] FIG. 10 shows ECAP recordings with the patient walking on
the spot;
[0051] FIGS. 11a and 11b show non evoked activity measured from a
patient;
[0052] FIGS. 12a, 12b, and 12c illustrate stimulus regimes applied
in accordance with some embodiments of the present invention;
[0053] FIG. 13 illustrates the neural voltage recorded during a
blockade;
[0054] FIG. 14 illustrates operation of a motion activity
detector;
[0055] FIGS. 15-17 illustrate neural response signals observed
during patient movement, and the resulting stimuli regimes
delivered by the detector of FIG. 14; and
[0056] FIG. 18 illustrates operation of a neural activity detector
in accordance with another embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0057] FIG. 1 schematically illustrates an implanted spinal cord
stimulator 100. Stimulator 100 comprises an electronics module 110
implanted at a suitable location in the patient's lower abdominal
area or posterior superior gluteal region, and an electrode
assembly 150 implanted within the epidural space and connected to
the module 110 by a suitable lead. Numerous aspects of operation of
implanted neural device 100 are reconfigurable by an external
control device 192. Moreover, implanted neural device 100 serves a
data gathering role, with gathered data being communicated to
external device 192.
[0058] FIG. 2 is a block diagram of the implanted neurostimulator
100. Module 110 contains a battery 112 and a telemetry module 114.
In embodiments of the present invention, any suitable type of
transcutaneous communication 190, such as infrared (IR),
electromagnetic, capacitive and inductive transfer, may be used by
telemetry module 114 to transfer power and/or data between an
external device 192 and the electronics module 110.
[0059] Module controller 116 has an associated memory 118 storing
patient settings 120, control programs 122 and the like. Controller
116 controls a pulse generator 124 to generate stimuli in the form
of current pulses in accordance with the patient settings 120 and
control programs 122. Electrode selection module 126 switches the
generated pulses to the appropriate electrode(s) of electrode array
150, for delivery of the current pulse to the tissue surrounding
the selected electrode(s). Measurement circuitry 128 is configured
to capture measurements of neural responses sensed at sense
electrode(s) of the electrode array as selected by electrode
selection module 126.
[0060] FIG. 3 is a schematic illustrating interaction of the
implanted stimulator 100 with a nerve 180, in this case the spinal
cord however alternative embodiments may be positioned adjacent any
desired neural tissue including a peripheral nerve, visceral nerve,
parasympathetic nerve or a brain structure. Electrode selection
module 126 selects a stimulation electrode 2 of electrode array 150
to deliver an electrical current pulse to surrounding tissue
including nerve 180, and also selects a return electrode 4 of the
array 150 for stimulus current recovery to maintain a zero net
charge transfer.
[0061] Delivery of an appropriate stimulus to the nerve 180 evokes
a neural response comprising a compound action potential which will
propagate along the nerve 180 as illustrated, for therapeutic
purposes which in the case of a spinal cord stimulator for chronic
pain might be to create paraesthesia at a desired location. To this
end the stimulus electrodes are used to deliver stimuli at 30 Hz.
To fit the device, a clinician applies stimuli which produce a
sensation that is experienced by the user as a paraesthesia. When
the paraesthesia is in a location and of a size which is congruent
with the area of the user's body affected by pain, the clinician
nominates that configuration for ongoing use.
[0062] The device 100 is further configured to sense the existence
and intensity of compound action potentials (CAPs) propagating
along nerve 180, whether such CAPs are evoked by the stimulus from
electrodes 2 and 4, or otherwise evoked. To this end, any
electrodes of the array 150 may be selected by the electrode
selection module 126 to serve as measurement electrode 6 and
measurement reference electrode 8. Signals sensed by the
measurement electrodes 6 and 8 are passed to measurement circuitry
128, which for example may operate in accordance with the teachings
of International Patent Application Publication No. WO2012155183 by
the present applicant, the content of which is incorporated herein
by reference.
[0063] However the present invention recognises that it is unclear
whether or not the experience of paresthesia is necessary for pain
reduction on an ongoing basis. Although paraesthesia is generally
not an unpleasant sensation there may nevertheless be benefits in a
stimulus regime which provides pain relief without the generation
of sensation.
[0064] The threshold for action potential generation in an axon
follows the strength duration curve as shown in FIG. 4. As the
pulse width of the stimulus is increased the current needed for an
axon to reach threshold decreases. The Rheobase current is an
asymptotic value, being the largest current that is incapable of
producing an action potential even at very long pulse widths. The
Chronaxie is then defined as the minimum pulse width required to
evoke an action potential at a current that is twice the Rheobase
current.
[0065] FIG. 5 illustrates the effect on the strength duration curve
of delivering a high frequency pulse train. As shown, a high
frequency pulse train can effectively act as a single pulse with a
longer pulse width with respect to activating a nerve. That is,
closely spaced stimuli can effectively add up and recruit
additional populations of fibres when compared with widely spaced
stimuli with the same pulse width. Stimuli can either depolarize
axon membranes to threshold and generate action potentials, or they
can depolarize the axon membrane potential just below threshold and
not produce an action potential. When an axon produces an action
potential in response to a stimulus it is unable to produce a
second potential for a period of time called the refractory period.
On the other hand, those axons that did not reach threshold in
response to the first stimulus may reach threshold on subsequent
stimuli as their membrane potential is raised closer and closer to
threshold with every stimulus, provided that the next stimuli
occurs prior to recovery of the membrane potential from the
previous stimuli. This effect equilibrates over a small number of
high frequency stimuli, and may account for an effective doubling
of the number of fibres recruited, when compared with a single
stimulus of the same pulse width at low frequency.
[0066] Activation of A.beta. fibres in the dorsal column can vary
considerably in response to changes in posture. This postural
affect is primarily due to the movement of the stimulus electrodes
with respect to the fibres. Changes in posture can be measured by
recording the evoked compound action potential (ECAP). Momentary
changes in posture, for instance a sneeze or a cough, can produce a
factor of 10 increase in the amplitude of an evoked CAP, or more.
FIG. 6 shows the amplitude growth curves for an individual at a
number of different postures. It demonstrates a significant change
in recruitment threshold as the patient moves from one posture to
another, with the recruitment threshold being almost as low as 0.5
mA when the user is lying supine and being about 3 mA when the user
is lying prone.
[0067] FIG. 7 shows the strength duration curve corresponding to
the activation of the dorsal columns for a single posture. The
current corresponding to the threshold for an ECAP versus the pulse
width. For example a pulse width of 35 .mu.s corresponds to a
threshold current of 11.5 mA. Noting the recruitment curves of FIG.
6, when the sitting patient moves to a supine position the
threshold in FIG. 7 could be expected to drop to a third of the
value, which for a pulse width of 35 .mu.s indicates that the
threshold will be 11.5/3=3.83 mA. To maintain threshold in response
to a change in posture, either the pulse width can be increased or
as demonstrated earlier a high frequency train using a shorter
pulse width could be used.
[0068] The present invention further recognises that cutaneous
sensation is suppressed by movement and by sensory input, that the
level of suppression is dependent on the intensity of the movement
or sensory input, and that movement induced suppression attenuates
both flutter and pressure. The reduction in the pressure sensation
was 30, 38 and 79% for slow, medium and rapid movement,
respectively. In general, sensory input displays a masking
phenomenon where the presence of a large stimulus can mask the
perception of a smaller stimulus. This can even happen when the
smaller stimulus is presented before the larger stimulus (forward
masking). This phenomenon occurs during cutaneous input.
[0069] A first embodiment of the invention therefore provides a
spinal cord stimulation system which has the ability to detect
movement, and to apply or increase electrical stimulation only
during the periods where movement is sufficiently strong so as to
mask the sensation produced by electrical stimulation. Such a
system achieves relief from pain for the individuals implanted but
without generation of sensation due to the fact that the sensation
which would be perceived by the subject when they are stationary is
below threshold for perception during movement.
[0070] There are a number of ways in which the movement of the
individual might be detected. One method is to use an
accelerometer, which senses movement of the stimulator, another is
to use the impedance of the electrode array which changes as a
result of the motion in the epidural space of the spinal cord. A
third method for detecting movement is to use the modulation of the
evoked compound action potential. Closed loop neuromodulation
systems have been developed which employ recordings of the compound
action potential to achieve a constant recruitment, for example as
described in International Patent publications WO2012155183 and
WO2012155188, the contents of which are incorporated by reference
in their entirety. The amplitude of the ECAP has been shown to
sensitively vary with the changes in posture. The amplitude can
thus be used to detect movements and time the delivery of bursts of
stimuli to coincide with those movements. Measurement of the ECAP
provides a method of directly assessing the level of recruitment in
the dorsal columns of the spinal cord depending on posture. A
further method for detecting movement, which is also suitable for
detecting sensory input, is to monitor neural activity on the nerve
which has not been evoked by the neurostimulator, for example in
the manner described in the present applicant's Australian
provisional patent application no. 2014904595, the content of which
is incorporated herein by reference. Such non-evoked neural
activity can result from efferent motor signals or afferent sensory
or proprioceptive signals, which present opportunities at which
masking can occur and thus define times at which delivery of an
increased stimulus dosage may be appropriate.
[0071] The algorithm in this embodiment works as follows. Feedback
control of a sub paraesthesia amplitude of ECAP is established with
the patient stationary. Movement is detected by monitoring the
stimulation current, which is constantly adjusted to maintain a
constant ECAP response. A set point is established for the
amplitude of the change over time which when reached indicates a
sufficiently rapid movement to change stimulation parameters. A
change in the current may be insufficient to meet the criteria for
detecting a sufficiently large movement (as occurs in time period
P1 in FIG. 8) or it may meet or exceed the criteria (as occurs in
time period P2 in FIG. 8).
[0072] On detection of this change a new stimulation condition is
set, by adjusting stimulation parameters. The stimulation
parameters may be any of those which effect the recruitment of
dorsal column fibres such as the amplitude, pulse width,
stimulation frequency or combination thereof. The stimulator
outputs a stimulus train at the new settings for a period of time.
The output can be controlled in a feedback loop as well so that a
constant level of recruitment is achieved. The timing for the
increased period of stimulation is adjusted so that it ceases in a
short period coincident with the movement detected, and terminates
before the motion ceases, such that it is not perceived by the
individual.
[0073] The timing and amplitude can be set by a number of means,
such as a fixed amplitude applied for a fixed time, an amplitude
which is adjusted proportionally to the amplitude of the measured
ECAP or movement and terminated after a fixed interval, or a fixed
amplitude of stimulation and termination after the variation, being
the first derivative over time of the ECAP amplitude, drops. Recall
that the stimulation parameters are adjusted on reaching a set
level of variation. Thus, a fixed ECAP amplitude can be adjusted
via feedback which is terminated when the 1st derivative over time
of the applied current drops below a set level.
[0074] After the stimuli train is delivered the system reverts to a
stimulation mode that is below perception threshold to monitor for
further changes in postures, and the sequence is repeated. The
adjustment of the stimulation parameters can be controlled over
time (ramp up and ramp down) or other time varying function.
[0075] Without intending to be limited by theory, current
postulated mechanisms of action of SCS are based on the A.beta.
fibre activity in the dorsal column resulting, via synaptic
transmission, in the release of GABA, an inhibitory
neuro-transmitter, in the dorsal horn. GABA then reduces
spontaneous activity in wide dynamic range neurons and hence
produces pain relief. The kinetics of GABA mediated inhibition are
unknown, however there is a post switch off effect from SCS which
can be quite prolonged in some patients. This suggests that
build-up of GABA may be possible over short periods, which would
lead to longer term pain inhibition. If the quanta for GABA release
is proportional to the stimuli then it is instructive to compare
tonic continuous stimulation to bursts of higher frequency
stimulation. Continuous tonic stimulation provides 216 000 stimuli
over a one hour period at a stimulation frequency of 60 Hz, whereas
at 1.2 kHz delivery of the same number of stimuli is achieved in
three minutes. Given control over stimulus delivery as described
above then 3 minutes of activity in an hour would result in the
same number of supra-threshold stimuli delivered with tonic
stimulation. Hence a higher frequency stimulus burst may be as
efficacious as tonic stimulation but with a much shorter elapsed
duration of stimuli.
[0076] The use of ECAPS allows the dosage of stimuli applied to the
recipient during the day to be carefully controlled and additional
stimuli could be applied if the number of stimuli falls below a
target level which is required to achieve optimal therapy. This may
occur because an individual is not active enough, or because the
system set points are not optimally adjusted. Given such conditions
the system can alert the user or the clinician or even revert to
periods of tonic continuous super threshold stimulation.
[0077] In some embodiments the applied therapeutic stimuli may be
supra threshold stimuli for neural activation, however in other
embodiments sub threshold stimuli may be applied for psychophysical
perception in other therapeutic areas.
[0078] ECAP measurements as described above may be used as a method
to time the application of pain relieving stimuli to coincide with
detected movement. A number of other methods may also be used
including a measure of the patient's own non-evoked neural
activity. FIG. 9 show examples of ECAP recordings with a patient at
rest and FIG. 10 shows ECAP recordings with the patient walking on
the spot.
[0079] In FIGS. 9 and 10 there is a significant difference in the
amplitude of the noise due to non-evoked activity immediately post
the stimulus with the patient walking on the spot. Simple visual
inspection shows that in FIG. 9 during the time period 15-20 s the
neural activity amplitude is generally less than 5 microvolts,
whereas during the same period in FIG. 10 the neural activity
amplitude often exceeds 10 microvolts. A number of automated
techniques may be used to determine the amplitude of the non-evoked
neural activity. The amplitude can be directly measured by
determining the maximum and minimum values of the response or
alternatively the RMS (root mean square) can be determined over a
window.
[0080] The non-evoked activity can be measured on a continuous
basis without outputting stimuli. In this manner the extent of
activity or movement of the individual can be assessed on a
continuous basis, so that sufficiently swift movements can be
detected and used as triggers for increased stimulus dosing.
[0081] FIG. 11a shows non evoked activity measured from a patient,
and shows the RMS non-evoked activity for an individual undergoing
a range of movement activities from rubbing the leg to walking on
the spot and coughing. As is evident in the figure the RMS signal
is much larger when the patient is active and walking on the spot.
FIG. 11b is another illustration of non-evoked neural activity
measured from a patient, and shows the RMS non-evoked activity for
an individual whom at 1102 is not moving, at 1104 is rubbing their
leg, at 1106 is lifting one leg while seated and at 1108 is
walking. In particular FIG. 11b shows that sensory input of rubbing
the leg at 1104, and motor and/or proprioceptive input of lifting
the leg at 1106, are each only subtly different from times of no
movement as shown at 1102, and some embodiments of the present
invention are specifically configured to address this problem.
[0082] In one embodiment, an algorithm which exploits the
non-evoked activity operates as follows: [0083] i. The implant
system monitors the non-evoked activity (N) until a threshold
measure of activity is reached (T.sub.nn). [0084] ii. On reaching
the threshold, stimuli are generated and, after any evoked response
has concluded, the magnitude of the post-stimulus non-evoked
activity is re-measured (N.sub.s). [0085] iii. Stimuli are
generated at a rate (R.sub.s) until the non-evoked activity
(N.sub.s) falls below a second threshold measure of activity
(T.sub.ns) at which point stimulation ceases. T.sub.ns typically
takes a smaller value than T.sub.nn, selected to provide a suitable
degree of hysteresis. [0086] iv. The implant system then continues
to monitor the non-evoked activity and returns to step (i).
[0087] The stimulus rate (R.sub.s) may be a fixed rate or it may
also be set to vary with the magnitude of the non-evoked
activity
[0088] The amplitude of the evoked activity can be used to control
the amplitude of the stimulus generated with each successive
stimuli in a feedback loop as has been described in International
Patent Publication No. WO2012155188, for example. The advantage of
employing a feedback loop in such a manner is to keep the ECAP
amplitude constant during a period of active movement during which
it is known to vary considerably.
[0089] The parameters for this algorithm can be determined in the
following manner [0090] i. The patient is programmed with a
traditional method with continuous stimulation with patient at
rest. The stimulus location and amplitude is adjusted in order to
obtain paraesthesia coverage of the pain full area. The amplitude
of the ECAP (E.sub.a) for obtaining pain relief is noted. [0091]
ii. The stimulation is turned off and the range of non-evoked
activity is measured. The threshold T.sub.nn is set such that it is
above the base line of non-evoked activity with the patient at
rest.
[0092] The presence of the non-evoked activity is the result of
movement of and/or sensory input to the individual. Movement also
affects the amplitude of the evoked activity, so that if the evoked
activity is controlled with a feedback loop, then a change in the
current or other stimulus parameter which is set to maintain a
constant amplitude can be used to monitor for a change in movement
and set the point for cessation of the stimuli.
[0093] By delivering increased stimuli only at times at which
movement and/or sensory input is detected, the present invention
provides for a considerably reduced power budget. For example if
movement is detected every 15 seconds, and the delivered stimulus
comprises 5 stimuli, the system will deliver 20 stimuli per minute
as compared to 1200 stimuli per minute for a continuous 20 Hz
stimulus regime, i.e. 98.3% fewer stimuli.
[0094] FIG. 12a illustrates the threshold 1210 of dorsal column
activation, which varies over time for example with postural
changes. At times 1222, 1224 this threshold 1210 drops below the
stimulus level 1230. The present invention may initiate or increase
the stimulus regime during these periods 1222, 1224, either
throughout the entire period as shown in FIG. 12b or for example at
the start and/or finish of the period as shown in FIG. 12c. It is
to be noted that each affected fibre will also respond in a
corresponding manner albeit at slightly different times depending
on the distance of the electrode from that fibre and the time at
which the user movement causes the fibre to come within the
effective stimulus range of the electrode. The delivered stimuli
1240, 1242 delivered in FIG. 12b comprise a burst of high frequency
stimuli at 10 kHz, 40 .mu.s pulse width and 2 mA amplitude. Such
stimuli are configured to effect a blockade during respective time
periods 1222 and 1224, so that in FIG. 12b only a single action
potential 1250, 1252 is produced in each time period 1222, 1224 and
the fibre is then blockaded for the remainder of the respective
time period.
[0095] In FIG. 12c an alternative stimulus regime is applied, with
stimuli being applied only at threshold crossings, these being the
moments at which the user is actually moving from one posture to
the next. In accordance with the first aspect of the invention, the
sequences of stimuli 1260, 1262, 1264, 1266 deliver an increased
stimulus dosage during times of movement, so that an increased
number of action potentials 1270 are evoked at such times. This
embodiment recognises that, during movement, the psychophysics of
perception can result in the individual perceiving a reduced
sensation from a given stimulus as compared to when the same
stimulus is applied while the individual is not moving. However,
the benefits of delivering a large dosage of stimuli remain for a
period of time after conclusion of the stimuli.
[0096] FIG. 13 illustrates the neural voltage recorded during a
blockade as may be produced by stimuli 1240, 1242. As can be seen
the period of the high frequency sequence of stimuli is less than
the period of the action potential 1302. Thus, while a first
stimulus of the sequence generates action potential 1302, each
subsequent stimulus alters a membrane potential of the neural
tissue without causing depolarisation of the neural tissue and
without evoking an action potential, each subsequent stimulus being
delivered prior to recovery of the membrane potential of the neural
tissue from a preceding stimulus.
[0097] FIGS. 14-17 illustrate operation of a motion activity
detector 1410 which detects movement of a patient 1440 by analysis
of observed neural responses 1450 evoked by applied stimuli 1430.
The algorithm performed by detector 1410 enables stimulation to be
delivered only when movement-related slow spinal cord potentials
are recorded, and otherwise disables stimulation. Movement-related
spinal cord potentials are defined in this embodiment as signals
greater than 200 .mu.V.sub.p-p, normalised for lead position, with
a band width between 1 and 30 Hz.
[0098] One goal of the detector 1410 is to accurately detect
movement of the particular limb or part of the body associated with
the area that pain occurs, e.g. for leg pain the detector 1410
seeks to detect walking, lifting the leg, and the like. The
detector 1410 is also configured to detect movement quickly enough
to be able to commence stimulation while the movement is still
occurring. The detector 1410 is also parameterised, so that the
algorithm can be made to work for patients with varying stimulation
parameters.
[0099] The detector 1410 operates by applying a sequence of stimuli
over time and obtaining a neural response amplitude measurement
after each stimuli. The sequence of neural response amplitudes
obtained in this manner over the course of 30 seconds is plotted at
1502 in FIG. 15. During this period the patient was walking on the
spot. The neural response signal 1502 is low pass filtered,
differentiated, and rectified, to produce rectified differentiated
neural response signal 1504. The differentiator allows movements to
be detected early, and the rectifier ensures that both negative and
positive-going signals are captured. The gradient value m[n], i.e.
signal 1504, is then fed to an envelope detector with the following
equation:
l .function. [ n ] = { m .function. [ n ] , m .function. [ n ] >
l .function. [ n - 1 ] .alpha. .times. .times. l .function. [ n - 1
] + ( 1 - .alpha. ) .times. m .function. [ n - 1 ] , m .function. [
n ] .ltoreq. l .function. [ n - 1 ] ##EQU00001##
[0100] The parameter .alpha. is a value between 0 and 1. Values
closer to one will cause a slower envelope delay and thus cause the
stimulus to be applied for a longer period after each detection.
The envelope 1506 produced in the above manner from the
differentiated signal 1504 is shown in FIG. 15. The detector output
1508 is thresholded from envelope 1506, where a detector output
value of 1 causes stimuli to be applied, and an output of zero
disables stimuli delivery. As can be seen in this embodiment, the
detector output 1508 thus causes stimuli to be selectively
delivered only at times when movement is detected.
[0101] Tuning of the threshold and the parameter .alpha. allows the
stimulus dosing to be adjusted. For example FIGS. 16 and 17 show
the algorithm output during various patient movements with
parameters which give rise to smaller or more sparse periods of
stimulation than seen in 1508 in FIG. 15.
[0102] Other embodiments of the activity detector may also provide
a movement magnitude output, indicating the magnitude of the
movement, which may be used to modulate the magnitude or duration
of the stimulation, or other stimulation parameters.
[0103] As can be seen the embodiment of FIGS. 14-17 is effective
for periods when the patient is walking. FIG. 18 illustrates
another embodiment which is further operable to appropriately
detect sensory input such as rubbing the leg. In this embodiment,
the detector operates by applying a sequence of stimuli over time
and obtaining a neural response amplitude measurement after each
stimuli. The sequence of neural response amplitudes obtained in
this manner over the course of about 30 seconds is plotted at 1802
in FIG. 18. Prior to about 19 seconds into the measurements, and
after about 39 seconds of measurements 1802, the patient was
inactive as indicated by 1822. During period 1824 the patients
rubbed their leg. The difference in signal 1802 between period 1822
and 1824 is fairly subtle, however the sensory input of leg rubbing
presents an opportunity to deliver stimuli during period 1824 in
order to take advantage of masking. Therefore the present
embodiment is configured to analyse the measurements signal 1802
and to differentiate a period of sensory input 1824 from periods
1822 of inactivity.
[0104] To achieve this goal, the embodiment of FIG. 18 obtains the
neural measurements 1802 at 60 Hz. Each measurement, or sample
x[n], is saved to a circular buffer of a length defined by a
Detection Window Length parameter, N. Each new sample is used to
update a moving average using the formula:
avg[n]=1/2avg[n-1]+1/2x[n]
[0105] The two-sample moving average is beneficial in minimising
processing time. Next, the variance 1804 of the signal 1802 is
calculated from all the samples in the circular buffer, and using
the above-noted moving average:
var .times. [ n ] = 1 N .times. i = 0 N - 1 .times. ( x .function.
[ n - i ] - a .times. v .times. g .function. [ n ] ) 2
##EQU00002##
[0106] The variance 1804, var[n], is then fed to an envelope
detector with the following equation:
l .function. [ n ] = { var .function. [ n ] , m .function. [ n ]
> l .function. [ n - 1 ] ( 1 - .alpha. ) .times. l .function. [
n - 1 ] + .alpha. .times. .times. var .function. [ n ] , m
.function. [ n ] .ltoreq. l .function. [ n - 1 ] ##EQU00003##
[0107] The parameter a is a value between 0 and 1, and can be
adjusted whereby smaller values will cause the stimulus to be
applied for a longer period after an initial detection. The output
of the envelope detector is shown at 1806 in FIG. 18.
[0108] The detector output 1808 is produced by being thresholded
from envelope 1806 by comparison to threshold 1810, where a
detector output value of 1 causes stimuli to be applied, and an
output of zero disables stimuli delivery. The threshold can be
adjusted to suit given hardware and/or a given patient. As can be
seen in this embodiment, the detector output 1808 thus causes
stimuli to be selectively delivered only at times when sensory
input is occurring. In particular, in this embodiment the detector
output 1808 appropriately disables stimuli during period 1822,
while taking good advantage of the masking opportunity afforded by
leg rubbing during period 1824 to deliver an increased dosage of
stimulation, despite the somewhat subtle differences in signal 1802
between the periods of inactivity 1822 and the period of leg
rubbing 1824.
[0109] 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. The
present embodiments are, therefore, to be considered in all
respects as illustrative and not limiting or restrictive.
* * * * *