U.S. patent application number 13/472988 was filed with the patent office on 2012-11-22 for method and apparatus for neurostimulation with prevention of neural accommodation.
Invention is credited to Jason J. Hamann, Juan Gabriel Hincapie Ordonez, Stephen Ruble, David J. Ternes.
Application Number | 20120296395 13/472988 |
Document ID | / |
Family ID | 46147787 |
Filed Date | 2012-11-22 |
United States Patent
Application |
20120296395 |
Kind Code |
A1 |
Hamann; Jason J. ; et
al. |
November 22, 2012 |
METHOD AND APPARATUS FOR NEUROSTIMULATION WITH PREVENTION OF NEURAL
ACCOMMODATION
Abstract
A neurostimulation system delivers neurostimulation to a patient
using one or more primary parameters and one or more secondary
parameters. The one or more primary parameters are controlled for
maintaining efficacy of the neurostimulation. The one or more
secondary parameters are adjusted for preventing the patient from
developing neural accommodation. In various embodiments, values for
the one or more secondary parameters are varied during the delivery
of the neurostimulation for prevention of neural accommodation that
may result from a constant or periodic pattern of stimulation
pulses.
Inventors: |
Hamann; Jason J.; (Blaine,
MN) ; Ternes; David J.; (Roseville, MN) ;
Ruble; Stephen; (Lino Lakes, MN) ; Hincapie Ordonez;
Juan Gabriel; (Maple Grove, MN) |
Family ID: |
46147787 |
Appl. No.: |
13/472988 |
Filed: |
May 16, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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61486573 |
May 16, 2011 |
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Current U.S.
Class: |
607/59 |
Current CPC
Class: |
A61N 1/36053 20130101;
A61N 1/36135 20130101; A61N 1/36114 20130101; A61N 1/36167
20130101 |
Class at
Publication: |
607/59 |
International
Class: |
A61N 1/36 20060101
A61N001/36 |
Claims
1. An implantable medical device, comprising: a stimulation output
circuit configured to deliver neurostimulation during therapy
sessions; a storage device configured to store values of a
plurality of stimulation parameters including one or more primary
parameters each having a value selected for efficacy of the
neurostimulation and one or more secondary parameters each having a
value adjustable for preventing neural accommodation while
maintaining the efficacy of the neurostimulation, the values
including a plurality of value sets for the one or more secondary
parameters, the value sets each being a set of one or more values
each given to one of the one or more secondary parameters; a
control circuit configured to control the delivery of the
neurostimulation using the plurality of stimulation parameters, the
control circuit including a parameter adjuster configured to adjust
one or more parameters of the plurality of parameters, the
parameter adjuster including a secondary parameter adjuster
configured to select a subset of one or more value sets from the
stored plurality of value sets for the one or more secondary
parameters for each session of the therapy sessions such that the
one or more secondary parameters are adjusted randomly through the
therapy sessions; and an implantable housing encapsulating the
stimulation output circuit, the storage device, and the control
circuit.
2. The device of claim 1, wherein the secondary parameter adjuster
is configured to randomly select each value set of the subset of
one or more value sets from the stored plurality of value sets for
each session of the therapy sessions.
3. The device of claim 1, further comprising: a sensing circuit
configured to sense one or more physiological signals indicative of
a degree of modulation of one or more physiological functions by
the neurostimulation; and a neural accommodation detector
configured to detect neural accommodation indicated by a
substantial decrease in the degree of modulation of the one or more
physiological functions by the neurostimulation; and wherein the
secondary parameter adjuster is configured to adjust the one or
more secondary parameters in response to a detection of the
indication of neural accommodation.
4. The device of claim 1, wherein the secondary parameter adjuster
is configured to select value sets from the stored plurality of
value sets for the one or more secondary parameters, generate a
sequence of value sets for the each therapy session including the
selected value sets, and dynamically adjust the one or more
secondary parameters according to the sequence of value sets during
the each therapy session.
5. The device of claim 4, wherein the secondary parameter adjuster
is configured to randomize an order of the selected value sets in
the sequence of value sets.
6. The device of claim 1, wherein the control circuit is configured
to control the delivery of the neural stimulation using a dosing
parameter of the one or more primary parameters, the dosing
parameter specifying a measure of total dose of the
neurostimulation for a therapy session and representing a number of
electrical pulses delivered during the therapy session.
7. The device of claim 6, wherein the control circuit is configured
to control the delivery of the neurostimulation using a duty cycle
including an on-period during which the neurostimulation is
delivered and an off-period during which the neurostimulation is
not delivered, the duty cycle being a parameter of the one or more
primary parameters.
8. The device of claim 7, wherein the secondary parameter adjuster
is configured to adjust a duration of a ramp during which a
stimulation intensity gradually increases from zero to its value
specified for the on-period when the ramp ends at a beginning of
the on-period, or gradually decreases from its value specified for
the on-period to zero the ramp starting at an end of the on-period,
the duration of the ramp being a parameter of the one or more
secondary parameters.
9. The device of claim 7, wherein the secondary parameter adjuster
is configured to adjust the on-period and the off-period without
varying the duty cycle, the on-period and the off-period each being
a parameter of the one or more secondary parameters.
10. The device of claim 6, wherein the control circuit is
configured to control the delivery of the neurostimulation using a
measure of total dosing for a therapy session of the therapy
sessions, the therapy session having a session duration that is
divided into a plurality of segments, the measure of total dosing
being a parameter of the one or more primary parameters, and
wherein the secondary parameter adjuster is configured to adjust an
on-off parameter specifying whether each segment of the plurality
of segments is an on-segment or an off-segment, the on-segment
being a segment of the plurality of segment during which the
neurostimulation is delivered, the off-segment being a segment of
the plurality of segment during which the neurostimulation is not
delivered, the on-off parameter being a parameter of the one or
more secondary parameters.
11. A method for operating an implantable medical device,
comprising: receiving values of a plurality of stimulation
parameters including one or more primary parameters each having a
value selected for efficacy of neurostimulation and one or more
secondary parameters each having a value adjustable for preventing
neural accommodation while maintaining the efficacy of the
neurostimulation, the values including a plurality of value sets
for the one or more secondary parameters, the value sets each being
a set of one or more values each given to one of the one or more
secondary parameters; storing the received values of the plurality
of stimulation parameters; delivering neurostimulation during
therapy sessions; and controlling the delivery of the
neurostimulation using the plurality of stimulation parameters, the
controlling including selecting a subset of one or more value sets
from the stored plurality of value sets for the one or more
secondary parameters for each session of the therapy sessions and
adjusting the one or more secondary parameters during the therapy
sessions, wherein the subset is selected to allow for adjusting the
one or more secondary parameters randomly through the therapy
sessions.
12. The method of claim 11, wherein the selecting comprises
randomly selecting each value set of the subset of one or more
value sets from the stored plurality of value sets for each session
of the therapy sessions.
13. The method of claim 11, further comprising: sensing one or more
physiological signals indicative of a degree of modulation of one
or more physiological functions by the neurostimulation; detecting
neural accommodation indicated by a substantial decrease in the
degree of modulation of the one or more physiological functions by
the neurostimulation; and adjusting the one or more secondary
parameters in response to a detection of the neural
accommodation.
14. The method of claim 11, comprising: selecting value sets from
the stored plurality of value sets for the one or more secondary
parameters; generating a sequence of value sets for the each
therapy session including the selected value sets; and dynamically
adjusting the one or more secondary parameters according to the
sequence of value sets during the each therapy session.
15. The method of claim 14, wherein generating the sequence of
value sets comprises randomizing an order of the selected value
sets in the sequence of value sets.
16. The method of claim 11, wherein the one or more primary
parameters comprises a dosing parameter specifying a measure of
total dose of the neurostimulation for a therapy session and
representing a number of electrical pulses delivered during the
therapy session.
17. The method of claim 16, wherein the one or more primary
parameters comprises a duty cycle including an on-period during
which the neurostimulation is delivered and an off-period during
which the neurostimulation is not delivered.
18. The method of claim 17, wherein the one or more secondary
parameters comprise a duration of a ramp during which a stimulation
intensity gradually increases from zero to its value specified for
the on-period when the ramp ends at a beginning of the on-period,
or gradually decreases from its value specified for the on-period
to zero the ramp starting at an end of the on-period.
19. The method of claim 17, wherein the one or more secondary
parameters comprise the on-period and the off-period.
20. The method of claim 13, wherein the one or more primary
parameters comprise a measure of total dosing for a therapy session
of the therapy sessions, the therapy session having a session
duration that is divided into a plurality of segments, and the one
or more secondary parameters comprise an on-off parameter
specifying whether each segment of the plurality of segment is an
on-segment or an off segment, the on-segment being a segment of the
plurality of segment during which the neurostimulation is
delivered, the off-segment being a segment of the plurality of
segment during which the neurostimulation is not delivered.
Description
CLAIM OF PRIORITY
[0001] This application claims the benefit of priority under 35
U.S.C. .sctn.119(e) of Hamann et al., U.S. Provisional Patent
Application Ser. No. 61/486,573, entitled "METHOD AND APPARATUS FOR
NEUROSTIMULATION WITH PREVENTION OF NEURAL ACCOMMODATION", filed on
May 16, 2011, which is herein incorporated by reference in its
entirety.
TECHNICAL FIELD
[0002] This document relates generally to neurostimulation and more
particularly to a neurostimulation system that varies stimulation
parameters to prevent neural accommodation while maintaining
effectiveness of neurostimulation.
BACKGROUND
[0003] Neurostimulation has been applied to modulate various
physiologic functions and treat various diseases. For example,
cardiovascular functions are modulated by neural signals in
portions of the autonomic nervous system. The heart is innervated
with sympathetic and parasympathetic nerves. Neural activities in
these nerves are known to regulate, among other things, heart rate,
blood pressure, and myocardial contractility. Modulation of such
neural activities by neurostimulation therefore provides for
modulation of such cardiovascular functions. One example is the
modulation of cardiac functions in a patient suffering heart
failure or myocardial infarction. Electrical stimulation applied to
the vagus nerve is known to decrease the heart rate and the
contractility, lengthening the systolic phase of a cardiac cycle,
and shortening the diastolic phase of the cardiac cycle. Such
effects of vagus nerve stimulation allow for control of myocardial
remodeling. In addition to treating cardiac disorders such as
myocardial remodeling, vagus nerve stimulation is also known to be
effective in treating disorders including, but not limited to,
depression, anorexia nervosa/eating disorders, pancreatic function,
epilepsy, hypertension, inflammatory disease, and diabetes.
[0004] However, neurostimulation may decrease its effectiveness in
a patient after it has been applied to the patient for a period of
time. Such neural accommodation or tolerance may be due to neural
reorganization (plasticity) or attenuation of end organ
responsiveness. Neural plasticity is the change of structure,
function, and organization of neurons in response to new
experience. An end organ may decrease its responsiveness to
stimulation due to receptor down regulation, reduced sensitivity of
receptors, change in second messenger systems, cell signaling
cascades, etc. Thus, there is a need for maintaining efficacy of
neurostimulation over time, especially when the neurostimulation is
applied as a long-term therapy.
SUMMARY
[0005] A neurostimulation system delivers neurostimulation to a
patient using one or more primary parameters and one or more
secondary parameters. The one or more primary parameters are
controlled for maintaining efficacy of the neurostimulation. The
one or more secondary parameters are adjusted for preventing the
patient from developing neural accommodation. In various
embodiments, values for the one or more secondary parameters are
varied during the delivery of the neurostimulation for prevention
of neural accommodation that may result from a constant or periodic
pattern of stimulation pulses.
[0006] In one embodiment, an implantable medical device includes a
stimulation output circuit, a storage device, a control circuit,
and an implantable housing encapsulating the stimulation output
circuit, the storage device, and the control circuit. The
stimulation output circuit delivers neurostimulation during therapy
sessions. The storage device stores values of a plurality of
stimulation parameters including one or more primary parameters and
one or more secondary parameters. The one or more primary
parameters each have a value selected for efficacy of the
neurostimulation. The one or more secondary parameters each have a
value adjustable for preventing neural accommodation while
maintaining the efficacy of the neurostimulation. The values
include a plurality of value sets for the one or more secondary
parameters. The value sets are each a set of one or more values
each given to one of the one or more secondary parameters. The
control circuit controls the delivery of the neurostimulation using
the plurality of stimulation parameters. The control circuit
includes a parameter adjuster that adjusts one or more parameters
of the plurality of parameters. The parameter adjuster includes a
secondary parameter adjuster that selects a subset of one or more
value sets from the stored plurality of value sets for the one or
more secondary parameters for each session of the therapy sessions
such that the one or more secondary parameters are adjusted
randomly through the therapy sessions.
[0007] In one embodiment, a method for operating an implantable
medical device is provided. Values of a plurality of stimulation
parameters are received and stored. The plurality of stimulation
parameters includes one or more primary parameters and one or more
secondary parameters. The one or more primary parameters each have
a value selected for efficacy of neurostimulation. The one or more
secondary parameters each have a value adjustable for preventing
neural accommodation while maintaining the efficacy of the
neurostimulation. The values include a plurality of value sets for
the one or more secondary parameters. The value sets are each a set
of one or more values each given to one of the one or more
secondary parameters. Neurostimulation is delivered during therapy
sessions, and the delivery is controlled using the plurality of
stimulation parameters. This includes selecting a subset of one or
more value sets from the stored plurality of value sets for the one
or more secondary parameters for each session of the therapy
sessions and adjusting the one or more secondary parameters during
the therapy sessions. The subset is selected to allow for adjusting
the one or more secondary parameters randomly through the therapy
sessions.
[0008] This Summary is an overview of some of the teachings of the
present application and not intended to be an exclusive or
exhaustive treatment of the present subject matter. Further details
about the present subject matter are found in the detailed
description and appended claims. Other aspects of the invention
will be apparent to persons skilled in the art upon reading and
understanding the following detailed description and viewing the
drawings that form a part thereof. The scope of the present
invention is defined by the appended claims and their legal
equivalents.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The drawings illustrate generally, by way of example,
various embodiments discussed in the present document. The drawings
are for illustrative purposes only and may not be to scale.
[0010] FIG. 1 is an illustration of an embodiment of a
neurostimulation system and portions of an environment in which the
system is used.
[0011] FIG. 2 is a block diagram illustrating an embodiment of a
neurostimulation circuit.
[0012] FIG. 3 is a block diagram illustrating another embodiment of
the neurostimulation circuit.
[0013] FIG. 4 is a block diagram illustrating an embodiment of the
neurostimulation system.
[0014] FIG. 5 is a flow chart illustrating an embodiment of a
method for neurostimulation.
[0015] FIG. 6 is a flow chart illustrating an embodiment of a
method for controlling neurostimulation for a specified duty cycle
while preventing neural accommodation.
[0016] FIG. 7 is a flow chart illustrating another embodiment of a
method for controlling neurostimulation for a specified duty cycle
while preventing neural accommodation.
[0017] FIG. 8 is a flow chart illustrating an embodiment of a
method for controlling neurostimulation for a specified total dose
while preventing neural accommodation.
[0018] FIG. 9 is a flow chart illustrating an embodiment of a
method for adjusting parameters in response to detection of neural
accommodation.
[0019] FIG. 10 is a flow chart illustrating an embodiment of a
method for adjusting parameters in response to detection of an
adverse effect.
DETAILED DESCRIPTION
[0020] In the following detailed description, reference is made to
the accompanying drawings which form a part hereof, and in which is
shown by way of illustration specific embodiments in which the
invention may be practiced. These embodiments are described in
sufficient detail to enable those skilled in the art to practice
the invention, and it is to be understood that the embodiments may
be combined, or that other embodiments may be utilized and that
structural, logical and electrical changes may be made without
departing from the spirit and scope of the present invention. The
following detailed description provides examples, and the scope of
the present invention is defined by the appended claims and their
legal equivalents.
[0021] References to "an", "one", or "various" embodiments in this
disclosure are not necessarily to the same embodiment, and such
references contemplate more than one embodiment.
[0022] This document discusses a system and method for delivering
neurostimulation to a patient and controlling stimulation
parameters to prevent the effectiveness of the neurostimulation
from being substantially attenuated by neural accommodation. Neural
accommodation tends to develop in response to neurostimulation with
a constant or periodic stimulus pattern, such as substantially
identical electrical stimulation pulses delivered continuously or
periodically at a substantially constant pulse frequency and
substantially constant duty cycle. The present system avoids such a
constant or periodic pattern by varying values of one or more
stimulation parameters during the delivery of the neurostimulation
while maintaining the effectiveness of the neurostimulation by
controlling one or more other parameters.
[0023] For the purpose of the present subject matter as discussed
in this document, "prevention" of neural accommodation includes
attempts to avoid or attenuate neural accommodation before it is
detected by avoiding a constant or periodic pattern of stimulation
pulses and, if neural accommodation occurs, abating neural
accommodation after it is detected. In various embodiments, such
prevention may be applied at any time during a neurostimulation
therapy, when there is a concern of therapy efficacy being
compromised by neural accommodation.
[0024] FIG. 1 is an illustration of an embodiment of a
neurostimulation system 100 and portions of an environment in which
system 100 is used. FIG. 1 shows a portion of a nerve 102 and a
stimulation electrode 136 placed on nerve 102 to allow for delivery
of neurostimulation to nerve 102. In various embodiments,
stimulation electrode 136 may be placed on nerve 102 or in a
location suitable for delivering the neurostimulation to nerve 102.
In one embodiment, nerve 102 represents a portion of the autonomic
nervous system, such as the vagus nerve and the carotid sinus
nerve. In another embodiment, nerve 102 represents a portion of the
spinal cord or the spinal nerves. A neurostimulation therapy is
applied by delivering controlled stimulation to nerve 102 to
modulate one or more physiological functions controlled by nerve
102. In various embodiments, system 100 is used to treat abnormal
conditions such as heart failure with low ejection fraction, heart
failure with moderate ejection fraction, post-myocardial
infarction, refractory hypertension, angina, arrhythmia, apnea,
diabetes, and inflammation. In various embodiments, system 100 is
used to deliver neurostimulation to any nerve in a patient to
modulate a physiological function of the patient while preventing
the patient from developing neural accommodation.
[0025] In the illustrated embodiment, system 100 includes an
implantable medical device 110 electrically coupled to electrode
136 through an implantable lead 130. Implantable medical device 110
includes a neurostimulation circuit 120 encapsulated in an
implantable housing 112, and a header 114 attached to implantable
housing 112 and providing for connection between neurostimulation
circuit 120 and lead 130. In one embodiment, implantable medical
device 110 is a neurostimulator. In other embodiments, in addition
to a neurostimulator including neurostimulation circuit 120,
implantable medical device 110 includes one or more of a cardiac
pacemaker, a cardioverter/defibrillator, a drug delivery device, a
biologic therapy device, and any other monitoring or therapeutic
devices. These devices may interact with each other. For example,
neural activities may be sensed by neurostimulation circuit 120 to
indicate a need for cardiac stimulation and/or to control the
timing of pacing pulse deliveries from the cardiac pacemaker.
Likewise, cardiac activities are sensed by the cardiac pacemaker to
control the timing of neural stimulation pulse deliveries from
neurostimulation circuit 120, such as to synchronize neural
stimulation to cardiac cycles or respiratory cycles. Lead 130
includes a proximal end 132, a distal end 133, and an elongate body
131 coupled between proximal end 132 and distal end 133. Proximal
end 132 is configured to be connected to implantable medical device
110. Distal end 133 includes, or is otherwise coupled to,
stimulation electrode 136. In various other embodiments,
stimulation electrodes 136 includes any form of electrode that
allows for activation of nerve 102 by electrical stimulation
delivered from neurostimulation circuit 120.
[0026] Neurostimulation circuit 120 delivers neurostimulation to
nerve 102 through lead 130 and controls the delivery of the
neurostimulation using a plurality of stimulation parameters. The
plurality of stimulation parameters includes one or more parameters
each having a value adjustable for preventing neural accommodation
while maintaining efficacy of the neurostimulation. Examples of
such one or more parameters when the neurostimulation is delivered
as electrical pulses include length of the on-portion of the duty
cycle, length of the off-portion of the duty cycle, pulse
amplitude, pulse width, frequency, pulse waveform, and envelop of
the on-portion of the duty cycle (amplitude, width, etc.). Various
embodiments of neurostimulation circuit 120 are discussed below
with reference to FIGS. 2 and 3.
[0027] System 100 also includes an external system 116, which
communicates with implantable medical device 110 via a telemetry
link 118. External system 116 allows a user such as a physician or
other caregiver or the patient to control operation of implantable
medical device 110 and monitor the status of the patient and/or
implantable medical device 110.
[0028] FIG. 2 is a block diagram illustrating an embodiment of a
neurostimulation circuit 220. Neurostimulation circuit 220
represents an embodiment of neurostimulation circuit 120 and
includes a stimulation output circuit 240, a control circuit 242,
and a storage device 244. Stimulation output circuit 240 delivers
neurostimulation to the patient during therapy sessions. In one
embodiment, the delivery of the neurostimulation includes delivery
of electrical pulses. Storage device 244 stores values of a
plurality of stimulation parameters including one or more primary
parameters and one or more secondary parameters. The one or more
primary parameters each have a value selected for maintaining
efficacy of the neurostimulation. The one or more secondary
parameters each have a value adjustable for preventing neural
accommodation without substantially compromising the efficacy of
the neurostimulation. The stored values of the plurality of
stimulation parameters include a plurality of value sets for the
one or more secondary parameters. The value sets are each a set of
one or more values each given to one of the one or more secondary
parameters. Control circuit 242 controls the delivery of the
neurostimulation using the plurality of stimulation parameters and
includes a parameter adjuster 246. Parameter adjuster 246 adjusts
one or more parameters of the plurality of parameters. In various
embodiments, parameter adjuster 246 selects a different subset of
one or more value sets from the stored plurality of value sets for
the one or more secondary parameters for each session of the
therapy sessions. The selection is performed according to various
rules determined to prevent the patient from developing neural
accommodation in response to the delivery of the
neurostimulation.
[0029] In one embodiment, parameter adjuster 246 selects a subset
of one or more value sets from the stored plurality of value sets
for the one or more secondary parameters for each session of the
therapy sessions such that the one or more secondary parameters are
adjusted randomly or pseudo-randomly through the therapy sessions.
This may be achieved by storing the value sets for the one or more
secondary parameters in a randomized or pseudo-randomized order in
storage device 244, or by configuring parameter adjuster 246 to
randomly or pseudo-randomly select value sets from the plurality of
value sets for the one or more secondary parameters stored in
storage device 244. For various embodiments, pseudo-randomness
refers to, for example, an order of values that is not truly
randomized but arranged in a way approximating randomness by its
potential effect in prevention of neural accommodation. In various
embodiments as discussed in this document, randomness may include
true randomness or pseudo-randomness.
[0030] In various embodiments, the one or more primary parameters
are each a parameter whose value is determined and/or adjusted for
efficacy. In one embodiment, each parameter of the one or more
primary parameters is given a predetermined value. In one
embodiment, parameter adjuster 246 adjusts each parameter of the
one or more primary parameters as needed to maintain efficacy of
the neurostimulation. One example of the one or more primary
parameters includes one or more parameters being a measure of a
total dose of the neurostimulation applied over a therapy
session.
[0031] In various embodiments, the one or more secondary parameters
are each a parameter whose value can be substantially adjusted
without substantially affecting the efficacy of the
neurostimulation. The value sets of the one or more secondary
parameters are each determined to maintain efficacy of the
neurostimulation and are substantially different from each other.
One example of the one or more secondary parameters includes pulse
amplitude and pulse width. The value sets each include a pulse
amplitude value and a pulse width value selected based on a
predetermined strength-duration curve.
[0032] In various embodiments, the circuit of system 100, including
its various elements discussed in this document, is implemented
using a combination of hardware and software (including firmware).
In various embodiments, control circuit 242, including their
various elements discussed in this document, may be implemented
using an application-specific circuit constructed to perform one or
more particular functions or a general-purpose circuit programmed
to perform such function(s). Such a general-purpose circuit
includes, but is not limited to, a microprocessor or a portion
thereof, a microcontroller or portions thereof, and a programmable
logic circuit or a portion thereof.
[0033] FIG. 3 is a block diagram illustrating an embodiment of a
neurostimulation circuit 320. Neurostimulation circuit 320
represents another embodiment of neurostimulation circuit 120 and
includes stimulation output circuit 240, a sensing circuit 350, an
accommodation detector 352, an adverse effect detector 354, a
control circuit 342, and a storage device 344.
[0034] Sensing circuit 350 senses one or more physiological signals
indicative of one or more effects of the delivery of the
neurostimulation from stimulation output circuit 240. In one
embodiment, at least one of the one or more physiological signals
is indicative of a degree of modulation of one or more
physiological functions by the neurostimulation. Such modulation
results from responses of one or more nerves to which the
neurostimulation is applied, and the one or more nerves innervate
or otherwise control the one or more organs.
[0035] Accommodation detector 352 detects an indication of neural
accommodation using the one or more physiological signals. In one
embodiment, the indication of neural accommodation includes a
substantial decrease in the degree of modulation of the one or more
physiological functions by the neurostimulation. In another
embodiment, the indication of neural accommodation includes a
substantial increase in stimulation threshold as a percentage or
absolute value, where the stimulation threshold is the minimum
intensity of the neurostimuation that results in a detectable
modulation of the one or more physiological functions in response
to the neurostimulation.
[0036] Adverse effect detector 354 detects an indication of an
adverse effect of the neurostimulation using the one or more
physiological signals. In various embodiments, the adverse effect
is an unintended effect of the neurostimulation. In one embodiment,
the adverse effect is an unintended effect of the neurostimulation
that is considered to be harmful to the patient.
[0037] Storage device 344 represents an embodiment of storage
device 244 and stores values of the plurality of stimulation
parameters including the one or more primary parameters and the one
or more secondary parameters. In one embodiment, the plurality of
value sets for the one or more secondary parameters are stored in
storage device 344 as one or more sequences of value sets for the
one or more secondary parameters. The one or more sequences are
each generated for a therapy session. In one embodiment, a
plurality of such sequences is stored to be used for multiple
therapy sessions. A therapy session includes a programmed period of
time during which the patient is treated by continuous or
intermittent delivery of the neurostimulation. An intermittent
delivery of the neustimulation is programmed to include periods
during which the neurostimulation is delivered and periods during
which the neurostimulation is not delivered. In one embodiment, the
therapy sessions are timed according to a programmed schedule, such
as being started on a substantially periodic basis.
[0038] Control circuit 342 represents an embodiment of control
circuit 242 and controls the delivery of the neurostimulation using
the plurality of stimulation parameters. Control circuit 342
includes a parameter adjuster 346, which represents an embodiment
of parameter adjuster 246 and adjusts one or more parameters of the
plurality of stimulation parameters. Parameter adjuster 346
includes a primary parameter adjuster 356 and a secondary parameter
adjuster 358.
[0039] Primary parameter adjuster 356 adjusts the one or more
primary parameters. In one embodiment, primary parameter adjuster
356 sets the value of each of the one or more primary parameters to
a predetermined value, such as a value received from the user
through external system 116 and telemetry link 118. In one
embodiment, primary parameter adjuster 356 adjusts the value of
each of the one or more primary parameters using the one or more
physiological signals, such as to maintain a specified degree of
modulation of one or more physiological functions by the
neurostimulation as indicated by the one or more physiological
signals.
[0040] Secondary parameter adjuster 358 adjusts the one or more
secondary parameters. In various embodiments, secondary parameter
adjuster 358 selects for each therapy session a subset of one or
more value sets from the plurality of value sets for the one or
more secondary parameters stored in storage device 344. In one
embodiment, secondary parameter adjuster 358 randomly selects each
value set of the one or more value sets from the stored plurality
of value sets for each therapy session. In another embodiment,
secondary parameter adjuster 358 selects each value set of the one
or more value sets by cycling through the plurality of value sets
in a predetermined order, such as cycling through the plurality of
value sets stored in storage device 344 as a circular list.
Secondary parameter adjuster 358 adjusts the one or more secondary
parameters using the selected one or more value sets for the
therapy session. In one embodiment, secondary parameter adjuster
358 adjusts the one or more secondary parameters in response to a
detection of the indication of the neural accommodation by
accommodation detector 352. In one embodiment, secondary parameter
adjuster 358 adjusts the one or more secondary parameters in
response to a detection of the indication of the adverse effect of
the neurostimulation by adverse effect detector 354. In one
embodiment, secondary parameter adjuster 358 adjusts the one or
more secondary parameters in response to an adjustment to the one
or more primary parameters by primary parameter adjuster 356.
[0041] In various embodiments, secondary parameter adjuster 358
selects prior to each therapy session a value set from the
plurality of value sets for the one or more secondary parameters
stored in storage device 344, and sets the one or more secondary
parameters to the selected value set for the entire therapy
session. In one embodiment, secondary parameter adjuster 358
randomly selects prior to the therapy session the value set from
the plurality of value sets stored in storage device 344. In
another embodiment, secondary parameter adjuster 358 selects prior
to the therapy session the value set by cycling through the
plurality of value sets in a predetermined order, such as cycling
through the plurality of value sets stored in storage device 344 as
a circular list.
[0042] In various embodiments, secondary parameter adjuster 358
selects value sets from the plurality of value sets for the one or
more secondary parameters stored in storage device 344, and
generates a sequence of value sets for each therapy session. The
sequence of value sets includes the selected value sets with timing
specified for using each of the selected value sets during the
therapy session. In one embodiment, secondary parameter adjuster
358 randomly selects the value sets from the plurality of value
sets stored in storage device 344. In another embodiment, secondary
parameter adjuster 358 selects the value set by cycling through the
plurality of value sets in a predetermined order, such as cycling
through the plurality of value sets stored in storage device 344 as
a circular list. In another embodiment, secondary parameter
adjuster 358 randomizes an order of the selected value sets in the
sequence of value sets. Secondary parameter adjuster 358
dynamically adjusts the one or more secondary parameters according
to the sequence of value sets during the therapy session.
[0043] In various embodiments, one or more predetermined sequences
of value sets for the one or more secondary parameters are stored
in storage device 344, and secondary parameter adjuster 358 selects
a sequence from the stored one or more predetermined sequences. In
one embodiment, secondary parameter adjuster 358 randomly selects
the sequence from the stored plurality of sequences. In another
embodiment, secondary parameter adjuster 358 selects the sequence
by cycling through the plurality of sequences in a predetermined
order, such as cycling through the plurality of sequences stored in
storage device 344 as a circular list. Secondary parameter adjuster
358 dynamically adjusts the one or more secondary parameters using
the selected sequence during the therapy session.
[0044] FIG. 4 is a block diagram illustrating an embodiment of a
neurostimulation system 400. System 400 represents an embodiment of
system 100 and includes one or more leads 430, an implantable
medical device 410, and an external system 416 communicating with
implantable medical device 410 via telemetry link 118.
[0045] Lead(s) 430 provides therapy interface between system 400
and the patient receiving the neurostimulation therapy. In various
embodiments, lead(s) 430 include any one or more leads suitable for
delivering the neurostimulation to the patient, with lead 130
illustrating one example.
[0046] Implantable medical device 410 represents an embodiment of
implantable medical device 110 and includes neurostimulation
circuit 120 and an implant telemetry circuit 460. Implant telemetry
circuit 460 allows implantable medical device 410 to communicate
with external system 416 via telemetry link 118.
[0047] External system 416 represents an embodiment of external
system 116 and includes an external telemetry circuit 462, a user
interface 464, and a parameter generator 466. External telemetry
circuit 462 allows external system 416 to communicate with
implantable medical device 410 via telemetry link 118. User
interface 464 allows the user to control operation of, and obtain
information from, system 400. Parameter generator 466 generates
values for the plurality of stimulation parameters, which are
transmitted to implantable medical device 410 to be stored in
storage device 244 or 344. In the illustrated embodiment, parameter
generator 466 includes a value generator 468 and a sequence
generator 470.
[0048] Value generator 468 generates the plurality of value sets
for the one or more secondary parameters. In one embodiment, value
generator 468 receives predetermined value sets from the user
through user interface 464 or through a data interface. In another
embodiment, value generator 468 generates the value sets according
to predetermined criteria. For example, value generator 468
receives one or more values of the one or more primary parameters
and generates the value sets using the received one or more values
of the one or more primary parameters and the predetermined
criteria. The predetermined criteria requires that the value sets
each approximately maintain the one or more primary parameters at
the received one or more values and including one or more values
each within a specified value range for the one or more secondary
parameters. In one embodiment, the values for each parameter of the
one or more secondary parameters are given or generated in
specified increments, and tested for the efficacy of the
neurostimulation. In one embodiment, the efficacy of the
neurostimulation is tested by sensing electromyogram (EMG) or
accelerometer signals indicative of laryngeal response to the
neurostimulation using different value sets for the one or more
secondary parameters. In other embodiments, the efficacy of the
neurostimulation is tested by monitoring one or more intended
effects of the neurostimulation when the neurostimulation is
delivered using different value sets for the one or more secondary
parameters.
[0049] Sequence generator 470 generates the one or more sequences
of value sets for the one or more secondary parameters to be stored
in implantable medical device 410 when needed. In one embodiment,
sequence generator 470 selects value sets from the value sets for
the one or more secondary parameters generated from value generator
468, and determines an order for the selected value sets. In
various embodiments, each of the one or more sequences of value
sets for the one or more secondary parameters includes the selected
value sets in a random order, a pseudo-random order, or other
substantially aperiodic order (with no identical value sets
repeating on a substantially periodic basis).
[0050] FIG. 5 is a flow chart illustrating an embodiment of a
method 500 for neurostimulation. Method 500 provides for delivery
of neurostimulation using a system such as system 100, including
its various embodiments as discussed in this document, for
prevention of neural accommodation while maintaining efficacy of
the neurostimulation.
[0051] At 510, one or more primary parameters are identified for
maintaining efficacy of the neurostimulation. At 520, a value or
value range is determined for each parameter of the one or more
primary parameters. The value or value range may be experimentally
determined by monitoring the response of a patient to the delivery
of the neurostimulation, and may be adjusted to maintain the
efficacy of neurostimulation if necessary during or between therapy
sessions.
[0052] At 530, one or more secondary parameters are identified for
preventing neural accommodation without substantially affecting the
efficacy of the neurostimulation. At 540, a value range is
determined for each parameter of the one or more secondary
parameters. The value range may be experimentally tested to verify
that when the parameter varies within it, the efficacy of the
neurostimulation is not substantially affected.
[0053] At 550, a plurality of value sets for the one or more
secondary parameters is generated. The value sets each include a
value for each parameter of the one or more secondary parameters,
and are substantially different from each other. In one embodiment,
one or more sequences of value sets are generated by selecting
value sets from the plurality of value sets generated. At 560, the
values of the one or more primary parameters and the one or more
secondary parameters are stored in a neurostimulation circuit, such
as neurostimulation circuit 120, including its various embodiments
discussed in this document.
[0054] At 570, values for the one or more primary parameters and
the one or more secondary parameters are selected by the
neurostimulation circuit for a therapy session. In one embodiment,
this includes selecting one or more value sets from the plurality
of value sets for the one or more secondary parameters. In another
embodiment, this includes selecting a sequence of value sets from
the one or more sequences of value sets.
[0055] At 580, delivery of the neurostimulation is controlled using
the selected values for the one or more primary parameters and the
one or more secondary parameters during the therapy session. At
590, the neurostimulation is delivered from the neurostimulation
circuit during the therapy session.
[0056] FIG. 6 is a flow chart illustrating an embodiment of a
method 600 for controlling neurostimulation for a specified duty
cycle while preventing neural accommodation. In one embodiment,
method 600 is performed using system 100, including its various
embodiments discussed in this document. In method 600, the
neurostimulation is delivered at a specified duty cycle during
therapy sessions. Each therapy session includes a plurality of
total periods each being a sum of an on-period and an off-period.
The on-period is a time period during which the neurostimulation is
delivered. The off-period is a time period during which the
neurostimulation is not delivered. The duty cycle is the ratio of
the on-period to the total period and can be expressed in
percentage. The duty cycle can also be expressed as a duty cycle
ratio, which is a ratio of the on-period to the off-period. When
the neurostimulation is delivered as electrical pulses with a
specified duration of the therapy session and a specified pulse
frequency, the duty cycle is a dosing parameter representative of
the dose of the neurostimulation for the therapy session measured
by the number of the electrical pulses delivered during the therapy
session.
[0057] It is observed that when a ramp is introduced for the
transition from the off-period to the on-period, and/or from the
on-period to the off-period, within a limited range, the ramp
duration does not substantially affect the efficacy of the
neurostimulation. The ramp duration is a time interval during which
the intensity of the neurostimulation gradually increases from zero
to its value specified for the on-period, or a time interval during
which the intensity of the neurostimulation gradually decreases to
zero from its value specified for the on-period. In one embodiment,
the ramp ends at the beginning of the on-period, or begins at the
end of the on-period. Therefore, in method 600, the one or more
primary parameters include the duty cycle (or equivalently, duty
cycle ratio). The one or more secondary parameters include the ramp
duration. In various embodiments, the intensity of the
neurostimulation steps up or down in specified increments during
the ramp duration.
[0058] At 610, a value for the duty cycle of the neurostimulation
is determined for maintaining efficacy of the neurostimulation. At
620, a sequence of values for the ramp duration is determined for a
therapy session. The values are within a limited range within which
the ramp duration does not substantially affect the efficacy of the
neurostimulation. In various embodiments, the sequence of values
for the ramp duration includes the values arranged in a random
order, a pseudo-random order, or other substantially aperiodic
order. At 630, the therapy session is started. At 640, the
neurostimulation is delivered using the first value of the sequence
of values for the ramp duration. If the specified total dose of the
neurostimulation has not been delivered at 650, the
neurostimulation continues to be delivered using the next value in
the sequence of values for the ramp duration at 660. If the
specified total dose of the neurostimulation has been delivered at
650, the therapy session ends at 670.
[0059] FIG. 7 is a flow chart illustrating an embodiment of a
method 700 for controlling neurostimulation for a specified duty
cycle while preventing neural accommodation. In one embodiment,
method 700 is performed using system 100, including its various
embodiments discussed in this document. In method 700, the
neurostimulation is also delivered at a specified duty cycle during
therapy sessions, with parameters including the total period, the
on-period, the off-period, the duty cycle (or equivalently the duty
cycle ratio), as discussed above for method 600.
[0060] It is observed that within a limited range, the value of the
total period does not substantially affect the efficacy of the
neurostimulation as long as the specified duty cycle is maintained.
In other words, the values of the on-period and the off-period do
not substantially affect the efficacy of the neurostimulation as
long as the ratio of the on-period to the total period (the duty
cycle) or the ratio of the on-period to the off-period (the duty
cycle ratio) is maintained. Therefore, in method 700, the one or
more primary parameters include the duty cycle (or equivalently,
duty cycle ratio). The one or more secondary parameters include the
on-period and the off-period (or equivalently, any two of the
on-period, the off-period, and the total period).
[0061] At 710, a value for the duty cycle of the neurostimulation
is determined for maintaining efficacy of the neurostimulation. At
720, a sequence of values sets for the on-period and the off-period
is determined for a therapy session. The values are within a
limited range within which the on-period and the off-period do not
substantially affect the efficacy of the neurostimulation as long
as the duty cycle is maintained. In various embodiments, the
sequence of value sets for the on-period and the off-period
includes the value sets arranged in a random order, a pseudo-random
order, or other substantially aperiodic order. At 730, the therapy
session is started. At 740, the neurostimulation is delivered using
the first value of the sequence of value sets for the on-period and
the off-period. If the specified total dose of the neurostimulation
has not been delivered at 750, the neurostimulation continues to be
delivered using the next value of the sequence of value sets for
the on-period and the off-period at 760. If the specified total
dose of the neurostimulation has been delivered at 750, the therapy
session ends at 770.
[0062] FIG. 8 is a flow chart illustrating an embodiment of a
method 800 for controlling neurostimulation for a specified total
dose while preventing neural accommodation. In one embodiment,
method 800 is performed using system 100, including its various
embodiments discussed in this document. In method 800, the
neurostimulation is delivered for a specified dose for each therapy
session. The therapy session has a session duration that is
sufficiently long to allow the specified dose to be administrated
intermittently. In one embodiment, the specified does is expressed
as duration. When the neurostimulation is delivered as electrical
pulses with a specified duration of the therapy session and a
specified pulse frequency, the specified dose (as a duration) is a
dosing parameter representative of the dose of the neurostimulation
for the therapy session measured by the number of the electrical
pulses delivered during the therapy session.
[0063] When the neurostimulation is to be delivered intermittently,
the session duration may be divided into a plurality of on-segments
and off-segments. The on-segment is a segment of time during which
the neurostimulation is delivered. The off-segment is a segment of
time during which the neurostimulation is not delivered. It is
observed that within a limited range, the distribution of the
on-segments and the off-segments does not substantially affect the
efficacy of the neurostimulation as long as the specified dose is
delivered during the on-segments. Therefore, in method 800, the one
or more primary parameters include the specified dose, which is a
measure of total dosing of the neurostimulation for a therapy
session. The session duration is divided into a plurality of
segments. In one embodiment in which the neurostimulation includes
electrical pulses, the specified dose is a specified total
stimulation duration over which the neurostimulation is delivered.
The one or more secondary parameters include a segment duration
parameter and an on-off parameter. The segment duration parameter
specifies a segment duration being the duration of each segment of
the plurality of segments. The on-off parameter specifies whether
each segment of the plurality of segments is an on-segment or an
off-segment.
[0064] At 810, a total dose of the neurostimulation for a therapy
session is determined to be used as the specified dose. At 820, the
therapy session is divided into a plurality of time segments. At
830, a total number of the on-segments required to deliver the
total dose is determined. At 840, each segment of the plurality of
time segments is assigned as one of the on-segment and the
off-segment. In various embodiments, the segments are assigned on a
random, pseudo-random, or other substantially aperiodic basis. In
other words, the on-segments are distributed over the session
duration in a random, pseudo-random, or other substantially
aperiodic manner. At 850, the therapy session is started. At 860,
the neurostimulation is delivered during the assigned on-segments.
At 870, the therapy session ends, after the total dose has been
delivered.
[0065] Various stimulation parameters used as the primary and
secondary parameters are discussed in methods 600, 700, and 800,
with reference to FIGS. 6-8, by way of example, but not by way of
limitation. In methods 600, 700, and 800, the one or more
parameters specify a measure of total dose of the neurostimulation
for a therapy session. When the neurostimulation is delivered as
electrical pulses with a specified duration of the therapy session
and a specified pulse frequency, this measure of total dose of the
neurostimulation is expressed as a duty cycle or a total
stimulation duration and represents the total number of the
electrical pulses delivered during the therapy session. In various
embodiments, the one or more primary parameters include any
parameter or combination of parameters identified to be useable for
maintaining efficacy of neurostimulation, and the one or more
secondary parameters include any parameter or combination of
parameters identified to be useable for preventing neural
accommodation without substantially affecting the efficacy of
neurostimulation. In various embodiments, the one or more secondary
parameters can be set to varying values without substantially
changing the one or more values of the one or more primary
parameters.
[0066] FIG. 9 is a flow chart illustrating an embodiment of a
method 900 for adjusting parameters in response to detection of
neural accommodation. In one embodiment, method 900 is performed
using system 100, including its various embodiments discussed in
this document. In method 900, the one or more secondary parameters
are adjusted only in response to detection of neural accommodation.
That is, in response to the detection of neural accommodation,
methods 600, 700, and/or 800 are performed. For example, secondary
parameter adjuster 358 is enabled by the detection of neural
accommodation.
[0067] At 910, the neurostimulation is delivered according to a
programmed schedule of therapy sessions. At 920, neural
accommodation is being detected. In response to a detection of
neural accommodation at 930, the one or more values of the one or
more secondary parameters are adjusted at 940. If neural
accommodation is not detected at 930, the neural accommodation
continues to be delivered, without adjusting the one or more
secondary parameters.
[0068] FIG. 10 is a flow chart illustrating an embodiment of a
method 1000 for adjusting parameters in response to detection of an
adverse effect. In one embodiment, method 1000 is performed using
system 100, including its various embodiments discussed in this
document. In method 1000, the one or more secondary parameters are
adjusted only in response to detection of an adverse effect. That
is, in response to the detection of the adverse effect, methods
600, 700, and/or 800 are performed. For example, secondary
parameter adjuster 358 is enabled by the detection of the adverse
effect, This provides system 100 with a safety measure in case the
one or more secondary parameters are set to one or more values that
causes an unintended effect that may be harmful to the patient.
[0069] At 1010, the neuro stimulation is delivered according to a
programmed schedule of therapy sessions. At 1020, an adverse effect
is being detected. In response to a detection of the adverse effect
at 1030, the one or more values of the one or more secondary
parameters are adjusted at 1040. If no adverse effect is detected
at 1030, the neural accommodation continues to be delivered,
without adjusting the one or more secondary parameters.
[0070] It is to be understood that the above detailed description
is intended to be illustrative, and not restrictive. Other
embodiments will be apparent to those of skill in the art upon
reading and understanding the above description. The scope of the
invention should, therefore, be determined with reference to the
appended claims, along with the full scope of equivalents to which
such claims are entitled.
* * * * *