U.S. patent application number 12/697971 was filed with the patent office on 2010-06-03 for technique for adjusting the locus of excitation of electrically excitable tissue.
This patent application is currently assigned to Medtronic, Inc.. Invention is credited to Michael D. Baudino, Greg Hrdlicka, Gary W. King, Robert Leinders.
Application Number | 20100137926 12/697971 |
Document ID | / |
Family ID | 46279628 |
Filed Date | 2010-06-03 |
United States Patent
Application |
20100137926 |
Kind Code |
A1 |
King; Gary W. ; et
al. |
June 3, 2010 |
Technique for Adjusting the Locus of Excitation of Electrically
Excitable Tissue
Abstract
The locus of electrically excitable tissue where action
potentials are induced can be controlled using the physiological
principle of electrotonus. In one embodiment, first and second
pulses are applied to first and second electrodes, respectively, to
generate first and second subthreshold potential areas,
respectively, within the tissue. The locus within the tissue where
action potentials are induced is determined by a superposition of
the first and second subthreshold areas according to the
physiological principle of electrotonus. In another embodiment, a
two-dimensional array of electrodes are formed. The cathode may be
positioned near the center of the two-dimensional array or may be
left out. The first and second subthreshold areas may thereby be
steered. An array of anodal rings may be used to contain the field
of excitation.
Inventors: |
King; Gary W.; (Fridley,
MN) ; Leinders; Robert; (Maaslandstaat, NL) ;
Hrdlicka; Greg; (Plymouth, MN) ; Baudino; Michael
D.; (Coon Rapids, MN) |
Correspondence
Address: |
BANNER & WITCOFF, LTD.
TEN SOUTH WACKER DRIVE, SUITE 3000
CHICAGO
IL
60606
US
|
Assignee: |
Medtronic, Inc.
Minneapolis
MN
|
Family ID: |
46279628 |
Appl. No.: |
12/697971 |
Filed: |
February 1, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11273310 |
Nov 14, 2005 |
7657318 |
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12697971 |
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10247981 |
Sep 20, 2002 |
6988006 |
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11273310 |
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09523072 |
Mar 10, 2000 |
6505078 |
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10247981 |
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09312470 |
May 17, 1999 |
6083252 |
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09523072 |
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08814432 |
Mar 10, 1997 |
5925070 |
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09312470 |
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08637361 |
Apr 25, 1996 |
5713922 |
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08814432 |
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08627578 |
Apr 4, 1996 |
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08637361 |
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Current U.S.
Class: |
607/2 |
Current CPC
Class: |
A61N 1/36071 20130101;
A61N 1/36167 20130101; A61N 1/0534 20130101; A61N 1/36164 20130101;
A61N 1/36017 20130101; A61N 1/0531 20130101; A61N 1/0551
20130101 |
Class at
Publication: |
607/2 |
International
Class: |
A61N 1/08 20060101
A61N001/08 |
Claims
1. A method of controlling for therapeutic purposes a volume of
neural tissue stimulation of a predetermined portion of a brain of
a patient, the method comprising the steps of: placing a first
electrode, a second electrode, and a third electrode at least near
said predetermined portion of the brain; establishing anode/cathode
relationships between said first electrode and said second
electrode and between said first electrode and said third
electrode; and presenting electrical pulses to each established
anode/cathode relationship to cause a steerable locus of excitation
of nerve fibers or cells of said brain.
Description
[0001] This is a continuation of application Ser. No. 11/273,310
filed Nov. 14, 2005, which is a continuation of application Ser.
No. 10/247,981, filed Sep. 20, 2002, now U.S. Pat. No. 6,988,006,
which is a continuation of patent application Ser. No. 09/523,072,
filed Mar. 10, 2000, now U.S. Pat. No. 6,505,078, which is a
continuation-in-part of application Ser. No. 09/312,470, filed on
May 17, 1999, now U.S. Pat. No. 6,083,252, which is a divisional of
application Ser. No. 08/814,432, filed Mar. 10, 1997, now U.S. Pat.
No. 5,925,070, which is a continuation-in-part of application Ser.
No. 08/637,361, filed on Apr. 25, 1996, now U.S. Pat. No.
5,713,922, which is a continuation-in-part of application Ser. No.
08/627,578, filed on Apr. 4, 1996, now abandoned, for which
priority is claimed. These patents and patent applications are each
incorporated herewith by reference in their entireties.
FIELD OF THE INVENTION
[0002] This invention relates to means of stimulating electrically
excitable tissue, and more particularly relates to means for
adjusting the locus at which action potentials are induced in such
tissue.
DESCRIPTION OF THE RELATED ART
[0003] Two major practical problems reduce the efficacy of epidural
spinal cord stimulation (SCS) for pain control. One is the
difficulty of directing the stimulation-induced paresthesia to the
desired body part and the other is the problem of disagreeable
sensations or motor responses to the stimulation, which reduce the
comfortable amplitude range of the stimulation. It is generally
agreed that in SCS, for chronic pain, paresthesia should cover the
whole pain region. With present stimulation methods and equipment,
only highly skilled and experienced practitioners are able to
position a stimulation lead in such a way that the desired overlap
is reached and desired results are obtained over time with minimal
side effects. It requires much time and effort to focus the
stimulation on the desired body region during surgery and, using
pulses with single value cathodes, it is difficult to redirect it
afterwards, even though some readjustments can be made by selecting
a different contact combination, pulse rate, pulse width or
voltage.
[0004] Redirecting paresthesia after surgery is highly desirable.
Even if paresthesia covers the pain area perfectly during surgery,
the required paresthesia pattern often changes later due to lead
migration, or histological changes (such as the growth of
connective tissue around the stimulation electrode) or disease
progression. The problem of lead placement has been addressed by
U.S. Pat. No. 5,121,754 by the use of a lead with a deformable
distal shape. These problems are not only found with SCS, but also
with peripheral nerve stimulation (PNS), depth brain stimulation
(DBS), cortical stimulation and also muscle or cardiac
stimulation.
[0005] The era of precise control of electrical fields for
excitation of tissue by use of multiple voltages is disclosed in
PCT International Publication No. WO 95/19804 (counterpart to
Holsheimer et al., U.S. Pat. No. 5,501,703) (the "Holsheimer
references"). The Holsheimer references describe the use of
electrodes that are "in-line," namely that they are disposed
"symmetrically" along a line. The three juxtaposed electrodes have
two simultaneous voltages relative to one of them, each with its
own amplitude. This approach allows "steering" of the electric
fields created by these electrodes. Particularly, the electrical
field pattern is adjusted by varying the electrical field generated
between those electrodes along that line. The locus of excitation
is correspondingly varied with that variation in the electrical
field pattern. For example, if a central electrode of three roughly
collinear electrodes is a cathode (-) then the outer anodes push
the areas of excitation toward the middle, and shield outer areas
from excitation. As the anodal pulses are varied in amplitude, the
field steers toward the outside.
[0006] However, the Holsheimer references disclose a system that
requires three electrodes that are optimally spaced symmetrically
along a line. It is a serious handicap during the surgical
procedure to place these electrodes in the body. Often, a lead such
as a paddle is used for mounting the multiple electrodes in the
optimally spaced positions. This lead is then inserted within a
patient near the tissue to be excited, and electrical excitation is
applied to the lead. Unfortunately, placement of a lead such as the
paddle within a patient, can be difficult since the paddle can be
surgically difficult to manipulate adjacent the spinal cord. Thus,
it would be desirable to be able to adjust the locus of excitation
in electrically excitable tissue without the use of optimally
spaced electrodes.
[0007] In addition, the Holsheimer system is limited in that
steering is accomplished over a linear path. It would be desirable
to adjust the locus of excitation in electrically excitable tissue
over a greater area.
OBJECTS OF THE INVENTION
[0008] Accordingly, a primary object of the present invention is to
provide a method and apparatus for adjusting the locus of
excitation in electrically excitable tissue using electrodes that
do not have to be optimally spaced in a line.
[0009] In particular, an object of the present invention is to
adjust areas of subthreshold excitation in order to adjust an area
of superposition of such areas of subthreshold excitation. The area
of superposition determines the locus of excitation of electrically
excitable tissue.
[0010] Another object of the invention is to provide a method and
apparatus for adjusting the locus of superthreshold excitation in
electrically excitable tissue using electrodes that are spaced in a
two dimensional array.
[0011] Another object of the invention is to add outer anodes to a
grouping of cathodal electrodes to shield areas farther out and to
keep activation of tissue nearer to the cathodes.
SUMMARY OF THE INVENTION
[0012] In a principle aspect, the present invention takes the form
of an apparatus and method for inducing action potentials at an
adjustable locus of electrically excitable tissue. In accordance
with the invention, a first pulse having a first amplitude and a
first pulse width is applied to the tissue via a first electrode
adapted to be adjacent said tissue. Similarly, a second pulse
having a second amplitude and a second pulse width is applied to
the tissue via a second electrode adapted to be adjacent said
tissue.
[0013] The application of the first pulse generates a first
subthreshold potential area in said tissue, and the application of
the second pulse generates a second subthreshold potential area.
The first subthreshold area is determined by the first amplitude
and the first pulse width of the first pulse, and the second
subthreshold area is determined by the second amplitude and the
second pulse width of the second pulse. A superposition of the
first and second subthreshold areas results in a suprathreshold
potential area of said adjustable locus where the action potentials
are induced.
[0014] This embodiment of the present invention may be applied to
particular advantage when adjusting the locus where the action
potentials are induced. The first amplitude or the first pulse
width of the first pulse can be adjusted for a corresponding
adjustment of the first subthreshold area and contribute, in turn,
to the volume where suprathreshold potentials are produced.
Similarly, the second amplitude or the second pulse width of the
second pulse can be adjusted for a corresponding adjustment of the
second subthreshold area and contribute, in turn, to the volume of
where suprathreshold potentials are produced. The size and location
of the suprathreshold potential area can thus be controlled.
[0015] In another aspect of the present invention, a time delay
between the application of the first and second pulses can be
varied for a corresponding adjustment in size and location of the
suprathreshold potential area. The time delay between the
application of the first and second pulses can be measured from the
end time of the first pulse to the begin time of the second pulse.
Additionally, that delay can be measured as a difference between a
first weighted average time of the first pulse and a second
weighted average time of the second pulse, or between a first peak
time of the first pulse and a second peak time of the second
pulse.
[0016] In another aspect of the invention, simultaneous pulses of
varying amplitudes are delivered to multiple electrodes (cathodes),
which are arranged in a two-dimensional array. As a cross-pattern,
there may be a central electrode at the center of the pattern,
which is the most cathodal (negative). By having the outer four
electrodes to be less cathodal (not as negative), or even fully
positive (anodal), the locus of cells that have suprathreshold
activation can be shifted in two dimensions. With such constraining
of the fields, the amplitude can be increased, driving the locus of
activation deeper into the tissue, thereby creating a third
dimensional effect.
[0017] In yet another aspect of the invention, the two-dimensional
array of cathodes may be surrounded by an outer ring of anodes to
keep the locus of activation contained and to shield outside tissue
from activation.
[0018] In still another aspect of the invention, a combination of
simultaneous and delayed cathodal pulses are applied on some
electrodes in an array. Each pulse creates an area of subthreshold
excitation, and the combination provides a controlled locus to the
threshold for the production of action potentials.
[0019] These and other features and advantages of the present
invention will be better understood by considering the following
detailed description of the invention which is presented with the
attached drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] These and other advantages and features of the invention
will become apparent upon reading the following detailed
description and referring to the accompanying drawings in which
like numbers refer to like parts throughout and in which:
[0021] FIG. 1 is a diagrammatic view of a patient in which a
preferred form of apparatus for SCS made in accordance with the
invention has been implanted;
[0022] FIG. 2 is a cross-sectional view of an exemplary spinal
column showing a typical position at which electrodes made in
accordance with the preferred practice of the invention have been
implanted in the epidural space;
[0023] FIG. 3 is a cross-sectional view like FIG. 2 showing locus
of potential changes induced in cells of the spinal cord from a
pulse applied to a first one of two electrodes;
[0024] FIG. 4 is a view like FIG. 3 showing the locus of potential
changes induced in cells of the spinal cord from the application of
a pulse to the second of the electrodes;
[0025] FIG. 5 is a view like FIG. 4 showing the combined loci in
the spinal cord at which potential changes are induced from pulses
applied to the first and second electrodes;
[0026] FIG. 6 is a view like FIG. 5 showing the alteration of the
loci due to increase in the amplitude of the pulse applied to the
first electrode and a decrease in amplitude of the pulse applied to
the second electrode;
[0027] FIG. 7 is a view like FIG. 6 showing the alteration of the
loci due to an increase in amplitude of the pulse applied to the
second electrode and a decrease in amplitude of the pulse applied
to the first electrode;
[0028] FIG. 8 is a timing diagram showing pulses applied to the
first and second electrodes illustrated in FIG. 2 in relationship
to the potential changes induced in tissue adjacent the
electrodes;
[0029] FIGS. 9 and 10 are timing diagrams illustrating alternative
forms of pulses applied to the electrodes illustrated in FIG. 2;
and
[0030] FIG. 11 is a timing diagram illustrating a preferred form of
pulses applied to the electrodes shown in FIG. 2.
[0031] FIG. 12 shows the suprathreshold potential area generated
from application of two pulses to two electrodes where the two
pulses having a first time delay between the end of the first pulse
and the start of the second pulse.
[0032] FIG. 13 shows the suprathreshold potential area generated
from application of two pulses to two electrodes where the two
pulses have a second time delay between the end of the first pulse
and the start of the second pulse, with the second time delay being
greater than the first time delay of FIG. 12.
[0033] FIG. 14 shows the suprathreshold potential area generated
from application of two pulses to two electrodes where the two
pulses have a third time delay between the end of the first pulse
and the start of the second pulse, with the third time delay being
greater than the second time delay of FIG. 13.
[0034] FIG. 15 shows the suprathreshold potential area generated
from application of two pulses to two electrodes where the two
pulses have a fourth time delay between the end of the first pulse
and the start of the second pulse, with the fourth time delay being
greater than the third time delay of FIG. 14; and
[0035] FIGS. 16-25 depict various arrays of electrodes that may be
used in accordance with the present invention.
[0036] FIG. 26 is a cross-sectional view of an exemplary spinal
column showing a typical position at which electrodes made in
accordance with the preferred practice of the invention have been
implanted in the subdural space and a locus of fiber
activation;
[0037] FIG. 27 is a cross-sectional view like FIG. 26 showing a
locus of fiber activation in the intraspinal tissue due to
implantation of electrodes in such location;
[0038] FIG. 28 is a view like FIG. 27 showing the locus of fiber
activation in the intraspinal tissue due to a change in amplitude
of the pulses applied to the electrodes compared to the amplitudes
used in connection with FIG. 27;
[0039] FIG. 29 is a cross-sectional view of the brain showing one
form of placement of the electrodes of a preferred embodiment;
and
[0040] FIG. 30 is a view like FIG. 29 showing an alternative
placement of the electrodes in the brain.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0041] Referring to FIG. 8, a single electrical pulse P1 can cause
depolarization near a cathode in electrically excitable tissue
which includes neural tissue or muscle tissue. Neural tissue
includes peripheral nerves, ganglia, the spinal cord surface, deep
spinal cord tissue, deep brain tissue, and brain surface tissue.
Muscle tissue includes skeletal (red) muscle, smooth (white)
muscle, and cardiac muscle. A locus includes a set of points in
three-dimensional space and refers to a volume of cells or parts of
cells. Due to the electrical characteristics of both the
three-dimensional volume conductor and the membrane properties, the
potentials outside and inside a neuron respond to the
depolarization, usually with inverse exponential-type increases
during the pulse and then attenuation over time after the pulse.
The time constant for an isolated neuron membrane typically is 5-15
milliseconds (Nerve, Muscle and Synapse by Bernard Katz, circa
1972). For myelinated axons or muscle cells, it may be considerably
shorter.
[0042] A living cell at any time has a transmembrane potential
across its membrane. This transmembrane potential is typically
defined as the potential in the inside of the cell with respect to
the outside of the cell. At rest, a living cell has a constant
transmembrane potential called a resting potential of approximately
-60 mV to -90 mV, with the inside of the cell being more negative
than outside of the cell. A variety of changes to the environment
of the living cell can result in a corresponding change in the
transmembrane potential.
[0043] A change in the environment that causes the inside of the
cell to become less negative is referred to as a "depolarization"
of the cell, and depolarization is then a positive change in the
transmembrane potential. Similarly, a change in the environment
that causes the inside of the cell to become more negative is
referred to as a "hyperpolarization" of the cell, and
hyperpolarization is a negative change in the transmembrane
potential. An example of change in the environment of a living cell
is when a voltage pulse is applied near the cell. Depending on the
direction of the electric current caused by this stimulation pulse,
the pulse can be either depolarizing or hyperpolarizing.
[0044] FIG. 8 shows an example pulse P1 that can cause time varying
depolarization in a cell, and this depolarization from application
of pulse P1 adjacent the cell can result in changes in a
transmembrane potential TPA1. A further application of another
pulse P2 adjacent the cell results in a portion of the curve TPA2.
TPA3 is a superposition of the depolarizations caused by both
pulses P1 and P2. The remaining depolarization from the prior
application of pulse P1 between times T3 and T7 is shown by the
dashed line curve in TPA3.
[0045] The transmembrane potential TPA1 is comprised of two
components. The first component is the resting potential of the
cell. This component is a constant gradient that exists across the
membrane of the cell due to steady state ionic concentrations.
Added to that first component is the depolarization that results
from the application of pulse P1. Thus, transmembrane potential
TPA1 is the sum total of the resting potential with the
depolarization effects from application of pulse P1.
[0046] The sum total transmembrane potential TPA1 or TPA2 at any
time must reach a certain transmembrane potential threshold TPT in
order for the electrically excitable cell to get an action
potential induced therein. The peak of potential TPA1 or TPA2 is
below the transmembrane potential threshold TPT, and thus potential
TPA1 or TPA2 can be characterized as a subthreshold potential. As a
result, the potential changes from pulses P1 or P2 alone fail to
produce an action potential in that cell. Even when pulses P1 and
P2 occur with a time delay (T3-T2), the transmembrane potential
TPA3 may still not reach the transmembrane potential TPT.
[0047] Action potential is an all-or-none, nonlinear phenomenon,
caused by opening of sodium gates, inrush of sodium ions, and a
delayed opening of potassium gates and a restoration of the
membrane potential. In general, a certain amount of charge must be
passed at the electrodes (amplitude [Volts]/resistance
[Ohms].times.pulse width [time]) in order to cause enough
depolarization for an action potential to begin. There is a
reciprocal relationship between amplitude and pulse width: the
product must reach a certain value before the transmembrane
potential threshold is reached. This relationship does not reach
the Volts=0 axis. There is a certain minimum voltage needed, called
rheobase, before an action potential can happen.
[0048] Basic neurophysiological principles, called "electrotonus",
show that in any volume of electrically excitable tissue, if two or
more depolarizing pulses tending to induce action potentials, each
of which alone is insufficient to bring the cells to threshold,
arrive closely together in time, at least part of their effect is
additive, i.e., the memory of the first pulse is still present when
the second pulse arrives. If the sum of the potentials (distorted
by resistive and capacitive properties of the surroundings and the
cell membranes) can get some cells depolarized to threshold, then
an action potential will start in those cells. A reference that
explains these principles of "electrotonus" including the creation
of subthreshold potentials is Medical Physiology, 13th Edition,
Vol. 1, by Vernon B. Mountcastle, C. V. Mosby Co., 1974.
[0049] Still referring to FIG. 8, the inducement of an action
potential in a cell is illustrated by a transmembrane potential TPB
reaching the transmembrane potential threshold TPT at time T4. TPB
can be characterized as a suprathreshold potential, and the nerve
tissue has an action potential started when TPB reaches the
transmembrane potential threshold (at time T4). The transmembrane
potential TPB is comprised of the constant resting potential and a
depolarization that is sufficient enough to push the total
transmembrane potential TPB above the transmembrane potential
threshold. TPB at time T4 has sufficient depolarization to go above
the transmembrane potential threshold because the amplitude of
pulse P2 may have either been larger than in the case of the
subthreshold transmembrane potential TPA2 or have come soon enough
before the memory of the effect of pulse P1 has subsided.
[0050] FIG. 1 is a schematic view of a patient 10 having an implant
of a neurological stimulation system employing a preferred form of
the present invention to stimulate spinal cord 12 of the patient.
The preferred system employs an implantable pulse generator 14 to
produce a number of independent stimulation pulses which are sent
to spinal cord 12 by insulated leads 16 and 18 coupled to the
spinal cord by electrodes 16A and 18A (FIG. 2). Electrodes 16A and
18A also can be attached to separate conductors included within a
single lead.
[0051] Implantable pulse generator 14 preferably is a modified
ITREL II implantable pulse generator available from Medtronic, Inc.
with provisions for multiple pulses occurring either simultaneously
or with one pulse shifted in time with respect to the other, and
having independently varying amplitudes and pulse widths. This
preferred system employs a programmer 20 which is coupled via a
conductor 22 to a radio frequency antenna 24. This system permits
attending medical personnel to select the various pulse output
options after implant using radio frequency communications. While
the preferred system employs fully implanted elements, systems
employing partially implanted generators and radio-frequency
coupling may also be used in the practice of the present invention
(e.g., similar to products sold by Medtronic, Inc. under the
trademarks X-trel and Mattrix).
[0052] FIG. 2 is a cross-sectional view of spine 12 showing
implantation of the distal end of insulated leads 16 and 18 which
terminate in electrodes 16A and 18A within epidural space 26. The
electrodes may be conventional percutaneous electrodes, such as
PISCES.RTM. model 3487A sold by Medtronic, Inc. Also shown is the
subdural space 28 filled with cerebrospinal fluid (cfs), bony
vertebral body 30, vertebral arch 31, and dura mater 32. The spine
also includes gray matter 34 and dorsal horns 36 and 37 and white
matter, for example, dorsal columns 46 and dorsal lateral columns
47.
[0053] Stimulation pulses are applied to electrodes 16A and 18A
(which typically are cathodes) with respect to a return electrode
(which typically is an anode) to induce a desired area of
excitation in the spine 12 having nerve tissue capable of producing
action potentials. (A cathode has a more negative potential with
respect to an anode, and the electrical current caused by the
cathode tends to induce an action potential whereas the electrical
current caused by the anode tends to inhibit an action potential.)
The return electrode, for example a ground or other reference
electrode, is also present but is not shown in the cross sectional
view of spine 12 because the return electrode is located typically
at a different plane from the shown cross section of FIG. 2. For
example, the return electrode may be located near a point up or
down the line along the spinal column 12 or at a more remote part
of the body 10 carrying the spine, such as at the metallic case of
the pulse generator 14. Alternatively, more than one return
electrode may be present in the body. There can be a respective
return electrode for each cathode such that a distinct
cathode/anode pair is formed for each cathode.
[0054] Referring to FIG. 8, pulse P1 is applied to electrode 18A
(FIG. 2) and pulse P2 is applied to electrode 16A (FIG. 2). Pulses
P1 and P2 have a timing relationship. For optimal operation of the
present invention with the application of the principle of
"electrotonus", pulses P1 and P2 should not overlap in time. For
example, the end of pulse P1 at time T2 and the start of pulse P2
at time T3 in FIG. 8 are displaced by a predetermined time period
less than 500-2000 microseconds, and preferably less than 50-500
microseconds. Amplitude A1 of P1 is adjustable independently from
amplitude A2 of pulse P2. The pulse widths of pulses P1 and P2 also
are independently adjustable. Widening the pulse widths of each
pulse (i.e., P1 and P2) can also expand the loci of
depolarizations, just like increasing amplitude, either voltage or
current amplitude.
[0055] The pulses P1 and P2 also could have other time delay
relationships in order to accomplish the goals of the present
invention. Referring to FIG. 9, pulses P3 and P4, having different
rise times, could be used. P3 has a rise time from T1 to T8 and P4
has a rise time from T1 to T9. Referring to FIG. 10, pulses P5 and
P6, having different fall times, could be used. P5 has a fall time
from T10 to T11, and P6 has a fall time from T10 to T12. The
weighted average time WA3 of pulse P3 (FIG. 9) is displaced from
the weighted average time WA4 of pulse P4 by a predetermined time
period of less than 500-2000 microseconds and preferably less than
50-500 microseconds. A weighted average time is the integral of a
pulse over the pulse interval divided by the pulse amplitude of the
pulse interval. The rise time and fall time of a pulse can affect
the weighted average time of the pulse.
[0056] Similarly, the peak PK3 of pulse P3 is displaced from the
peak PK4 of pulse P4 by a predetermined time period of less than
500-2000 microseconds and preferably less than 50-500 microseconds.
The rise time of a pulse can affect the peak time of the pulse.
Objectives of the invention also can be achieved using combinations
of the foregoing timing relationships. For example, the time delay
between the first pulse and the second pulse can be the time
difference between a first weighted average time of the first pulse
and a second weighted average time of the second pulse.
Alternatively, the time delay can be the time difference between a
first peak time of the first pulse and a second peak time of the
second pulse.
[0057] Referring to FIGS. 3 and 8, line L1 represents the edge of a
three-dimensional locus L1A of cells in excitable tissue in which
pulse P1 applied to electrode 18A results in a transmembrane
potential which can be represented by curve TPA1 of FIG. 8. That
transmembrane potential is less than the transmembrane potential
threshold TPT for cells of interest in that locus. That
transmembrane potential is comprised of a constant resting
potential and a depolarization caused by application of pulse P1 to
electrode 18A. Thus, locus L1A, which results from pulse P1 being
applied to electrode 18A without a recent pulse being applied to
electrode 16A is an area having subthreshold potential since TPA1
is less than the transmembrane potential threshold TPT.
[0058] Similarly, referring to FIGS. 4 and 8, line L2 represents
the edge of another three-dimensional locus L2A in which the
application of pulse P2 to electrode 16A results in a transmembrane
potential which also can be represented by the transmembrane
potential curve TPA2 of FIG. 8. That transmembrane potential is
less than the transmembrane potential threshold TPT for cells of
interest in that locus. That transmembrane potential is the sum of
a constant resting potential and a depolarization potential caused
by application of pulse P2 to electrode 16A. Thus, locus L2A, which
results from pulse P2 being applied to electrode 16A without a
recent pulse being applied to electrode 18A is also an area of
subthreshold potential since TPA2 is less than the transmembrane
potential threshold TPT.
[0059] FIG. 5 illustrates a locus L3A representing the intersection
of loci L1A and L2A in which the combined potentials induced in
locus L3A from pulses P1 and P2 create an action potential in cells
of interest in locus L3A as illustrated by the transmembrane
potential TPB in FIG. 8. The total potential in cells in locus L1A
outside locus L3A is illustrated by the transmembrane potential
TPA1 in FIG. 8. Since TPA1 is lower than the transmembrane
potential threshold TPT, the total potential is a subthreshold
potential, and there is no action potential created in cells in
locus L1A outside L3A. The total potential created in cells in
locus in L2A outside L3A is illustrated by transmembrane potential
TPA2 in FIG. 8. Again, the total potential is a subthreshold
potential, and there is no action potential created in cells in
locus L2A outside locus L3A.
[0060] The suprathreshold potential induced in cells in locus L3A
results from a superposition of the subthreshold potentials TPA1
and TPA2 created in that area by excitation from a pulse applied to
electrode 16A and from another pulse applied to electrode 18A.
Locus L3A has nerve cells that get action potentials resulting from
this suprathreshold potential induced in that locus. The total
potential in cells in locus L3A is illustrated by the transmembrane
potential TPB of FIG. 8. That transmembrane potential is comprised
of the constant resting potential and the superposition of
depolarizations from application of pulse P1 to electrode 18A and
pulse P2 to electrode 16A.
[0061] Referring to FIGS. 6 and 8, line L4 represents the edge of
another three-dimensional locus L4A having subthreshold potential
resulting from the application of a pulse P1 to electrode 18A
having an amplitude greater than amplitude A1. Line L5 represents
the edge of another three-dimensional locus L5A having subthreshold
potential resulting from the application of a pulse P2 to electrode
16A having an amplitude less than amplitude A2. The intersection of
loci L4A and L5A creates a locus L6A in which a suprathreshold
action potential results from a superposition of subthreshold
potentials created by application of pulses P1 and P2. Locus L6A is
moved mostly to the right relative to locus L3A shown in FIG. 5.
Action potentials are not induced outside locus L6A since the area
outside that locus has subthreshold potentials.
[0062] Referring to FIGS. 7 and 8, line L8 represents the edge of
another three-dimensional locus L8A having subthreshold potential
resulting from the application of a pulse P2 to electrode 16A
having an amplitude greater than amplitude A2. Line L7 represents
the edge of another three-dimensional locus L7A having subthreshold
potential resulting from the application of a pulse P1 to electrode
18A having an amplitude less than amplitude A1. The intersection of
loci L7A and L8A creates a locus L9A in which a suprathreshold
action potential is induced from a superposition of subthreshold
potentials created by application of both pulses P1 and P2. It will
be noted that the locus L9A is moved to the left compared with
locus L3A shown in FIG. 5. Action potentials are not induced
outside locus L9A since the area outside that locus has
subthreshold potentials.
[0063] A benefit of utilizing the neurophysiological principle of
"electrotonus" is that the area of suprathreshold potential can be
controlled by varying the time delay between application of the two
pulses to each respective driven electrode for creating the areas
of subthreshold potential. Referring to FIG. 8, this time delay can
be the time period between the end of pulse P1 at time T2 and the
start of pulse P2 at time T3.
[0064] Principles of "electrotonus" indicate that a potential for
any nerve cell decays with a RC time constant after a stimulation
pulse has been applied to that nerve cell. R is a resistive value
determined by the resistive characteristic for that nerve cell, and
C is a capacitive value determined by the capacitive characteristic
for that nerve cell.
[0065] Because of this memory effect of electrotonus, the
transmembrane potential created within a nerve cell by a pulse
starts to decay at the end of the excitation pulse, and this
transmembrane potential is a function of time. By taking advantage
of this time variation of the transmembrane potential, the area of
suprathreshold potential can be adjusted by correspondingly varying
the time delay between the pulses that are applied to two
electrodes that each produce a subthreshold area.
[0066] This benefit is further illustrated in FIGS. 12-15 where
elements similar to elements in the prior figures are labeled with
the same numeric label. FIG. 12 illustrates the case where the
pulses applied to the two cathodes follow closely in time. Element
12 is a simplified illustration of electrically excitable tissue
such as spinal cord tissue. Pulse P2 immediately follows after the
end of pulse P1, and the time delay between the end of pulse P1 at
T2 and the start of pulse P2 at T3 is small in this case.
[0067] Line L10 represents the isopotential line defining a
subthreshold area L10A created by application of pulse P1 at
electrode 18A. Line L11 represents the isopotential line defining
another subthreshold area L11A created by application of pulse P2
at electrode 16A. (A return electrode is not shown in FIGS. 12-15
since that electrode is typically located on a different plane from
the shown tissue plane 12 or on a more remote location on the body
carrying the tissue 12 such as at the metallic case of the pulse
generator 14 of FIG. 1.) Each isopotential line varies with time
and progresses away from the electrode producing that isopotential
line during the application of a pulse to that electrode and
recedes back toward that electrode after the completion of the
pulse by the principle of "electrotonus". In FIG. 12, the
isopotential lines L10 and L11 are what result at the end of pulse
P2 at time T4. These individual subthreshold areas by themselves do
not have sufficient potential changes to induce an action potential
within tissue 12. However, a superposition of the subthreshold
potential areas at time T4 creates an area L12A of suprathreshold
potential that is greater than the transmembrane potential
threshold such that nerve cells within that area have an action
potential induced therein.
[0068] FIG. 13 shows a case where the two pulses P1 and P2 are more
separated in time than the case illustrated in FIG. 12. The
transmembrane potentials in FIG. 13 that are created in
electrically excitable tissue 12 are those that remain at the end
of pulse P2 at time T4. By that time, the application of pulse P1
was already completed at time T2. Isopotential line L13 defines the
subthreshold area L13A that remains from the application of pulse
P1 to electrode 18A by time T4. Isopotential line L14 defines the
subthreshold area L14A that is created by application of pulse P2
to electrode 16A by time T4.
[0069] These individual subthreshold areas by themselves do not
have sufficient potential changes to induce an action potential.
However, a superposition of the subthreshold potential areas
creates an area L15A of suprathreshold potential that is greater
than the transmembrane potential threshold such that nerve cells
within that area have an action potential induced therein. Note
that the area of suprathreshold potential L15A of FIG. 13 differs
from the area of suprathreshold potential L12A of FIG. 12 because
of the larger time delay between the end of pulse P1 at T2 and the
start of pulse P2 at T3 in FIG. 13 than in FIG. 12.
[0070] Similarly, FIG. 14 shows a case where the two pulses P1 and
P2 are still even more separated in time than those of FIG. 13.
FIG. 14 shows the isopotential lines that are created by pulses P1
and P2 at the end of pulse P2 at time T4. The isopotential line L16
defines the subthreshold area L16A created by the application of
pulse P1 at electrode 18A by time T4, and the isopotential line L17
defines the subthreshold area L17A created by the application of
pulse P2 at electrode 16A by time T4.
[0071] The individual subthreshold areas within isopotential lines
L16 and L17 by themselves do not have sufficient potential changes
to induce an action potential. However, a superposition of
subthreshold potential areas creates an area L18A of suprathreshold
potential that is greater than the transmembrane potential
threshold such that nerve cells within that area have an action
potential induced therein. Note that because of the larger delay
between pulses P1 and P2, isopotential line L16 has receded further
toward electrode 18A by the end of pulse P2 at time T4, and the
area L18A of suprathreshold potential has decreased and has shifted
more toward electrode 18A.
[0072] Finally, FIG. 15 shows a case where pulse P1 and P2 have a
time delay sufficiently far enough such that no area of
suprathreshold potential is created within the electrically
excitable tissue 12. Isopotential line L19 is the result of
application of pulse P1 at electrode 18A by the end of pulse P2 at
time T4, and isopotential line L20 is the result of application of
pulse P2 at electrode 16A by time T4. Because of the large delay
between pulses P1 and P2, isopotential line L19 has receded so far
back toward electrode 18A that there is no area of superposition of
the two subthreshold areas created by isopotential lines L19 and
L20 within tissue 12.
[0073] The ability to move the locus in which action potentials are
induced by controlling the area of superposition of subthreshold
potential areas is an important feature. In many therapies, it is
important to prevent action potentials being induced in gray matter
34 or dorsal horns 36 and 37, dorsal roots 38 and 40, dorsal
lateral columns 47 or peripheral nerves 42 and 44 in order to
minimize the possibility of causing pain, motor effects, or
uncomfortable paresthesia. With the described techniques, the locus
in which action potentials are induced (e.g., L3A, L6A, L9A, L12A,
L15A, or L18A) can be manipulated to a desired area of the dorsal
columns 46 without inducing action potentials in dorsal horns 36
and 37, gray matter 34 or dorsal lateral columns 47 or dorsal root
ganglia 38 and 40. Moreover, the ability to move the locus in which
action potentials are induced drastically reduces the accuracy
necessary for surgically implanting electrodes 16A and 18A, and may
eliminate the need for surgical lead revisions.
[0074] Another advantageous result from being able to determine the
locus of excitation by controlling the area of suprathreshold
potential from superposition of subthreshold potential areas is
that the location of the two driven electrodes 16A and 18A and the
return electrode with respect to each other is not critical to the
practice of this invention. In contrast to the invention disclosed
by Holsheimer et al. in U.S. Pat. No. 5,501,703, the two driven
electrodes and the return electrode in the present invention are
not optimally spaced in line with respect to each other. In fact,
the return electrode of the present invention can be located
remotely from the driven electrodes 16A and 18A near a point up or
down the spinal column or another part of the body carrying the
spine being excited. Alternatively, there may be more than one
return electrode within the body.
[0075] FIG. 11 illustrates a preferred timing relationship between
pulse P7 applied to electrode 18A and pulse P8 applied to electrode
16A. Currently available pulse generators use a biphasic pulse to
insure no net direct current flows into the tissue. This is known
as charge-balanced pulsing, and is accomplished by driving the
pulse negative for a duration of time. For example, in FIG. 11,
pulse P8 has a net charge delivered proportional to A2*(T4-T3).
This injected charge is balanced by the negative pulse P10, whose
charge is proportional to A3*(T5-T4), where A3<<A2 and
(T5-T4)>>(T4-T3). Similar principles apply even if the first
and second pulses are not of constant amplitude.
[0076] In a preferred embodiment, pulse P7 may be generated with a
trailing negative pulse P9 from time T4 to time T5, so that the
output on electrode 18A is substantially at neutral or 0 potential
until the termination of pulse P8 at time T4. Having this delay in
charge balancing prevents the loss of potential in adjacent tissue
that otherwise would occur if pulse P9 immediately followed pulse
P7 and overlapped with pulse P8, thus offsetting the benefit of
pulse P8. At time T4 both negative pulses P9 and P10 begin in order
to maintain the charge balance in tissue adjacent to the respective
electrodes 18A and 16A.
[0077] In another embodiment of the present invention, the present
invention utilizes an array of electrodes to more finely control
the shape of the field of excitation. These electrodes provide
multi-channel stimulation of the desired treatment area.
Multi-channel stimulation generally refers to the stimulation of
several sites at differing pulse parameters including, for example
and without limitation, pulse amplitude, pulse width, pulse
frequency, pulse shape, pulse rise, pulse fall, pulse peak, and
pulse polarity. These pulses may be either voltage or current
pulses. For example, if one site receives a voltage or current
pulse, and then another site gets a pulse at the same time, an
overlapping time, or a separate time. The stimulation and steering
techniques discussed above may be used to achieve suprathreshold
potentials within the desired treatment areas. The field of
excitation may be created and controlled using any number of
techniques, including but not limited to, simultaneous pulses of
two cathodal amplitudes and one anode, paired (delayed) pulses
using two or more electrodes, a combination of simultaneous and
paired (delayed) pulses among various electrodes, and conventional
full polarity pulses of anodes and cathodes. Each of these
techniques are discussed herein in further detail.
[0078] FIG. 16 shows a way to perform two-dimensional steering
using an array 1600 of electrodes. These electrodes may be placed
on a paddle lead or may be positioned across three adjacent
percutaneous leads. Array 1600 may include a central cathode C1 and
up to four surrounding anodes C2-C5. Simultaneous anodal pulses can
then be delivered, each with their own potential, to the
surrounding electrodes C2-C5. Advantageously, the electric field
may be steered in any number of directions over a 2-dimensional
space. As exemplified in FIG. 17, the effect may be steered from
left to right by using electrodes C1, C2 and C4 and turning off
electrodes C3 and C5. Further, as exemplified in FIG. 18, the
effect may be steered from top to bottom by using electrodes C1, C3
and C5. FIG. 19 illustrates a method to shield activation of cells
in a lower direction and to maintain the field of excitation in the
middle and slightly upward. The field of excitation L19 is skewed
by using only anodal electrodes C2-C4, where electrode C3 is
stronger in voltage than electrodes C2 and C4. FIG. 20 illustrates
steering of field L20 along a diagonal by using surrounding
electrodes C2-05 but with varying voltages.
[0079] As shown in FIG. 21, central electrode C1 may also be
eliminated altogether. In this case, one of the remaining
electrodes, say C2 is the most cathodal (-), and the remaining
three electrodes C2-C4 can be programmed to have three equal or
different anodal voltages to provide the necessary steering of the
field L21. Although the currents from electrode C2 move off in the
other direction in a less controlled manner, this embodiment
advantageously avoids current waste that would be present with a
nearby central cathode C1.
[0080] FIGS. 22(a-e) shows a number of electrode shape
configurations that may prevent unnecessary shorting of currents in
the epidural space, or help direct energy into certain patterns.
FIG. 22(a) has greater efficiency since the electrodes are
relatively far from each other. FIGS. 22(b and c) depict electrodes
having relatively larger surface areas, thereby reducing resistance
and allowing for higher currents. FIG. 22(d) has four electrodes
farther apart forming a ring. FIG. 22(e) depicts relatively smaller
electrodes that are further apart from each other to increase
efficiency and minimize shunting of current between the
electrodes.
[0081] FIG. 23 illustrates a similar concept but with 6 electrodes
in a ring pattern to provide greater control of the direction of
the electric field. Here, up to five or more anodal voltage levels
may be used (if one is most cathodal), or up to six cathodal
voltage levels may be used (if there is one distant anode, say, on
a power source case). Those skilled in the art will appreciate that
even other electrode configurations can be used together with more
simultaneous pulses or varying amplitudes. Delivery of subthreshold
pulses at various times may result in a two-dimensional locus of
superactivation.
[0082] FIG. 24 shows the initial cross-pattern of five electrodes
C1-C5 with some outer electrodes C6-C9. If any of the ring of
electrodes C2-C5 is made a cathode, electrode C1 may be turned off
and one or more outer electrodes C6-C9 can be made anodal to help
maintain the field of excitation bounded on that side.
[0083] FIG. 25 is yet another embodiment having five or more
electrodes in an outer ring that could be anodal to contain the
electric field toward the center.
[0084] Advantageously, these 2-dimensional configurations may be
used to create suprathreshold potential areas as discussed above.
Stimulation may be provided using a two-dimensional array of
electrodes and configuring a range of anode/cathode relationships
from the array. Moreover, simultaneous pulsing may be achieved by
applying pulses of varying amplitudes to a selected group of
cathodes in the array.
[0085] FIG. 26 is a cross-sectional view of spine 2612 showing
implantation of the distal end of insulated leads 2616-2618 which
terminate in electrodes 2616A-2618A within subdural space 2628
filled with cerebral spinal fluid. The electrodes may be
conventional percutaneous electrodes, such as PISCES.RTM. model
3487A sold by Medtronic, Inc. Alternatively, electrodes 2616A-2618A
may be constructed like electrical contacts 2656, 2658 and 2660
shown in the above-identified PCT International Publication No. WO
95/19804 which is incorporated by reference (hereafter the "PCT
Publication"). Also shown in FIG. 26 is a bony vertebral body 2630,
vertebral arch 2631, and dura mater 3632. The spine also includes
gray matter 2634, dorsal horns 2636 and 2637, dorsal roots 2638 and
2640, and peripheral nerves 2642 and 2644.
[0086] Still referring to FIG. 26, an anode/cathode relationship is
established between electrodes 2616A-2618A in the manner described
in the PCT Publication. For example, electrodes 2616A and 2618A are
established as anodes (+) and electrode 2617A is established as a
cathode (-). Electrodes 2616A-2618A are placed in a generally
planar configuration and are aligned along a common axis as shown
and as taught in the PCT Publication. The electrodes could be
placed on a flat or curved paddle, or they could be individually
inserted in a percutaneous fashion. The electrodes are implanted
near the dorsal surface of the spinal cord, under the dura
mater.
[0087] Pulses are then applied to the electrodes as taught in the
PCT Publication in order to redirect a locus of action potentials
in nerve fibers in the spinal cord. The pulses may overlap in time
and are independently variable in amplitude to best control the
areas of activation, or they may also have independently variable
pulse widths. The dotted line L1 shows the edge of a locus of
excitation of nerve cells caused by pulses in electrodes
2616A-2618A. In this volume of tissue, 26L2, cells are depolarized
beyond the threshold for production of action potentials. As shown
in FIG. 26, when simultaneous pulses between electrode pairs 2616A,
2617A and between electrode pairs 2617A, 2618A are nearly equal in
amplitude, volume 26L2 is nearly symmetrical about electrode
2617A.
[0088] FIG. 27 illustrates the same configuration shown in FIG. 26,
except that electrodes 2616A-2618A are implanted inside the spinal
cord tissue. One or more of electrodes 2616A-2618A, especially the
lateral ones, might be placed on the outer surface of the spinal
cord. With balanced or equal amplitudes of simultaneous stimulation
pulses, the locus of recruitment is nearly symmetrical about the
cathode (i.e., electrode 2617A). The electrodes should be inserted
into the spinal cord with, for example, a percutaneous-type
lead.
[0089] FIG. 28 illustrates the same configuration shown in FIG. 27.
However, the amplitude of the anodal pulse on electrode 2618A has
been increased in value, causing the locus of excitation 26L2 to
shift away from that electrode. This is an unbalanced stimulation,
and demonstrates the ability of this system to adjust the locus of
excitation laterally by programming.
[0090] It also is possible to place the electrodes in a line that
is parallel to the longitudinal axis of the spinal cord, and hence
steer the locus of excitation rostrally or caudally. This could be
used to activate certain dorsal roots over others, or affect
certain spinal cord segments more than others.
[0091] FIG. 29 illustrates cortical surface stimulation by
electrodes 2616A-2618A that have been mounted on a paddle PD and
implanted on the surface of the brain as shown. Pulses are supplied
to the electrodes from device 14 over conductors 2616-2618 that are
located within a cable 2922 implanted between the scalp 29125 and
skull 29123. The distal end of cable 2922 is implanted in the brain
through a hole in the skull by conventional stereotactic surgical
techniques. Electrodes 2616A-2618A may be above the dura, or placed
beneath the dura, in both cases accomplishing cortical surface
stimulation.
[0092] In the center of the brain is a deep groove, called the
central sulcus CS. Toward the anterior is the primary motor cortex
PMC, consisting of neurons and axons that control motor movements
on the opposite side of the body. Toward the posterior is the
primary sensory cortex PSC. Generally, stimulation of the motor
cortex causes discrete movements, and stimulation of the sensory
cortex causes sensations, although effects may be mixed due to
crossing, communicating axons. With the cathode 2617A over the
sulcus, and anodes both anteriorly (2618A) and posteriorly (2616A),
the locus of excitation 26L2 may include both motor and sensory
cortex as shown, or might, by steering, include only one or the
other. The steering may be accomplished in the same manner
described in connection with FIGS. 27 and 28. There is a
somatotopic map of the body on both the primary motor cortex and
the primary sensory cortex. It runs from medial to lateral, with
the buttocks on the midline and top, the feet on the midline deep,
and the back, arms, head, mouth and tongue progressively more
lateral on the surface of the brain. If electrodes 2616A, 2617A and
2618A are placed in a medial/lateral direction along this map
(called a homunculus), or in a rostral/caudal direction along the
part that goes deep into the brain, with steering of the electric
fields, the paresthesia or motor event that is elicited can be
moved to new body parts. This is another important application of
this invention.
[0093] As shown in FIG. 30, electrodes 2616A, 2617A and 2618A have
been placed on a single lead 3022A deep in the brain B.
Alternatively, electrodes 2616A, 2617A and 2618A could be placed
deep in the brain on separate leads. By changing the amplitudes of
pulses applied to the electrodes as illustrated in connection with
FIGS. 27 and 28, the locus of excitation could be shifted along the
axis of lead 3022A. If the lead was not on a midline plane, or was
in other deep brain sites, one, two or all three electrodes might
be in brain tissue. In particular, DBS is done today to excite
particular neural tissue elements of the thalamus, globus pallidus
and other nuclear groups for the relief of chronic pain or to
control movements. Sometimes the neural tissue elements to be
excited (low frequency, less than 100 Hz) or inhibited (high
frequency, greater than 100 Hz) are organized into thin sheets or
lamina, e.g., the VIM thalamic nucleus. Other times, nearby groups
of neurons or axons, e.g., the optic nerve, internal capsule, or
medial lemniscus, are also in special orientations and groupings.
It may be advantageous to avoid affecting them (e.g., preventing
flashes of light effects) or deliberately to affect them (e.g.,
excite or inhibit axons of passage). Therefore, the precise
location and orientation of the three electrodes is very important,
and to be able to steer the fields along the generally coplanar
axis of the three electrodes can be most beneficial. In addition,
there are somatotopic maps of the body on the surface of the
cerebellum, one in three dimensions in parts of the thalamus and
also one in the dorsal column nuclei of the medulla. It would be
advantageous to orient the lead relative to these maps, and to
excite/inhibit groups of cell bodies or axons accordingly. In
addition, lamina for visual fields are found in the lateral
geniculate body, lamina for tones for hearing are found in the
medial geniculate body, and maps of the retina are found in the
occipital cortex. Hence, steering of excitation or inhibition by
use of this invention can be most useful.
[0094] The advantages of the invention described herein can be
generalized to applications for exciting any electrically excitable
tissue within any organism, in addition to such tissue within a
spine. Particularly, the same techniques of the present invention
could be used for intraspinal, cortical, deep brain, peripheral
nerve, heart or other muscle or organ stimulation as well. Further,
the fields to be generated might have either constant current or
constant voltage sources. Moreover, the invention can be
generalized to using more than two cathodal electrodes to generate
more than two subthreshold areas to be superposed in generating the
suprathreshold potential area. Accordingly, the forgoing
description is by way of example only and is not intended to be
limiting. The invention is limited only as defined in the following
claims and equivalents thereof.
* * * * *