U.S. patent application number 11/346684 was filed with the patent office on 2006-06-15 for method and system for cortical stimulation with rectangular and/or complex electrical pulses to provide therapy for stroke and other neurological disorders.
Invention is credited to Birinder R. Boveja, Angely Widhany.
Application Number | 20060129205 11/346684 |
Document ID | / |
Family ID | 36576584 |
Filed Date | 2006-06-15 |
United States Patent
Application |
20060129205 |
Kind Code |
A1 |
Boveja; Birinder R. ; et
al. |
June 15, 2006 |
Method and system for cortical stimulation with rectangular and/or
complex electrical pulses to provide therapy for stroke and other
neurological disorders
Abstract
A method and system for providing rectangular and/or complex
electrical pulses to cortical tissues of a patient for at least one
of, providing therapy or alleviating symptoms of neurological
disorders including Parkinson's disease, or for providing
improvement of functional recovery following stroke. The
intracranial electrodes may be implanted epidurally, or subdurally
on the pia mater of the cortical surface. The electrical pulses may
be provided using one of the following pulse generation means: a)
an implanted stimulus-receiver with an external stimulator; b) an
implanted stimulus-receiver comprising a high value capacitor for
storing charge, used in conjunction with an external stimulator;.
c) a programmer-less implantable pulse generator (IPG) which is
operable with a magnet; d) a microstimulator; e) a programmable
implantable pulse generator; f) a combination implantable device
comprising both a stimulus-receiver and a programmable implantable
pulse generator (IPG); and g) an implantable pulse generator (IPG)
comprising a rechargeable battery. The pulse generator means may
also comprise selected number of predetermined/pre-packaged
programs. In one embodiment, the pulse generation means may also
comprise telemetry means, for remote interrogation and/or
programming of said pulse generation means utilizing a wide area
network.
Inventors: |
Boveja; Birinder R.;
(Milwaukee, WI) ; Widhany; Angely; (Milwaukee,
WI) |
Correspondence
Address: |
BIRINDER R. BOVEJA & ANGELY WIDHANY
P. O. BOX 210095
MILWAUKEE
WI
53221
US
|
Family ID: |
36576584 |
Appl. No.: |
11/346684 |
Filed: |
February 3, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10195961 |
Jul 16, 2002 |
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11346684 |
Feb 3, 2006 |
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09752083 |
Dec 29, 2000 |
6505074 |
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10195961 |
Jul 16, 2002 |
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09178060 |
Oct 26, 1998 |
6205359 |
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09752083 |
Dec 29, 2000 |
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10841995 |
May 8, 2004 |
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11346684 |
Feb 3, 2006 |
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10196533 |
Jul 16, 2002 |
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10841995 |
May 8, 2004 |
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10142298 |
May 9, 2002 |
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10841995 |
May 8, 2004 |
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Current U.S.
Class: |
607/45 |
Current CPC
Class: |
A61N 1/3787 20130101;
A61N 1/36007 20130101; A61N 1/36017 20130101; A61N 1/0551 20130101;
A61N 1/3605 20130101; A61N 1/372 20130101 |
Class at
Publication: |
607/045 |
International
Class: |
A61N 1/32 20060101
A61N001/32 |
Claims
1. A method of providing rectangular and/or complex electrical
pulses to cortical tissues of a patient for treating and/or
alleviating symptoms of Parkinson's disease, and/or for providing
improvement of functional recovery following stroke, comprising the
steps of: selecting a patient for providing said rectangular and/or
complex electrical pulses; providing pulse generator means for
generating said rectangular and complex electrical pulses, wherein
said complex electrical pulses comprises at least one of
multi-level pulses, biphasic pulses, non-rectangular pulses, or
pulses with varying amplitude during the pulse; providing at least
two predetermined/pre-packaged programs stored in said pulse
generator means, wherein said predetermined/pre-packaged programs
control the variable components of said rectangular and/or complex
electric pulses, wherein said variable components comprise at least
one of pulse amplitude, pulse width, pulse frequency, on-time and
off-time sequence; providing at least one lead(s) with plurality of
electrodes, wherein said at least one lead(s) is in electrical
connection with said pulse generator means, and said plurality of
electrodes are adapted to be in proximity to cortical tissues; and
selectively choosing and activating one of said at least two
predetermined/pre-packaged programs to provide said rectangular
and/or complex electrical pulses to cortical tissues.
2. The method of claim 1, wherein the configuration of said
plurality of electrode(s) for providing said electrical pulses is
at least partly based on sensing electrical activity from the
patient's cortical tissues.
3. The method of claim 1, wherein placement of said plurality of
electrodes on patient's cortex is based at least in part upon
digital imaging techniques, such as fMRI or CT scans.
4. The method of claim 1, wherein placement of said plurality of
electrodes on patient's cortex is based on digital imaging
techniques and on sensing electrical activity from said cortical
tissues of said patient.
5. The method of claim 1, wherein the configuration between said
plurality of electrodes for providing electrical pulses is changed
between two or more different configurations.
6. The method of claim 1, wherein said predetermined/pre-packaged
programs can be modified.
7. The method of claim 1, wherein said pulse generation means can
further be remotely interrogated and/or programmed via a telemetry
means over a wide area network.
8. The method of claim 1, wherein said pulses further comprise
pulse amplitude approximately between 0.1 volt-15 volts; pulse
width between 20 micro-seconds-5 milli-seconds; stimulation
frequency between 5 Hz and 200 Hz, and/or blocking frequency
between 0 and 750 Hz.
9. The method of claim 1, wherein said pulse generator means for
providing said electrical pulses comprises an external stimulator
used in conjunction with an implanted stimulus-receiver.
10. The method of claim 9, wherein said pulse generator means for
providing said electrical pulses comprises an external stimulator
used in conjunction with an implanted stimulus-receiver which
further comprises a temporary power source.
11. The method of claim 1, wherein said pulse generator means for
providing said electrical pulses is one from a group comprising: i)
a programmable implantable pulse generator (IPG); ii) a combination
implantable device comprising both a programmable implantable pulse
generator (IPG) and a stimulus-receiver; iii) a programmable
implantable pulse generator (IPG) having a rechargeable
battery.
12. A method of providing rectangular and/or complex electrical
pulses to cortical tissues of a patient for providing improvement
of functional recovery following stroke, comprising the steps of:
selecting a patient for providing said electrical pulses to said
cortical tissues; providing means for obtaining sensed electrograms
from cortical tissues; providing pulse generation means for
generating rectangular and/or complex electrical pulses, wherein
said complex electrical pulses comprises at least one of
multi-level pulses, biphasic pulses, non-rectangular pulses, or
pulses with varying amplitude during the pulse; providing at least
one lead(s) with plurality of electrodes, wherein said at least one
lead(s) is in electrical connection with said pulse generation
means, and said plurality of electrodes are adapted to be in
proximity to cortical tissues; and supplying said rectangular
and/or complex electrical pulses to cortical tissues through
electrode configuration(s) based at least partly on sensed cortical
electrograms.
13. The method of claim 12, wherein said rectangular and/or complex
electrical pulses are provided according to
predetermined/pre-packaged programs.
14. The method of claim 12, wherein placement of said plurality of
electrodes on patient's cortex is based at least in part upon
digital imaging techniques, such as fMRI or CT scans.
15. The method of claim 12, wherein the configuration between said
plurality of electrodes for providing electrical pulses is changed
between two or more different configurations.
16. The method of claim 12, wherein said pulse generation means can
further be remotely interrogated and/or programmed with a telemetry
means over a wide area network.
17. The method of claim 12, wherein said pulses further comprise
pulse amplitude approximately between 0.1 volt-15 volts; pulse
width between 20 micro-seconds-5 milli-seconds; stimulation
frequency between 5 Hz and 200 Hz, and/or blocking frequency
between 0 and 750 Hz.
18. A method of providing therapy for involuntary movement
disorders such as caused by Parkinson's disease and/or for
providing improvement of functional recovery following stroke by
providing cortical electrical stimulation to a portion of a
patient's brain comprising the steps of: selecting a patient for
providing said cortical electrical stimulation; providing pulse
generation means to generate rectangular and/or complex electrical
pulses, wherein one said pulse generation means is selected from a
group comprising of: i) an external stimulator used in conjunction
with an implanted stimulus-receiver; ii) an external stimulator
used in conjunction with an implanted stimulus-receiver comprising
a high value capacitor for storing electric charge; iii) a
microstimulator; iv) a programmer-less implantable pulse generator
(IPG) which is operable with a magnet; v) a programmable
implantable pulse generator (IPG); vi) a combination implantable
device comprising both a programmable implantable pulse generator
(IPG) and a stimulus-receiver; or vii) a programmable implantable
pulse generator (IPG) having a rechargeable battery; providing at
least one lead(s) with plurality of electrodes, wherein said at
least one lead(s) is in electrical connection with said pulse
generation means, and with said plurality of electrodes adapted to
be in proximity to or in contact with said cortical tissues; and
providing a programming means for at least one of activating,
programming, controlling said rectangular and/or complex electrical
pulses provided to said cortical portion of patient's brain.
19. The method of claim 18, wherein said pulse generation means
further comprises at least two predetermined/pre-packaged programs
stored in said pulse generator means to control the variable
component of said rectangular and/or complex electric pulses
comprising at least one variable component of pulse amplitude,
pulse width, pulse frequency, on-time and off-time sequence.
20. The method of claim 18, wherein said pulse generation means can
further be remotely interrogated and/or programmed via a telemetry
means over a wide area network.
Description
[0001] This application is a continuation of application Ser. No.
10/195,961, having filing date of Aug. 16, 2002 which is a
continuation of patent application Ser. No. 09/752,083 having
filing date of Dec. 29, 2000, and now U.S. Pat. No. 6,505,074,
which is a continuation of patent application Ser. No. 09/178,060
having filing date of Oct. 26, 1998, and now U.S. Pat. No.
6,205,359. This application is also a continuation of application
Ser. No. 10/841,995 having a filing date of Jun. 8, 2004, which is
a continuation of application Ser. No. 10/196,533, which is a
continuation of application Ser. No. 10/142,298 having a filing
date of Jun. 9, 2002. The prior applications being incorporated
herein in their entirety by reference, and priority is claimed from
the above applications.
FIELD OF INVENTION
[0002] The present invention relates to brain stimulation, more
specifically to cortical stimulation for providing improvement of
functional recovery following stroke, and to provide adjunct
(add-on) therapy for other neurological diseases such as
Parkinson's disease using rectangular and/or complex electrical
pulses.
BACKGROUND
[0003] This patent disclosure is directed to providing rectangular
and/or complex electrical pulses to the cortical areas in the
brain. The objective of supplying electrical pulses to the cortical
areas is for neuroplasticity, such as for providing improvement of
functional recovery following stroke, as well as, for providing
therapy or alleviating symptoms for other neurological disorders
such as Parkinson's disease.
[0004] One or more leads are implanted with the electrodes in
proximity to the cortical surface of the brain, with the electrodes
being either subdural or epidural. fMRI or other imaging tools may
also be used to aid in the proper location placement of the
cortical electrodes. The terminal portion of the lead is tunneled
subcutaneously to a convenient location, such as behind the ear or
the pectoral or axillary region. The terminal end of the lead is
connected to a pulse generator means, which is then implanted
subcutaneously or submuscularly.
[0005] The pulse generator means may be one from a group
comprising:
[0006] a) an implanted stimulus-receiver used with an external
stimulator;
[0007] b) an implanted stimulus-receiver comprising a high value
capacitor for storing charge, used in conjunction with an external
stimulator;
[0008] c) a programmer-less implantable pulse generator (IPG) which
is operable with a magnet;
[0009] d) a microstimulator;
[0010] e) a programmable implantable pulse generator;
[0011] f) a combination implantable device comprising both a
stimulus-receiver and a programmable IPG; and
[0012] g) an IPG comprising a rechargeable battery.
Background of Stroke
[0013] Stroke is a cardiovascular disease that affects the blood
vessels supplying blood to the brain. Stroke occurs when a blood
vessel that carries oxygen and nutrients to the brain is clogged by
a blood clot or bursts. Because of this blockage or rupture, part
of the brain does not get the blood flow it needs. Deprived of
oxygen, nerve cells in the affected area of the brain cannot
function and die within minutes. When nerve cells cannot function,
the part of the body controlled by these cells cannot function
either. The devastating effects of stroke are often permanent
because dead brain cells cannot be replaced.
[0014] Stroke is the third leading cause of death among Americans
and probably first as a cause of chronic functional incapacity.
Approximately two million people in the United States today are
impaired by the neurological consequences of cerebrovascular
disease. Many of them are between 25 and 64 years of age. Every
year there are in this country approximately 700,000 cases of
stroke--roughly 600,000 ischemic lesions and 100,000 hemorrhages,
intracerebral or subarachnoid--with 175,000 fatalities from these
causes. Since 1950, coincident with the introduction of effective
treatment for hypertension, there has been a substantial reduction
in the frequency of stroke.
[0015] Stroke is an acute focal neurologic deficit from a vascular
disorder that injures brain tissue. There are two main types of
strokes: ischemic stroke and hemorrhagic stroke. Ischemic strokes
are caused by cerebrovascular obstruction by thrombosis or emboli,
and are the most common type of stroke, accounting for 70% to 80%
of all strokes. Focal cerebral ischemia follows reduction or
cessation of blood flow to a localized area of the brain due to
large-vessel disease (such as embolic or thrombotic arterial
occlusion, often in a setting of atherosclerosis). Although most
occlusive strokes are due to atherosclerosis and thrombosis and
most hemorrhagic strokes are associated with hypertension or
aneurysms, strokes of either type may occur at any age from many
causes, including cardiac disease, trauma, infection, neoplasm,
blood dyscrasia, vascular malformation, immunological disorder, and
exogenous toxins.
[0016] The less common hemorrhagic strokes are caused by bleeding
into brain tissue. Hemorrhagic stroke occurs with rupture of a
blood vessel, hemorrhage into the brain tissue occurs, resulting in
edema, compression of the brain contents. This type of stroke
usually is from a blood vessel rupture caused by hypertension,
aneurysms, arteriovenous malformations, head injury, or blood
dyscrasias and has much higher fatality rate than ischemic
strokes.
[0017] More than any other organ, the brain depends from moment to
moment on an adequate supply of oxygenated blood. Constancy of the
cerebral circulation is assured by a series of baroreceptors and
vasomotor reflexes under the control of centers in the lower
brainstem. In humans, the complete stoppage of blood flow for
longer than 5 minutes produces irreversible damage. Brain tissue
deprived of blood undergoes ischemic necrosis or infarction.
[0018] Neuronal function is affected in two stages during ischemia.
Neuronal electrical function is lost when the blood flow falls
below a critical threshold of approximately 20 mL of blood per 100
g of brain tissue per minute. At this level, brain tissue is
thought to be revivable, with the potential to reverse ischemic
damage. However, irreversible damage occurs when blood flow falls
below 10 mL of blood per 100 g of brain tissue per minute.
Inefficient anaerobic metabolism of glucose occurs which rapidly
leads to lactic acidosis and failure of the normal energy-dependent
cellular ion homeostasis. Potassium leaves the cell, and sodium and
water enter the cell and lead to cytotoxic edema. Calcium also
enters the cell and sets a cascade of molecular events into motion
that eventually leads to neuronal death.
[0019] Pharmaceutical treatment for stroke utilizes, drugs that may
enhance activity-dependent gains include, amphetamine, piracetam,
and cholinergic and dopaminergic agents have suggested efficacy of
these agents for particular aphasic syndromes and language
impairments.
Neural Plasticity
[0020] Neural plasticity is the capacity of the nervous system to
change. Neural plasticity is obvious during the development of
neural circuits, however, the adult brain also posses substantial
plasticity in order to learn new skills, establish new memories,
and respond to injury throughout life. In adult brains the altered
neural function in maturity appears to rely primarily on carefully
regulated changes in the strength of existing synapses. Extensive
changes can occur when the adult nervous system is damaged by
trauma or disease. It is known that new neurons can be generated
throughout life in a limited number of brain regions, whereby new
cells can be integrated into existing circuits.
[0021] Biomedical research with primates has also supported this.
The four cortical areas that define the primate somatic sensory
cortex (Broadmann's areas 3a, 3b, 1, and 2) each contain a complete
topographic representation of the body surface. J. Kaas and M.
Merzenich took advantage of this arrangement by carefully defining
the normal spatial organization of topographic maps in these
regions. They then amputated a digit (or cut one of the nerves that
innervated the hand) and reexamined topographical maps in the same
animals several weeks later. Surprisingly, the somatic sensory
cortex had changed: The cortical neurons that had been deprived of
their normal peripheral input now responded to stimulation of other
parts of the animal's hand. For example, if the third digit was
amputated, cortical neurons that formerly responded to stimulation
of digit 3 responded to stimulation of digits 2 or 4. Thus, the
central representation of the remaining digits had expanded to take
over the cortical territory that had lost its main input. Such
"functional re-mapping" also occurs in the somatic sensory nuclei
in the thalamus and brainstem; indeed, some of the reorganization
of cortical circuits may depend on this concurrent subcortical
plasticity. This sort of adjustment in the somatic sensory system
may contribute to the altered sensation of phantom limbs after
amputation. Similar plastic changes now have been demonstrated in
the visual, auditory, and motor cortices, suggesting that some
ability to reorganize after peripheral deprivation or injury is a
general property of the mature neocortex
Background of Parkinson's Disease and Movement Disorders
[0022] Parkinson's disease (PD) belongs to a group of conditions
called motor system disorders, which are the result of the loss of
dopamine producing brain cells. Parkinsonism is the most common
movement disorder in adults affecting 1% to 2% of patients >60
years old. Parkinson's disease (PD) is a progressive
neurodegenerative disorder whose pathologic hallmark is loss of
dopaminergic neurons in the substantia nigra pars compacta. The
cardinal motor signs of PD are tremor, rigidity, bradykinesia,
akinesia, and a gait disorder characterized by a flexed posture and
short, shuffling steps. Patients may also develop postural
instability and freezing, a phenomenon characterized by a sudden
inability to continue or initiate movement. Decreased associated
movements (masked facies, decreased eye blink, and reduced arm
swing) are common early signs of PD. Hyprophonia, micrographia, and
difficulty with fine motor control (buttoning buttons, handling
utensils, shaving, or applying makeup), and getting out of a chair
or rolling over in bed at night are common early complaints of PD
patients.
[0023] The symptoms of PD are tremor, or trembling in hand, arms,
legs, jaw, and face; rigidity, or stiffness of the limbs and trunk;
bradykinesia, or slowness of movement; and postural instability, or
impaired balance and coordination. As these symptoms become more
pronounced, patients may have difficulty walking, talking, or
completing other simple tasks. PD usually affects people over the
age of 50. Early symptoms of PD are subtle and occur gradually. In
some people the disease progresses more quickly than in others. As
the disease progresses, the shaking, or tremor, which affects the
majority of PD patients may begin to interfere with daily
activities. Other symptoms may include depression and other
emotional changes; difficulty in swallowing, chewing, and speaking;
urinary problems or constipation; skin problems; and sleep
disruptions.
[0024] There is no known treatment that will halt or reverse the
neuronal degeneration that presumably underlies Pakinson's
disease.
Other Concomitant Disorders
[0025] Sleep disorders are common in Parkinsonian patients and may
exacerbate Parkinsonian motor signs as a result of the excessive
fatigue and daytime sleepiness.
[0026] Depression is a common occurrence in patients with PD, but
it is often overlooked. It has been clinically observed that
successful treatment of their depression is almost always
associated with a concurrent improvement in parkinsonian motor
signs.
Other Movement Disorders
[0027] Essential tremor (ET), which is the most common movement
disorder is an insidiously progressive and often inheritable
disorder usually beginning before the age of 50. The genetic basis
is uncertain. It is characterized by involuntary rhythmic
oscillations of a body part resulting from either alternating or
synchronous contractions of opposing muscles. Tremor is essentially
the only symptom present, although subtle gait abnormalities may be
noted when the legs are affected. Weakness is not a primary symptom
although tremor can produce weakness by reducing the strength of
contraction.
[0028] Huntington's Disease (HD) is characterized as a triad of
symptoms and signs: a movement disorder, a cognitive disorder, and
a psychiatric disorder. Each of these domains may be problematic
for the individual at various states of the illness, which on
average spans 15 to 20 years.
[0029] Progressive supranuclear palsy (PSP) is the most common
Parkinsonian disorder after Parkinson's disease (PD). Typically,
PSP patients present with early postural instability, supranuclear
vertical gaze palsy, and levodopa-nonresponsive parkinsonism
(bradykinesia and axial more than limb rigidity).
Existing Medical and Surgical Therapy
[0030] General Approach to Therapy: Initial medical treatment
typically involves the use of drugs to replace striatal dopamine or
drugs that have dopaminergic properties, e.g., dopamine
agonists.
[0031] Disease Progression and Development of Motor Complication
Wearing Off (End-of-Dose Phenomenon): Over time, patients' symptoms
typically become more severe, and they begin to develop wearing-off
phenomenon (i.e., symptoms return before the next dose of
medication). When this occurs, one can increase the dose of
medication, decrease the time interval between doses, add an
agonist or begin a COMT inhibitor to minimize the amount of "off"
time. There should be a small amount of time before the next dose
when the patient notes some loss of effect because this indicates
that the patient is not receiving more medication than
necessary.
[0032] Patients with PD whose motor symptoms can no longer be
controlled adequately be medical therapy are candidates for
surgical therapy. Surgical procedures of PD consist of ablative
procedures (thalamotomy, pallidotomy) and stimulation procedures
(thalamic, pallidal, subthalamic).
[0033] Thalamotomy: Thalamotomy is effective for the treatment of
parkinsonian tremor. Lesions are generally placed in the cerebellar
receiving area, ventralis intermedius (VIM). If the lesion is
extended more anteriorly into the basal ganglia receiving area,
ventralis oralis posterior and ventralis oralis anterior.
Thalamotomy may also improve rigidity and drug-induced
dyskinesias.
[0034] Pallidotomy: Pallidotomy is effective for all the cardinal
motor signs of PD, including tremor, rigidity, and bradykinesia, as
well as motor fluctiations and drug-induced dyskinesias and
dystomia. It may also improve axial symptoms, including gait,
balance, and freezing. The improvement in axial symptoms after
unilateral pallidotomy, however, is less consistent than that for
appenducular symptoms, with many patients losing their benefit
anywhere form 6 months to 2 years postpallidotomy.
[0035] Deep Brain Stimulation (DBS): DBS in the GPi or the STN for
PD can be performed either as a staged procedure or simultaneously.
Simultaneous procedures may be associated with a higher incidence
of postoperative confusion. Based on the patient's symptoms,
unilateral implantaion may benefit the patient enough to preclude
or at least delay the necessity for a second implantation on the
other side. Most patients, however, will require bilateral
implantation to gain optimal control over axial symptoms or to gain
bilateral control over appendicular symptoms. Both targets, the GPi
and the STN, are effective in treating the cardinal motor signs of
PD, including gait, balance, and freezing symptoms.
Background for Cortical Stimulation
[0036] A simplified general anatomy of the human brain is shown in
conjunction with FIGS. 1A, 1B, 1C and will be referred to
throughout the disclosure. FIG. 1A depicts the brain from a top
view, highlighting the frontal lobe, parietal lobe, occipital lobe,
as well as, highlighting the precentral gyrus 28 and postcentral
gyrus 30 separated by the central sulcus 29. FIG. 1B depicts the
brain from a lateral view highlighting the anatomical regions of
interest in this patent disclosure, such as primary somatosensory
cortex 37, primary motor cortex 36, and premotor cortex 35. Other
cortical areas such as primary visual cortex, primary auditory
cortex, and limbic and anterior association areas are also
highlighted. FIG. 1C shows a perspective of the brain via a
midsection view, again showing the region around the central sulcus
29, and some of deeper aspects of the brain tissues.
[0037] In the method and system of this invention, it will be
appreciated that even though the electrodes are placed only on the
cortical surface, the electrical field will penetrate deeper layers
of the cortical brain tissue. The deeper layers of the cortex are
depicted in an overview fashion in FIG. 2A, and a detail of the
layers of cells is shown in conjunction with FIG. 2B, where the
layer of pyramidal cells is shown as layer III.
[0038] The human brain has been mapped to a significant extent. In
the early part of the twentieth century, K. Brodmann divided the
human cerebral cortex into 52 discrete areas on the basis of
distinctive nerve cell structures and characteristic arrangements
of cell layers, this is shown in conjunction with FIG. 3.
Brodmann's scheme of the cortex is still widely used today and is
continually updated. In this drawing (FIG. 3) each area is
represented by its own symbol and is assigned a unique number.
Several areas defined by Brodmann have been found to control
specific brain functions; For instance, area 4, the motor cortex,
is responsible for voluntary movement. Areas 1, 2, and 3 comprise
the primary somatosensory cortex, which receives information on
bodily sensation. Area 17 is the primary visual cortex, which
receives signals from the eyes and relays them to other areas for
further deciphering. Areas 41 and 42 comprise the primary auditory
cortex. Areas not visible from the outer surface of the cortex are
not shown in this drawing.
[0039] Electrical stimulation has been used to identify the
specific motor effects of discrete sites in the frontal lobe in
humans, and the resulting motor maps have been correlated with
anatomical and clinical observations on the effects of local
lesions. The contralateral precentral gyrus (Brodmann's area 4),
the region now called the primary motor cortex, proved to be the
area in which the lowest intensity stimulation elicited
movements.
[0040] By stimulating motor cortical areas in alert humans by
inducing electrical fields in the brain using rapidly alternating
magnetic fields produced by wire coils applied to the scalp. The
responses in muscles (e.g. of the hand) are recorded with surface
electrodes. The motor action potentials are large and have a short
latency, consistent with the fact that they are conducted by
corticospinal fibers, shown in FIG. 4. Magnetic stimulation has
also been used to map the body representation in the primary motor
cortex or to perturb processing in local cortical areas.
[0041] Initially, a simplistic idea was believed that the primary
motor cortex acts as a massive switchboard with individual switches
controlling individual muscles or small groups of adjacent muscles.
More detailed studies, however, using microelectrodes inserted into
the depths of the cortex (intracortical microstimulation or ICMS)
to stimulate small groups of output neurons indicate that this
simple view is incorrect. Whereas the weakest stimuli may evoke the
concentration of individual muscles, the same muscles are
invariably activated from several separate sites as well,
indicating that neurons in several cortical sites project axons to
the same target. This provides the basis for cortical stimulation
to enhance neuroplasticity in post-stroke patients, as disclosed in
this patent application.
[0042] In addition, most stimuli activate several muscles, with
muscles rarely being activated individually. This is corroborated
by recent anatomical and physiological experiments showing that the
terminal distributions of individual corticospinal axons diverge to
motor neurons innervating more than one muscle. Instead of a simple
switchboard of muscle representation, detailed maps of monkey motor
cortex suggest a concentric organization: sites influencing distal
muscles are contained at the center of a wider area containing
sites that also influence more proximal muscles, while sites in the
peripheral ring around this central area influence proximal muscles
alone. An implication of the redundancy in muscle representation is
that inputs to motor cortex from other cortical can combine
proximal and distal muscles in different ways in different
tasks.
[0043] FIG. 5A depicts the cerebral cortex with simplified map of
functional areas labeled on the cerebral cortex. FIG. 5B depicts
further details of motor cortical areas which are of interest in
this patent disclosure particularly as pertaining to stroke and
Parkinson's disease. FIG. 5B highlights primary somatic sensory
cortex, primary motor cortex, supplementary motor area, and
premotor cortex. These functional areas are superimposed with
Broadman's area shown in FIG. 3.
[0044] The motor maps show an orderly arrangement along the gyrus
of control areas for the face, digits, hand, arm, trunk, leg, and
foot. However, the fingers, hands, and face--which are used in
tasks requiring the greatest precision and finest control--have
disproportionately large representations in the motor areas of
cortex (FIG. 5B), much as the inputs from regions of the body that
have important roles in perception predominate in the sensory areas
of the cortex. Consistent with the overall somatotopic
organization, lesions in the arm representation lead to
degeneration of myelinated fibers in the cervical cord, while
lesions in the leg representation produce degeneration extending
all the way to the lumbar spinal cord. These are Betz cells whose
axons arise from specialized large pyramidal neurons in lamina
V.
[0045] It is known that different areas of the cortex are activated
during simple, complex, and imagined sequences of finger movements.
Local increases in cerebral blood flow during a behavior indicate
which areas of motor cortex are involved in the behavior, since
local tissue perfusion varies with neural activity. For example, as
shown in conjunction with FIG. 6A, when a finger is pressed
repeatedly against a spring, increased blood flow is detected in
the hand-control areas of the primary motor and sensory cortices.
The increase in the motor area is related to the execution of the
response, whereas the increase in the sensory area reflects the
activation of peripheral receptors. Shown in conjunction with FIG.
6B, during a complex sequence of finger movements the increase in
blood flow extends to the medial premotor area, which includes the
supplementary motor area and presupplementary motor area. Shown in
conjunction with FIG. 6C, during mental rehearsal of the same
sequence illustrated in FIG. 6B, blood flow increases only in the
medial motor area.
[0046] An overall map of the convoluted outer layer of gray matter
that forms the cerebral cortex is shown in conjunction with FIG.
7A. The larger the area, the more nerve cells and fibers it
contains. The diagram separates the breakdown of the motor cortex
(on the right side of the figure's brain, controlling the left side
of the body) from that of the sensory cortex (left brain,
right-hand side of the body). The two "stripes" are located on the
whole brain, at the bottom portion of FIG. 7A. For clarity, a
somatotopic map of the body surface onto primary somatosensory
cortex is shown in conjunction with FIG. 7B. This map is a cross
section through the postcentral gyrus, shown at the top of figure.
Neurons in each area are most responsive to the parts of the body
illustrated above them. FIG. 7C shows a somatotopic map of the
human precentral gyrus (primary motor cortex). Systematic probing
of this region has shown that there is a somatotopic organization
in the human precentral gyrus much like that seen in the
somatosensory areas of the postcentral gyrus.
Background Cellular Neurophysiology for the Invention
[0047] At the cellular level, nerve cells have membranes that are
composed of lipids and proteins (shown schematically in FIGS. 8A
and 8B), and have unique properties of excitability such that an
adequate disturbance of the cell's resting potential can trigger a
sudden change in the membrane conductance. Under resting
conditions, the inside of the nerve cell is approximately -90 mV
relative to the outside. The electrical signaling capabilities of
neurons are based on ionic concentration gradients between the
intracellular and extracellular compartrments. The cell membrane is
a complex of a bilayer of lipid molecules with an assortment of
protein molecules embedded in it (shown in FIG. 8A), separating
these two compartments. Electrical balance is provided by
concentration gradients which are maintained by a combination of
selective permeability characteristics and active pumping
mechanism.
[0048] The lipid component of the membrane is a double sheet of
phospholipids, elongated molecules with polar groups at one end and
the fatty acid chains at the other. The ions that carry the
currents used for neuronal signaling are among these water-soluble
substances, so the lipid bilayer is also an insulator, across which
membrane potentials develop. In biophysical terms, the lipid
bilayer is not permeable to ions. In electrical terms, it functions
as a capacitor, able to store charges of opposite sign that are
attracted to each other but unable to cross the membrane. Embedded
in the lipid bilayer is a large assortment of proteins. These are
proteins that regulate the passage of ions into or out of the cell.
Certain membrane-spanning proteins allow selected ions to flow down
electrical or concentration gradients or by pumping them
across.
[0049] These membrane-spanning proteins consist of several subunits
surrounding a central aqueous pore (shown in FIG. 8B). Ions whose
size and charge "fit" the pore can diffuse through it, allowing
these proteins to serve as ion channels. Hence, unlike the lipid
bilayer, ion channels have an appreciable permeability (or
conductance) to at least some ions. In electrical terms, they
function as resistors, allowing a predicable amount of current flow
in response to a voltage across them.
[0050] FIG. 9A illustrates a segment of the surface of the membrane
of an excitable cell. Metabolic activity maintains ionic gradients
across the membrane, resulting in a high concentration of potassium
(K.sup.+) ions inside the cell and a high concentration of sodium
(Na.sup.+) ions in the extracellular environment. The net result of
the ionic gradient is a transmembrane potential that is largely
dependent on the K.sup.+ gradient. Typically in nerve cells, the
resting membrane potential (RMP) is slightly less than 90 mV, with
the outside being positive with respect to inside.
[0051] To stimulate an excitable cell, it is only necessary to
reduce the transmembrane potential by a critical amount. When the
membrane potential is reduced by an amount .DELTA.V, reaching the
critical or threshold potential (TP); Which is shown in FIG. 9B.
When the threshold potential (TP) is reached, a regenerative
process takes place: sodium ions enter the cell, potassium ions
exit the cell, and the transmembrane potential falls to zero
(depolarizes), reverses slightly, and then recovers or repolarizes
to the resting membrane potential (RMP).
[0052] For a stimulus to be effective in producing an excitation,
it must have an abrupt onset, be intense enough, and last long
enough. These facts can be drawn together by considering the
delivery of a suddenly rising cathodal constant-current stimulus of
duration d to the cell membrane as shown in FIG. 9B.
[0053] Cell membranes can be reasonably well represented by a
capacitance C, shunted by a resistance R as shown by a simplified
electrical model in the diagram in FIG. 9C, and shown in a more
realistic electrical model in FIG. 10, where neuronal process is
divided into unit lengths, which is represented in an electrical
equivalent circuit. Each unit length of the process is a circuit
with its own membrane resistance (r.sub.m), membrane capacitance
(c.sub.m), and axonal resistance (r.sub.a).
[0054] A nerve cell can be excited by increasing the electrical
charge within the neuron, thus increasing the membrane potential
inside the nerve with respect to the surrounding extracellular
fluid. As shown in FIG. 11A, stimuli 43 and 44 are subthreshold,
and do not induce a response. Stimulus 45 exceeds a threshold value
and induces an action potential (AP) 27 which will be propagated.
The threshold stimulus intensity is defined as that value at which
the net inward current (which is largely determined by Sodium ions)
is just greater than the net outward current (which is largely
carried by Potassium ions), and is typically around -55mV inside
the nerve cell relative to the outside (critical firing threshold).
If however, the threshold is not reached, the graded depolarization
will not generate an action potential and the signal will not be
propagated along the axon. This fundamental feature of the nervous
system i.e., its ability to generate and conduct electrical
impulses, can take the form of action potentials 27, which are
defined as a single electrical impulse passing down an axon. This
action potential 27 (also called nerve impulse or spike) is an "all
or nothing" phenomenon, that is to say once the threshold stimulus
intensity is reached, an action potential will be generated.
Depicted in conjunction with FIG. 11B, the information in the
nervous system is coded by frequency and pattern of firing rather
than the size of the action potential.
[0055] As is well known in the art, the operation of the nervous
system depends on the flow of information through chains of neurons
functionally connected by synapses. Most synapses occur between the
axon terminal of one neuron and the dendrite or cell body of a
second neuron. Sometimes, however, synapses occur between two
dendrites or between a dendrite and a cell body or between an axon
terminal and a second axon terminal to modulate its output. A
neuron that conducts a signal toward a synapse is a presynaptic
neuron, whereas a neuron conducting signals away from a synapse is
a postsynaptic neuron. FIG. 12A shows how, in a multineuronal
pathway, a single neuron can be postsynaptic to one cell and
presynaptic to another. A post synaptic neuron may have thousands
of synaptic junctions on the surface of its dendrites and cell
body, so that signals from many presynaptic neurons can affect
it.
[0056] There are variety of synapse contacts. Although most
synapses in the nervous system occur between axons and dendrites,
synaptic contact can occur at any region of the neuron. For
example, the somas of nearly all cells in the central nervous
system (CNS) receive synapses from axons. Shown in conjunction with
FIG. 12B, synapses can be formed between almost any neuronal
structures. The most common sites for synaptic contact are between
axon boutons and neuron somas (A), between two axons (B), and
between axon boutons and dendrites (C). Much less common are
synapses between dendrites and somas (D) and between two dendrites
(E).
[0057] Most CNS neurons receive thousands of synaptic inputs. The
transformation of many synaptic inputs to a single neuronal output
constitutes neural computation. The brain performs billions of
neural computations every second.
[0058] The simplest form of synaptic integration in the CNS is
excitatory postsynaptic potential (EPSP) summation. Excitatory
postsynaptic potentials (EPSPs) are local graded depolarization
events which occur at excitatory post synaptic membranes. The
function of EPSPs is to help trigger an action potential distally
at the axon hillock of the postsynaptic neuron. Shown in
conjunction with FIG. 13A, there are two types of summation:
Spatial and Temporal, and typically they occur together. Spatial
summation is the adding together of EPSPs generated simultaneously
at many different synapses on a dendrite. Temporal summation is the
adding together of EPSPs generated at the same synapse if they
occur in rapid succession, within 1-15 msec of one another.
[0059] When summation results from buildup of neurotransmitter
released simultaneously by several presynaptic end bulbs, it is
spatial summation, shown in the left part of FIG. 13A. When
summation results from buildup of neurotransmitter released by a
single presynaptic end bulb two or more times in rapid succession,
it is temporal summation, shown in the right part of FIG. 13A; As a
typical EPSP lasts about 15 msec, the second (and subsequent)
release of neurotransmitter must occur soon after the first one if
temporal summation is to occur.
[0060] A single postsynaptic neuron receives input from many
presynaptic neurons, some of which release excitatory
neurotransmitters and some of which release inhibitory
neurotransmitters. The sum of all the excitatory and inhibitory
effects at any given time determines the effect on the postsynaptic
neuron, which may respond in the following ways: [0061] 1. EPSP. If
the total excitatory effects are greater than the total inhibitory
effects but less than the threshold level of stimulation, the
result is a subthreshold EPSP. Subsequent stimuli can more easily
generate a nerve impulse through summation because the neuron is
partially depolarized. [0062] 2. Nerve impule(s). If the total
excitatory effects are greater than the total inhibitory effects
and the threshold level of stimulation is reached or surpassed, the
EPSP spreads to the initial segment of the axon and triggers one or
more nerve impulses. Impulses continue to be generated as long as
the EPSP stays above the threshold level. [0063] 3. IPSP. If the
total inhibitory effects are greater than the excitatory effects,
the membrane hyperpolarizes (IPSP). The result is inhibition of the
postsynaptic neuron and an inability to generate a nerve
impulse
[0064] Similarly, inhibitory postsynaptic potentials (IPSPS) also
summate, both temporally and spatially. In the case of IPSPs, the
postsynaptic neuron is inhibited to a greater degree. Most neurons
receive both stimulatory and inhibitory inputs from thousands of
other neurons.
[0065] A typical neuron in the CNS receives input from 1000-10,000
synapses. Integration of these inputs occurs at the trigger zone.
The greater the summation of EPSPs, the greater the chance that
threshold will be reached and a nerve impulse will be
initiated.
[0066] Shown in conjunction with FIG. 13B, synapses that produce
IPSPs tend to be concentrated at the base of large dendrites and on
the soma of neurons. Generally speaking, the excitatory synapses
are more distal. Consequently, proximal inhibitory synapses have
more influence on the membrane potential at the initial segment
than the distal excitatory synapses. By providing a low-resistance
pathway, or sink, for electrical current to leave the cell, the
IPSP can short-circuit the positive currents generated by EPSPs.
The smooth integration of excitatory and inhibitory events over
time and space ultimately determines whether or not the
postsynaptic cell initiates an action potential. This integration
brings together information from diverse sources and at a single
moment transforms this collective set of information into a single
postsynaptic event, the action potential. The summation of synaptic
currents, both excitatory and inhibitory, at the initial segment of
the axons is the fundamental decision-making process of the nervous
system.
[0067] The physical relation between synaptic boutons that produce
EPSPs and IPSPs affects the amplitude and time course of the
postsynaptic potential as recorded at the soma of the neuron. As
shown in FIG. 13, the graph portion at the bottom of the figure
illustrates a hypothetical computer-generated EPSPs at the base of
a dendrite which are calculated for three physical arrangements;
[0068] A. an EPSP generated at the indicated site produces a
response at the initial segment as shown by the broken black line
in the graph. A simultaneous IPSP applied at a site distal to the
EPSP hardly affects the amplitude or shape of the EPSP (solid red
line). [0069] B. If the EPSP and the IPSP are simultaneously
generated at the same site along the dendrite, the amplitude of the
EPSP is diminished by about half and its time course is slowed.
[0070] C. If the IPSP-generating synaptic bouton is between the
recording site and the EPSP-generating synaptic bouton, the
inhibitory effect is even more profound.
[0071] FIG. 14 depicts a more realistic model of neuron as an
integrative structure approaching the complexity of the neurons
pictured in FIGS. 2A and 2B, replete with an enormous and complex
dendritic tree and a nonuniform distribution of ion channels. The
responses of a neuron like this reflect the principles of
spatiotemporal summation. Such a neuron receives thousands or tens
of thousands of synaptic contacts distributed over its entire
dendritic tree, the cell body, and on the axon near terminal
boutons, as shown in FIG. 14. The voltage-sensitive sodium channels
critical to the initiation of an action potential are
preferentially distributed in a region at the base of the axon
known as the initial segment, which is immediately adjacent to the
axon hillock. The transmission of electrical impulses along the
axon is "all or none" because it takes advantage of the
self-perpetuating dynamics of the action potential: once an action
potential is generated at the axon hillock, it regenerates itself
all the way down the axon (3E in FIG. 14). However, transmission of
impulses along dendritic branches is passive and therefore subject
to the attenuating effects of fiber resistance and capacitance.
Therefore, synaptic contacts that are on large dendritic branches
(low resistance) are going to have more influence on the neuron
than synaptic contacts on small branches (high resistance), and
synaptic contacts near the cell body (or even better, the initial
segment near the axon hillock) (input A, FIG. 14) are going to have
more influence than synaptic contacts distant in the dendritic tree
(input B, FIG. 14). Further, synaptic contacts may be excitatory
(e.g., glutamate, generating EPSPs) or inhibitory (e.g., GABA,
generating IPSPs) (as in input C, FIG. 14). Synaptic contacts on
the axon terminal are capable of modifying the amount of
neurotransmitter emitted by an action potential, something referred
to as presynaptic excitation or inhibition (input D, FIG. 14).
[0072] Any given neuron produces action potentials at a rate that
reflects a spatially weighted integral of all its inputs over
time--that is, spatiotemporal summation. This arrangement seems to
provide neurons with the potential for enormous information
processing sophistication.
[0073] FIG. 15 summarizes a graphical representation of spatial and
temporal summation at synaptic junctions. (a) When presynaptic
neurons A and A separately cause EPSPs (arrows) in postsynaptic
neuron C, the threshold level is not reached in neuron C. Spatial
summation occurs only when neurons A and B act simultaneously on
neuron C; Their EPSPs sum to reach the threshold level and trigger
a nerve impulse. (b) Temporal summation occurs when stimuli applied
to the same axon in rapid succession (arrows at the bottom of the
graph) cause overlapping EPSPs that sum. When depolarization
reaches the threshold level, a nerve impulse is triggered.
[0074] Shown in conjunction with FIG. 16A, at the cellular level by
passing continuous depolarizing current into a neuron through a
microelectrode 493A, 493B, many action potentials are generated in
succession. Further, as shown in conjunction with FIG. 16B the rate
of action potential generation in a single cell depends on the
magnitude of the continuous depolarizing current. As shown in FIG.
16B, in the left part 492 the injected current does not depolarize
the membrane to threshold, and no action potentials are generated.
In the middle portion 494 of FIG. 16B, the injected current
depolarizes the membrane beyond threshold, and some action
potentials are generated. In the right portion 496 of FIG. 16B, as
the injected current increases, the firing rate of action
potentials also increases.
Tissue Stimulation
[0075] In the method and system of this invention, this concept is
applied at the tissue level, where as shown in conjunction with
FIG. 17, instead of injecting current into a cell, the stimulating
current (electrical pulses) is/are applied to the cortical tissues
at the relevant portions of the brain. In certain situations it
would be desirable to apply subthreshold (low level) electrical
stimulation, and in certain other situations it would be desirable
to apply suprathreshold electrical stimulation.
[0076] An objective of this invention is to provide subthreshold
stimulation to target tissues using cortical electrodes, to either
enhance or induce neuroplasticity, for providing improvement of
functional recovery following stroke. The subthreshold stimulation
lead to partially depolarized neurons, which are more easily prone
to action potentials, because they are already nearer to threshold.
It is expected that cortical stimulation of the healthy brain
tissue adjacent to the "stroke," in combination With
rehabilitation, enhances motor recovery and that cortical
stimulation for stroke patients will facilitate neuroplasticity.
This approach will lead to synaptic and morphologic changes
associated with activity-dependent plasticity at the levels of the
cerebral hemispheres.
[0077] Recovery of function after stroke is associated with a
series of changes in the motor cortex that allow uninjured areas of
the cortex to compensate for functions lost due to the stroke. When
the brain is stimulated with a small amount of electric current
during rehabilitation therapy, it is believed that it makes it
easier for the brain to form new connections and relearn lost motor
skills.
[0078] Surgery is done to open the skull. A small grid is implanted
on the covering of the brain (the dura), which in turn covers the
area of motor cortex. The motor cortex is the part of the brain
that controls movement. A wire connected to the grid sticks out of
the patient's head. In one embodiment, during therapy sessions the
wire is connected to a battery pack in a vest, as described later.
The battery stimulates the grid and, therefore, the motor cortex.
While the nerves that were killed in the stroke will not regain
function, new connections in the brain can be made and that's what
is expected to happen. Also, research shows the stimulation
increases blood flow to the part of the brain that is being
stimulated. Patients have therapy for a period of time determined
by the physician.
[0079] Another objective of this invention is to provide cortical
stimulation, to provide therapy or alleviate symptoms of
Parkinson's disease and other neurological disorders that are
amenable to brain stimulation utilizing one or more implanted
cortical electrodes and a pulse generator means.
PRIOR ART
[0080] U.S. Pat. No. 6,959,215 B2 (Gliner et al.) is generally
directed to methods for treating essential tremor.
[0081] U.S. patent applications Ser. No. 0097161 A1 (Firlik et
al.), 0091419 (Firlik et al.), Ser. No. 0130706 A1 (Sheffield et
al.), Ser. No. 0021105A1 (Firlik et al.), and Ser. No. 0087201 A1
(Firlik et al.) are all generally directed to methods and apparatus
for effectuating a lasting change in a neural-function of a
patient.
SUMMARY OF THE INVENTION
[0082] The method and system of current invention provides pulsed
electrical stimulation to the cortical portion of a patient's brain
to provide therapy or alleviate symptoms of neurological disorders
such as Parkinson's disease, or for providing improvement of
functional recovery following stroke. The method and system
comprises both implantable and external components. The power
source may also be external or implanted in the body. The system to
provide selective stimulation to the cortex may be selected from a
group consisting of:
[0083] a) an implantable stimulus-receiver used in conjunction with
an external stimulator;
[0084] b) an implantable stimulus-receiver comprising a high value
capacitor for storing charge, used in conjunction with an external
stimulator;
[0085] c) a programmer-less implantable pulse generator (IPG) which
is operable with a magnet;
[0086] d) a microstimulator;
[0087] e) a programmable implantable pulse generator (IPG);
[0088] f) a combination implantable device comprising both a
stimulus-receiver and a programmable IPG; and
[0089] g) an IPG comprising a rechargeable battery.
[0090] In one aspect of the invention, rectangular and/or complex
electrical pulses are provided to the cortical tissues of a
patient, wherein complex electrical pulses comprise at least one of
multi-level pulses, biphasic pulses, non-rectangular pulses, or
pulses with varying amplitude during the pulse.
[0091] In another aspect of the invention, the electrical pulses
are provided according to predetermined/pre-packaged programs
[0092] In another aspect of the invention, the electrode
configuration for providing said electrical pulses is at least
partly based on sensed electrical activity from the patient's
cortical tissues.
[0093] In another aspect of the invention, the electrode placement
on the patient's cortex is based at least in part to digital
imaging techniques, such as fMRI or CT scans.
[0094] In another aspect of the invention, the electrode placement
on the patient's cortex is based both on digital imaging techniques
and on sensing from the cortical tissues of the patient.
[0095] In another aspect of the invention, the configuration of
electrodes for providing electrical pulses is alternated between at
least two configurations.
[0096] In another aspect of the invention, the
predetermined/pre-packaged programs can be modified.
[0097] In another aspect of the invention, the range of electrical
pulses comprises, pulse amplitude between 0.1 volt-15 volts; pulse
width between 20 micro-seconds-5 milli-seconds; stimulation
frequency between 5 Hz and 200 Hz, and blocking frequency between 0
and 750 Hz.
[0098] In yet another aspect of the invention, the pulse generation
system comprises telemetry means and can be remotely interrogated
and/or programmed over a wide area network.
[0099] Various other features, objects and advantages of the
invention will be made apparent from the following description
taken together with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0100] For the purpose of illustrating the invention, there are
shown in accompanying drawing forms which are presently preferred,
it being understood that the invention is not intended to be
limited to the precise arrangement and instrumentalities shown.
[0101] FIG. 1A depicts a top view of a human brain.
[0102] FIG. 1B depicts a lateral view of a human brain.
[0103] FIG. 1C depicts a midsection of a human brain.
[0104] FIG. 2A depict deeper layers of a section of the human
cortex.
[0105] FIG. 2B is a close-up of a cross section of human cortex,
showing six layers of cells.
[0106] FIG. 3 depicts a lateral view of a human brain, showing
various Brodmann's area.
[0107] FIG. 4 depicts recordings from hand resulting from
electrical stimulation of the human motor cortex.
[0108] FIG. 5A is a figure of a human brain depicting various broad
functional areas correlating to different areas in the brain.
[0109] FIG. 5B depicts functional areas in the brain relating to
voluntary movement, particularly motor cortex and sensory
cortex.
[0110] FIGS. 6A, 6B, and 6C depicts different areas of human cortex
which are activated during simple, complex, and imagined sequences
of finger movements.
[0111] FIG. 7A depicts parts of the body that are correlated with
sensory and motor areas of the human brain.
[0112] FIG. 7B depicts a map which is a cross section through the
postcentral gyrus showing neurons in each area that are most
responsive to the parts of the body illustrated above them.
[0113] FIG. 7C depicts a somatotopic map of the human precentral
gyrus which corresponds to the motor cortex.
[0114] FIGS. 8A and 8B are schematic illustrations of the
biochemical makeup of nerve cell membrane.
[0115] FIGS. 9A, 9B, 9C. are schematic illustrations of the
electrical properties of nerve cell membrane.
[0116] FIG. 10 is a schematic illustration of the electrical
circuit model of nerve cell membrane.
[0117] FIG. 11A is a figure demonstrating subthreshold and
suprathreshold stimuli.
[0118] FIG. 11B depicts subthreshold potentials and a train of
action potentials.
[0119] FIG. 12A depicts an arrangement of nerve cells showing both
presynaptic and postsynaptic junctions.
[0120] FIG. 12B depicts another form of synaptic arrangement
between nerve cells.
[0121] FIG. 13A depicts in graphical form the spatial and temporal
summation of excitatory postsynaptic potentials (EPSPs).
[0122] FIG. 13B depicts graphically summation of EPSPs and
IPSPs.
[0123] FIG. 14 depicts another arrangement of nerve cells
connecting and communicating to process information.
[0124] FIG. 15 depicts excitatory and inhibitory synapses, as well
as, temporal and spatial summation for reaching threshold.
[0125] FIG. 16A depicts an injected current leading to action
potentials.
[0126] FIG. 16B depicts the relationship between injected current
and nerve cell firings of action potentials.
[0127] FIG. 17 is a figure that depicts an electrical field
penetrating through the cells of the cortical layers.
[0128] FIG. 18 is a figure that depicts sensing from ischemic and
"healthy" cortical tissues via multiple electrode pairs.
[0129] FIGS. 19A and 19B depict electrode configurations for
stimulation of cortical tissues.
[0130] FIG. 20 depicts placement of stimulation electrodes relative
to an ischemic region, based on imaging techniques.
[0131] FIG. 21 depicts placement of paddle stimulation electrodes
which are implanted approximately perpendicular to each other
[0132] FIGS. 22A and 22B depict electrode configurations for
stimulating cortical tissues.
[0133] FIG. 23A depicts placement of paddle electrodes on the motor
cortex of the brain.
[0134] FIG. 23B depicts placement of electrodes on the motor cortex
of the brain comprising two layers of electrodes.
[0135] FIG. 23C depicts placement of electrodes on the motor cortex
of the brain comprising three layers of electrodes.
[0136] FIG. 24 is a simplified block diagram depicting supplying
amplitude and pulse width modulated electromagnetic pulses to an
implanted coil.
[0137] FIG. 25 depicts a customized garment for placing an external
coil to be in close proximity to an implanted coil.
[0138] FIG. 26 is a diagram showing an implanted stimulus-receiver
with the distal electrodes in proximity with the cortical
tissues.
[0139] FIG. 27A depicts the placement of a primary coil of an
external stimulator using a head band.
[0140] FIG. 27B depicts using eye glasses for placement of a
primary coil in close proximity to a secondary coil which is
implanted behind the ear.
[0141] FIG. 27C depicts using an ear piece for properly placing a
primary coil of an external stimulator.
[0142] FIG. 28 is a schematic of the passive circuitry in the
implanted stimulus-receiver.
[0143] FIG. 29A is a schematic of an alternative embodiment of the
implanted stimulus-receiver.
[0144] FIG. 29B is another alternative embodiment of the implanted
stimulus-receiver.
[0145] FIG. 30 shows coupling of the external stimulator and the
implanted stimulus-receiver.
[0146] FIG. 31 is a top-level block diagram of the external
stimulator and proximity sensing mechanism.
[0147] FIG. 32 is a diagram showing the proximity sensor
circuitry.
[0148] FIG. 33A shows a pulse train that may be transmitted to the
cortical tissues.
[0149] FIG. 33B shows the ramp-up and ramp-down characteristic of
the pulse train.
[0150] FIG. 34 is a schematic diagram of one embodiment of an
implantable lead for supplying electrical pulses to the cortical
tissues.
[0151] FIG. 35 is a schematic diagram showing the implantable lead
and one form of stimulus-receiver.
[0152] FIG. 36 is a schematic block diagram showing a system for
neuromodulation of the cortical tissues, with an implanted
component which is both RF coupled and contains a capacitor power
source.
[0153] FIG. 37 is a simplified block diagram showing control of the
implantable neurostimulator with a magnet.
[0154] FIG. 38 is a schematic diagram showing implementation of a
multi-state converter.
[0155] FIG. 39 is a schematic diagram depicting digital circuitry
for state machine.
[0156] FIGS. 40A-C depicts various forms of implantable
microstimulators.
[0157] FIG. 41 is a figure depicting an implanted microstimulator
for providing pulses to cortical tissues.
[0158] FIG. 42 is a diagram depicting the components and assembly
of a microstimulator.
[0159] FIG. 43 shows functional block diagram of the circuitry for
a microstimulator.
[0160] FIGS. 44A, 44B, and 44C are simplified block diagrams of the
implantable pulse generator.
[0161] FIG. 45 is a functional block diagram of a
microprocessor-based implantable pulse generator.
[0162] FIG. 46 shows details of implantable pulse generator.
[0163] FIGS. 47A and 47B show details of digital components of the
implantable circuitry.
[0164] FIG. 48A shows a schematic diagram of the register file,
timers and ROM/RAM.
[0165] FIG. 48B shows datapath and control of custom-designed
microprocessor based pulse generator.
[0166] FIG. 49 is a block diagram for generation of a
pre-determined stimulation pulse.
[0167] FIG. 50 is a simplified schematic for delivering stimulation
pulses.
[0168] FIG. 51 is a circuit diagram of a voltage doubler.
[0169] FIG. 52A is a diagram depicting ramping-up of a pulse
train.
[0170] FIG. 52B depicts rectangular pulses.
[0171] FIGS. 52C, 52D, and 52E depict multi-step pulses.
[0172] FIGS. 52F, 52G, and 52H depict complex pulse trains.
[0173] FIG. 52-I depicts the use of tripolar electrodes.
[0174] FIGS. 52J and 52K depict step pulses used in conjunction
with tripolar electrodes.
[0175] FIGS. 52L and 52M depict biphasic pulses used in conjunction
with tripolar 'pulses.
[0176] FIGS. 52N and 52-O depict modified square pulses to be used
in conjunction with tripolar electrodes.
[0177] FIGS. 53A and 53B are diagrams showing communication of
programmer with the implanted stimulator.
[0178] FIGS. 54A and 54B show diagrammatically encoding and
decoding of programming pulses.
[0179] FIG. 55 is a simplified overall block diagram of implanted
pulse generator (IPG) programmer.
[0180] FIG. 56 shows a programmer head positioning circuit.
[0181] FIG. 57 depicts typical encoding and modulation of
programming messages.
[0182] FIG. 58 shows decoding one bit of the signal from FIG.
57.
[0183] FIG. 59 shows a diagram of receiving and decoding circuitry
for programming data.
[0184] FIG. 60 shows a diagram of receiving and decoding circuitry
for telemetry data.
[0185] FIG. 61 is a block diagram of a battery status test
circuit.
[0186] FIG. 62 is a diagram showing the two modules of the
implanted pulse generator (IPG).
[0187] FIG. 63A depicts coil around the titanium case with two
feedthroughs for a bipolar configuration.
[0188] FIG. 63B depicts coil around the titanium case with one
feedthrough for a unipolar configuration.
[0189] FIG. 63C depicts two feedthroughs for the external coil
which are common with the feedthroughs for the lead terminal.
[0190] FIG. 63D depicts one feedthrough for the external coil which
is common to the feedthrough for the lead terminal.
[0191] FIG. 64 shows a block diagram of an implantable stimulator
which can be used as a stimulus-receiver or an implanted pulse
generator with rechargeable battery.
[0192] FIG. 65 is a block diagram highlighting battery charging
circuit of the implantable stimulator of FIG. 64.
[0193] FIG. 66 is a schematic diagram highlighting
stimulus-receiver portion of implanted stimulator of one
embodiment.
[0194] FIG. 67A depicts bipolar version of stimulus-receiver
module.
[0195] FIG. 67B depicts unipolar version of stimulus-receiver
module.
[0196] FIG. 68 depicts power source select circuit.
[0197] FIG. 69A shows energy density of different types of
batteries.
[0198] FIG. 69B shows discharge curves for different types of
batteries.
[0199] FIG. 70 depicts externalizing recharge and telemetry coil
from the titanium case.
[0200] FIGS. 71A and 71B depict recharge coil on the titanium case
with a magnetic shield in-between.
[0201] FIG. 72 shows in block diagram form, an implantable
rechargeable pulse generator.
[0202] FIG. 73 depicts in block diagram form, the implanted and
external components of an implanted rechargeable system.
[0203] FIG. 74 depicts the alignment function of rechargeable
implantable pulse generator.
[0204] FIG. 75 is a block diagram of the external re-charger.
[0205] FIG. 76 depicts remote monitoring of stimulation
devices.
[0206] FIG. 77 is an overall schematic diagram of the external
stimulator, showing wireless communication.
[0207] FIG. 78 is a schematic diagram showing application of
Wireless Application Protocol (WAP).
[0208] FIG. 79 is a simplified block diagram of the networking
interface board.
[0209] FIGS. 80A and 80B is a simplified diagram showing
communication of modified PDA/phone with an external stimulator via
a cellular tower/base station.
DETAILED DESCRIPTION OF THE INVENTION
[0210] The following description is of the best mode presently
contemplated for carrying out the invention. This description is
not to be taken in a limiting sense, but is made merely for the
purpose of describing the general principles of the invention. The
scope of the invention should be determined with reference to the
claims.
[0211] In one aspect of the invention, electrical pulses are
supplied to the cortical tissue 54 based at least in part to
sensing intrinsic electrical activity from the neural cortical
tissue. This is shown in conjunction with FIG. 18, where preferably
paddle electrodes are placed in relation to an ischemic region 21,
such as may be caused by stroke. The paddle electrodes are placed
such that one electrode pair is closest to the ischemic tissue and
one electrode pair is farthest from the ischemic tissue, and
closest to "healthy" neural tissue. Based on the underlying
electrophysiologic principles, it would be expected that the
electrode pair 61A, 61B adjacent to the ischemic tissue 21 will
record voltages 26 that are much smaller in amplitude than the
voltages recorded 23 from an electrode pair 64A, 64B that is
adjacent to "healthy" neural tissue. Further, it would be expected
that the electrode pairs in-between will have sensed voltages 24,
25 that are somewhere in-between those of the "healthy" tissue and
ischemic tissue. The differential between the sensed electrograms
may be utilized for determining where to supply the electrical
pulses for subthreshold stimulation.
[0212] In one embodiment, the sensed electrograms 23, 24, 25, 26
are telemetered out and recorded on paper or storage device, using
a programmer and a wand placed on the implanted device. The
physician can then make a determination regarding which electrodes
are to be used for supplying electrical pulses, and program the
pulse generator accordingly.
[0213] In another embodiment, the microcontroller/microprocessor of
the implanted pulse generator (IPG) may be used to determine the
configuration for delivering stimulation pulses, based upon a
predetermined criteria.
[0214] For stimulation, in one example shown in conjunction with
FIGS. 19A and 19B, if the electrode pairs 61, 62, 63, 64 are used
the electrode configuration for stimulation may be 61A vs. 61B, 62A
vs. 62B, 63A vs. 63B, 64A vs. 64B as shown in FIG. 19A, or the
electrode stimulation configuration may be 61A vs. 64B, 62A vs.
63B, 63A vs. 62B, 64A vs. 61B, as shown in FIG. 19B, or the pulse
delivery may be configured to be alternated between these two
configurations. Each paddle electrode may comprise more than four
electrodes, and similar electrode configurations may be used for
sensing or for stimulation. The object of alternating between these
two configurations is to get a more even distribution of the
electrical field for the tissue region being stimulated. As
described later, the implantable pulse generator of this embodiment
comprises sense amplifier circuitry and power source within the
implanted pulse generator (FIG. 44C).
[0215] In another embodiment of the invention, the paddle
electrodes are implanted based on digital imaging techniques such
as fMRI, or MRI scans. In this embodiment sensing of the brain
tissue is not utilized for supplying electrical pulses. This
embodiment is shown in conjunction with FIG. 20, where the paddle
electrodes 61, 62, 63, 64 are placed in relation to the ischemic
tissue 21 based on various imaging techniques. The stimulation
configuration may be the same as shown in FIGS. 19A and 19B. That
is the stimulation electrode configuration may be 61A vs. 61B, 62A
vs. 62B, 63A vs. 63B, 64A vs. 64B as shown in FIG. 19A, or the
electrode stimulation configuration may be 61A vs. 64B, 62A vs.
63B, 63A vs. 62B, 64A vs. 61B, as shown in FIG. 19B, or the pulse
delivery may be configured to be alternated between these two
configurations. Again, the object of alternating between these two
configurations is to get a more even distribution of the electrical
field for the tissue region being stimulated.
[0216] In another embodiment, the placement of paddle electrodes on
the cortical surface is based on both digital imaging techniques,
as well as, sensing from the cortical tissues intraoperatively. In
this embodiment, the initial approximate placement site is based on
imaging techniques, and upon exposure of the cortical surface, the
paddle electrodes are temporally placed at different locations, and
recordings of the intrinsic neural activity are collected. The site
with the most appropriate recording is used for implanting the
intracranial electrodes.
[0217] The intent of the stimulation pulses is to supply a
relatively even electrical field to the location where
neuroplasticity is likely to be occurring, whereby neuroplasticity
would be enhanced
[0218] Another configuration for stimulating between two paddle
electrodes is shown in conjunction with FIG. 21, where the two
paddle electrodes are placed perpendicular to each other. The
electrode configuration and electrical field may be as shown in
conjunction with FIGS. 22A and 22B. Similar to previous examples,
for stimulation the electrode configuration may be 61A vs. 61B, 62A
vs. 62B, 63A vs. 63B, 64A vs. 64B as shown in FIG. 22A, or the
electrode stimulation configuration may be 61A vs. 64B, 62A vs.
63B, 63A vs. 62B, 64A vs. 61B, as shown in FIG. 22B, or the pulse
delivery may be configured to be alternated between these two
configurations.
[0219] To provide therapy for other neurological disorders such as
Parkinson's disease and involuntary movement disorders, a single
lead with paddle electrodes as shown in FIG. 23A, or a lead with an
electrode array as shown in FIGS. 23B and 23C, may be used.
Placement of the electrodes may be around the motor cortex as
determined by imaging studies and/or at the discretion of the
physician.
[0220] For the system to be implanted, part of the skull bone is
temporarily removed to provide exposure to the brain surface, as is
well known in the art. The sensing and stimulating electrodes are
implanted on the surface of the brain, either subduraly or
epiduraly. The terminal portion of the lead is tunneled
subcutaneously and connected to a pulse generator means. The pulse
generator means is implanted in a convenient location either
subcutaneously or submuscularly.
[0221] The pulse generator means may be one from a group
comprising:
[0222] a) an implanted stimulus-receiver with an external
stimulator;
[0223] b) an implanted stimulus-receiver comprising a high value
capacitor for storing charge, used in conjunction with an external
stimulator;
[0224] c) a programmer-less implantable pulse generator (IPG) which
is operable with a magnet;
[0225] d) a microstimulator;
[0226] e) a programmable implantable pulse generator;
[0227] f) a combination implantable device comprising both a
stimulus-receiver and a programmable IPG; and
[0228] g) an IPG comprising a rechargeable battery.
[0229] All of these pulse generator means can generate and emit
rectangular and complex electrical pulses. Complex electrical
pulses comprise at least one of multi-level pulses, biphasic
pulses, non-rectangular pulses, or pulses with varying amplitude
during the pulse.
Implanted Stimulus-Receiver with an External Stimulator
[0230] The selective stimulation of cortical brain tissues as
performed by one embodiment of the method and system of this
invention is shown schematically in FIG. 24, as a block diagram. A
modulator 246 receives analog (sine wave) high frequency "carrier"
signal and modulating signal. The modulating signal can be
multilevel digital, binary, or even an analog signal. In this
embodiment, mostly multilevel digital type modulating signals are
used. The modulated signal is amplified 250, conditioned 254, and
transmitted via a primary coil 46 which is external to the body. A
secondary coil 48 of an implanted stimulus receiver, receives,
demodulates, and delivers these pulses to the cortical tissues 54
via electrodes 61 and 62. This embodiment may also comprise more
than two electrodes. The receiver circuitry 256 is described
later.
[0231] The carrier frequency is optimized. One preferred embodiment
utilizes electrical signals of around 1 Mega-Hertz, even though
other frequencies can be used. Low frequencies are generally not
suitable because of energy requirements for longer wavelengths,
whereas higher frequencies are absorbed by the tissues and are
converted to heat, which again results in power losses.
[0232] Shown in conjunction with FIG. 25, the coil for the external
transmitter (primary coil 46) may be placed in the pocket 301 of a
customized garment 302, for patient convenience.
[0233] Shown in conjunction with FIG. 26, the primary (external)
coil 46 of the external stimulator 42 is inductively coupled to the
secondary (implanted) coil 48 of the implanted stimulus-receiver
34. The implantable stimulus-receiver 34 has circuitry at the
proximal end, and has two stimulating electrodes at the distal end
61,62. Even though, the implantable stimulus-receiver 34 shown here
is configured to have two electrodes, the implantable
stimulus-receiver 34 may also be configured to have more than two
electrodes.
[0234] In one embodiment, the implanted stimulus-receiver
comprising the implanted (secondary) coil is tunneled
subcutaneously, and implanted approximately in the region behind
the ear. This embodiment is shown in conjunction with FIGS. 27A,
27B, and 27C. As known in the art, the primary (external) coil 46
needs to be approximately adjacent to secondary (implanted) coil
48. In one embodiment, as shown in conjunction with FIG. 27A, a
head band may be used as an aid for placing the primary (external)
coil 46 in proximity with the secondary (implanted) coil 48, which
is implanted subcutaneously approximately in the area behind the
ear.
[0235] In another embodiment, as shown in conjunction with FIG.
27B, the primary (external) coil 46 may be placed in proximity to
the secondary (implanted) coil 48 with the aid of eyeglasses. In
yet another embodiment, as shown in conjunction with FIG. 27, the
external stimulator may be miniaturized, and adapted to be placed
around the ear similar to a hearing aid, such that the primary
(external) coil 46 is conveniently positioned in proximity to the
secondary (implanted) coil 48.
[0236] For the stimulus-receiver 34 with two electrode
configuration, the circuitry contained in the proximal end of the
implantable stimulus-receiver 34 is shown schematically in FIG. 28,
for one embodiment. In this embodiment, the circuit uses all
passive components: Approximately 25 turn copper wire of 30 gauge,
or comparable thickness, is used for the primary coil 46 and
secondary coil 48. This wire is concentrically wound with the
windings all in one plane. The frequency of the pulse-waveform
delivered to the implanted coil 48 can vary, and so a variable
capacitor 152 provides ability to tune secondary implanted circuit
167 to the signal from the primary coil 46. The pulse signal from
secondary (implanted) coil 48 is rectified by the diode bridge 154
and frequency reduction obtained by capacitor 158 and resistor 164.
The last component in line is capacitor 166, used for isolating the
output signal from the electrode wire. The return path of signal
from cathode 61 will be through anode 62 placed in proximity to the
cathode 61 for "Bipolar" stimulation. In this embodiment bipolar
mode of stimulation is used, however, the return path can be
connected to the remote ground connection (case) of implantable
circuit 167, providing for much larger intermediate tissue for
"Unipolar" stimulation. The "Bipolar" stimulation offers localized
stimulation of tissue compared to "Unipolar" stimulation and is
therefore, preferred in this embodiment. Unipolar stimulation is
more likely to stimulate skeletal muscle in addition to nerve
stimulation. The implanted circuit 167 in this embodiment is
passive, so a battery does not have to be implanted.
[0237] The circuitry shown in FIGS. 29A and 29B can be used as an
alternative, for the implanted stimulus-receiver. The circuitry of
FIG. 29A is a slightly simpler version, and circuitry of FIG. 29B
contains a conventional NPN transistor 168 connected in an
emitter-follower configuration.
[0238] For stimulation therapy to commence, the primary (external)
coil 46 is placed on the skin 60 on top of the surgically implanted
(secondary) coil 48. An adhesive tape on the skin 60 may be used to
hold primary (external) coil 46 in the appropriate position. For
efficient energy transfer to occur, it is important that the
primary (external) and secondary (internal) coils 46,48 be
positioned along the same axis and be optimally positioned relative
to each other. In this embodiment, the external coil 46 may be
connected to proximity sensing circuitry 50. The correct
positioning of the external coil 46 with respect to the internal
coil 48 is indicated by turning "on" of a light emitting diode
(LED) on the external stimulator 42 (FIG. 30).
[0239] Optimal placement of the external (primary) coil 46 is done
with the aid of proximity sensing circuitry incorporated in the
system, in this embodiment. Proximity sensing occurs utilizing a
combination of external and implantable components. The implanted
components contains a relatively small magnet composed of materials
that exhibit Giant Magneto-Resistor (GMR) characteristics such as
Samarium-cobalt, a coil, and passive circuitry. Shown in
conjunction with FIG. 30, the external coil 46 and proximity sensor
circuitry 50 are rigidly connected in a convenient enclosure which
is attached externally on the skin. The sensors measure the
direction of the field applied from the magnet to sensors within a
specific range of field strength magnitude. The dual sensors
exhibit accurate sensing under relatively large separation between
the sensor and the target magnet. As the external coil 46 placement
is "fine tuned", the condition where the external (primary) coil 46
comes in optimal position, i.e. is located adjacent and parallel to
the subcutaneous (secondary) coil 48, along its axis, is recorded
and indicated by a light emitting diode (LED) on the external
stimulator 42.
[0240] FIG. 31 shows an overall block diagram of the components of
the external stimulator 42 and the proximity sensing mechanism. The
proximity sensing components are the primary (external) coil 46,
supercutaneous (external) proximity sensors 648, 652 (FIG. 32) in
the proximity sensor circuit unit 50, and a subcutaneous secondary
coil 48 with a Giant Magneto Resister (GMR) magnet 53 associated
with the proximity sensor unit. The proximity sensor circuit 50
provides a measure of the position of the secondary implanted coil
48. The signal output from proximity sensor circuit 50 is derived
from the relative location of the primary and secondary coils 46,
48. The sub-assemblies consist of the coil and the associated
electronic components, that are rigidly connected to the coil.
[0241] The proximity sensors (external) contained in the proximity
sensor circuit 50 detect the presence of a GMR magnet 53, composed
of Samarium Cobalt, that is rigidly attached to the implanted
secondary coil 48. The proximity sensors, are mounted externally as
a rigid assembly and sense the actual separation between the coils,
also known as the proximity distance. In the event that the
distance exceeds the system limit, the signal drops off and an
alarm sounds to indicate failure of the production of adequate
signal in the secondary implanted circuit 167, as applied in this
embodiment of the device. This signal is provided to the location
indicator LED 280.
[0242] FIG. 32 shows the circuit used to drive the proximity
sensors 648, 652 of the proximity sensor circuit 50. The two
proximity sensors 648, 652 obtain a proximity signal based on their
position with respect to the implanted GMR magnet 53. This circuit
also provides temperature compensation. The sensors 648, 652 are
`Giant Magneto Resistor` (GMR) type sensors packaged as proximity
sensor unit 50. There are two components of the complete proximity
sensor circuit. One component is mounted supercutaneously 50, and
the other component, the proximity sensor signal control unit 57 is
within the external stimulator 42. The resistance effect depends on
the combination of the soft magnetic layer of magnet 53, where the
change of direction of magnetization from external source can be
large, and the hard magnetic layer, where the direction of
magnetization remains unchanged. The resistance of this sensor 50
varies along a straight motion through the curvature of the
magnetic field. A bridge differential voltage is suitably amplified
and used as the proximity signal.
[0243] The Siemens GMR B6 (Siemens Corp., Special Components Inc.,
New Jersey) is used for this function in one embodiment. The
maximum value of the peak-to-peak signal is observed as the
external magnetic field becomes strong enough, at which point the
resistance increases, resulting in the increase of the field-angle
between the soft magnetic and hard magnetic material. The bridge
voltage also increases. In this application, the two sensors 648,
652 are oriented orthogonal to each other.
[0244] The distance between the magnet 53 and sensor 50 is not
relevant as long as the magnetic field is between 5 and 15 KA/m,
and provides a range of distances between the sensors 648, 652 and
the magnetic material 53. The GMR sensor registers the direction of
the external magnetic field. A typical magnet to induce permanent
magnetic field is approximately 15 by 8 by 5 mm.sup.3, for this
application and these components. The sensors 648, 652 are
sensitive to temperature, such that the corresponding resistance
drops as temperature increases. This effect is quite minimal until
about 100.degree. C. A full bridge circuit is used for temperature
compensation, as shown in temperature compensation circuit 50 of
FIG. 25. The sensors 648, 652 and a pair of resistors 650, 654 are
shown as part of the bridge network for temperature compensation.
It is also possible to use a full bridge network of two additional
sensors in place of the resistors 650, 654.
[0245] The signal from either proximity sensor 648, 652 is
rectangular if the surface of the magnetic material is normal to
the sensor and is radial to the axis of a circular GMR device. This
indicates a shearing motion between the sensor and the magnetic
device. When the sensor is parallel to the vertical axis of this
device, there is a fall off of the relatively constant signal at
about 25 mm. separation. The GMR sensor combination varies its
resistance according to the direction of the external magnetic
field, thereby providing an absolute angle sensor. The position of
the GMR magnet can be registered at any angle from 0 to 360
degrees.
[0246] In the external stimulator 42 shown in FIG. 31, an indicator
unit 280 which is provided to indicate proximity distance or coil
proximity failure (for situations where the patch containing the
external coil 46, has been removed, or is twisted abnormally etc.).
Indication is also provided to assist in the placement of the
patch. In case of general failure, a red light with audible signal
is provided when the signal is not reaching the subcutaneous
circuit. The indicator unit 280 also displays low battery status.
The information on the low battery, normal and out of power
conditions forewarns the user of the requirements of any corrective
actions.
[0247] Also shown in FIG. 31, the programmable parameters are
stored in a programmable logic 264. The predetermined programs
stored in the external stimulator 42 are capable of being modified
through the use of a separate programming station 77. The
Programmable Array Logic Unit 264 and interface unit 270 are
interfaced to the programming station 77. The programming station
77 can be used to load new programs, change the existing
predetermined programs or the program parameters for various
stimulation programs. The programming station is connected to the
programmable array unit 75 (comprising programmable array logic 304
and interface unit 270) with an RS232-C serial connection. The main
purpose of the serial line interface is to provide an RS232-C
standard interface. Other suitable connectors such as a USB
connector or other connectors with standard protocols may also be
used.
[0248] This method enables any portable computer with a serial
interface to communicate and program the parameters for storing the
various programs. The serial communication interface receives the
serial data, buffers this data and converts it to a 16 bit parallel
data. The programmable array logic 264 component of programmable
array unit receives the parallel data bus and stores or modifies
the data into a random access matrix. This array of data also
contains special logic and instructions along with the actual data.
These special instructions also provide an algorithm for storing,
updating and retrieving the parameters from long-term memory. The
programmable logic array unit 264, interfaces with long term memory
to store the predetermined programs. All the previously modified
programs can be stored here for access at any time, as well as,
additional programs can be locked out for the patient. The programs
consist of specific parameters and each unique program will be
stored sequentially in long-term memory. A battery unit is present
to provide power to all the components. The logic for the storage
and decoding is stored in a random addressable storage matrix
(RASM).
[0249] Conventional microprocessor and integrated circuits are used
for the logic, control and timing circuits. Conventional bipolar
transistors are used in radio-frequency oscillator, pulse amplitude
ramp control and power amplifier. A standard voltage regulator is
used in low-voltage detector. The hardware and software to deliver
the pre-determined programs is well known to those skilled in the
art.
[0250] The pulses delivered to the cortical neural tissue for
stimulation therapy are shown graphically in FIG. 33A. As shown in
FIG. 33B, for patient comfort when the electrical stimulation is
turned on, the electrical stimulation may be configured to be
ramped up and ramped down, instead of abrupt delivery of electrical
pulses. In addition to rectangular pulses shown in FIG. 33A, the
external pulse generator may also be configured to provide complex
electrical pulses. Complex electrical pulses are described later
and shown in conjunction with FIGS. 52A to 52-O.
[0251] The selective stimulation of the cortical neural tissue can
be performed in one of two ways. One method is to activate one of
several predetermined/pre-packaged programs. A second method is to
"custom" program the electrical parameters which can be selectively
programmed, for specific therapy to the individual patient. The
electrical parameters which can be individually programmed, include
variables such as pulse amplitude, pulse width, frequency of
stimulation, stimulation on-time, and stimulation off-time. Table
one below defines the approximate range of parameters,
TABLE-US-00001 TABLE 1 Electrical parameter range delivered to the
cortical tissues PARAMER RANGE Pulse Amplitude 0.1 Volt-15 Volts
Pulse width 20 .mu.S-5 mSec. Stim. Frequency 5 Hz-200 Hz Freq. for
blocking DC to 750 Hz On-time 5 Secs-24 hours Off-time 5 Secs-24
hours
[0252] The parameters in Table 1 are the electrical signals
delivered to the cortical tissue via the two electrodes 61,62
(distal and proximal) around the tissue 54. It being understood
that the signals generated by the external pulse generator 42 and
transmitted via the primary coil 46 are larger, because the
attenuation factor between the primary coil and secondary coil is
approximately 10-20 times, depending upon the distance, and
orientation between the two coils. Accordingly, the range of
transmitted signals of the external pulse generator are
approximately 10-20 times larger than shown in Table 2.
[0253] FIG. 34 depicts the implanted lead 40 component of the
system, showing both the proximal end and the paddle electrodes at
the distal end, which may comprise between one and six electrodes.
An embodiment of paddle shaped distal end comprising 4 electrodes
is depicted in FIG. 34. The lead terminal preferably is linear
bipolar, even though it can be bifurcated, and plug(s) into the
cavity of the pulse generator means. The lead body 59 insulation
may be constructed of medical grade silicone, silicone reinforced
with polytetrafluoro-ethylene (PTFE), or polyurethane. The
electrodes 61,62, 63, 64 for stimulating the cortical neural tissue
54 may be "button" shaped or "pancake" shaped. These stimulating
electrodes may be made of pure platinum, platinum/Iridium alloy or
platinum/iridium coated with titanium nitride. The conductor
connecting the terminal to the electrodes 61,62 is made of an alloy
of nickel-cobalt. The implanted lead design variables are also
summarized in table two below. TABLE-US-00002 TABLE 2 Lead design
variables Proximal Distal End End Conductor (connecting Lead body-
proximal Lead Insulation and distal Electrode- Electrode- Terminal
Materials Lead-Coating ends) Material Type Linear Polyurethane
Antimicrobial Alloy of Pure "Button" bipolar coating Nickel-
Platinum shaped Cobalt Bifurcated Silicone Anti- Platinum-
"Pancake" Inflammatory Iridium shaped coating (Pt/Ir) Alloy
Silicone with Lubricious Pt/Ir coated Polytetrafluoro- coating with
Titanium ethylene Nitride (PTFE) Carbon
[0254] Once the lead is fabricated, coating such as anti-microbial,
anti-inflammatory, or lubricious coating may be applied to the body
of the lead.
Implanted Stimulus-Receiver Comprising a High Value Capacitor for
Storing Charge, Used in Conjunction with an External Stimulator
[0255] In one embodiment, the implanted stimulus-receiver 34C may
be a system which is RF coupled combined with a power source. In
this embodiment, the implanted stimulus-receiver 34C contains high
value, small sized capacitor(s) for storing charge and delivering
electrical stimulation pulses for up to several hours by itself,
once the capacitors are charged. The packaging is shown in
conjunction with FIG. 35. Using mostly hybrid components and
appropriate packaging, the implanted portion of the system
described below is conducive to miniaturization. As shown in FIG.
35, a solenoid coil 382 wrapped around a ferrite core 380 is used
as the secondary of an air-gap transformer for receiving power and
data to the implanted device. The primary coil is external to the
body. Since the coupling between the external transmitter coil and
receiver coil 382 may be weak, a high-efficiency
transmitter/amplifier is used in order to supply enough power to
the receiver coil 382. Class-D or Class-E power amplifiers may be
used for this purpose. The coil for the external transmitter
(primary coil) may be placed in the pocket of a customized garment,
as was previously shown.
[0256] As shown in conjunction with FIG. 36 of the implanted
stimulus-receiver 490 and the system, the receiving inductor 48A
and tuning capacitor 403 are tuned to the frequency of the
transmitter. The diode 408 rectifies the AC signals, and a small
sized capacitor 406 is utilized for smoothing the input voltage
V.sub.I fed into the voltage regulator 402. The output voltage
V.sub.D of regulator 402 is applied to capacitive energy power
supply and source 400 which establishes source power V.sub.DD.
Capacitor 400 is a big value, small sized capacative energy source
which is classified as low internal impedance, low power loss and
high charge rate capacitor, such as Panasonic Model No. 641.
[0257] The refresh-recharge transmitter unit 460 includes a primary
battery 426, an ON/Off switch 427, a transmitter electronic module
442, an RF inductor power coil 46A, a modulator/demodulator 420 and
an antenna 422.
[0258] When the ON/OFF switch is on, the primary coil 46A is placed
in close proximity to skin 60 and secondary coil 48A of the
implanted stimulator 490. The inductor coil 46A emits RF waves
establishing EMF wave fronts which are received by secondary
inductor 48A. Further, transmitter electronic module 442 sends out
command signals which are converted by modulator/demodulator
decoder 420 and sent via antenna 422 to antenna 418 in the
implanted stimulator 490. These received command signals are
demodulated by decoder 416 and replied and responded to, based on a
program in memory 414 (matched against a "command table" in the
memory). Memory 414 then activates the proper controls and the
inductor receiver coil 48A accepts the RF coupled power from
inductor 46A.
[0259] The RF coupled power, which is alternating or AC in nature,
is converted by the rectifier 408 into a high DC voltage. Small
value capacitor 406 operates to filter and level this high DC
voltage at a certain level. Voltage regulator 402 converts the high
DC voltage to a lower precise DC voltage while capacitive power
source 400 refreshes and replenishes.
[0260] When the voltage in capacative source 400 reaches a
predetermined level (that is V.sub.DD reaches a certain
predetermined high level), the high threshold comparator 430 fires
and stimulating electronic module 412 sends an appropriate command
signal to modulator/decoder 416. Modulator/decoder 416 then sends
an appropriate "fully charged" signal indicating that capacitive
power source 400 is fully charged, is received by antenna 422 in
the refresh-recharge transmitter unit 460.
[0261] In one mode of operation, the patient may start or stop
stimulation by waving the magnet 442 once near the implant. The
magnet emits a magnetic force L.sub.m which pulls reed switch 410
closed. Upon closure of reed switch 410, stimulating electronic
module 412 in conjunction with memory 414 begins the delivery (or
cessation as the case may be) of controlled electronic stimulation
pulses to the cortical neural tissue 54 via electrodes 61, 62, 63,
64. In another mode (AUTO), the stimulation is automatically
delivered to the implanted lead based upon programmed ON/OFF
times.
[0262] The programmer unit 450 includes keyboard 432, programming
circuit 438, rechargeable battery 436, and display 434. The
physician or medical technician programs programming unit 450 via
keyboard 432. This program regarding the frequency, pulse width,
modulation program, ON time etc. is stored in programming circuit
438. The programming unit 450 must be placed relatively close to
the implanted stimulator 490 in order to transfer the commands and
programming information from antenna 440 to antenna 418. Upon
receipt of this programming data, modulator/demodulator and decoder
416 decodes and conditions these signals, and the digital
programming information is captured by memory 414. This digital
programming information is further processed by stimulating
electronic module 412. In the DEMAND operating mode, after
programming the implanted stimulator, the patient turns ON and OFF
the implanted stimulator via hand held magnet 442 and the reed
switch 410. In the automatic mode (AUTO), the implanted stimulator
turns ON and OFF automatically according to the programmed values
for the ON and OFF times.
[0263] Other simplified versions of such a system may also be used.
For example, a system such as this, where a separate programmer is
eliminated, and simplified programming is performed with a magnet
and reed switch, can also be used.
Programmer-Less Implantable Pulse Generator (IPG)
[0264] In one embodiment, a programmer-less implantable pulse
generator (IPG) may be used, as disclosed in applicant's commonly
assigned U.S. Pat. No. 6,760,626 B1, which is incorporated herein
by reference. In this embodiment, shown in conjunction with FIG.
37, the implantable pulse generator 171 is provided with a reed
switch 92 and memory circuitry 102. The reed switch 92 being
remotely actuable by means of a magnet 90 brought into proximity of
the pulse generator 171, in accordance with common practice in the
art. In this embodiment, the reed switch 92 is coupled to a
multi-state converter/timer circuit 96, such that a single short
closure of the reed switch can be used as a means for non-invasive
encoding and programming of the pulse generator 171 parameters.
[0265] In one embodiment, shown in conjunction with FIG. 38, the
closing of the reed switch 92 triggers a counter. The magnet 90 and
timer are ANDed together. The system is configured such that during
the time that the magnet 82 is held over the pulse generator 171,
the output level goes from LOW stimulation state to the next higher
stimulation state every 5 seconds. Once the magnet 82 is removed,
regardless of the state of stimulation, an application of the
magnet, without holding it over the pulse generator 171, triggers
the OFF state, which also resets the counter.
[0266] Once the prepackaged/predetermined logic state is activated
by the logic and control circuit 102, as shown in FIG. 37, the
pulse generation and amplification circuit 106 deliver the
appropriate electrical pulses to the cortical neural tissues 54 of
the patient via an output buffer 108. In this embodiment, the
electrode configuration for delivery of output pulses is preset
Timing signals for the logic and control circuit 102 of the pulse
generator 171 are provided by a crystal oscillator 104. The battery
86 of the pulse generator 171 has terminals connected to the input
of a voltage regulator 94. The regulator 94 smoothes the battery
output and supplies power to the internal components of the pulse
generator 171. A microprocessor 100 controls the program parameters
of the device, such as the voltage, pulse width, frequency of
pulses, on-time and off-time. The microprocessor may be a
commercially available, general purpose microprocessor or
microcontroller, or may be a custom integrated circuit device
augmented by standard RAM/ROM components.
[0267] In one embodiment, there are four stimulation states. A
larger (or lower) number of states can be achieved using the same
methodology, and such is considered within the scope of the
invention. These four states are, LOW stimulation state, LOW-MED
stimulation state, MED stimulation state, and HIGH stimulation
state. Examples of stimulation parameters (delivered to the
cortical tissues) for each state are as follows,
For Enhancing Neuroplasticity (Post-Stroke Patients)
[0268] LOW stimulation state example is, TABLE-US-00003 Current
output: 0.30 milli-Amps. Pulse width: 50 micro-secs. Pulse
frequency: 50 Hertz Cycles: 5 sec. on-time and 5 sec. off-time in
repeating cycles.
[0269] LOW-MED stimulation state example is, TABLE-US-00004 Current
output: 0.50 milli-Amps. Pulse width: 70 micro-secs. Pulse
frequency: 75 Hertz Cycles: 10 sec. on-time and 5 sec. off-time in
repeating cycles.
[0270] MED stimulation state example is, TABLE-US-00005 Current
output: 0.75 milli-Amps. Pulse width: 80 micro-secs. Pulse
frequency: 90 Hertz Cycles: ON continuously
[0271] HIGH stimulation state example is, TABLE-US-00006 Current
output: 1.0 milli-Amp. Pulse width: 100 micro-secs. Pulse
frequency: 120 Hertz Cycles: 20 sec. on-time and 5 sec. off-time in
repeating cycles.
[0272] These prepackaged/predetermined programs are mearly
examples, and the actual stimulation parameters will deviate from
these depending on the treatment application.
For Parkinson's Disease
[0273] LOW stimulation state example is, TABLE-US-00007 Current
output: 1.5 milliAmps. Pulse width: 125 micro-secs. Pulse
frequency: 20 Hz Cycles: 20 min. on-time and 5 min. off-time in
repeating cycles.
[0274] LOW-MED stimulation state example is, TABLE-US-00008 Current
output: 2.5 milli-Amps. Pulse width: 200 micro-secs. Pulse
frequency: 50 Hz Cycles: ON continuously for 2.5 hours
[0275] MED stimulation state example is, TABLE-US-00009 Current
output: 3.5 milli-Amps. Pulse width: 300 micro-secs. Pulse
frequency: 75 Hz Cycles: ON continuously for 4 hours
[0276] HIGH stimulation state example is, TABLE-US-00010 Current
output: 5.0 milli-Amps. Pulse width: 400 micro-secs. Pulse
frequency: 100 Hz Cycles: ON continuously for 6 hours
[0277] These prepackaged/predetermined programs are mearly
examples, and the actual stimulation parameters will deviate from
these depending on the treatment application.
[0278] It will be readily apparent to one skilled in the art, that
other schemes can be used for the same purpose. For example,
instead of placing the magnet 90 on the pulse generator 171 for a
prolonged period of time, different stimulation states can be
encoded by the sequence of magnet applications. Accordingly, in an
alternative embodiment there can be three logic states, OFF, LOW
stimulation (LS) state, and HIGH stimulation (HS) state. Each logic
state again corresponds to a prepackaged/predetermined program such
as presented above. In such an embodiment, the system could be
configured such that one application of the magnet triggers the
generator into LS State. If the generator is already in the LS
state then one application triggers the device into OFF State. Two
successive magnet applications triggers the generator into MED
stimulation state, and three successive magnet applications
triggers the pulse generator in the HIGH Stimulation State.
Subsequently, one application of the magnet while the device is in
any stimulation state, triggers the device OFF.
[0279] FIG. 39 shows a representative digital circuitry used for
the basic state machine circuit. The circuit consists of a PROM 462
that has part of its data fed back as a state address. Other
address lines 469 are used as circuit inputs, and the state machine
changes its state address on the basis of these inputs. The clock
104 is used to pass the new address to the PROM 462 and then pass
the output from the PROM 462 to the outputs and input state
circuits. The two latches 464, 465 are operated 180.degree. out of
phase to prevent glitches from unexpectedly affecting any output
circuits when the ROM changes state. Each state responds
differently according to the inputs it receives.
[0280] The advantage of this embodiment is that it is cheaper to
manufacture than a fully programmable implantable pulse generator
(IPG).
Microstimulator
[0281] In one embodiment, a microstimulator 130 may be used for
providing pulses to the cortical tissues 54. Shown in conjunction
with FIG. 40A, is a microstimulator where the electrical circuitry
132 and power source 134 are encased in a miniature hermetically
sealed enclosure, and only the electrodes 65A, 67A are exposed.
FIGS. 40B and 40C depict the same microstimulator, except that the
electrode array and circuitry is configured to have a larger number
of electrodes. The embodiment shown in FIG. 40B comprises eight
pairs of electrodes, and the embodiment shown in FIG. 40C comprises
12 pairs of electrodes. Because of its small size, the whole
microstimulator may be implanted closer in proximity to tissues
being stimulated such as cortical tissues. In one example, the
microstimulator may be implanted approximately behind the ear, as
was shown in conjunction with FIGS. 27A, 27B, and 27C.
Alternatively as shown in conjunction with FIG. 41, the
microstimulator may be implanted at a different site, and connected
to the electrodes via conductors insulated with silicone and
polyurethane.
[0282] Shown in reference with FIG. 42 is the overall structure of
an implantable microstimulator 130. It consists of a micromachined
silicon substrate that incorporates two stimulating electrodes
which are the cathode and anode of a bipolar stimulating electrode
pair 65D, 67D; a hybrid-connected tantalum chip capacitor 140 for
power storage; a receiving coil 142; a bipolar-CMOS integrated
circuit chip 138 for power regulation and control of the
microstimulator; and a custom made glass capsule 146 that is
electrostatically bonded to the silicon carrier to provide a
hermetic package for the receiver-stimulator circuitry and hybrid
elements. The stimulating electrode(s) 65D, 67D resides outside of
the package and feedthroughs are used to connect the internal
electronics to the electrodes.
[0283] FIG. 43 shows the overall system electronics required for
the microstimulator, and the power and data transmission protocol
used for radiofrequency telemetry. The circuit receives an
amplitude modulated RF carrier from an external transmitter and
generates 8-V and 4-V dc supplies, generates a clock from the
carrier signal, decodes the modulated control data, interprets the
control data, and generates a constant current output pulse when
appropriate. The RF carrier used for the telemetry link has a
nominal frequency of around 1.8 MHz, and is amplitude modulated to
encode control data. Logical "1" and "0" are encoded by varying the
width of the amplitude modulated carrier, as shown in the bottom
portion of FIG. 43. The carrier signal is initially high when the
transmitter is turned on and sets up an electromagnetic field
inside the transmitter coil. The energy in the field is picked up
by receiver coils 142, and is used to charge the hybrid capacitor
140. The carrier signal is turned high and then back down again,
and is maintained at the low level for a period between 1-200
.mu.sec. The microstimulator 130 will then deliver a constant
current pulse into the cortical neural tissue through the
stimulating electrode(s) 65D, 67D for the period that the carrier
is low. Finally, the carrier is turned back high again, which will
indicate the end of the stimulation period to the microstimulator
130, thus allowing it to charge its capacitor 140 back up to the
on-chip voltage supply.
[0284] On-chip circuitry has been designed to generate two
regulated power supply voltages (4V and 8V) from the RF carrier, to
demodulate the RF carrier in order to recover the control data that
is used to program the microstimulator, to generate the clock used
by the on-chip control circuitry, to deliver a constant current
through a controlled current driver into the nerve tissue, and to
control the operation of the overall circuitry using a low-power
CMOS logic controller.
Programmable Implantable Pulse Generator (IPG)
[0285] In one embodiment, a fully programmable implantable pulse
generator (IPG), capable of generating stimulation and blocking
pulses may be used. Shown in conjunction with FIGS. 44A, 44B, and
44C, the implantable pulse generator unit 391 is preferably a
microprocessor based device, where the entire circuitry is encased
in a hermetically sealed titanium can. The circuitry in FIGS. 44A,
44B, and 44C is similar, except FIG. 44B depicts more than one
channel of output which shown as output circuitry 385A and 385B.
The block diagram depicted in FIG. 44C also comprises sensing
circuitry, with multiple channels of output circuitry and sensing
circuitry. As shown in the overall block diagram (FIG. 44A), the
logic & control unit 398 provides the proper timing for the
output circuitry 385 to generate electrical pulses that are
delivered to electrodes 61A, 62A, 61B and 62B via a lead 40.
Programming of the implantable pulse generator (IPG) is done via an
external programmer 85, as described later. Once activated or
programmed via an external programmer 85, the implanted pulse
generator 391 provides appropriate electrical stimulation pulses to
the cortical neural tissues 54 via electrodes 61A, 62A, 61 B and
62B. This embodiment may also be adapted and configured for lead(s)
comprising multiple electrodes.
[0286] This embodiment also comprises predetermined/pre-packaged
programs. Examples of four stimulation states were given in the
previous section, under "Programmer-less Implantable Pulse
Generator (IPG)". These predetermined/pre-packaged programs
comprise unique combinations of pulse amplitude, pulse width, pulse
morphology, pulse frequency, ON-time and OFF-time, and electrode
configurations for stimulations. Any number of
predetermined/pre-packaged programs, even 100, can be stored in the
implantable pulse generator of this invention, and are considered
within the scope of the invention.
[0287] Examples of additional predetermined/pre-packaged programs
are:
For Enhancing Neuroplasticity (Post-Stroke Patients)
[0288] TABLE-US-00011 Program one: Current output: 0.25 milli-Amps.
Pulse width: 40 micro-secs. Pulse frequency: 50 Hertz Cycles: 10
sec. on-time and 5 sec. off-time in repeating cycles.
[0289] TABLE-US-00012 Program two: Current output: 0.40 milli-Amps.
Pulse width: 50 micro-secs. Pulse frequency: 60 Hertz Cycles: 12
sec. on-time and 4 sec. off-time in repeating cycles.
[0290] TABLE-US-00013 Program three: Current output: 0.50
milli-Amps. Pulse width: 70 micro-secs. Pulse frequency: 75 Hertz
Cycles: 15 sec. on-time and 5 sec. off-time in repeating
cycles.
[0291] TABLE-US-00014 Program four: Current output: 0.60
milli-Amps. Pulse width: 85 micro-secs. Pulse frequency: 90 Hertz
Cycles: ON continuously
[0292] TABLE-US-00015 Program five: Current output: 0.75
milli-Amps. Pulse width: 100 micro-secs. Pulse frequency: 125 Hertz
Cycles: 25 sec. on-time and 5 sec. off-time in repeating
cycles.
[0293] TABLE-US-00016 Program six (complex pulses): Current output:
0.50 milli-Amps. Pulse width: 150 micro-secs. Pulse frequency: 50
Hertz Pulse type: step pulses Cycles: 20 sec. on-time and 5 sec.
off-time in repeating cycles.
[0294] TABLE-US-00017 Program seven (complex pulses): Current
output: 0.75 milli-Amps. Pulse width: 150 micro-secs. Pulse
frequency: 80 Hertz Pulse type: step pulses Cycles: 25 sec. on-time
and 5 sec. off-time in repeating cycles.
[0295] TABLE-US-00018 Program eight (complex pulse train): Current
output: 0.85 milli-Amps. Pulse width: 200 micro-secs. Pulse
frequency: 125 Hertz Pulse type: step pulses with alternating pulse
train (as shown in FIG. 52H) Cycles: ON continuously
[0296] These pre-packaged/predetermined programs are mearly
examples, and the actual stimulation parameters will deviate from
these depending on the treatment application and physician
preference.
For Parkinson's Disease
[0297] TABLE-US-00019 Program one: Current output: 0.75 milli-Amps.
Pulse width: 50 micro-seconds Pulse frequency: 25 Hertz Cycles: 5
min. on-time and 30 sec. off-time in repeating cycles for 12
hours.
[0298] TABLE-US-00020 Program two: Current output: 1.0 milli-Amps,
Pulse width: 150 micro-seconds Pulse frequency: 40 Hertz Cycles: ON
continuously for 2.5 hours
[0299] TABLE-US-00021 Program three: Current output: 2.5
milli-Amps. Pulse width: 200 micro-seconds Pulse frequency: 75
Hertz Cycles: ON continuously for 4.0 hours
[0300] TABLE-US-00022 Program four: Current output: 3.5 milli-Amps,
Pulse width: 500 micro-seconds Pulse frequency: 85 Hertz Cycles: ON
continuously for 6.0 hours
[0301] TABLE-US-00023 Program five: Current output: 5.0 milli-Amps,
Pulse width: 0.50 milli-second Pulse frequency: 100 Hertz Cycles:
ON continuously for 8.5 hours
[0302] TABLE-US-00024 Program six (complex pulses): Current output:
2.5 milli-Amps. Pulse width: 300 micro-seconds Pulse frequency: 50
Hertz Pulse type: step pulses Cycles: ON continuously for 4.0
hours
[0303] TABLE-US-00025 Program seven (complex pulses): Current
output: 3.5 milli-Amps. Pulse width: 450 micro-seconds Pulse
frequency: 75 Hertz Pulse type: step pulses Cycles: ON continuously
for 6.0 hours
[0304] TABLE-US-00026 Program eight (complex pulse train): Current
output: 4.0 milli-Amps. Pulse width: 0.50 milli-sec. Pulse
frequency: 85 Hertz Pulse type: step pulses with alternating pulse
train (as shown in FIG. 52H) Cycles: ON continuously for 8.0
hours
[0305] These pre-packaged/predetermined programs are mearly
examples, and the actual stimulation parameters will deviate from
these depending on the treatment application and physician
preference. One advantage of predetermined/pre-packaged program is
that it can be readily activated by a program number. A simple
version of a programmer, adapted to activate only a limited number
of predetermined/pre-packaged programs may also be supplied to the
patient.
[0306] In addition, each parameter may be individually adjusted and
stored in the memory 394. The range of programmable electrical
stimulation parameters include both stimulating and blocking
frequencies, and are shown in table three below. TABLE-US-00027
TABLE 3 Programmable electrical parameter range PARAMER RANGE Pulse
Amplitude 0.1 Volt-15 Volts Pulse width 20 .mu.S-5 mSec. Stim.
Frequency 5 Hz-200 Hz Freq. for blocking DC to 750 Hz On-time 5
Secs-24 hours Off-time 5 Secs-24 hours Ramp ON/OFF
[0307] Shown in conjunction with FIGS. 45 and 46, the electronic
stimulation module comprises both digital 350 and analog 352
circuits. A main timing generator 330 (shown in FIG. 45), controls
the timing of the analog output circuitry for delivering
neuromodulating pulses to the cortical neural tissues 54, via
output-amplifier 334. Limiter 183 prevents excessive stimulation
energy from getting into the cortical neural tissues 54. The main
timing generator 330 receiving clock pulses from crystal oscillator
393. Main timing generator 330 also receiving input from programmer
85 via coil 399. FIG. 36 highlights other portions of the digital
system such as CPU 338, ROM 337, RAM 339, program interface 346,
interrogation interface 348, timers 340, and digital O/I 342.
[0308] Most of the digital functional circuitry 350 is on a single
chip (IC). This monolithic chip along with other IC's and
components such as capacitors and the input protection diodes are
assembled together on a hybrid circuit. As well known in the art,
hybrid technology is used to establish the connections between the
circuit and the other passive components. The integrated circuit is
hermetically encapsulated in a chip carrier. A coil 399 situated
under the hybrid substrate is used for bidirectional telemetry. The
hybrid and battery 397 are encased in a titanium can 65. This
housing is a two-part titanium capsule that is hermetically sealed
by laser welding. Alternatively, electron-beam welding can also be
used. The header 79 is a cast epoxy-resin with hermetically sealed
feed-through, and form the lead 40 connection block.
[0309] For further details, FIG. 47A highlights the general
components of an 8-bit microprocessor as an example. It will be
obvious to one skilled in the art that higher level microprocessor,
such as a 16-bit or 32-bit may be utilized, and is considered
within the scope of this invention. It comprises a ROM 337 to store
the instructions of the program to be executed and various
programmable parameters, a RAM 339 to store the various
intermediate parameters, timers 340 to track the elapsed intervals,
a register file 321 to hold intermediate values, an ALU 320 to
perform the arithmetic calculation, and other auxiliary units that
enhance the performance of a microprocessor-based IPG system.
[0310] The size of ROM 337 and RAM 339 units are selected based on
the requirements of the algorithms and the parameters to be stored.
The number of registers in the register file 321 are decided based
upon the complexity of computation and the required number of
intermediate values. Timers 340 of different precision are used to
measure the elapsed intervals. Even though this embodiment does not
have external sensors to control timing, future embodiments may
have sensors 322 to effect the timing as shown in conjunction with
FIG. 47B.
[0311] In this embodiment, the two main components of
microprocessor are the datapath and control. The datapath performs
the arithmetic operation and the control directs the datapath,
memory, and I/O devices to execute the instruction of the program.
The hardware components of the microprocessor are designed to
execute a set of simple instructions. In general the complexity of
the instruction set determines the complexity of datapth elements
and controls of the microprocessor.
[0312] In this embodiment, the microprocessor is provided with a
fixed operating routine. Future embodiments may be provided with
the capability of actually introducing program changes in the
implanted pulse generator. The instruction set of the
microprocessor, the size of the register files, RAM and ROM are
selected based on the performance needed and the type of the
algorithms used. In this application of pulse generator, in which
several algorithms can be loaded and modified, Reduced Instruction
Set Computer (RISC) architecture is useful. RISC architecture
offers advantages because it can be optimized to reduce the
instruction cycle which in turn reduces the run time of the program
and hence the current drain. The simple instruction set
architecture of RISC and its simple hardware can be used to
implement any algorithm without much difficulty. Since size is also
a major consideration, an 8-bit microprocessor is used for the
purpose. As most of the arithmetic calculation are based on a few
parameters and are rather simple, an accumulator architecture is
used to save bits from specifying registers. Each instruction is
executed in multiple clock cycles, and the clock cycles are broadly
classified into five stages: an instruction fetch, instruction
decode, execution, memory reference, and write back stages.
Depending on the type of the instruction, all or some of these
stages are executed for proper completion.
[0313] Initially, an optimal instruction set architecture is
selected based on the algorithm to be implemented and also taking
into consideration the special needs of a microprocessor based
implanted pulse generator (IPG). The instructions are broadly
classified into Load/store instructions, Arithmetic and logic
instructions (ALU), control instructions and special purpose
instructions.
[0314] The instruction format is decided based upon the total
number of instructions in the instruction set. The instructions
fetched from memory are 8 bits long in this example. Each
instruction has an opcode field (2 bits), a register specifier
field (3-bits), and a 3-bit immediate field. The opcode field
indicates the type of the instruction that was fetched. The
register specifier indicates the address of the register in the
register file on which the operations are performed. The immediate
field is shifted and sign extended to obtain the address of the
memory location in load/store instruction. Similarly, in branch and
jump instruction, the offset field is used to calculate the address
of the memory location the control needs to be transferred to.
[0315] Shown in conjunction with FIG. 48A, the register file 321,
which is a collection of registers in which any register can be
read from or written to specifying the number of the register in
the file. Based on the requirements of the design, the size of the
register file is decided. For the purposes of implementation of
stimulation pulses algorithms, a register file of eight registers
is sufficient, with three special purpose register (0-2) and five
general purpose registers (3-7), as shown in FIG. 48A. Register "0"
always holds the value "zero". Register "1" is dedicated to the
pulse flags. Register "2" is an accumulator in which all the
arithmetic calculations are performed. The read/write address port
provides a 3-bit address to identify the register being read or
written into. The write data port provides 8-bit data to be written
into the registers either from ROM/RAM or timers. Read enable
control, when asserted enables the register file to provide data at
the read data port. Write enable control enables writing of data
being provided at the write data port into a register specified by
the read/write address.
[0316] Generally, two or more timers are required to implement the
algorithm for the IPG. The timers are read and written into just as
any other memory location. The timers are provided with read and
write enable controls.
[0317] The arithmetic logic unit is an important component of the
microprocessor. It performs the arithmetic operation such as
addition, subtraction and logical operations such as AND and OR.
The instruction-format of ALU instructions consists of an opcode
field (2 bits), a function field (2 bits) to indicate the function
that needs to be performed, and a register specifier (3 bits) or an
immediate field (4 bits) to provide an operand.
[0318] The hardware components discussed above constitute the
important components of a datapath. Shown in conjunction with FIG.
48B, there are some special purpose registers such a program
counter (PC) to hold the address of the instruction being fetched
from ROM 337 and instruction register (IR) 323, to hold the
instruction that is fetched for further decoding and execution. The
program counter is incremented in each instruction fetch stage to
fetch sequential instruction from memory. In the case of a branch
or jump instruction, the PC multiplexer allows to choose from the
incremented PC value or the branch or jump address calculated. The
opcode of the instruction fetched (IR) is provided to the control
unit to generate the appropriate sequence of control signals,
enabling data flow through the datapath. The register specification
field of the instruction is given as read/write address to the
register file, which provides data from the specified field on the
read data port. One port of the ALU is always provided with the
contents of the accumulator and the other with the read data port.
This design is therefore referred to as accumulator-based
architecture. The sign-extended offset is used for address
calculation in branch and jump instructions. The timers are used to
measure the elapsed interval and are enabled to count down on a
low-frequency clock. The timers are read and written into, just as
any other memory location (FIG. 48B).
[0319] In a multicycle implementation, each stage of instruction
execution takes one clock cycle. Since the datapath takes multiple
clock cycles per instruction, the control must specify the signals
to be asserted in each stage and also the next step in the
sequence. This can be easily implemented as a finite state
machine.
[0320] A finite state machine consists of a set of states and
directions on how to change states. The directions are defined by a
next-state function, which maps the current state and the inputs to
a new state. Each stage also indicates the control signals that
need to be asserted. Every state in the finite state machine takes
one clock cycle. Since the instruction fetch and decode stages are
common to all the instruction, the initial two states are common to
all the instruction. After the execution of the last step, the
finite state machine returns to the fetch state.
[0321] A finite state machine can be implemented with a register
that holds the current stage and a block of combinational logic
such as a PLA. It determines the datapath signals that need to be
asserted as well as the next state. A PLA is described as an array
of AND gates followed by an array of OR gates. Since any function
can be computed in two levels of logic, the two-level logic of PLA
is used for generating control signals.
[0322] The occurrence of a wakeup event initiates a stored
operating routine corresponding to the event. In the time interval
between a completed operating routine and a next wake up event, the
internal logic components of the processor are deactivated and no
energy is being expended in performing an operating routine.
[0323] A further reduction in the average operating current is
obtained by providing a plurality of counting rates to minimize the
number of state changes during counting cycles. Thus intervals
which do not require great precision, may be timed using relatively
low counting rates, and intervals requiring relatively high
precision, such as stimulating pulse width, may be timed using
relatively high counting rates.
[0324] The logic and control unit 398 of the IPG controls the
output amplifiers. The pulses have predetermined energy (pulse
amplitude and pulse width) and are delivered at a time determined
by the therapy stimulus controller. The circuitry in the output
amplifier, shown in conjunction with (FIG. 49) generates an analog
voltage or current that represents the pulse amplitude. The
stimulation controller module initiates a stimulus pulse by closing
a switch 208 that transmits the analog voltage or current pulse to
the nerve tissue through the tip electrode 61 of the lead 40. The
output circuit receiving instructions from the stimulus therapy
controller 398 that regulates the timing of stimulus pulses and the
amplitude and duration (pulse width) of the stimulus. The pulse
amplitude generator 206 determines the configuration of charging
and output capacitors necessary to generate the programmed stimulus
amplitude. The output switch 208 is closed for a period of time
that is controlled by the pulse width generator 204. When the
output switch 208 is closed, a stimulus is delivered to the tip
electrode 61 of the lead 40.
[0325] The constant-voltage output amplifier applies a voltage
pulse to the distal electrode (cathode) 61 of the lead 40. A
typical circuit diagram of a voltage output circuit is shown in
FIG. 50. This configuration contains a stimulus amplitude generator
206 for generating an analog voltage. The analog voltage represents
the stimulus amplitude and is stored on a holding capacitor C.sub.h
225. Two switches are used to deliver the stimulus pulses to the
lead 40, a stimulating delivery switch 220, and a recharge switch
222, that reestablishes the charge equilibrium after the
stimulating pulse has been delivered to the nerve tissue. Since
these switches have leakage currents that can cause direct current
(DC) to flow into the lead system 40, a DC blocking capacitor
C.sub.b 229, is included. This is to prevent any possible corrosion
that may result from the leakage of current in the lead 40. When
the stimulus delivery switch 220 is closed, the pulse amplitude
analog voltage stored in the (C.sub.h 225) holding capacitor is
transferred to the cathode electrode 61 of the lead 40 through the
coupling capacitor, C.sub.b 229. At the end of the stimulus pulse,
the stimulus delivery switch 220 opens. The pulse duration being
the interval from the closing of the switch 220 to its reopening.
During the stimulus delivery, some of the charge stored on C.sub.h
225 has been transferred to C.sub.b 229, and some has been
delivered to the lead system 40 to stimulate the nerve tissue.
[0326] To re-establish equilibrium, the recharge switch 222 is
closed, and a rapid recharge pulse is delivered. This is intended
to remove any residual charge remaining on the coupling capacitor
C.sub.b 229, and the stimulus electrodes on the lead
(polarization). Thus, the stimulus is delivered as the result of
closing and opening of the stimulus delivery 220 switch and the
closing and opening of the RCHG switch 222. At this point, the
charge on the holding C.sub.h 225 must be replenished by the
stimulus amplitude generator 206 before another stimulus pulse can
be delivered.
[0327] The pulse generating unit charges up a capacitor and the
capacitor is discharged when the control (timing) circuitry
requires the delivery of a pulse. This embodiment utilizes a
constant voltage pulse generator, even though a constant current
pulse generator can also be utilized. Pump-up capacitors are used
to deliver pulses of larger magnitude than the potential of the
batteries. The pump up capacitors are charged in parallel and
discharged into the output capacitor in series. Shown in
conjunction with FIG. 51 is a circuit diagram of a voltage doubler
which is shown here as an example. For higher multiples of battery
voltage, this doubling circuit can be cascaded with other doubling
circuits. As shown in FIG. 51, during phase I (top of FIG. 51), the
pump capacitor C.sub.p is charged to V.sub.bat and the output
capacitor C.sub.o supplies charge to the load. During phase 11, the
pump capacitor charges the output capacitor, which is still
supplying the load current. In this case, the voltage drop across
the output capacitor is twice the battery voltage.
[0328] FIG. 52A shows one example of the pulse trains that may be
delivered with this embodiment or in prior art nerve stimulators.
The microcontroller is configured to deliver the pulse train as
shown in the figure, i.e. there is "ramping up" of the pulse train.
The purpose of the ramping-up is to avoid sudden changes in
stimulation, when the pulse train begins. The ramping-up or
ramping-down is optional, and may be programmed into the
microcontroller.
[0329] In the method and system of the current invention, the
microcontroller is configured to deliver rectangular and complex
pulses. Complex pulses comprise non-rectangular, biphasic,
multi-step, and other complex pulses where the amplitude is varying
during the pulse. Advantageously, these complex pulses provide a
new dimension to selective stimulation or neuromodulation of
cortical neural tissues to provide therapy for neurological
disorders such as involuntary movement disorders, or for enhancing
or inducing neuroplasticity.
[0330] Examples of these pulses and pulse trains are shown in FIGS.
52B to 52H. Selective stimulation with these complex pulses takes
into account the threshold properties of different types of neural
cells, as well as, their different refractory properties.
[0331] For example in the multi-step pulse shown in FIG. 52C, the
first part of the pulse will tend to recruit large diameter (and
myelinated) fibers. The middle portion of the pulse where the
amplitude is highest, will tend to recruit different cells.
Further, as shown in the examples of FIGS. 52F and 52H, complex and
simple pulses, or pulse trains may be alternated.
[0332] The pulses and pulse trains of this disclosure gives
physicians a lot of flexibility for trying various different
neuromodulation algorithms, for providing and optimizing therapy
for involuntary movement disorders, or for neuroplasticity.
[0333] Furthermore, as shown in conjunction with FIG. 52-I, a
combination of tripolar electrodes with different pulse shapes may
be used for selective stimulation of different types of nerve cells
in the brain. The different pulses used in conjunction with
tripolar electrodes are shown in conjunction with FIGS. 52J, 52K,
52L, 52M, 52N, and 52-O. This combination is advantageous, because
it can be used to provide selective large fiber block as well.
[0334] The combination of tripolar electrodes and the pulse shapes
of FIGS. 52-J to 52-O gives physicians more flexibility or
providing stimulation therapy for their patients. In the tripolar
electrodes (FIG. 52-I), the electrode consists of a cathode,
flanked by two anodes. When stimulation is applied, the nerve
membrane is depolarized near the cathode and hyperpolarized near
the anodes. If the membrane is sufficiently hyperpolarized, an
action potential (AP) that travels into the depolarized zone cannot
pass the hyperpolarized zone and is arrested.
[0335] As shown in FIGS. 52J and 52K, the microcontroller 398 in
the pulse generator 391 is configured to provide stepped pulses.
The current of the first step is too low to induce an action
potential (AP), but only depolarizes the membrane. The AP is
generated during the second step. The pulses in FIGS. 52J and 52K
are similar, except that the pulses in FIG. 52J have a longer first
step. In addition to anodel blocking, another advantage of these
stepped pulses is that the total charge per pulse can be reduced by
almost a third.
[0336] Other examples of complex pulses, that may be used with
tripolar electrodes are shown in FIGS. 52-L to 52-O. FIG. 52L shows
biphasic pulses with a time delay t.sub.d between the positive and
negative pulse. FIG. 52M shows biphasic pulses with a time delay
t.sub.d, where the second part of the pulse is a step pulse. FIG.
52N shows ramp pulses, and FIG. 52-O show pulses with exponential
components. Theoretical work, computer modeling, and animal studies
have all shown that lower charge is obtained with these modified
pulses when compared to square pulses. The charge reduction of
these pulses can be approximately 30% less when compared to square
pulses, which is fairly significant. The microcontroller 398 of the
pulse generator 391 can be configured to deliver these pulses, as
is well known to one skilled in the art.
[0337] Since the number of types of pulses and pulse trains to
provide therapy can be complex for many physician's, in one aspect
predetermined/pre-packaged program comprise a complete program for
the pulse trains that deliver therapy. The advantage of the
pre-packaged programs is that the physician may program a
complicated program simply by selecting a program number.
[0338] The programming of the implanted pulse generator (IPG) 391
is shown in conjunction with FIGS. 53A and 53B. With the magnetic
Reed Switch 389 (FIG. 44A) in the closed position, a coil in the
head of the programmer 85, communicates with a telemetry coil 399
of the implanted pulse generator 391. Bi-directional inductive
telemetry is used to exchange data with the implanted unit 391 by
means of the external programming unit 85.
[0339] The transmission of programming information involves
manipulation of the carrier signal in a manner that is recognizable
by the pulse generator 391 as a valid set of instructions. The
process of modulation serves as a means of encoding the programming
instruction in a language that is interpretable by the implanted
pulse generator 391. Modulation of signal amplitude, pulse width,
and time between pulses are all used in the programming system, as
will be appreciated by those skilled in the art. FIG. 54A shows an
example of pulse count modulation, and FIG. 54B shows an example of
pulse width modulation, that can be used for encoding.
[0340] FIG. 55 shows a simplified overall block diagram of the
implanted pulse generator (IPG) 391 programming and telemetry
interface. The left half of FIG. 55 is programmer 85 which
communicates programming and telemetry information with the IPG
391. The sections of the IPG 391 associated with programming and
telemetry are shown on the right half of FIG. 55. In this case, the
programming sequence is initiated by bringing a permanent magnet in
the proximity of the IPG 391 which closes a reed switch 389 in the
IPG 391. Information is then encoded into a special
error-correcting pulse sequence and transmitted electromagnetically
through a set of coils. The received message is decoded, checked
for errors, and passed on to the unit's logic circuitry. The IPG
391 of this embodiment includes the capability of bidirectional
communication.
[0341] The reed switch 389 is a magnetically-sensitive mechanical
switch, which consists of two thin strips of metal (the "reed")
which are ferromagnetic. The reeds normally spring apart when no
magnetic field is present. When a field is applied, the reeds come
together to form a closed circuit because doing so creates a path
of least reluctance. The programming head of the programmer
contains a high-field-strength ceramic magnet.
[0342] When the switch closes, it activates the programming
hardware, and initiates an interrupt of the IPG central processor.
Closing the reed switch 389 also presents the logic used to encode
and decode programming and telemetry signals. A nonmaskable
interrupt (NMI) is sent to the IPG processor, which then executes
special programming software. Since the NMI is an edge-triggered
signal and the reed switch is vulnerable to mechanical bounce, a
debouncing circuit is used to avoid multiple interrupts. The
overall current consumption of the IPG increases during programming
because of the debouncing circuit and other communication
circuits.
[0343] A coil 399 is used as an antenna for both reception and
transmission. Another set of coils 383 is placed in the programming
head, a relatively small sized unit connected to the programmer 85.
All coils are tuned to the same resonant frequency. The interface
is half-duplex with one unit transmitting at a time.
[0344] Since the relative positions of the programming head 87 and
IPG 391 determine the coupling of the coils, this embodiment
utilizes a special circuit which has been devised to aid the
positioning of the programming head, and is shown in FIG. 56. It
operates on similar principles to the linear variable differential
transformer. An oscillator tuned to the resonant frequency of the
pacemaker coil 399 drives the center coil of a three-coil set in
the programmer head. The phase difference between the original
oscillator signal and the resulting signal from the two outer coils
is measured using a phase shift detector. It is proportional to the
distance between the implanted pulse generator and the programmer
head. The phase shift, as a voltage, is compared to a reference
voltage and is then used to control an indicator such as an LED. An
enable signal allows switching the circuit on and off.
[0345] Actual programming is shown in conjunction with FIGS. 53 and
54. Programming and telemetry messages comprise many bits; however,
the coil interface can only transmit one bit at a time. In
addition, the signal is modulated to the resonant frequency of the
coils, and must be transmitted in a relatively short period of
time, and must provide detection of erroneous data.
[0346] A programming message is comprised of five parts FIG. 57(a).
The start bit indicates the beginning of the message and is used to
synchronize the timing of the rest of the message. The parameter
number specifies which parameter (e.g., mode, pulse width, delay)
is to be programmed. In the example, in FIG. 57(a) the number
10010000 specifies the pulse rate to be specified. The parameter
value represents the value that the parameter should be set to.
This value may be an index into a table of possible values; for
example, the value 00101100 represents a pulse stimulus rate of 80
pulses/min. The access code is a fixed number based on the stimulus
generator model which must be matched exactly for the message to
succeed. It acts as a security mechanism against use of the wrong
programmer, errors in the message, or spurious programming from
environmental noise. It can also potentially allow more than one
programmable implant in the patient. Finally, the parity field is
the bitwise exclusive-OR of the parameter number and value fields.
It is one of several error-detection mechanisms.
[0347] All of the bits are then encoded as a sequence of pulses of
0.35-ms duration FIG. 57(b). The start bit is a single pulse. The
remaining bits are delayed from their previous bit according to
their bit value. If the bit is a zero, the delay is short (1.0); if
it is a one, the delay is long (2.2 ms). This technique of pulse
position coding, makes detection of errors easier.
[0348] The serial pulse sequence is then amplitude modulated for
transmission FIG. 57(c). The carrier frequency is the resonant
frequency of the coils. This signal is transmitted from one set of
coils to the other and then demodulated back into a pulse sequence
FIG. 57(d).
[0349] FIG. 58 shows how each bit of the pulse sequence is decoded
from the demodulated signal. As soon as each bit is received, a
timer begins timing the delay to the next pulse. If the pulse
occurs within a specific early interval, it is counted as a zero
bit (FIG. 58(b)). If it otherwise occurs with a later interval, it
is considered to be a one bit (FIG. 58(d)). Pulses that come too
early, too late, or between the two intervals are considered to be
errors and the entire message is discarded (FIG.58(a, c, e)). Each
bit begins the timing of the bit that follows it. The start bit is
used only to time the first bit.
[0350] Telemetry data may be either analog or digital. Digital
signals are first converted into a serial bit stream using an
encoding such as shown in FIG. 58(b). The serial stream or the
analog data is then frequency modulated for transmission.
[0351] An advantage of this and other encodings is that they
provide multiple forms of error detection. The coils and receiver
circuitry are tuned to the modulation frequency, eliminating noise
at other frequencies. Pulse-position coding can detect errors by
accepting pulses only within narrowly-intervals. The access code
acts as a security key to prevent programming by spurious noise or
other equipment. Finally, the parity field and other checksums
provides a final verification that the message is valid. At any
time, if an error is detected, the entire message is discarded.
[0352] Another more sophisticated type of pulse position modulation
may be used to increase the bit transmission rate. In this, the
position of a pulse within a frame is encoded into one of a finite
number of values, e.g. 16. A special synchronizing bit is
transmitted to signal the start of the frame. Typically, the frame
contains a code which specifies the type or data contained in the
remainder of the frame.
[0353] FIG. 59 shows a diagram of receiving and decoding circuitry
for programming data. The IPG coil, in parallel with capacitor
creates a tuned circuit for receiving data. The signal is band-pass
filtered 602 and envelope detected 604 to create the pulsed signal
in FIG. 57 (d). After decoding, the parameter value is plated in a
RAM at the location specified by the parameter number. The IPG can
have two copies of the RAM--a permanent set and a temporary
set--which makes it easy for the physician to set the IPG to a
temporary configuration and later reprogram it back to the usual
settings.
[0354] FIG. 60 shows the basic circuit used to receive telemetry
data. Again, a coil and capacitor create a resonant circuit tuned
to the carrier frequency. The signal is further band-pass filtered
614 and then frequency-demodulated using a phase-locked loop
618.
[0355] This embodiment also comprises an optional battery status
test circuit. Shown in conjunction with FIG. 61, the charge
delivered by the battery is estimated by keeping track of the
number of pulses delivered by the IPG 391. An internal charge
counter is updated during each test mode to read the total charge
delivered. This information about battery status is read from the
IPG 391 via telemetry.
Combination Implantable Device Comprising Both a Stimulus-Receiver
and a Programmable Implantable Pulse Generator (IPG)
[0356] In one embodiment, the implantable device may comprise both
a stimulus-receiver and a programmable implantable pulse generator
(IPG) in one device. Another embodiment of a similar device is
disclosed in applicant's co-pending Application Ser. No.
10/436,017. This embodiment also comprises
predetermined/pre-packaged programs. Examples of several
stimulation states were given in the previous sections, under
"Programmer-less Implantable Pulse Generator (IPG)" and
"Programmable Implantable Pulse Generator". These
predetermined/pre-packaged programs comprise unique combinations of
pulse amplitude, pulse width, pulse frequency, ON-time and
OFF-time.
[0357] FIG. 62 shows a close up view of the packaging of the
implanted stimulator 75 of this embodiment, showing the two
subassemblies 120, 170. The two subassemblies are the
stimulus-receiver module 120 and the battery operated pulse
generator module 170. The electrical components of the
stimulus-receiver module 120 may be substantially in the titanium
case along with other circuitry, except for a coil. The coil may be
outside the titanium case as shown in FIG. 62, or the coil 48C may
be externalized at the header portion 79 of the implanted device,
and may be wrapped around the titanium can. In this case, the coil
is encased in the same material as the header 79, as shown in FIGS.
63A-63D. FIG. 63A depicts a bipolar configuration with two separate
feed-throughs, 56, 58. FIG. 63B depicts a unipolar configuration
with one separate feed-through 66. FIG. 63C, and 63D depict the
same configuration except the feed-throughs are common with the
feed-throughs 66A for the lead.
[0358] FIG. 64 is a simplified overall block diagram of the
embodiment where the implanted stimulator 75 is a combination
device, which may be used as a stimulus-receiver (SR) in
conjunction with an external stimulator, or the same implanted
device may be used as a traditional programmable implanted pulse
generator (IPG). The coil 48C which is external to the titanium
case may be used both as a secondary of a stimulus-receiver, or may
also be used as the forward and back telemetry coil.
[0359] In this embodiment, as disclosed in FIG. 64, the IPG
circuitry within the titanium case is used for all stimulation
pulses whether the energy source is the internal battery 740 or an
external power-source. The external device serves as a source of
energy, and as a programmer that sends telemetry to the IPG. For
programming, the energy is sent as high frequency sine waves with
superimposed telemetry wave driving the external coil 46C. Once
received by the implanted coil 48C, the telemetry is passed through
coupling capacitor 727 to the IPG's telemetry circuit 742. For
pulse delivery using external power source, the stimulus-receiver
portion will receive the energy coupled to the implanted coil 48C
and, using the power conditioning circuit 726, rectify it to
produce DC, filter and regulate the DC, and couple it to the IPG's
voltage regulator 738 section so that the IPG can run from the
externally supplied energy rather than the implanted battery
740.
[0360] The system provides a power sense circuit 728 that senses
the presence of external power communicated with the power control
730 when adequate and stable power is available from an external
source. The power control circuit controls a switch 736 that
selects either battery power 740 or conditioned external power from
726. The logic and control section 732 and memory 744 includes the
IPG's microcontroller, pre-programmed instructions, and stored
chagneable parameters. Using input for the telemetry circuit 742
and power control 730, this section controls the output circuit 734
that generates the output pulses.
[0361] It will be clear to one skilled in the art that this
embodiment of the invention can also be practiced with a
rechargeable battery. This version is shown in conjunction with
FIG. 65. The circuitry in the two versions are similar except for
the battery charging circuitry 749. This circuit is energized when
external power is available. It senses the charge state of the
battery and provides appropriate charge current to safely recharge
the battery without overcharging.
[0362] The stimulus-receiver portion of the circuitry is shown in
conjunction with FIG. 66. Capacitor C1 (729) makes the combination
of C1 and L1 sensitive to the resonant frequency and less sensitive
to other frequencies, and energy from an external (primary) coil
46C is inductively transferred to the implanted unit via the
secondary coil 48C. The AC signal is rectified to DC via diode 731,
and filtered via capacitor 733. A regulator 735 sets the output
voltage and limits it to a value just above the maximum IPG cell
voltage. The output capacitor C4 (737), typically a tantalum
capacitor with a value of 100 micro-Farads or greater, stores
charge so that the circuit can supply the IPG with high values of
current for a short time duration with minimal voltage change
during a pulse while the current draw from the external source
remains relatively constant. Also shown in conjunction with FIG.
66, a capacitor C3 (727) couples signals for forward and back
telemetry.
[0363] FIGS. 67A and 67B show alternate connection of the receiving
coil. In FIG. 67A, each end of the coil is connected to the circuit
through a hermetic feedthrough filter. In this instance, the DC
output is floating with respect to the IPG's case. In FIG. 67B, one
end of the coil is connected to the exterior of the IPG's case. The
circuit is completed by connecting the capacitor 729 and bridge
rectifier 739 to the interior of the IPG's case The advantage of
this arrangement is that it requires one less hermetic feedthrough
filter, thus reducing the cost and improving the reliabilty of the
IPG. Hermetic feedthrough filters are expensive and a possible
failure point. However, the case connection may complicit the
output circuitry or limit its versatility. When using a bipolar
electrode (or multipolar electrodes), care must be taken to prevent
an unwanted return path for the pulse to the IPG's case. This is
not a concern for unipolar pulses using a single conductor
electrode because it relies on the IPG's case a return for the
pulse current.
[0364] In the unipolar configuration, a bigger tissue area is
stimulated since the difference between the tip (cathode) and case
(anode) is larger. Stimulations using unipolar, bipolar, and
multipolar configurations is considered within the scope of this
invention.
[0365] The power source select circuit is highlighted in
conjunction with FIG. 68. In this embodiment, the IPG provides
stimulation pulses according to the stimulation programs stored in
the memory 744 of the implanted stimulator, with power being
supplied by the implanted battery 740. When stimulation energy from
an external stimulator is inductively received via secondary coil
48C, the power source select circuit (shown in block 743) switches
power via transistor Q1 745 and transistor Q2 743. Transistor Q1
and Q2 are preferably low loss MOS transistor used as switches,
even though other types of transistors may be used.
Implantable Pulse Generator (IPG) Comprising a Rechargable
Battery
[0366] In one embodiment, an implantable pulse generator with
rechargeable power source can be used. Because of the rapidity of
the pulses required for modulating nerve tissue 54 with stimulating
and/or blocking pulses, there is a real need for power sources that
will provide an acceptable service life under conditions of
continuous delivery of high frequency pulses. FIG. 69A shows a
graph of the energy density of several commonly used battery
technologies. Lithium batteries have by far the highest energy
density of commonly available batteries. Also, a lithium battery
maintains a nearly constant voltage during discharge. This is shown
in conjunction with FIG. 69B, which is normalized to the
performance of the lithium battery. Lithium-ion batteries also have
a long cycle life, and no memory effect. However, Lithium-ion
batteries are not as tolerant to overcharging and over-discharging.
One of the most recent development in rechargable battery
technology is the Lithium-ion polymer battery. Recently the major
battery manufacturers (Sony, Panasonic, Sanyo) have announced plans
for Lithium-ion polymer battery production. In one embodiment,
existing nerve stimulators and cardiac pacemakers can be modified
to incorporate rechargeable batteries.
[0367] This embodiment also comprises predetermined/pre-packaged
programs. Examples of several stimulation states were given in the
previous sections, under "Programmer-less Implantable Pulse
Generator (IPG)" and "Programmable Implantable Pulse Generator".
These pre-packaged/pre-determined programs comprise unique
combinations of pulse amplitude, pulse width, pulse frequency,
ON-time and OFF-time. Additionally, predetermined programs
comprising blocking pulses may also be stored in the memory of the
pulse generator.
[0368] As shown in conjunction with FIG. 70, the coil is
externalized from the titanium case 65. The RF pulses transmitted
via coil 46 and received via subcutaneous coil 48A are rectified
via a diode bridge. These DC pulses are processed and the resulting
current applied to recharge the battery 694/740 in the implanted
pulse generator. In one embodiment the coil 48C may be externalized
at the header portion 79 of the implanted device, and may be
wrapped around the titanium can, as was previously shown in FIGS.
63A-D.
[0369] In one embodiment, the coil may also be positioned on the
titanium case as shown in conjunction with FIGS. 71A and 71B. FIG.
71A shows a diagram of the finished implantable stimulator 391 R of
one embodiment. FIG. 72B shows the pulse generator with some of the
components used in assembly in an exploded view. These components
include a coil cover 480, the secondary coil 48 and associated
components, a magnetic shield 482, and a coil assembly carrier 484.
The coil assembly carrier 484 has at least one positioning detail
486 located between the coil assembly and the feed through for
positioning the electrical connection. The positioning detail 486
secures the electrical connection.
[0370] A schematic diagram of the implanted pulse generator (IPG
391 R), with re-chargeable battery 694, is shown in conjunction
with FIG. 72. The IPG 391 R includes logic and control circuitry
673 connected to memory circuitry 691. The operating program and
stimulation parameters are typically stored within the memory 691
via forward telemetry. Stimulation pulses are provided to the nerve
tissue 54 via output circuitry 677 controlled by the
microcontroller.
[0371] The operating power for the IPG 391 R is derived from a
rechargeable power source 694. The rechargeable power source 694
comprises a rechargeable lithium-ion or lithium-ion polymer
battery. Recharging occurs inductively from an external charger to
an implanted coil 48B underneath the skin 60. The rechargeable
battery 694 may be recharged repeatedly as needed. Additionally,
the IPG 391 R is able to monitor and telemeter the status of its
rechargable battery 691 each time a communication link is
established with the external programmer 85.
[0372] Much of the circuitry included within the IPG 391 R may be
realized on a single application specific integrated circuit
(ASIC). This allows the overall size of the IPG 391 R to be quite
small, and readily housed within a suitable hermetically-sealed
case. The IPG case is preferably made from a titanium and is shaped
in a rounded case.
[0373] Shown in conjunction with FIG. 73 are the recharging
elements of this embodiment. The re-charging system uses a portable
external charger to couple energy into the power source of the IPG
391R. The DC-to-AC conversion circuitry 696 of the re-charger
receives energy from a battery 672 in the re-charger. A charger
base station 680 and conventional AC power line may also be used.
The AC signals amplified via power amplifier 674 are inductively
coupled between an external coil 46B and an implanted coil 48B
located subcutaneously with the implanted pulse generator (IPG) 391
R. The AC signal received via implanted coil 48B is rectified 686
to a DC signal which is used for recharging the rechargeable
battery 694 of the IPG, through a charge controller IC 682.
Additional circuitry within the IPG 391R includes, battery
protection IC 688 which controls a FET switch 690 to make sure that
the rechargeable battery 694 is charged at the proper rate, and is
not overcharged. The battery protection IC 688 can be an
off-the-shelf IC available from Motorola (part no. MC 33349N-3R1).
This IC monitors the voltage and current of the implanted
rechargeable battery 694 to ensure safe operation. If the battery
voltage rises above a safe maximum voltage, the battery protection
IC 688 opens charge enabling FET switches 690, and prevents further
charging. A fuse 692 acts as an additional safeguard, and
disconnects the battery 694 if the battery charging current exceeds
a safe level. As also shown in FIG. 73, charge completion detection
is achieved by a back-telemetry transmitter 684, which modulates
the secondary load by changing the full-wave rectifier into a
half-wave rectifier/voltage clamp. This modulation is in turn,
sensed by the charger as a change in the coil voltage due to the
change in the reflected impedance. When detected through a back
telemetry receiver 676, either an audible alarm is generated or a
LED is turned on.
[0374] A simplified block diagram of charge completion and
misalignment detection circuitry is shown in conjunction with FIG.
74. As shown, a switch regulator 686 operates as either a full-wave
rectifier circuit or a half-wave rectifier circuit as controlled by
a control signal (CS) generated by charging and protection
circuitry 698. The energy induced in implanted coil 48B (from
external coil 46B) passes through the switch rectifier 686 and
charging and protection circuitry 698 to the implanted rechargeable
battery 694. As the implanted battery 694 continues to be charged,
the charging and protection circuitry 698 continuously monitors the
charge current and battery voltage. When the charge current and
battery voltage reach a predetermined level, the charging and
protection circuitry 698 triggers a control signal. This control
signal causes the switch rectifier 686 to switch to half-wave
rectifier operation. When this change happens, the voltage sensed
by voltage detector 702 causes the alignment indicator 706 to be
activated. This indicator 706 may be an audible sound or a flashing
LED type of indicator.
[0375] The indicator 706 may similarly be used as a misalignment
indicator. In normal operation, when coils 46B (external) and 48B
(implanted) are properly aligned, the voltage V.sub.s sensed by
voltage detector 704 is at a minimum level because maximum energy
transfer is taking place. If and when the coils 46B and 48B become
misaligned, then less than a maximum energy transfer occurs, and
the voltage V.sub.s sensed by detection circuit 704 increases
significantly. If the voltage V.sub.s reaches a predetermined
level, alignment indicator 706 is activated via an audible speaker
and/or LEDs for visual feedback. After adjustment, when an optimum
energy transfer condition is established, causing V.sub.s to
decrease below the predetermined threshold level, the alignment
indicator 706 is turned off.
[0376] The elements of the external recharger are shown as a block
diagram in conjunction with FIG. 75. In this disclosure, the words
charger and recharger are used interchangeably. The charger base
station 680 receives its energy from a standard power outlet 714,
which is then converted to 5 volts DC by a AC-to-DC transformer
712. When the re-charger is placed in a charger base station 680,
the re-chargeable battery 672 of the re-charger is fully recharged
in a few hours and is able to recharge the battery 694 of the IPG
391R. If the battery 672 of the external re-charger falls below a
prescribed limit of 2.5 volt DC, the battery 672 is trickle charged
until the voltage is above the prescribed limit, and then at that
point resumes a normal charging process.
[0377] As also shown in FIG. 75, a battery protection circuit 718
monitors the voltage condition, and disconnects the battery 672
through one of the FET switches 716, 720 if a fault occurs until a
normal condition returns. A fuse 724 will disconnect the battery
672 should the charging or discharging current exceed a prescribed
amount.
[0378] In summary, in the method of the current invention for
neuromodulation of cortical neural tissue to provide therapy or
alleviate symptoms of Parkinson's disease, or to enhance or induce
neuroplasticity in post-stroke patients can be practiced with any
of the several pulse generator systems disclosed including,
[0379] a) an implanted stimulus-receiver with an external
stimulator;
[0380] b) an implanted stimulus-receiver comprising a high value
capacitor for storing charge, used in conjunction with an external
stimulator;
[0381] c) a programmer-less implantable pulse generator (IPG) which
is operable with a magnet;
[0382] d) a microstimulator;
[0383] e) a programmable implantable pulse generator;
[0384] f) a combination implantable device comprising both a
stimulus-receiver and a programmable IPG; and
[0385] g) an IPG comprising a rechargeable battery.
[0386] Electrical stimulation of cortical neural tissues with any
of these systems is considered within the scope of this
invention.
[0387] In one embodiment, the external stimulator and/or the
programmer has a telecommunications module, as described in a
co-pending application, and summarized here for reader convenience.
The telecommunications module has two-way communications
capabilities.
[0388] FIGS. 76 and 77 depict communication between an external
stimulator 42 and a remote hand-held computer 502. A desktop or
laptop computer can be a server 500 which is situated remotely,
perhaps at a physician's office or a hospital. The stimulation
parameter data can be viewed at this facility or reviewed remotely
by medical personnel on a hand-held personal data assistant (PDA)
502, such as a "palm-pilot" from PALM corp. (Santa Clara, Calif.),
a "Visor" from Handspring Corp. (Mountain view, Calif.) or on a
personal computer (PC). The physician or appropriate medical
personnel, is able to interrogate the external stimulator 42 device
and know what the device is currently programmed to, as well as,
get a graphical display of the pulse train. The wireless
communication with the remote server 500 and hand-held PDA 502
would be supported in all geographical locations within and outside
the United States (US) that provides cell phone voice and data
communication service.
[0389] In one aspect of the invention, the telecommunications
component can use Wireless Application Protocol (WAP). The Wireless
Application Protocol (WAP), which is a set of communication
protocols standardizing Internet access for wireless devices. While
previously, manufacturers used different technologies to get
Internet on hand-held devices, with WAP devices and services
interoperate. WAP also promotes convergence of wireless data and
the Internet. The WAP programming model is heavily based on the
existing Internet programming model, and is shown schematically in
FIG. 78. Introducing a gateway function provides a mechanism for
optimizing and extending this model to match the characteristics of
the wireless environment. Over-the-air traffic is minimized by
binary encoding/decoding of Web pages and readapting the Internet
Protocol stack to accommodate the unique characteristics of a
wireless medium such as call drops.
[0390] The key components of the WAP technology, as shown in FIG.
78, includes 1) Wireless Mark-up Language (WML) 550 which
incorporates the concept of cards and decks, where a card is a
single unit of interaction with the user. A service constitutes a
number of cards collected in a deck. A card can be displayed on a
small screen. WML supported Web pages reside on traditional Web
servers. 2) WML Script which is a scripting language, enables
application modules or applets to be dynamically transmitted to the
client device and allows the user interaction with these applets.
3) Microbrowser, which is a lightweight application resident on the
wireless terminal that controls the user interface and interprets
the WMLNVMLScript content. 4) A lightweight protocol stack 520
which minimizes bandwidth requirements, guaranteeing that a broad
range of wireless networks can run WAP applications. The protocol
stack of WAP can comprise a set of protocols for the transport
(WTP), session (WSP), and security (WTLS) layers. WSP is binary
encoded and able to support header caching, thereby economizing on
bandwidth requirements. WSP also compensates for high latency by
allowing requests and responses to be handled asynchronously,
sending before receiving the response to an earlier request. For
lost data segments, perhaps due to fading or lack of coverage, WTP
only retransmits lost segments using selective retransmission,
thereby compensating for a less stable connection in wireless. The
above mentioned features are industry standards adopted for
wireless applications and greater details have been publicized, and
well known to those skilled in the art.
[0391] In this embodiment, two modes of communication are possible.
In the first, the server initiates an upload of the actual
parameters being applied to the patient, receives these from the
stimulator, and stores these in its memory, accessible to the
authorized user as a dedicated content driven web page. The
physician or authorized user can make alterations to the actual
parameters, as available on the server, and then initiate a
communication session with the stimulator device to download these
parameters.
[0392] Shown in conjunction with FIG. 79, in one embodiment, the
external stimulator 42 and/or the programmer 85 may also be
networked to a central collaboration computer 286 as well as other
devices such as a remote computer 294, PDA 502, phone 141,
physician computer 143. The interface unit 292 in this embodiment
communicates with the central collaborative network 290 via
land-lines such as cable modem or wirelessly via the internet. A
central computer 286 which has sufficient computing power and
storage capability to collect and process large amounts of data,
contains information regarding device history and serial number,
and is in communication with the network 290. Communication over
collaboration network 290 may be effected by way of a TCP/IP
connection, particularly one using the internet, as well as a PSTN,
DSL, cable modem, LAN, WAN or a direct dial-up connection.
[0393] The standard components of interface unit shown in block 292
are processor 305, storage 310, memory 308, transmitter/receiver
306, and a communication device such as network interface card or
modem 312. In the preferred embodiment these components are
embedded in the external stimulator 42 and can also be embedded in
the programmer 85. These can be connected to the network 290
through appropriate security measures (Firewall) 293.
[0394] Another type of remote unit that may be accessed via central
collaborative network 290 is remote computer 294. This remote
computer 294 may be used by an appropriate attending physician to
instruct or interact with interface unit 292, for example,
instructing interface unit 292 to send instruction downloaded from
central computer 286 to remote implanted unit.
[0395] Shown in conjunction with FIGS. 80A and 80B the physician's
remote communication's module is a Modified PDA/Phone 502 in this
embodiment. The Modified PDA/Phone 502 is a microprocessor based
device as shown in a simplified block diagram in FIGS. 76A and 76B.
The PDA/Phone 502 is configured to accept PCM/CIA cards specially
configured to fulfill the role of communication module 292 of the
present invention. The Modified PDA/Phone 502 may operate under any
of the useful software including Microsoft Window's based, Linux,
Palm OS, Java OS, SYMBIAN, or the like.
[0396] The telemetry module 362 comprises an RF telemetry antenna
142 coupled to a telemetry transceiver and antenna driver circuit
board which includes a telemetry transmitter and telemetry
receiver. The telemetry transmitter and receiver are coupled to
control circuitry and registers, operated under the control of
microprocessor 364. Similarly, within stimulator a telemetry
antenna 142 is coupled to a telemetry transceiver comprising RF
telemetry transmitter and receiver circuit. This circuit is coupled
to control circuitry and registers operated under the control of
microcomputer circuit.
[0397] With reference to the telecommunications aspects of the
invention, the communication and data exchange between Modified
PDA/Phone 502 and external stimulator 42 operates on commercially
available frequency bands. The 2.4-to-2.4853 GHz bands or 5.15 and
5.825 GHz, are the two unlicensed areas of the spectrum, and set
aside for industrial, scientific, and medical (ISM) uses. Most of
the technology today including this invention, use either the 2.4
or 5 GHz radio bands and spread-spectrum technology.
[0398] The telecommunications technology, especially the wireless
internet technology, which this invention utilizes in one
embodiment, is constantly improving and evolving at a rapid pace,
due to advances in RF and chip technology as well as software
development. Therefore, one of the intents of this invention is to
utilize "state of the art" technology available for data
communication between Modified PDA/Phone 502 and external
stimulator 42. The intent of this invention is to use 3G technology
for wireless communication and data exchange, even though in some
cases 2.5G is being used currently.
[0399] For the system of the current invention, the use of any of
the "3G" technologies for communication for the Modified PDA/Phone
502, is considered within the scope of the invention. Further, it
will be evident to one of ordinary skill in the art that as future
4G systems, which will include new technologies such as: improved
modulation and smart antennas, can be easily incorporated into the
system and method of current invention, and are also considered
within the scope of the invention.
[0400] The present invention may be embodied in other specific
forms without departing from the spirit or essential attributes
thereof. It is therefore desired that the present embodiment be
considered in all aspects as illustrative and not restrictive,
reference being made to the appended claims rather than to the
foregoing description to indicate the scope of the invention.
* * * * *