U.S. patent application number 17/186946 was filed with the patent office on 2022-01-13 for brain stimulation system including diagnostic tool.
This patent application is currently assigned to Functional Neuromodulation, Inc.. The applicant listed for this patent is Functional Neuromodulation, Inc.. Invention is credited to J. Christopher Flaherty, Todd Langevin, Dan O'Connell, Donald E. Reymers.
Application Number | 20220008727 17/186946 |
Document ID | / |
Family ID | 1000005869129 |
Filed Date | 2022-01-13 |
United States Patent
Application |
20220008727 |
Kind Code |
A1 |
O'Connell; Dan ; et
al. |
January 13, 2022 |
BRAIN STIMULATION SYSTEM INCLUDING DIAGNOSTIC TOOL
Abstract
A system for treating a patient comprises a stimulator for
stimulating brain tissue, a controller for setting stimulation
parameters and a diagnostic tool for measuring patient parameters
and producing diagnostic data. The stimulation parameters comprise
test stimulation parameters and treatment stimulation parameters.
The stimulator delivers test stimulation energy to the brain tissue
based on at least one test stimulation parameter and delivers
treatment stimulation energy to the brain tissue based on at least
one treatment stimulation parameter. One or more treatment
stimulator parameters are determined based on the diagnostic data
produced by the diagnostic tool The system is constructed and
arranged to treat a neurological disease or a neurological
disorder. Methods of treating a neurological disease or
neurological disorder are also provided.
Inventors: |
O'Connell; Dan;
(Earlysville, VA) ; Langevin; Todd; (Edina,
MN) ; Reymers; Donald E.; (Brevard, NC) ;
Flaherty; J. Christopher; (Auburndale, FL) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Functional Neuromodulation, Inc. |
Toronto |
|
CA |
|
|
Assignee: |
Functional Neuromodulation,
Inc.
Toronto
CA
|
Family ID: |
1000005869129 |
Appl. No.: |
17/186946 |
Filed: |
February 26, 2021 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15714782 |
Sep 25, 2017 |
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17186946 |
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14917917 |
Apr 8, 2016 |
9782590 |
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15714782 |
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PCT/IB2014/003188 |
Oct 16, 2014 |
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14917917 |
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61893023 |
Oct 18, 2013 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/055 20130101;
A61N 5/0601 20130101; A61N 1/36153 20130101; A61M 5/14276 20130101;
A61N 1/36064 20130101; A61N 1/36067 20130101; A61B 5/4088 20130101;
A61N 1/36175 20130101; A61N 1/36082 20130101; A61M 5/1723 20130101;
A61N 1/0531 20130101; A61N 1/36025 20130101; A61B 5/318 20210101;
A61N 2005/0626 20130101; A61N 1/0534 20130101; A61N 1/36139
20130101; A61N 1/36096 20130101; A61B 5/369 20210101; A61N 1/36171
20130101; A61N 2/006 20130101; A61N 1/36017 20130101; A61N 1/37241
20130101; A61N 2007/0026 20130101; A61N 5/0622 20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 2/00 20060101 A61N002/00; A61N 5/06 20060101
A61N005/06; A61M 5/172 20060101 A61M005/172; A61B 5/00 20060101
A61B005/00; A61N 1/05 20060101 A61N001/05; A61M 5/142 20060101
A61M005/142; A61B 5/318 20060101 A61B005/318; A61B 5/369 20060101
A61B005/369; A61B 5/055 20060101 A61B005/055; A61N 1/372 20060101
A61N001/372 |
Claims
1. A system for treating a patient comprising: a stimulator for
stimulating brain tissue; a controller for setting stimulation
parameters comprising at least one test stimulation parameter of
the stimulator and at least one treatment stimulation parameter of
the stimulator; and a diagnostic tool for measuring at least one
patient parameter and producing diagnostic data representing the at
least one measured patient parameter; wherein the stimulator is
constructed and arranged to deliver test stimulation energy to the
brain tissue based on the at least one test stimulation parameter
and to deliver treatment stimulation energy to the brain tissue
based on the at least one treatment stimulation parameter; wherein
the at least one treatment stimulator parameter is determined based
on the diagnostic data; and wherein the system is constructed and
arranged to treat at least one of a neurological disease or a
neurological disorder.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/714,782, filed Sep. 25, 2017, which is a
continuation of U.S. patent application Ser. No. 14/917,917, filed
Apr. 8, 2016, now U.S. Pat. No. 9,782,590, which is a continuation
of International Patent Application No. PCT/IB2014/003188, filed
Oct. 16, 2014, which claims priority under 35 USC 119(3) to U.S.
Provisional Patent Application Ser. No. 61/893,023, entitled "Brain
Stimulation System including Diagnostic Tool", filed Oct. 18, 2013,
the contents of which are incorporated herein by reference in their
entirety.
[0002] This application is related to: U.S. patent Ser. No.
11/303,293, entitled "Cognitive Function within a Human Brain",
filed Dec. 16, 2005; U.S. patent application Ser. No. 11/303,292,
entitled "Inducing Neurogenesis within a Human Brain", filed Dec.
16, 2005; U.S. patent Ser. No. 11/303,619, entitled "Regulation of
Neurotrophins", filed Dec. 16, 2005; U.S. patent application Ser.
No. 11/365,977, entitled "Method of Treating Cognitive Disorders
Using Neuromodulation", filed Mar. 1, 2006; and U.S. patent
application Ser. No. 13/655,652, entitled "Deep Brain Stimulation
of Memory Circuits in Alzheimer's Disease", filed Oct. 19, 2012;
the contents of which are each incorporated herein by reference in
their entirety.
FIELD OF INVENTION
[0003] The present invention relates generally to methods and
systems for treating a neurological disease or disorder, such as
Alzheimer's Disease or other cognitive disorder. In particular, a
system includes a stimulation device and a diagnostic tool used to
set one or more treatment stimulation parameters used to treat a
neurological disease or disorder.
BACKGROUND OF THE INVENTION
[0004] Brain stimulation has been performed to treat numerous
patient diseases and disorders, such as neurological and
psychiatric conditions. Both invasive and non-invasive technologies
have been developed. One non-invasive system includes a
transcranial magnetic stimulation device that directs a magnetic
field from outside the patient's head to induce electric currents
in the patient's brain. Deep brain stimulation (DBS) can be
accomplished using surgically implanted electrodes that deliver
electrical stimulation to precisely targeted areas in the brain.
More than 60,000 patients have been implanted with deep brain
electrodes, and its predominant application has been in the
treatment of movement disorders, most commonly Parkinson's
disease.
[0005] There is a need for enhanced DBS and other brain stimulation
systems, device and methods that result in increased safety and
improved efficacy in the treatment of patients.
SUMMARY
[0006] According to an aspect of the present inventive concepts, a
system for treating a patient comprises a stimulator for
stimulating brain tissue, a controller and at least one diagnostic
tool. The system is constructed and arranged to treat at least one
of a neurological disease or a neurological disorder. The
controller is configured to set one or more stimulation parameters
comprising at least one test stimulation parameter of the
stimulator and at least one treatment stimulation parameter of the
stimulator. The diagnostic tool is configured to measure at least
one patient parameter and produce diagnostic data representing the
at least one measured patient parameter. The stimulator is
constructed and arranged to deliver test stimulation energy to the
brain tissue based on the at least one test stimulation parameter
and to deliver treatment stimulation energy to the brain tissue
based on the at least one treatment stimulation parameter. The at
least one treatment stimulation parameter is determined based on
the diagnostic data.
[0007] In some embodiments, the system is constructed and arranged
to determine the treatment stimulation parameter to at least one of
prevent or reduce an adverse event.
[0008] In some embodiments, the system is constructed and arranged
to determine the treatment stimulation parameter to improve the
treatment of the at least one of a neurological disease or a
neurological disorder.
[0009] In some embodiments, the at least one treatment stimulation
parameter comprises the at least one test stimulation
parameter.
[0010] In some embodiments, the setting of the at least one
treatment stimulation parameter comprises at least one of setting
an initial treatment stimulation parameter or modifying an existing
treatment stimulation parameter.
[0011] In some embodiments, the stimulator is constructed and
arranged to stimulate brain tissue with a first set of test
stimulation parameters for a first time period and a second set of
test stimulation parameters for a second time period, and the
diagnostic data can comprise first diagnostic data associated with
the first stimulation time period and second diagnostic data
associated with the second time period. The at least one treatment
stimulation parameter can approximate the first set of test
stimulation parameters or the second set of test stimulation
parameters. The at least one treatment stimulation parameter can be
associated with a desired treatment of the at least one of a
neurological disease or a neurological disorder. The at least one
treatment stimulation parameter can be associated with a desired
memory recall by the patient. The at least one treatment
stimulation parameter can be associated with at least one of
prevention or reduction of an adverse event. The adverse event can
comprise an event selected from the group consisting of:
undesirable heart rate; undesirable respiration rate; undesirable
sweating; undesirable hallucinations; undesirable tingling;
flushing; undesirable psychiatric effect; undesirable cognitive
effect; unpleasant generalized warming; undesirable perceptions
described as deja vu; seizure; synchronized neuronal firing
pattern; undesired neural response time; undesired brain state;
undesired theta phase; undesired p300 amplitude; and combinations
thereof. The first time period and the second time period can
comprise approximately the same length of time. At least one of the
first time period or the second time period can comprise a time
period of less than or equal to 24 hours, such as a time period of
less than or equal to 6 hours, 3 hours, 1 hour, 30 minutes, 15
minutes, 10 minutes, 5 minutes or 2 minutes. The diagnostic tool
can comprise a memory test device. The memory test device can
comprise a form for recording memory test data. The at least one
treatment stimulation parameter can approximate the set of test
stimulation parameters that resulted in a higher test score. The
diagnostic tool can comprise a diagnostic device. At least one of
the first set of test stimulation parameters or the second set of
test stimulation parameters can be determined based on diagnostic
data produced by the diagnostic tool.
[0012] In some embodiments, at least one of the stimulation
parameters comprises an electrical stimulation parameter selected
from the group consisting of: voltage level such as an average
voltage level, root mean square (rms) voltage level and/or a peak
voltage level; current level such as an average current level, rms
current level and/or a peak current level; power level such as an
average power level, rms power level and/or a peak power level;
frequency of stimulation signal; series of frequencies of the
stimulation signal; phase of stimulation signal; pulse width
modulation ratio; signal pulse width; current density such as
current density applied to tissue; single electrode selected to
receive stimulation energy; set of electrodes selected to receive
monopolar and/or bipolar stimulation energy; and combinations
thereof.
[0013] In some embodiments, the stimulator comprises a brain
inserted lead comprising multiple electrodes, and at least one of
the stimulation parameters comprises a subset of electrodes that
receive stimulating energy. The subset of electrodes can comprise a
single electrode. The subset of electrodes can comprise a pair of
electrodes.
[0014] In some embodiments, at least one of the stimulation
parameters comprises a signal voltage ranging between 0.1 Volts and
10.0 Volts. The at least one stimulation parameter can comprise a
signal voltage ranging between 1.0 Volts and 6.0 Volts, such as a
voltage between 1.0 Volts and 3.0 Volts. The at least one
stimulation parameter can comprise a voltage of less than or equal
to 9.0 Volts, such as a stimulation parameter comprising a voltage
of less than or equal to 8.0 Volts, 7.0 Volts, 6.0 Volts, 5.0
Volts, 4.0 Volts or 3.5 Volts.
[0015] In some embodiments, at least one of the stimulation
parameters comprises a signal frequency ranging between 2 Hz and
1000 Hz. The at least one stimulation parameter can comprise a
signal frequency of approximately 130 Hz.
[0016] In some embodiments, at least one test stimulation parameter
comprises a signal pulse width ranging between 30 microseconds and
150 microseconds. The at least one test stimulation parameter can
comprise a signal pulse width of approximately 90 microseconds.
[0017] In some embodiments, at least one of the stimulation
parameters comprises a light stimulation parameter selected from
the group consisting of: power of light delivered to tissue;
frequency of light delivered to tissue; a modulation parameter of
light delivered to tissue; and combinations thereof.
[0018] In some embodiments, at least one of the stimulation
parameters comprises a sound stimulation parameter selected from
the group consisting of: amplitude of sound delivered to tissue;
frequency of sound delivered to tissue; a modulation parameter of
sound delivered to tissue; and combinations thereof.
[0019] In some embodiments, at least one of the stimulation
parameters comprises an agent delivery stimulation parameter
selected from the group consisting of: mass of agent delivered to
tissue; volume of agent delivered to tissue; concentration of agent
delivered to tissue; delivery rate of agent delivered to tissue;
and combinations thereof.
[0020] In some embodiments, the controller is constructed and
arranged to set at least one stimulation parameter based on a
threshold at which an adverse event is detected by the diagnostic
tool. The adverse event can comprise an event selected from the
group consisting of: undesirable heart rate; undesirable
respiration rate; undesirable sweating; undesirable hallucinations;
undesirable tingling; flushing; undesirable psychiatric effect;
undesirable cognitive effect; unpleasant generalized warming;
undesirable perceptions described as deja vu; seizure; synchronized
neuronal firing pattern; undesired neural response time; undesired
brain state; undesired theta phase; undesired p300 amplitude; and
combinations thereof. The at least one stimulation parameter can be
set using a safety margin, such as a safety margin of at least 10%,
or at least 20%, 30%, 40% or 50%. The at least one stimulation
parameter set based on the adverse event threshold can comprise the
at least one treatment stimulation parameter. The at least one
stimulation parameter set based on the adverse event threshold can
comprise the at least one test stimulation parameter.
[0021] In some embodiments, the controller is constructed and
arranged to set at least one stimulation parameter based on a
threshold at which a desired event was detected by the diagnostic
tool. The desired event can comprise an event selected from the
group consisting of: recall of a desired memory; achievement of
desired memory learning; desired level of neuronal activity;
acceptable physiologic condition such as an acceptable heart rate
or acceptable level of neuronal activity; experiential phenomena
such as those described in epilepsy literature; and combinations
thereof. The at least one stimulation parameter set based on the
desired event threshold can comprise the at least one treatment
stimulation parameter. The at least one stimulation parameter set
based on the desired event threshold can comprise the at least one
test stimulation parameter.
[0022] In some embodiments, the system is constructed and arranged
to provide open loop stimulation.
[0023] In some embodiments, the system is constructed and arranged
to provide closed loop stimulation. The closed loop stimulation can
be provided based on the diagnostic data produced by the diagnostic
tool. The system can further comprise a sensor for producing a
signal, wherein the closed loop stimulation is provided based on
the sensor signal.
[0024] In some embodiments, the measuring performed by the
diagnostic tool comprises a function selected from the group
consisting of: recording; gathering; assessing; collecting;
determining; processing; combining; and combinations thereof.
[0025] In some embodiments, the diagnostic tool is constructed and
arranged to detect an adverse event. The adverse event can comprise
an event selected from the group consisting of: undesirable heart
rate; undesirable respiration rate; undesirable sweating;
undesirable hallucinations; undesirable tingling; flushing;
undesirable psychiatric effect; undesirable cognitive effect;
unpleasant generalized warming; undesirable perceptions described
as deja vu; seizure; synchronized neuronal firing pattern;
undesired neural response time; undesired brain state; undesired
theta phase; undesired p300 amplitude; and combinations
thereof.
[0026] In some embodiments, the diagnostic tool comprises a device
selected from the group consisting of: heart rate monitor; EKG
measurement device; oximeter; combined heart rate and oximeter
device such as a pulse oximeter; blood pressure measurement device;
neuronal activity measurement device; EEG measurement device;
evoked response potential (ERP) measurement device; neurochemical
analysis device; memory test device; memory test form; respiration
measurement device; sweat measurement device; skin conductivity
measurement device; pH measurement device; body motion measurement
device; imaging device; and combinations thereof.
[0027] In some embodiments, the diagnostic tool comprises at least
two devices selected from the group consisting of: heart rate
monitor; EKG measurement device; oximeter; combined heart rate and
oximeter device such as a pulse oximeter; blood pressure
measurement device; neuronal activity measurement device; EEG
measurement device; evoked response potential (ERP) measurement
device; neurochemical analysis device; memory test device; memory
test form; respiration measurement device; sweat measurement
device; skin conductivity measurement device; pH measurement
device; body motion measurement device; imaging device; and
combinations thereof. The diagnostic tool can comprise at least a
heart rate monitor and a blood pressure measurement device. The
diagnostic tool can be constructed and arranged to detect a patient
issue. The patient issue can comprise an inaccurate representation
made by the patient detected by at least one of heart rate data or
blood pressure data.
[0028] In some embodiments, the diagnostic tool comprises an EKG
measurement device. At least one stimulation parameter can be set
based on detection of undesired EKG activity by the diagnostic
tool.
[0029] In some embodiments, the diagnostic tool comprises a
neuronal activity measurement device. The neuronal activity
measurement device can be constructed and arranged to measure a
neuronal parameter selected from the group consisting of: single
neuron activity; local field potential; event related potentials;
electroencephalogram readings; electrocorticogram readings; and
combinations thereof. At least one stimulation parameter can be set
based on the detection of a condition selected from the group
consisting of: seizure; synchronized neuronal firing pattern;
undesired neural response time; undesired brain state; undesired
theta phase; undesired p300 amplitude; and combinations
thereof.
[0030] In some embodiments, the diagnostic tool comprises an ERP
measurement device. At least one stimulation parameter can be set
based on the detection of undesired ERP activity by the diagnostic
tool.
[0031] In some embodiments, the diagnostic tool comprises a blood
pressure measurement device. At least one stimulation parameter can
be set based on the detection of an undesired blood pressure
reading by the diagnostic tool.
[0032] In some embodiments, the diagnostic tool comprises a blood
oxygen measurement device. At least one stimulation parameter can
be set based on the detection of an undesired blood oxygen reading
by the diagnostic tool.
[0033] In some embodiments, the diagnostic tool comprises a body
motion measurement device. At least one stimulation parameter can
be set based on the detection of an undesired body motion detected
by the diagnostic tool. The undesired body motion can comprise a
tremor.
[0034] In some embodiments, the diagnostic tool comprises a
neurochemical analysis device. The neurochemical analysis device
can be constructed and arranged to measure a patient parameter
selected from the group consisting of: a neurotransmitter level; a
pH concentration; an ion concentration; a lactate level; cerebral
blood flow; glucose utilization; oxygen extraction; and
combinations thereof. At least one stimulation parameter can be set
based on the detection of at least one of an undesired
neurochemical activity or an undesired neurochemical level.
[0035] In some embodiments, the diagnostic tool comprises an
imaging device. The stimulator can comprise multiple stimulating
elements and at least one stimulation parameter can comprise at
least one stimulating element selected to deliver stimulation
energy. The stimulator can comprise multiple stimulating electrodes
and at least one stimulation parameter can comprise at least one
stimulating electrode selected to deliver electrical stimulation
energy. The at least one stimulating electrode can be selected
based on its position relative to tissue to be stimulated. The
tissue to be stimulated can comprise at least the fornix.
[0036] In some embodiments, the diagnostic tool comprises an
algorithm for analyzing a patient assessment.
[0037] In some embodiments, the diagnostic tool comprises a patient
assessment recording tool. The patient assessment recording tool
can comprise a tool selected from the group consisting of: form; a
paper form; electronic form; tablet; personal computer; database;
and combinations thereof. The patient assessment can comprise an
assessment selected from the group consisting of: an assessment
received verbally from the patient; an assessment received in
written form from the patient; an assessment made by a caregiver of
the patient; and combinations thereof. The patient assessment can
comprise an assessment of the patient state selected from the group
consisting of: depression; paranoia; schizophrenia; suicidality;
suicide ideation; apathy; anxiety; mania; and combinations
thereof.
[0038] In some embodiments, the diagnostic tool comprises a sensor
constructed and arranged to sense, record or otherwise produce the
diagnostic data. The sensor can comprise at least one sensing
element selected from the group consisting of: neuronal activity
sensor; EEG sensor; local field potential sensor; neurochemical
sensor; pH sensor; pressure sensor; blood pressure sensor; an
optical sensor; blood gas sensor; blood oxygen sensor; a magnetic
sensor; a strain gauge; and combinations thereof. The sensor can
comprise an implanted sensor. The sensor can be further constructed
and arranged to stimulate brain tissue. The sensor can comprise at
least one electrode.
[0039] In some embodiments, at least a first portion of the
stimulator is constructed and arranged to be implanted in the
patient and the system can be constructed and arranged to collect
the diagnostic data after implantation of the stimulator first
portion. The diagnostic data can be collected at least 5 minutes
after implantation of the stimulator first portion, such as at
least 24 hours or at least two weeks after implantation of the
stimulator first portion.
[0040] In some embodiments, the system further comprises a
stimulation threshold, and the at least one treatment stimulation
parameter is set based on the stimulation threshold. The at least
one treatment stimulation can be set using a safety margin.
[0041] In some embodiments, the system further comprises a
stimulation threshold, and the at least one treatment stimulation
parameter is modified based on the stimulation threshold. The at
least one treatment stimulation parameter can be modified using a
safety margin.
[0042] In some embodiments, the at least one of a neurological
disease or disorder comprises a disease or disorder selected from
the group consisting of: Alzheimer's Disease (AD) such as Mild or
Moderate Alzheimer's Disease; probable Alzheimer's Disease; a
genetic form of Alzheimer's Disease; Mild Cognitive Impairment
(MCI); hippocampal damage such as hippocampal damage due to
Alzheimer's disease, anoxia, epilepsy or depression; neuronal loss;
neuronal damage; chemotherapy induced memory impairment; epilepsy;
a seizure disorder; dementia; amnesia; a memory disorder such a
spatial memory disorder; cognitive impairment associated with
Schizophrenia; Parkinson's Disease related cognitive impairment or
dementia; and combinations thereof.
[0043] In some embodiments, the system is constructed and arranged
to treat at least one of: negative symptoms of schizophrenia;
negative symptoms of depression; a condition of reversible impaired
memory; or a condition of reversible impaired cognition.
[0044] In some embodiments, the system is constructed and arranged
to treat at least one neurological disease and at least one
neurological disorder. In some embodiments, the system is
constructed and arranged to treat multiple neurological diseases.
In some embodiments, the system is constructed and arranged to
treat multiple neurological disorders. In some embodiments, the
system is constructed and arranged to regulate the level of one or
more neurotrophic factors and/or neurotransmitters. In some
embodiments, the system is constructed and arranged to ameliorate
cognitive decline associated with dementia.
[0045] In some embodiments, the patient has reduced integrity of
white matter tracts innervating limbic structures such as the
fornix as determined by fractional anisotropy maps using diffusion
tensor imaging. The innervated limbic structures can comprise at
least the fornix.
[0046] In some embodiments, the system is constructed and arranged
to achieve at least one of: treats memory impairment; improves
memory function; treats cognitive function loss; reverses synaptic
loss; improves cognitive function; reduces degradation of cognitive
function; promotes neurogenesis in the hippocampus of the patient's
brain; drives neurotrophin expression; regulates one or more
biomarkers related to Alzheimer's Disease such as amyloid-beta,
tau, and/or phosphorylated tau; regulates BDNF expression;
increases neurotransmitter release such as acetylcholine; or
improves glucose utilization in the temporal lobe, the parietal
lobe or both lobes of the patient's brain.
[0047] In some embodiments, the brain tissue stimulated comprises
tissue selected from the group consisting of: fornix; entorhinal
cortex; hippocampus; anterior thalamic nucleus; amygdala;
mammillary bodies; parahippocampal cortex; temporal neocortex;
septal nuclei; nucleus basalis of Meynert; subcallosal or subgenual
cingulate; ventral capsule; ventral striatum and combinations
thereof. In some embodiments, the brain tissue stimulated comprises
brain tissue selected from the group consisting of: Papez Circuit;
hippocampus; cingulate gyms; fornix; a mammilothalamic tract;
amygdala; hypothalamus; mammillary bodies; septal nuclei; temporal
neocortex; the medial forebrain bundle; anterior and mediodorsal
nuclei of the thalamus; the diagonal band of the Broca; temporal
stem and temporal white matter; brainstem; nucleus basalis of
Meynert; anterior thalamic nucleus; entorhinal cortex; rhinal
cortex; periventricular zone; anterior thalamus; anterior insula;
caudate; dorsal anterior cortex; dorsal cingulate; medial frontal
cortex; nucleus accumbens; orbital frontal cortex; parietal region;
periaqueductal gray area; posterior cingulate area; subcallosal
area; subcallosal cingulate; subgenual cingulate; Brodmann area 10;
Brodmann area 24; Brodmann area 25; Brodmann area 11/Brodmann area
10; Brodmann area 24b; Brodmann area 31; Brodmann area 32/Brodmann
area 10; Brodmann area 32/Brodmann area 11; Brodmann area 39;
Brodmann area 46; Brodmann area 46/Brodmann area 9; Brodmann area
47; Brodmann area 6; Brodmann area 9; ventral/medial prefrontal
cortex area; ventral/medial white matter; dorsolateral prefrontal
cortex; premotor cortex; ventrolateral prefrontal cortex; dorsal
anterior cingulate caudate nucleus; frontal pole periaqueductal
gray area; dorsolateral prefrontal area; subsingular cingulate;
parahippocampal cortex; parahippocampal gyms; ventral capsule;
ventral striatum; and combinations thereof. In some embodiments,
the brain tissue stimulated does not comprise tissue selected from
the group consisting of: hippocampal tissue; optical tract tissue;
and combinations thereof. In some embodiments, the brain tissue
stimulated does not comprise tissue selected from the group
consisting of: posterior hypothalamic area; ventral tegmental area;
lateral hypothalamic area; anterior hypothalamic nucleus;
paraventricular nucleus; dorsal medial hypothalamic nucleus;
ventromedial hypothalamic nucleus; arcuate nucleus; lateral tuberal
nucleus; medial preoptic nucleus; supraoptic nucleus; and
combinations thereof.
[0048] In some embodiments, the stimulator comprises at least an
implanted portion. The at least an implanted portion can comprise
at least one electrode constructed and arranged to stimulate brain
tissue. The at least one electrode can comprise an electrode
selected from the group consisting of: single component bipolar
electrode; multiple unipolar electrodes; stacked contact
electrodes; discrete electrodes, an electrode strip, a grid of
electrodes; paddle electrode; high-density/high channel or lead
count micro-electrodes; and combinations thereof. The at least one
electrode can comprise at least one electrode positioned in brain
tissue. The at least one electrode can comprise at least one
electrode positioned proximate the fornix. The at least one
electrode can comprise two electrodes constructed and arranged to
be placed bilaterally about the fornix. The at least one electrode
can comprise at least one electrode positioned in a location to
cause stimulation of the fornix. The at least one electrode can
comprise multiple electrodes. The at least one electrode can
comprise an electrode constructed and arranged for monopolar
delivery of electrical energy. The at least one electrode can
comprise an electrode constructed and arranged for multipolar
delivery of electrical energy. The at least an implanted portion
can comprise an implanted stimulation element selected from the
group consisting of: electrode such as one or more electrodes
configured to deliver electrical stimulation energy; magnetic field
delivery element; light delivery element such as a visible,
ultraviolet or infrared light delivery element; optogenetic
delivery element; sound delivery element such as a subsonic wave or
ultrasound wave delivery element; agent delivery element such as a
chemical or pharmaceutical agent delivery element; and combinations
thereof. The system can further comprise an energy generating
element constructed and arranged to deliver energy selected from
the group consisting of: electromagnetic energy such as electrical
energy and/or or magnetic energy; light energy such as visible,
ultraviolet and/or infrared light energy; sound energy such as
subsonic, sonic or ultrasound energy; and combinations thereof. The
at least an implanted portion can comprise an implanted signal
generator.
[0049] In some embodiments, the stimulator comprises at least an
external portion. The at least an external portion can comprise an
external stimulation element. The external stimulation element can
comprise an electromagnetic field generator. The external
stimulation element can comprise a sound generator. The external
stimulation element can comprise a light energy generator. The at
least an external portion can comprise an electrical signal
generator. The stimulator can further comprise an implanted
stimulation element electrically connected to the electrical signal
generator. The implanted stimulation element can comprise at least
one electrode.
[0050] In some embodiments, the stimulator comprises an implanted
portion and an external portion.
[0051] In some embodiments, the stimulator is constructed and
arranged to stimulate tissue with electrical stimulation.
[0052] In some embodiments, the stimulator is constructed and
arranged to stimulate tissue with a stimulation energy selected
from the group consisting of: electrical stimulation; magnetic
stimulation; optical stimulation such as visible, ultraviolet or
infrared light stimulation; sound stimulation such as ultrasound or
subsonic wave stimulation; chemical stimulation such as stimulation
from a drug or other agent; and combinations thereof.
[0053] In some embodiments, the stimulator is constructed and
arranged to stimulate the brain tissue in a continuous stimulation
mode. In some embodiments, the stimulator is constructed and
arranged to stimulate the brain tissue in a cyclical stimulation
mode.
[0054] In some embodiments, the stimulator is further constructed
and arranged to stimulate non-brain tissue. The non-brain tissue
can comprise non-brain nerve tissue. The non-brain tissue can
comprise non-brain organ tissue. The non-brain tissue can comprise
tissue selected from the group consisting of: vagus nerve;
trigeminal nerve; carotid sinus; spinal cord; dorsal root ganglia;
tibial nerve; sacral nerve; gastric nerve; and combinations
thereof.
[0055] In some embodiments, the stimulator comprises at least a
portion of the diagnostic tool.
[0056] In some embodiments, the stimulator comprises at least one
sensor.
[0057] In some embodiments, the controller is constructed and
arranged to transmit information to the stimulator via wireless
communication.
[0058] In some embodiments, the controller comprises at least a
portion of the diagnostic tool.
[0059] In some embodiments, the controller comprises an algorithm
for analyzing the diagnostic data produced by the diagnostic tool.
The algorithm can be constructed and arranged to compare the
diagnostic data to a threshold. The algorithm can be constructed
and arranged to set the at least one treatment stimulation
parameter based on a safety margin.
[0060] According to another aspect of the present inventive
concepts, a method for treating a patient comprises selecting a
patient and providing a stimulation system. The stimulation system
comprises a stimulator; a controller; and a diagnostic tool. The
method further includes measuring at least one patient parameter
with the diagnostic tool and producing diagnostic data representing
the at least one measured patient parameter; and setting a
stimulation parameter of the system with the controller based on
the diagnostic data. The method is constructed and arranged to
treat at least one of a neurological disease or a neurological
disorder.
[0061] In some embodiments, the system, stimulator, controller
and/or diagnostic tool are constructed and arranged as described
hereabove.
[0062] In some embodiments, the method further comprises implanting
at least a portion of the stimulator in the patient. The method can
further comprise performing an MRI procedure prior to and/or during
the stimulator implantation to produce at least one MRI image,
wherein the stimulator comprises a stimulating element that is
implanted relative to a fornix target identified on the at least
one MRI image. Implanting the stimulator can comprise implanting
one or more electrodes in a location selected from the group
consisting of: in the Papez Circuit of the patient's brain;
approximately 2 mm anterior and parallel to the vertical portion of
the fornix; in the optic tract such that the ventral-most contact
is 2 mm above the dorsal surface of the optic tract; approximately
5 mm from the midline; and combinations thereof.
[0063] In some embodiments, the stimulation parameter set comprises
a treatment stimulation parameter.
[0064] In some embodiments, the stimulation parameter set comprises
a test stimulation parameter.
[0065] In some embodiments, the stimulation parameter is set using
a safety margin.
[0066] The technology described herein, along with the attributes
and attendant advantages thereof, will best be appreciated and
understood in view of the following detailed description taken in
conjunction with the accompanying drawings in which representative
embodiments are described by way of example.
BRIEF DESCRIPTION OF THE DRAWINGS
[0067] The foregoing and other objects, features and advantages of
embodiments of the present inventive concepts will be apparent from
the more particular description of preferred embodiments, as
illustrated in the accompanying drawings in which like reference
characters refer to the same or like elements. The drawings are not
necessarily to scale, emphasis instead being placed upon
illustrating the principles of the preferred embodiments.
[0068] FIG. 1 illustrates a schematic view of a system for
stimulating one or more portions of a patient's brain, consistent
with the present inventive concepts.
[0069] FIG. 2 illustrates a flow chart of a method for treating a
patient with a brain stimulation system, consistent with the
present inventive concepts.
[0070] FIG. 3 illustrates a flow chart of a series of steps for
performing the diagnostic test of FIG. 2, consistent with the
present inventive concepts.
[0071] FIG. 4 illustrates a schematic of an electrical brain
stimulator, consistent with the present inventive concepts.
DETAILED DESCRIPTION OF THE DRAWINGS
[0072] The terminology used herein is for the purpose of describing
particular embodiments and is not intended to be limiting of the
inventive concepts. As used herein, the singular forms "a," "an"
and "the" are intended to include the plural forms as well, unless
the context clearly indicates otherwise.
[0073] It will be further understood that the words "comprising"
(and any form of comprising, such as "comprise" and "comprises"),
"having" (and any form of having, such as "have" and "has"),
"including" (and any form of including, such as "includes" and
"include") or "containing" (and any form of containing, such as
"contains" and "contain") when used herein, specify the presence of
stated features, integers, steps, operations, elements, and/or
components, but do not preclude the presence or addition of one or
more other features, integers, steps, operations, elements,
components, and/or groups thereof.
[0074] It will be understood that, although the terms first,
second, third etc. may be used herein to describe various
limitations, elements, components, regions, layers and/or sections,
these limitations, elements, components, regions, layers and/or
sections should not be limited by these terms. These terms are only
used to distinguish one limitation, element, component, region,
layer or section from another limitation, element, component,
region, layer or section. Thus, a first limitation, element,
component, region, layer or section discussed below could be termed
a second limitation, element, component, region, layer or section
without departing from the teachings of the present
application.
[0075] It will be further understood that when an element is
referred to as being "on", "attached", "connected" or "coupled" to
another element, it can be directly on or above, or connected or
coupled to, the other element or intervening elements can be
present. In contrast, when an element is referred to as being
"directly on", "directly attached", "directly connected" or
"directly coupled" to another element, there are no intervening
elements present. Other words used to describe the relationship
between elements should be interpreted in a like fashion (e.g.,
"between" versus "directly between," "adjacent" versus "directly
adjacent," etc.).
[0076] Spatially relative terms, such as "beneath," "below,"
"lower," "above," "upper" and the like may be used to describe an
element and/or feature's relationship to another element(s) and/or
feature(s) as, for example, illustrated in the figures. It will be
understood that the spatially relative terms are intended to
encompass different orientations of the device in use and/or
operation in addition to the orientation depicted in the figures.
For example, if the device in a figure is turned over, elements
described as "below" and/or "beneath" other elements or features
would then be oriented "above" the other elements or features. The
device can be otherwise oriented (e.g., rotated 90 degrees or at
other orientations) and the spatially relative descriptors used
herein interpreted accordingly.
[0077] The term "and/or" where used herein is to be taken as
specific disclosure of each of the two specified features or
components with or without the other. For example "A and/or B" is
to be taken as specific disclosure of each of (i) A, (ii) B and
(iii) A and B, just as if each is set out individually herein.
[0078] It is appreciated that certain features of the invention,
which are, for clarity, described in the context of separate
embodiments, may also be provided in combination in a single
embodiment. Conversely, various features of the invention which
are, for brevity, described in the context of a single embodiment,
may also be provided separately or in any suitable
sub-combination.
[0079] For example, it will be appreciated that all features set
out in any of the claims (whether independent or dependent) can be
combined in any given way.
[0080] The systems, devices and methods of the present inventive
concepts are applicable to treat a patient, such as to treat one or
more cognitive disorders of a patient. The cognitive disorders
include but are not limited to: Alzheimer's Disease (AD) such as
Mild or Moderate Alzheimer's Disease; probable Alzheimer's Disease;
a genetic form of Alzheimer's Disease; Mild Cognitive Impairment
(MCI); hippocampal damage such as hippocampal damage due to
Alzheimer's disease, anoxia, epilepsy or depression; neuronal loss;
neuronal damage; chemotherapy induced memory impairment; epilepsy;
a seizure disorder; dementia; amnesia; a memory disorder such a
spatial memory disorder; cognitive impairment associated with
Schizophrenia; Parkinson's Disease related cognitive impairment or
dementia; and combinations of these. Additionally or alternatively,
the patient can be selected to treat negative symptoms of a disease
or disorder selected from the group consisting of: schizophrenia;
depression; other conditions of reversible impaired memory or
cognition; and combinations of these.
[0081] In some embodiments, the patient is selected for treatment
as described in applicant's co-pending U.S. application Ser. No.
13/655,652, entitled "Deep Brain Stimulation of Memory Circuits in
Alzheimer's Disease", filed Oct. 19, 2012, the contents of which is
incorporated herein by reference in its entirety.
[0082] As used herein, the term "wired pathway" shall refer to an
energy and/or information transmission pathway including a physical
conduit such as a flexible conduit comprising: one or more wires;
one or more optical (e.g. light transmitting) fibers; one or more
fluid delivery tubes; and combinations of these.
[0083] As used herein, the term "wireless" or "wireless pathway"
shall refer to an energy and/or information transmission pathway
that does not include or otherwise rely on a physical conduit for
transmission, such as an electromagnetic or light transmission of
energy and/or information that passes through the tissue of a
patient without the use of a physical conduit.
[0084] Referring now to FIG. 1, a system for stimulating a
patient's brain is illustrated, consistent with the present
inventive concepts. System 10 includes stimulator 100, controller
200 and diagnostic tool 300. System 10 can be constructed and
arranged to treat a neurological disease, a neurological disorder
and/or another patient disease or disorder, as described in detail
herebelow. Stimulator 100 is configured to stimulate tissue, such
as to stimulate at least a portion of patient P's brain B, such as
via pathway 40. Controller 200 is configured to initiate and/or
adjust (hereinafter "set" or "setting") one or more stimulation
parameters of stimulator 100, such as one or more test stimulation
parameters 106 and/or one or more treatment stimulation parameters
107 (collectively or singly referred to as "stimulation parameters"
105), also as described in detail herebelow. Diagnostic tool 300 is
constructed and arranged to measure one or more patient parameters,
and to produce diagnostic data 305 representing the measured
patient parameters. The measuring of diagnostic data 305 by
diagnostic tool 300 can include but is not limited to performing a
data measurement function selected from the group consisting of:
recording; gathering; assessing; collecting; determining;
processing; combining; and combinations of these.
[0085] In some embodiments, system 10 is constructed and arranged
to treat a neurological disease and/or disorder selected from the
group consisting of: probable Alzheimer's Disease; a genetic form
of Alzheimer's Disease; Mild Cognitive Impairment; hippocampal
damage such as hippocampal damage due to Alzheimer's Disease,
anoxia, epilepsy or depression; dementia; amnesia; a memory
disorder such as a spatial memory disorder; cognitive impairment
associated with Schizophrenia; Parkinson's Disease related
cognitive impairment or dementia; neuronal loss; neuronal damage;
chemotherapy induced memory impairment; epilepsy; seizure disorder;
and combinations of these. In some embodiments, system 10 is
constructed and arranged to treat multiple neurological diseases,
multiple neurological disorders and/or at least one neurological
disease and at least one neurological disorder.
[0086] System 10 can be constructed and arranged such that
stimulator 100 delivers test stimulation energy to brain B based on
one or more test stimulation parameters 106. System 10 can be
further constructed and arranged to deliver treatment stimulation
energy to brain B based on one or more treatment stimulation
parameters 107, such as when the treatment stimulation parameters
107 are based on the diagnostic data 305 produced by diagnostic
tool 300. In some embodiments, stimulator 100 is constructed and
arranged as is described in reference to stimulator 100 of FIG. 4
described herebelow. In some embodiments, system 10 is used as is
described in reference to the method of FIG. 2 herebelow.
[0087] Pathway 40 can comprise a wired or wireless pathway as
described in detail herein. Stimulator 100 can comprise an
implantable stimulator, an external (e.g. non-implanted)
stimulator, or it can comprise both implantable and external
portions. Controller 200 is configured to communicate with
stimulator 100, via pathway 20, such as to set one or more
stimulation parameters 105 of stimulator 100. Pathway 20 can
comprise a wired or wireless pathway as described herein.
Stimulator 100 can comprise a user interface 101, such as a user
interface 101 positioned on an external portion of stimulator 100.
In some embodiments, system 10 is constructed and arranged such
that communication (e.g. wired or wireless communication) can occur
between controller 200 and diagnostic tool 300, such as to transfer
diagnostic data 305 and/or one or more stimulation parameters
105.
[0088] One or more components of system 10 can include another
component of system 10, such as when one or more of at least a
portion of stimulator 100, controller 200 and diagnostic tool 300
are combined (e.g. within a common housing). For example, at least
a portion of stimulator 100 can comprise at least a portion of
controller 200, such as when stimulator 100 includes an external
portion comprising user interface 101 which is configured to set
one or more stimulation parameters 105. In some embodiments, at
least a portion of stimulator 100 can comprise at least a portion
of diagnostic tool 300, such as when stimulator 100 comprises one
or more sensors 430 constructed and arranged to record one or more
patient parameters, such as are described in detail herebelow. In
some embodiments, one or more sensors 430 are further constructed
and arranged to stimulate tissue such as brain tissue. In some
embodiments, at least a portion of controller 200 comprises at
least a portion of diagnostic tool 300, such as when controller 200
comprises one or more sensors 230 (also as described in detail
herebelow) constructed and arranged such that controller 200 can
function as a heart rate monitor, a blood pressure monitor and/or
other diagnostic tool configured to produce diagnostic data
305.
[0089] Diagnostic tool 300 is constructed and arranged to record,
gather, assess, collect, determine and/or otherwise measure one or
more patient parameters and produce diagnostic data 305
representing these one or more patient parameters. Diagnostic tool
300 can be further constructed and arranged to process (e.g.
mathematically process) and/or combine measured data, such as when
diagnostic tool 300 comprises one or more algorithms configured to
analyze diagnostic data 305, such as one or more algorithms that
compare diagnostic data 305 to one or more "stimulation thresholds"
(as described herebelow) and record one or more stimulation
parameters associated with the one or more stimulation thresholds.
In some embodiments, an algorithm is constructed and arranged to
determine a stimulation threshold correlating to an undesired
clinical event or other undesired patient event (hereinafter
"adverse event") as described herein. In some embodiments, an
algorithm is constructed and arranged to determine a stimulation
threshold correlating to a desired clinical event or other desired
patent event (hereinafter "desired event"), such as an event in
which a desired memory recall occurs, a desired memory learning is
achieved and/or other desired event takes place, as described
herebelow.
[0090] System 10 (e.g. automatically or semi-automatically) and/or
an operator of system 10 can use the diagnostic data 305 to set
and/or modify the stimulation provided by stimulator 100. Setting
of one or more treatment stimulation parameters 107 using or
otherwise based on diagnostic data 305 can be performed to improve
therapy achieved by system 10, as described in detail herebelow.
Alternatively or additionally, setting of one or more treatment
stimulation parameters 107 using or otherwise based on diagnostic
data 305 can be performed to at least one of reduce and/or prevent
(hereinafter "reduce") an adverse event for patient P, also as is
described in detail herebelow. Diagnostic data 305 can be used to
determine if an adverse event has occurred or is about to occur.
Alternatively or additionally, diagnostic data 305 can be used to
determine if a desired event has occurred or is about to occur. In
each of these instances, the test stimulation parameters 106
causing the adverse event or desired event represent a stimulation
threshold for that particular event.
[0091] In some embodiments, a treatment stimulation parameter 107
is set at a level below or otherwise away from (hereinafter
"below") the stimulation threshold that caused an adverse event
(e.g. as determined in a diagnostic test of the present inventive
concepts). In these embodiments, the term "below" does not
necessarily correlate to a lower magnitude of stimulation energy,
but represents a lower, greater or different value that tends
toward avoiding occurrence of the adverse event. For example, if
flow rates of 5 ml/hr or less of an agent infused by an external
stimulation element 150a (e.g. via a catheter) or an implanted
stimulation element 150b, each described herebelow, caused an
adverse event, treatment stimulation parameter 107 could be set to
a level of more than 5 ml/hr to avoid the adverse event. In some
embodiments, a treatment stimulation parameter 107 is set at a
safety margin below the stimulation threshold (e.g. a voltage or
current level that is less than the level causing the adverse
event). In some embodiments, an approximate 50% safety margin is
used (e.g. a voltage or current is set to approximately half the
voltage or current causing the adverse event). In other
embodiments, a safety margin of at least 10% is used, such as a
safety margin of at least 20%, 30%, 40% or 50%.
[0092] In some embodiments, a treatment stimulation parameter 107
is set at a level at or above (hereinafter "above") a stimulation
threshold that caused a desired event (e.g. as determined in a
diagnostic test of the present inventive concepts). In these
embodiments, the term "above" does not necessarily correlate to a
higher magnitude of stimulation energy, but represents a higher,
lower or similar value that tends toward causing occurrence of the
desired event.
[0093] Stimulator 100 can comprise stimulation element 150a, which
is configured to generate and/or deliver energy to stimulate brain
B or other tissue of patient P. In some embodiments, stimulator 100
further comprises stimulation element 150b, which can also be
configured to generate and/or deliver energy to stimulate brain B
or other tissue of the patient. Stimulation elements 150a and/or
150b, collectively or singly referred to as "stimulation element
150", can comprise a stimulation delivery element configured to
deliver stimulation energy and/or to otherwise stimulate one or
more portions of brain B or other tissue of patient P.
Alternatively or additionally, stimulation element 150 can comprise
a stimulation energy generating element configured to produce
energy to stimulate tissue. In some embodiments, stimulation
element 150a comprises a stimulation generating element that
delivers energy to stimulation element 150b configured as a
stimulation delivery element, such as when stimulation element 150b
comprises one or more electrodes which receive electrical energy
from stimulation element 150a.
[0094] In some embodiments, a stimulation element 150 comprises one
or more stimulation delivery elements selected from the group
consisting of: electrode such as one or more electrodes configured
to deliver electrical stimulation energy; magnetic field delivery
element; light delivery element such as a visible, ultraviolet or
infrared light delivery element; optogenetic delivery element;
sound delivery element such as a subsonic wave or ultrasound wave
delivery element; agent delivery element such as a chemical or
pharmaceutical agent delivery element; and combinations of these.
Alternatively or additionally, stimulation element 150 can comprise
one or more stimulation generating elements constructed and
arranged to deliver a form of energy selected from the group
consisting of: electromagnetic energy such as electrical energy
and/or magnetic energy; light energy such as visible, ultraviolet
and/or infrared light energy; sound energy such as subsonic, sonic
or ultrasound energy; and combinations of these. Alternatively or
additionally, stimulation element 150 can comprise an agent
delivery pump or reservoir; such as a pump configured to deliver a
chemical or pharmaceutical agent through one or more catheters or
other fluid delivery conduits.
[0095] Stimulator 100 can comprise one or more implanted components
(e.g. one or more discrete or otherwise physically separated
components), one or more components external to the patient P's
body, or both at least one implanted component and at least one
external component. Stimulator 100 can comprise two or more
components, such as two or more components connected with a
physical cable including electrically conductive wires and/or
optical fibers, or two or more components which transmit and/or
receive information via wireless transmission. In some embodiments,
stimulator 100 and/or its implanted housing 110 (described
herebelow) are configured as is described in applicant's co-pending
U.S. patent application Ser. No. 13/655,652, entitled "Deep Brain
Stimulation of Memory Circuits in Alzheimer's Disease", filed Oct.
19, 2012, the contents of which is incorporated herein by reference
in its entirety.
[0096] Stimulator 100 can comprise at least one housing, such as
housing 110. Housing 110 can surround electronic components, a
power supply such as a battery, stimulation element 150a, and other
components such as those described in reference to FIG. 4
herebelow. Housing 110 can be constructed and arranged for
implantation in the patient or remain external.
[0097] In some embodiments, stimulator 100 comprises at least an
implanted portion and stimulation element 150a (positioned within
the implanted portion) comprises a signal generator, such as a
signal generator constructed and arranged to deliver electrical
and/or one or more other forms of energy to stimulation element
150b. In these embodiments, energy generated by stimulation element
150a can travel through a wired or wireless pathway 40 (e.g. a
pathway that comprises one or more wires or other energy carrying
conduits which pass under the skin from the chest to the brain) to
deliver stimulating energy to one or more stimulation elements
150b. Stimulation elements 150b can be positioned on, in and/or
proximate patient P's brain B and/or other tissue to be stimulated.
In some embodiments, one or more stimulation elements 150b can be
positioned in a location selected from the group consisting of: a
subdural location; a supradural location; on and/or in the skull;
on and/or in the scalp; and combinations of these.
[0098] In some embodiments, stimulator 100 comprises at least an
external portion and stimulation element 150a is positioned in an
external portion of stimulator 100. In these embodiments, an
externally positioned stimulation element 150a can be configured to
non-invasively deliver energy to tissue. For example, stimulation
element 150a can comprise an electromagnetic field generator, a
sound generator, a light energy generator, or other energy
generator configured to deliver energy non-invasively through the
skin through a wireless pathway 40 (e.g. through the skin and skull
of patient P) to stimulate one or more portions of brain B.
Wireless stimulation transmissions can comprise a transmission
selected from the group consisting of: electromagnetic waves; sound
waves such as ultrasonic and subsonic waves; light waves; and
combinations of these. Non-limiting examples of non-invasive
stimulation devices include: one or more transcranial magnetic
stimulation devices, such as is described in U.S. Pat. No.
7,087,008, entitled "Apparatus and Methods for Delivery of
Transcranial Magnetic Stimulation", filed May 3, 2002, the contents
of which is incorporated herein by reference in its entirety; one
or more external focused energy delivery devices, such as is
described in U.S. patent application Ser. No. 13/169,288, entitled
"Systems and Methods for Stimulating Tissue Using Focused Energy",
filed Jun. 27, 2011, the contents of which is incorporated herein
by reference in its entirety; ultrasound stimulation devices;
optogenetics-based stimulation devices; light-based stimulation
devices; fiber optic based stimulation devices; and combinations of
these.
[0099] Pathway 40 can comprise one or more physical conduits such
as wires, fluid delivery tubes, and/or optical fibers that connect
to one or more electrodes, agent delivery elements and/or other
stimulation delivery elements 150b positioned in and/or proximate
to a location within brain B or other tissue to be stimulated.
Pathway 40 can include a first lead that is positioned to stimulate
a specific site in brain B. In these embodiments, stimulation
elements 150b can comprise one or more electrodes positioned in the
hypothalamic area in proximity to the fornix, and/or at a different
location as described herebelow. Stimulator 100 can take the form
of a fully implanted signal generator, such as a signal generator
similar to signal generator Model 7424, manufactured by Medtronic,
Inc. under the trademark Itrel II. Pathway 40 can comprise one or
more forms, such as any of the leads compatible with the Model 7424
such as Model 3387 lead set, for stimulating brain B. The lead can
be coupled to stimulator 100 by a compatible lead extension.
[0100] Controller 200 can be configured to initiate, adjust and/or
otherwise set at least one test stimulation parameter 106 and/or
treatment stimulation parameter 107, such as a stimulation
parameter selected from the group consisting of: voltage level such
as an average voltage level, rms voltage level and/or a peak
voltage level; current level such as an average current level, rms
current level and/or a peak current level; power level such as an
average power level, rms power level and/or a peak power level;
frequency of stimulation signal; series of frequencies of the
stimulation signal; phase of stimulation signal; pulse width
modulation ratio; signal pulse width; current density such as
current density applied to tissue; single electrode selected to
receive stimulation energy; set of electrodes selected to receive
monopolar and/or bipolar stimulation energy; agent delivery rate;
physiologic concentration; power of light delivered to tissue;
frequency of light delivered to tissue; a modulation parameter of
light delivered to tissue; amplitude of sound delivered to tissue;
frequency of sound delivered to tissue; a modulation parameter of
sound delivered to tissue; mass of agent delivered to tissue;
volume of agent delivered to tissue; concentration of agent
delivered to tissue; delivery rate of agent delivered to tissue;
and combinations of these. System 10 test stimulation parameters
106 and/or treatment stimulation parameters 107 can be set by
signals sent from controller 200 to stimulator 100 via pathway
20.
[0101] In some embodiments, stimulation element 150b comprises up
to four implanted stimulation electrodes, such as four electrodes
implanted into a portion of brain B using conventional stereotactic
surgical techniques. In some embodiments, stimulation element 150b
comprises two or more electrodes spaced approximately 1.5 mm apart.
Each of the up to four electrodes (stimulation elements 150b) can
be individually connected to stimulator 100 through pathway 40
including a first lead with at least one conductor. The first lead
can be surgically implanted through a hole in the skull and the at
least one conductor can be implanted between the skull and the
scalp. The lead with the one or more conductors can be electrically
attached to stimulator 100. In some embodiments, at least a portion
of stimulator 100 is implanted in a human body, for example in the
chest, within an arm, and/or in the abdomen of a human body. In
some embodiments, at least a portion of stimulator 100 is implanted
in the chest and pathway 40 comprises one or more conductors that
are implanted subcutaneously along the head, neck and shoulder to
connect a housing of the portion of stimulator 100 implanted in the
chest. Pathway 40 can comprise twin leads, a first lead and a
second lead (e.g. each including one or more conductors), that are
connected to a first electrode (e.g. one or more electrodes) and a
second electrode (e.g. one or more electrodes), respectively, the
two leads implanted into brain B bilaterally (e.g. bilaterally
about the fornix of brain B), with each lead connected to a single
stimulator 100 portion. Alternatively, the second lead and second
electrode can be supplied with stimulating pulses from a separate
stimulator 100 portion (e.g. a second portion implanted in the
chest or other internal location of the patient P). In some
embodiments, first and second leads are also attached (e.g. on the
opposite end) to a stimulation element 150b comprising two or more
electrodes, such as two electrodes positioned in two separate
nuclei that potentiate each other's effects. In some embodiments,
the first and second leads are attached to a stimulation element
150b comprising two electrodes in two separate nuclei with opposite
effects, with the dual stimulation delivered being used to
fine-tune the response through opposing forces. It will be
appreciated, however, that any number of electrodes or other
stimulation elements 150a and/or 150b can be positioned within
brain B, on or proximate to brain B, remote from brain B, and/or
external to the patient P's body, in accordance with the present
inventive concepts. Additionally, one or more secondary electrodes
or secondary stimulation elements can be implanted or otherwise
positioned so that a secondary stimulation portion lies in
communication with another predetermined portion of a brain.
[0102] System 10 can be utilized in monopolar and/or multipolar
electrical stimulation configurations (e.g. monopolar, bipolar
and/or stimulation configurations including 3 or more poles). In
some embodiments, system 10 delivers monopolar energy, such as when
housing 110 and at least a portion of stimulator 100 are implanted
in the patient, such that housing 110 can function as a lead (e.g.
a positive lead). In these embodiments, stimulation element 150b
can comprise one or more electrodes positioned in brain B, the one
or more electrodes functioning as the associated lead (e.g. as
negative leads).
[0103] System 10 can be constructed and arranged to provide
stimulation continuously and/or intermittently, such as for a
chronic period of time of at least 1 month, at least 3 months or at
least 6 months. In some cases, stimulation can be provided for a
longer period of time such as 12 months or more. Intermittent
stimulation can include delivery of constant or pulsed stimulation
energy with stimulation "on" times of at least 30 minutes, or at
least 60 minutes. In some embodiments, the constant or pulsed
stimulation energy delivery duty cycle (ratio of "on" time to the
sum of "on" time plus "off" time) ranges from 20% to 80%.
Stimulation can be performed in either an open loop mode or a
closed loop mode. In some embodiments, stimulation is initiated
and/or modified to achieve an acute goal (e.g. by a caregiver or
the patient), such as to perform an acute task or activity in which
enhanced memory function is desirable. Stimulation can comprise
delivery of electrical energy, sound energy, chemical energy, light
energy, and/or the delivery of a pharmaceutical drug or other
agent. Stimulation elements 150a and/or 150b configured as
electrodes can be of various forms selected from the group
consisting of: single component bipolar electrode; multiple
unipolar electrodes; stacked contact electrodes; discrete
electrodes; electrode strip; grid of electrodes; paddle electrode;
high-density/high channel or lead count micro-electrodes; and
combinations of these.
[0104] Stimulator 100 can include an agent delivery mechanism, such
as a mechanism including a pump and one or more catheters
configured to deliver one or more agents to one or more brain or
other body locations. In some embodiments, system 10 is constructed
and arranged to deliver both electrical stimulation and agent
delivery, sequentially and/or simultaneously. In these embodiments,
a pump can be implanted below the skin of patient P, such as when
the pump has an access port into which a needle can be inserted
through the skin to inject a quantity of a liquid agent, such as a
medication or other drug. The liquid agent is delivered from the
pump through a catheter (e.g. after traveling from a pumping
chamber and through a catheter access port attached to the side of
the pump), and into patient P. The catheter can be positioned to
deliver the agent to one or more specific infusion sites of brain
B. The pump can take the form of any number of known implantable
pumps including for example that which is disclosed in U.S. Pat.
No. 4,692,147, "Drug Administration Device", the contents of which
is incorporated herein by reference in its entirety. The distal end
of the catheter can terminate in a cylindrical hollow tube having a
distal end implanted, such as by conventional stereotactic surgical
techniques, into a portion of brain B to affect tissue within brain
B. The tube can be surgically implanted through a hole in the skull
and the catheter can be implanted between the skull and the scalp,
with the catheter fluidly attached to the pump. The pump can be
implanted in a subcutaneous pocket located in the chest below the
clavicle. Alternatively, the pump can be implanted in the abdomen.
The catheter can include twin tubes (e.g. two separate catheters
attached to a single pump or a single catheter with two lumens)
that have their distal portions implanted into brain B in bilateral
locations. Alternatively, a second catheter can be implanted, for
example on the other side of brain B, and can be supplied with
drugs or other stimulating agents from a separate pump. The one or
more pumps can be programmed to deliver one or more agents
according to a particular dosage and/or time interval. For example,
a pump can deliver drug therapy over a first period with a high
dose configured to induce a high level of neurogenesis, after which
a lower dose is delivered to maintain neurogenesis and secondary
trophic effects (e.g. axonal sprouting and synaptogenesis). Any
number of neurotrophins or drugs that stimulate neurons can be
administered including, but not limited to: NGF; BDNF; NT-3; FGF;
EGF; GDNF; Neurteurin; Artemin; Persephin; and combinations of
these.
[0105] System 10 can be constructed and arranged to modulate memory
circuits to produce clinical benefits, such as to modulate memory
circuits in the brain B of patient P to reduce the progression of
or otherwise treat the effects of Alzheimer's Disease (AD). System
10 can modulate memory circuits in brain B via electrical or other
stimulation means. System 10 can be constructed and arranged to
stimulate brain B tissue selected from the group consisting of:
fornix; entorhinal cortex; hippocampus; anterior thalamic nucleus;
amygdala; mammillary bodies; parahippocampal cortex; temporal
neocortex; septal nuclei; nucleus basalis of Meynert; subcallosal
or subgenual cingulate; ventral capsule; ventral striatum; and
combinations thereof. In some embodiments, the brain tissue
stimulated comprises brain tissue selected from the group
consisting of: Papez Circuit; hippocampus; cingulate gyrus; fornix;
a mammilothalamic tract; amygdala; hypothalamus; mammillary bodies;
septal nuclei; temporal neocortex; the medial forebrain bundle;
anterior and mediodorsal nuclei of the thalamus; the diagonal band
of the Broca; temporal stem and temporal white matter; brainstem;
nucleus basalis of Meynert; anterior thalamic nucleus; entorhinal
cortex; rhinal cortex; periventricular zone; anterior thalamus;
anterior insula; caudate; dorsal anterior cortex; dorsal cingulate;
medial frontal cortex; nucleus accumbens; orbital frontal cortex;
parietal region; periaqueductal gray area; posterior cingulate
area; subcallosal area; subcallosal cingulate; subgenual cingulate;
Brodmann area 10; Brodmann area 24; Brodmann area 25; Brodmann area
11/Brodmann area 10; Brodmann area 24b; Brodmann area 31; Brodmann
area 32/Brodmann area 10; Brodmann area 32/Brodmann area 11;
Brodmann area 39; Brodmann area 46; Brodmann area 46/Brodmann area
9; Brodmann area 47; Brodmann area 6; Brodmann area 9;
ventral/medial prefrontal cortex area; ventral/medial white matter;
dorsolateral prefrontal cortex; premotor cortex; ventrolateral
prefrontal cortex; dorsal anterior cingulate caudate nucleus;
frontal pole periaqueductal gray area; dorsolateral prefrontal
area; subsingular cingulate; parahippocampal cortex;
parahippocampal gyms; ventral capsule; ventral striatum; and
combinations thereof. In some embodiments, the brain tissue
stimulated does not comprise tissue selected from the group
consisting of: hippocampal tissue; optical tract tissue; and
combinations thereof. In some embodiments, the brain tissue
stimulated does not comprise tissue selected from the group
consisting of: posterior hypothalamic area; ventral tegmental area;
lateral hypothalamic area; anterior hypothalamic nucleus;
paraventricular nucleus; dorsal medial hypothalamic nucleus;
ventromedial hypothalamic nucleus; arcuate nucleus; lateral tuberal
nucleus; medial preoptic nucleus; supraoptic nucleus; and
combinations thereof. The stimulation site within one or more
locations of brain B tissue can be used to stimulate, activate or
otherwise affect one or more similar or different brain B tissue
locations, such as a stimulation configured to affect a brain B
location selected from the group consisting of: fornix;
hippocampus; parahippocampal gyms; entorhinal cortex; amygdale;
mammillary bodies; parahippocampal cortex; temporal neocortex;
septal nuclei; nucleus basalis of Meynert; subcallosal or subgenual
cingulate; and combinations of these. Alternatively or
additionally, system 10 and one or more stimulation elements 150
can be constructed and arranged to stimulate non-brain tissue, such
as nerve or organ tissue separate from the brain. Stimulated tissue
can comprise tissue selected from the group consisting of: vagus
nerve; trigeminal nerve; carotid sinus; spinal cord; dorsal root
ganglia; tibial nerve; sacral nerve; gastric nerve; and
combinations thereof. In some embodiments, system 10 is constructed
and arranged to stimulate at least a portion of the hypothalamus,
such as at least a portion of the fornix. The fornix is a large
axonal bundle that constitutes a major inflow and output pathway
from the hippocampus and medial temporal lobe. The hippocampus is a
critical component of the limbic circuitry and is distinguished
among some of the regions of the brain by persistent production of
new neurons. The fornix is involved in memory formation and is
known to be affected early in the progression of AD. In some
embodiments, loss of fornix integrity associated with hippocampal
volume loss can be detected by diagnostic tool 300 and used by
system 10 to predict the progression of AD.
[0106] System 10 can be constructed and arranged to sustain and/or
improve the function of the fornix. Alternatively or additionally,
system 10 can be constructed and arranged to therapeutically affect
the hippocampus and/or cortical circuits (e.g. the cortico-cortico
circuits). Stimulation of the fornix by system 10 can be used to
activate the hippocampus and cortical regions in brain B's default
network, a network of brain regions that are active when the
individual is not focused on the outside world and/or the brain is
at wakeful rest. Patients with AD can exhibit a decrease in glucose
metabolism over time. System 10 can be constructed and arranged to
increase or maintain (e.g. prevent the decrease of) glucose
metabolism, such as by stimulating at least the fornix. System 10
can be constructed and arranged to increase or maintain (e.g.
prevent the decrease of) one or more portions of hippocampal
volume, such as by stimulating the fornix or other brain B location
as described hereabove. In some embodiments, the stimulation of
system 10 results in neurogenesis, such as hippocampal
neurogenesis.
[0107] System 10 can be constructed and arranged to produce
clinical benefits to patient P by modulating neurophysiologic
activity in pathological circuits. The pathological circuits can be
causing functional impairment in the neural elements and circuits
underlying cognitive and/or memory functions, and the stimulation
provided by system 10 can improve clinical and/or neurobiological
outcomes that result from these pathological circuits. Stimulation
provided by system 10 can be used to modulate dysfunctional
networks, such as to therapeutically manipulate the levels of one
or more deleterious proteins.
[0108] System 10 can be constructed and arranged to drive activity
in projection structures downstream from the stimulation site (e.g.
downstream from the fornix). System 10 can be constructed and
arranged to provide evoked responses that are unequivocal and/or
consistent. Stimulation received by system 10 can activate the
cingulated gyms and precuneus area of the parietal lobe, including
direct and trans-synaptic sequential activation of downstream
targets related to the connectivity of the fornix and
hippocampus.
[0109] System 10 can be constructed and arranged to regulate the
level of one or more neurotrophic factors and/or neurotransmitters.
System 10 can be constructed and arranged to ameliorate cognitive
decline associated with dementia. A patient receiving therapy from
system 10 can have reduced integrity of white matter tracts
innervating limbic structures such as the fornix (e.g. at least the
fornix) as determined by fractional anisotropy maps using diffusion
tensor imaging. System 10 can be constructed and arranged to
achieve at least one of: treats memory impairment; improves memory
function; treats cognitive function loss; reverses synaptic loss;
improves cognitive function; reduces degradation of cognitive
function; promotes neurogenesis in the hippocampus of patient P's
brain B; drives neurotrophin expression; regulates one or more
biomarkers related to Alzheimer's Disease such as amyloid-beta,
tau, and/or phosphorylated tau; regulates BDNF expression;
increases neurotransmitter release such as acetylcholine; or
improves glucose utilization in the temporal lobe, the parietal
lobe or both lobes of the patient's brain.
[0110] In some embodiments, a combination of treatment therapies
can be delivered by system 10 to provide influencing of multiple
neuronal types. Stimulator 100 can be constructed and arranged to
deliver multiple therapies, such as two or more stimulation
therapies selected from the group consisting of: electrical
stimulation; magnetic stimulation; optical stimulation (e.g.
visible, ultraviolet and/or infrared light); sound stimulation
(e.g. ultrasound or subsonic waves); chemical stimulation (e.g. a
drug or other agent); and combinations of these, such as described
hereabove. For example, it can be desirable to concurrently
influence, via chemical, electrical and/or other stimulation, the
neurons in the fornix, hippocampus and/or other portions of brain B
to achieve an improved result. Such a system 10 utilizing multiple
forms of treatment therapy can be similar to that which is
disclosed, for example, in U.S. Pat. No. 5,782,798, the content of
which is incorporated herein by reference in its entirety. In
addition to affecting the deep brain, it can be desirable for
system 10 to concurrently affect one or more other portions of the
brain.
[0111] In some embodiments, system 10 is constructed and arranged
to provide one or more pharmaceutical or other agents, such as an
agent delivered orally, via an injection, or delivered by a
component of system 10. In some embodiments, system 10 is
constructed and arranged to provide a cholinesterase inhibitor
medication or other agent to patient P. Stimulation element 150a
and/or 150b can be constructed and arranged to deliver one or more
pharmaceutical or other agents, such as when stimulation 150a
and/or 150b are further configured as a drug delivery element or
other liquid or solid dispensing element.
[0112] As described above, controller 200 is constructed and
arranged to set one or more treatment stimulation parameters 107 of
system 10, such as an initial setting of one or more treatment
stimulation parameters 107 (e.g. to cause an initial treatment
stimulation energy to be delivered to brain B) or a modification to
an existing set of one or more treatment stimulation parameters 107
(e.g. to modify the treatment stimulation energy being delivered to
brain B). Initial settings of treatment stimulation parameters 107
and/or modifications to existing settings can be made to provide
sufficient therapy (e.g. cause a desired event) and/or to reduce
the likelihood or effect of one or more adverse events. Setting of
one or more treatment stimulation parameters 107 can be made by an
operator of system 10 using controller 200, such as an operator who
is a clinician or other caregiver to patient P. Alternatively or
additionally, setting of one or more treatment stimulation
parameters 107 can be performed automatically or semi-automatically
by system 10, such as in a closed loop fashion based on information
received from diagnostic tool 300 or another component of system
10.
[0113] Controller 200 comprises user interface 201, such as a user
interface configured to provide information to and/or receive
commands from an operator of system 10. User interface 201 can
comprise one or more user input and/or user output components
selected from the group consisting of: a touchscreen; a graphical
and/or alphanumeric screen; a keypad; a mouse; and combinations of
these. Controller 200 can comprise one or more discrete
controllers, such as one or more handheld devices configured to
program or otherwise communicate with stimulator 100 and/or
diagnostic tool 300. Pathway 20 can comprise a uni-directional or
bi-directional communication pathway between controller 200 and
stimulator 100. Pathway 20 can comprise one or more physical
conduits such as electrically conductive wires and/or optical
fibers. Alternatively or additionally, pathway 20 can comprise a
wireless communication pathway, such as a transmission of
electromagnetic waves such as is used in wireless radiofrequency
(RF) communications.
[0114] Diagnostic tool 300 can comprise a user interface 301, such
as a user interface configured to provide information to and
receive commands from an operator of system 10. User interface 301
can comprise one or more user input and/or user output components
selected from the group consisting of: a touchscreen; a graphical
and/or alphanumeric screen; a keypad; a mouse; and combinations
thereof. As described above, diagnostic tool 300 is constructed and
arranged to measure one or more patient parameters and produce
diagnostic data 305 which is determined based on the one or more
measured patient parameters. Diagnostic data 305 can be displayed
on user interface 301 (such as heart rate information, blood
pressure information, or other data corresponding to a measured
patient parameter that is displayed on user interface 301). In some
embodiments, diagnostic tool 300 can communicate directly with
controller 200 and/or stimulator 100, such as via a wired or
wireless connection as described herein, such that diagnostic data
305 is recorded by controller 200 and/or stimulator 100, such as to
automatically and/or semi-automatically modify one or more
stimulation parameters 105.
[0115] As described herein, diagnostic data 305 can be used to
determine if an adverse event has occurred or is about to occur.
Treatment stimulation parameters 107 can be set at a level below or
otherwise different than the stimulation threshold at which the
adverse event occurred, such as at a safety margin below or
otherwise away from that stimulation threshold (e.g. a voltage or
current level that is less than the level causing the adverse
event). In some embodiments, one or more treatment stimulation
parameters 107 are modified based on a stimulation threshold (e.g.
modified to a level at or below the stimulation threshold, such as
at a safety margin below the stimulation threshold at which an
adverse event occurred). For example, an adverse event that occurs
at a signal voltage of 6 Volts, may result in delivering therapy at
5 Volts (a 16.6% safety margin), at 4 Volts (a 33.3% safety margin)
or at 3 Volts (a 50% safety margin).
[0116] Diagnostic tool 300 can comprise one or more diagnostic
devices, such as one or more devices selected from the group
consisting of: heart rate monitor; EKG measurement device;
oximeter; combined heart rate and oximeter device such as a pulse
oximeter; blood pressure measurement device; neuronal activity
measurement device; EEG measurement device; evoked response
potential (ERP) measurement device; neurochemical analysis device;
memory test device; memory test form; respiration measurement
device; sweat measurement device; skin conductivity measurement
device; pH measurement device; body motion measurement device;
imaging device; and combinations of these. Diagnostic tool 300 can
be constructed and arranged to detect and/or record an adverse
event, such as an adverse event selected from the group consisting
of: undesirable heart rate; undesirable respiration rate;
undesirable sweating; undesirable hallucinations; undesirable
tingling; flushing; undesirable psychiatric effect; undesirable
cognitive effect; unpleasant generalized warming; undesirable
perceptions described as deja vu; seizure; synchronized neuronal
firing pattern; undesired neural response time; undesired brain
state; undesired theta phase; undesired p300 amplitude; and
combinations of these.
[0117] In some embodiments, diagnostic tool 300 comprises two
independent diagnostic measurement devices, for example two devices
whose diagnostic data are used in combination. For example,
diagnostic tool 300 can comprise a blood pressure measurement
device and a heart rate measurement device, such as to identify
patient discomfort or other patient issue (e.g. a falsehood or
other inaccurate statement made by the patient that can be detected
through analysis of a patient parameter such as heart rate and/or
blood pressure).
[0118] Diagnostic tool 300 can comprise a memory test such as a
verbal, visual, motor function and/or spatial memory test.
Diagnostic tool 300 can be constructed and arranged to detect
and/or record a memory recall event, such as a tool including an
EEG measurement device and/or a form (e.g. a paper form or
electronic form) configured to manually record the results of a
memory test.
[0119] In embodiments where diagnostic tool 300 comprises an EKG
measurement device, one or more treatment stimulation parameters
107 can be set based on a stimulation threshold at which undesired
EKG activity (e.g. tachycardia or an arrhythmia) is identified in
diagnostic data 305.
[0120] In embodiments where diagnostic tool 300 comprises a
neuronal activity measurement device, diagnostic tool 300 can be
constructed and arranged to measure a neuronal parameter selected
from the group consisting of: single neuron activity; local field
potential (LFP); event related potential (ERP);
electroencephalogram reading; electrocorticogram reading; and
combinations of these. In these embodiments, a stimulation
threshold (e.g. a stimulation threshold at which an adverse event
is recorded by diagnostic tool 300) can be determined when an
adverse event occurs that is selected from the group consisting of:
seizure; synchronized neuronal firing pattern; undesired neural
response time; undesired brain state; undesired theta phase;
undesired p300 amplitude; and combinations of these.
[0121] In embodiments where diagnostic tool 300 comprises an event
related potential (ERP) measurement device, one or more treatment
stimulation parameters 107 can be set based on a stimulation
threshold at which undesired ERP activity is identified in
diagnostic data 305.
[0122] In embodiments where diagnostic tool 300 comprises a blood
pressure measurement device, one or more treatment stimulation
parameters 107 can be set based on a stimulation threshold at which
undesired blood pressure readings (e.g. above a threshold) are
identified in diagnostic data 305. In these embodiments, diagnostic
tool 300 can further comprise a heart rate measurement device, such
that diagnostic data comprises both blood pressure readings and
heart rate readings, such as when a stimulation threshold is based
on the occurrence of high blood pressure and/or tachycardia.
[0123] In embodiments where diagnostic tool 300 comprises a blood
oxygen measurement device, one or more treatment stimulation
parameters 107 can be set based on a stimulation threshold at which
undesired blood oxygen readings are identified in diagnostic data
305.
[0124] In embodiments where diagnostic tool 300 comprises a body
motion measurement device, one or more treatment stimulation
parameters 107 can be set based on a stimulation threshold at which
undesired body motion (e.g. a tremor) is identified in diagnostic
data 305.
[0125] In embodiments where diagnostic tool 300 comprises a
neurochemical analysis device, the neurochemical analysis device
can be constructed and arranged to measure a parameter selected
from the group consisting of: neurotransmitter level (GABA,
glutamate, acetylcholine, dopamine, epinephrine, etc.); a pH
concentration; an ion concentration; a lactate level; cerebral
blood flow; glucose utilization; oxygen extraction; and
combinations of these. One or more treatment stimulation parameters
107 can be set based on a stimulation threshold at which undesired
neurochemical activity and/or level is identified in diagnostic
data 305.
[0126] In embodiments where diagnostic tool 300 comprises an
imaging device, one or more treatment stimulation parameters 107
can be set based on a stimulation threshold at which an undesired
patient condition is identified in one or more images (diagnostic
data 305) produced by the imaging device. Diagnostic tool 300 can
comprise an imaging device selected from the group consisting of:
standardized Low Resolution Brain Electromagnetic Tomography
(sLORETA) device; functional magnetic resonance imaging (fMRI);
MagnetoEncephalography (MEG); and combinations of these, such as
when used to produce diagnostic data 305 that quantifies or
qualifies the effects of receiving stimulation from system 10. In
these embodiments, one or more images produced by diagnostic tool
300 can be used to optimize therapy or reduce an adverse event,
such as when used to select an electrode to receive stimulation
energy based on its position relative to a target as described
herein. One or more images produced by diagnostic tool 300 can be
use to select one or more stimulating elements from a set of
multiple stimulating elements (e.g. to select one or more
electrodes from a set of multiple electrodes based on an image of
the multiple electrodes in reference to a target stimulation
location such as the fornix).
[0127] In some embodiments, diagnostic tool 300 produces data (e.g.
image data) to assess axonal pathways, such as an assessment
performed during stimulation of the axonal pathways or locations
proximate the assessed pathways. In these embodiments, diagnostic
data 305 produced by diagnostic tool 300 can be used to identify
one or more axonal pathways that may be necessary or at least
desirable to optimize therapeutic benefit from the stimulation
provided by system 10. Diagnostic tool 300 can comprise at least a
diffusion tension imaging (DTI) device and/or a
tractography-activation model (TAM) used to identify the pathways
stimulated by system 10. The TAM can consist of: anatomical and
diffusion-weighted imaging data acquired on the patient;
probabilistic tractography from the brain region surrounding the
stimulation element 150a and/or 150b; finite element models of the
electric field generated by stimulator 100; and/or application of
the electric field produced by stimulation element 150a and/or 150b
to multi-compartment cable models of axons, with trajectories
defined by the tractography, to predict action potential generation
in the pathways. Diagnostic tool 300 can be configured to produce
clinical data, diffusion tensor tractography, and/or computer
models of tissue-specific stimulation areas, such as to determine
one or more axonal pathways being stimulated and/or to predict or
differentiate the therapeutic benefit of their stimulation.
[0128] Diagnostic tool 300 can comprise a patient assessment
recording tool, such as a tool selected from the group consisting
of: a form; a paper form; an electronic form; a tablet; a personal
computer; a database; and combinations of these. In these
embodiments, the patient assessment can comprise an assessment
selected from the group consisting of: an assessment received
verbally from the patient; an assessment received in written form
from the patient; an assessment made by a caregiver of the patient;
and combinations of these. The patient assessment can comprise an
assessment of a patient state selected from the group consisting
of: depression; paranoia; schizophrenia; suicidality; suicide
ideation; apathy; anxiety; mania; and combinations of these.
Diagnostic tool 300 can comprise an algorithm configured to analyze
data on a patient assessment form or other patient assessment
tool.
[0129] In some embodiments, diagnostic tool 300 comprises one or
more sensors 330 as shown. One or more sensors of system 10, such
as sensor 330, sensor 230 and/or sensor 430 can comprise a sensing
element selected from the group consisting of: neuronal activity
sensor; EEG sensor; local field potential (LFP) sensor;
neurochemical sensor; pH sensor; pressure sensor; blood pressure
sensor; optical sensor; blood gas sensor; blood oxygen sensor;
magnetic sensor; strain gauge; and combinations of these. Sensor
330, sensor 230 and/or sensor 430 can comprise an implanted or
external sensor. Stimulating element 150a and/or 150b can comprise
sensor 330. Sensor 330, sensor 230 and/or sensor 430 can comprise
at least one electrode. System 10 can be constructed and arranged
to provide closed loop stimulation based on one or more signals
received from one or more of sensors 330, 230 and/or 430.
[0130] As described hereabove, one or more portions of stimulator
100 can be implanted in the patient, such an implantation of
stimulation element 150b. Diagnostic tool 300 can be constructed
and arranged to gather diagnostic data 305 before and/or after
implantation of stimulation element 150b. In some embodiments,
diagnostic tool 300 gathers diagnostic data 305 to determine a
stimulation threshold at least 5 minutes after implantation of
stimulation element 150b. In some embodiments, diagnostic tool 300
gathers diagnostic data 305 to determine a stimulation threshold at
least 24 hours after implantation of stimulation element 150b, or
at least 2 weeks after implantation of stimulation element
150b.
[0131] As described above, controller 200 and stimulator 100 can be
constructed and arranged to stimulate brain B with one or more
temporary stimulation parameters, test stimulation parameters 106.
Diagnostic tool 300 can be constructed and arranged to measure one
or more patient parameters while brain B is being stimulated with
test stimulation parameters 106, producing diagnostic data 305
correlating to the test stimulation parameters 106. In some
embodiments, multiple sets of similar or dissimilar test
stimulation parameters 106 are delivered to brain B, while
diagnostic tool 300 measures at least one patient parameter and
produces diagnostic data 305. In some embodiments, a series of
varied test stimulation parameters 106 can be delivered to brain B
(e.g. a stepped or continuous increase in stimulation energy level,
such as a stepped or continuous increase of a stimulating voltage
and/or current), while diagnostic tool 300 measures one or more
patient parameters and produces a set of diagnostic data 305 which
is correlated to the particular level of test stimulation
parameters 106 associated with each subset of diagnostic data 305.
Subsequently, stimulator 100 delivers treatment stimulation energy
comprising one or more treatment stimulation parameters 107 that
are determined from or otherwise based on the produced diagnostic
data 305. In some embodiments, one or more treatment stimulation
parameters 107 are manually programmed into stimulator 100 via
controller 200. In some embodiments, system 10 is constructed and
arranged to automatically set one or more treatment stimulation
parameters 107 based on the produced diagnostic data 305.
[0132] In some embodiments, diagnostic data 305 produced by
diagnostic tool 300 is used to determine an initial (e.g. first
time) set of treatment stimulation parameters 107. In some
embodiments, diagnostic data 305 produced by diagnostic tool 300 is
used to modify a pre-existing set of treatment stimulation
parameters 107. In some embodiments, diagnostic data 305 produced
by diagnostic tool 300 is used to determine test stimulation
parameters 106, such as diagnostic data 305 collected in a previous
test. In these embodiments, a test stimulation parameter 106 can be
set based on a stimulation threshold at which an adverse event was
detected by diagnostic tool 300.
[0133] In some embodiments, stimulator 100 stimulates brain B with
a first set of test stimulation parameters 106' for a first time
period and a second set of test stimulation parameters 106'' for a
second time period. The first time period and the second time
period can comprise relatively the same length of time or different
lengths of time. The first and/or second time periods can comprise
a time period less than or equal to 24 hours, such as less than or
equal to 6 hours, 3 hours, 1 hour, 30 minutes, 15 minutes, 10
minutes, 5 minutes or 2 minutes. Diagnostic tool 300 measures one
or more patient parameters during all or a portion of both the
first time period and the second time period, and produces first
diagnostic data 305' and second diagnostic data 305'', representing
the measured at least one patient parameter recorded during the
first time period and the second time period, respectively.
Subsequently, stimulator 100 provides stimulation energy to brain B
comprising one or more treatment stimulation parameters 107 that
are determined using or otherwise based on the first diagnostic
data 305' and second diagnostic data 305''. In these embodiments,
treatment stimulation parameters 107 can be based on one or more
test stimulation parameters 106 associated with a desired treatment
and/or they can be based on one or more test stimulation parameters
106 associated with avoiding an adverse event, such as described
herein.
[0134] In some embodiments, the treatment stimulation parameters
107 equal or at least approximate the first set of test stimulation
parameters 106' or the second set of test stimulation parameters
106''. The treatment stimulation parameters 107 chosen can
approximate a test stimulation parameter 106 associated with an
improved or otherwise desired treatment of a neurological disease
and/or disorder. The improved treatment can correspond with a
therapeutic benefit such as a desired memory recall with the
patient. Alternatively or additionally, the treatment stimulation
parameters 107 chosen can approximate a test stimulation parameter
106 associated with avoidance of an adverse event. In some
embodiments, the treatment stimulation parameters 107 chosen can be
proportional or otherwise based on a test stimulation parameter 106
associated with avoidance of an adverse event as described
hereabove, such as when treatment stimulation parameters 107 are a
safety margin below the test stimulation parameters 106 at which
the adverse event occurred, as described herein.
[0135] In some embodiments, one or more treatment stimulation
parameters 107 are manually programmed into stimulator 100 via
controller 200. Alternatively, system 10 is constructed and
arranged to automatically set one or more treatment stimulation
parameters 107 based on the produced diagnostic data 305.
[0136] Diagnostic tool 300 used in the first time period and the
second time period can comprise one or more diagnostic devices or
other tools, such as are described herein, each producing
diagnostic data 305. In some embodiments, diagnostic data 305
produced by a diagnostic tool 300 is used to determine first test
stimulation parameters 106' and/or second test stimulation
parameters 106'', such as diagnostic data 305 collected in a
previous test performed using diagnostic tool 300. In some
embodiments, diagnostic tool 300 comprises a memory test tool, such
as a form used to record memory data. In these embodiments,
treatment stimulation parameters 107 can approximate or otherwise
be based on the test stimulation parameters 106 that resulted in a
higher memory test score recorded in one of a set of time periods
(e.g. two or more time periods) between which one or more test
stimulation parameters were varied.
[0137] One or more treatment stimulation parameters 107 can
comprise an electrical stimulation parameter selected from the
group consisting of: voltage level such as an average voltage
level, rms voltage level and/or a peak voltage level; current level
such as an average current level, rms current level and/or a peak
current level; power level such as an average power level, rms
power level and/or a peak power level; frequency of stimulation
signal; series of frequencies of the stimulation signal; phase of
stimulation signal; pulse width modulation ratio; signal pulse
width; current density such as current density applied to tissue;
single electrode selected to receive stimulation energy; set of
electrodes selected to receive monopolar and/or bipolar stimulation
energy; and combinations of these. In some embodiments, stimulation
element 150b comprises a lead inserted into brain B and comprising
multiple electrodes, and a treatment stimulation parameter 107 or
other stimulation parameter 105 can represent a selection (e.g. a
subset) of one or more specific electrodes of the lead to receive
stimulation energy. The selection of electrodes can comprise a
single electrode, a pair of electrodes, or more than two
electrodes, such as one or more electrodes that receive monopolar
or bipolar energy. In some embodiments, a stimulation parameter 105
comprises a signal voltage of between 0.1 Volts and 10.0 Volts,
such as a voltage between 1.0 Volts and 6.0 Volts, or between 1.0
Volts and 3.0 Volts. In some embodiments, a stimulation parameter
105 comprises a voltage less than or equal to 9.0 Volts, such as
less than or equal to 8.0 Volts, 7.0 Volts, 6.0 Volts, 5.0 Volts,
4.0 Volts or 3.5 Volts. In some embodiments, a stimulation
parameter 105 comprises a signal frequency between 2 Hz and 1000
Hz, such as a frequency of approximately 130 Hz. Energy delivery
can be given in a series of on and off times, such as when a
stimulation parameter 105 comprises an on-time of approximately 30
.mu.seconds to 200 .mu.seconds, such as with an on time of 90
.mu.seconds. A stimulation parameter 105 can comprise a parameter
associated with duration of energy delivery, such as a parameter
corresponding to continuous delivery of energy (e.g. continuous
delivery of pulsed energy) or a parameter corresponding to
intermittent energy delivery comprising one or more energy delivery
periods ranging from thirty minutes to 24 hours.
[0138] In some embodiments, a stimulation parameter 105 comprises a
light stimulation parameter selected from the group consisting of:
power of light delivered to tissue; frequency of light delivered to
tissue; modulation parameter of light delivered to tissue; and
combinations of these.
[0139] In some embodiments, a stimulation parameter 105 comprises a
sound stimulation parameter selected from the group consisting of:
amplitude of sound delivered to tissue; frequency of sound
delivered to tissue; modulation parameter of sound delivered to
tissue; and combinations of these.
[0140] In some embodiments, a stimulation parameter 105 comprises
an agent delivery stimulation parameter selected from the group
consisting of: mass of agent delivered to tissue; volume of agent
delivered to tissue; concentration of agent delivered to tissue;
delivery rate of agent delivered to tissue; and combinations of
these.
[0141] In some embodiments, controller 200 and/or another component
of system 10 are constructed and arranged to set at least one
treatment stimulation parameter 107 based on a stimulation
threshold at which an adverse event is detected by diagnostic tool
300, such as an adverse event as described hereabove. In these
embodiments, the at least one treatment stimulation parameter 107
can be set to a level at or below the stimulation threshold, such
as at a safety margin below the stimulation threshold as described
hereabove.
[0142] In some embodiments, controller 200 and/or another component
of system 10 are constructed and arranged to set at least one
treatment stimulation parameter 107 based on a stimulation
threshold at which a desired event is detected by diagnostic tool
300. Patient desired events include events selected from the group
consisting of: recall of a desired memory; achievement of desired
memory learning; desired level of neuronal activity; acceptable
physiologic condition such as an acceptable heart rate or
acceptable level of neuronal activity; experiential phenomena such
as those described in epilepsy literature; and combinations of
these. In these embodiments, the at least one treatment stimulation
parameter 107 can be set to a level at or above the stimulation
threshold, such as at a pre-determined percentage above the
stimulation threshold. In these embodiments, the at least one
treatment stimulation parameter 107 can also be set based on a
second stimulation threshold at which an adverse event occurred,
such as a safety margin below the adverse event stimulation
threshold. For example, a memory recall event may be recorded by
diagnostic tool 300 at a stimulation voltage of X Volts, and an
adverse event may be recorded by diagnostic tool 300 at a
stimulation voltage of Y Volts, where Y is greater than X. A
treatment stimulation parameter 107 can be set to a signal voltage
between X Volts and Y Volts.
[0143] System 10 can be constructed and arranged to provide open
loop stimulation to brain B. Alternatively or additionally, system
10 can be constructed and arranged to provide closed loop
stimulation to brain B, such as closed loop stimulation based on
diagnostic data 305 provided by diagnostic tool 300 and/or a signal
provided by one or more of sensors 330, 430 and 230, or a separate
implanted or external sensor, such as sensor 430 described in
reference to FIG. 4 herebelow.
[0144] In some embodiments, diagnostic tool 300 and/or another
component of system 10 comprises data logging assembly 350. Data
logging assembly 350 can be constructed and arranged to record one
or more events that occur during delivery of test stimulation
energy using test stimulation parameters 106, such as when
stimulation energy is varied. Data logging assembly 350 can be
configured to record diagnostic data 305, such as to determine a
minimum, maximum, average and/or other statistical value of
diagnostic data 305 (e.g. a maximum heart rate and/or a maximum
blood pressure that occurs during delivery of test stimulation
energy). In some embodiments, data logging assembly 350 comprises
an assembly with a button that a patient can activate (e.g. press),
such as during a patient adverse event or a memory recall event, as
noticed by the patient. In some embodiments, at least a portion of
data logging assembly 350 can be at a location remote from the
patient, such as at one or more file locations accessible via the
Internet or other information access network. Diagnostic data 305
from multiple patients could be stored in one or more locations
remote from those patients. Diagnostic data 305 recorded by one or
more diagnostic tools 300 during diagnostic tests performed on one
or more patients can be processed, analyzed and/or otherwise used
to determine one or more treatment stimulation parameters 107 for
one or more patients.
[0145] Referring now to FIG. 2 a flow chart of a series of steps
for treating a patient with a stimulation system is illustrated,
consistent with the present inventive concepts. The method
comprises STEPs 510 through 550, which can be performed using one
or more components of system 10 of FIG. 1 described hereabove. In
STEP 510, a patient is selected for implantation. In a preferred
method, the patient is screened for candidacy as described in
reference applicants co-pending U.S. patent application Ser. No.
13/655,652, entitled "Deep Brain Stimulation of Memory Circuits in
Alzheimer's Disease", filed Oct. 19, 2012, the content of which is
incorporated herein by reference in its entirety. In some
embodiments, the selected patient is a patient diagnosed and/or
prognosed with a cognitive disorder selected from the group
consisting of: Alzheimer's Disease (AD) such as Mild or Moderate
Alzheimer's Disease; probable Alzheimer's Disease; a genetic form
of Alzheimer's Disease; Mild Cognitive Impairment (MCI);
hippocampal damage such as hippocampal damage due to Alzheimer's
disease, anoxia, epilepsy or depression; neuronal loss; neuronal
damage; chemotherapy induced memory impairment; epilepsy; a seizure
disorder; dementia; amnesia; a memory disorder such a spatial
memory disorder; cognitive impairment associated with
Schizophrenia; Parkinson's Disease related cognitive impairment or
dementia; and combinations of these. Additionally or alternatively,
the patient can be selected to treat negative symptoms of a disease
or disorder selected from the group consisting of: schizophrenia;
depression; other conditions of reversible impaired memory or
cognition; and combinations of these.
[0146] In STEP 520, at least one imaging procedure is performed on
the patient, collecting at least one patient image. In some
embodiments, the imaging procedure is an MRI procedure performed to
identify the fornix of the patient and/or one or more other brain
locations. Alternatively or additionally, different patient imaging
procedures can be used including imaging procedures selected from
the group consisting of X-ray; ultrasound imaging; fMRI; PET scan;
and combinations of these. Multiple imaging procedures can be
performed, such as similar imaging procedures performed at
different times, or different imaging procedures performed at the
same or different times. In one embodiment, a first imaging
procedure is performed at least 7 days prior to a second imaging
procedure. In another preferred embodiment, a first imaging
procedure is an MRI procedure and a second imaging procedure is
selected from the group consisting of: a second MRI procedure; an
X-ray; an ultrasound imaging procedure; an fMRI; a PET scan; and
combinations of these. Multiple patient images, collected in one or
more similar or dissimilar imaging procedures, can be collected.
These images can be used in combination, in comparison, or both. In
some embodiments, the two procedures are performed at different
times and one or more patient parameters are compared, such as
parameters selected from the group consisting of: brain size; brain
shape; and brain thickness. In some embodiments, an amyloid PET
scan can be used to assess the presence of amyloid in a patient. In
some embodiments, a resting state BOLD fMRI sequence is performed
to evaluate Default Mode Network or other brain state. In some
embodiments, Diffusion Tensor Imaging and tractography are
performed, such as to create an image of microstructures of the
brain to assess white matter abnormalities (e.g. of the
fornix).
[0147] In STEP 530, at least a portion of a brain stimulator can be
implanted, such as an implantation of one or more portions of brain
stimulator 100 described in reference to FIG. 1 hereabove and/or
stimulator 100 described in reference to FIG. 4 herebelow. The one
or more implantable portions of brain stimulator 100 can be
implanted in one or more surgeries. The surgery can include
implantation of a lead comprising one or more electrodes, such as
one or more electrodes to be positioned proximate the fornix of the
patient's brain B. One or more stimulating elements such as
electrodes can be implanted in a location selected from the group
consisting of: in the Papez Circuit of the patient's brain;
approximately 2 mm anterior and parallel to the vertical portion of
the fornix; in the optic tract such that the ventral-most contact
is 2 mm above the dorsal surface of the optic tract; approximately
5 mm from the midline; and combinations of these. A post-operative
imaging procedure such as an MRI can be performed to assess and/or
confirm position of one or more implanted electrodes or other
components of the system, such as to confirm location of multiple
electrodes relative to the fornix or other target location within
the patient's brain. The diagnostic tool can be an imaging device,
and the diagnostic data can include one or more images produced by
the diagnostic device used to select one or more electrodes or
other stimulating elements configured to receive stimulation
energy. The one or more stimulating elements can be selected based
on their proximity and/or relative position to a stimulation
target, such as the fornix. For example a first electrode providing
stimulating energy generating a first set of diagnostic data can be
selected over a second electrode providing stimulating energy and
generating a second set of similar diagnostic data (e.g. similar
therapeutic benefit) based on information provided by an imaging
device (e.g. when the first electrode is in a more desirable
position relative to a stimulation target than the second
electrode). In some embodiments, electrode selection is made based
on image data to prevent stimulation on non-target tissue (i.e.
tissue whose stimulation is to be avoided or at least reduced).
[0148] In alternative embodiments, brain stimulation is provided by
an external, non-invasive stimulation device (i.e. one or more
fully non-implanted stimulation system components). In embodiments
including an implanted stimulator or a stimulator including at
least an implanted portion, at least one stimulation element can be
implanted in, on or near the brain of a patient. The at least one
stimulation element of the stimulator can be positioned in, on or
near the brain of the patient based on the at least one patient
image. The at least one stimulation element can be placed via a
visual analysis of the at least one image, and/or one or more
mathematical or other computational analysis or analyses of the
patient image. In some embodiments, the at least one stimulation
element is positioned in and/or proximate the fornix of the
patient's brain, as has been described in hereabove. In another
embodiment, the at least one stimulation element, such as a
stimulation element comprising at least two electrodes, is
positioned to provide bipolar stimulation of the fornix or other
brain tissue. The at least one stimulation element can comprise at
least one electrode configured to deliver electrical energy. Proper
positioning of the stimulation element can be confirmed after
placement, such as with a subsequent MRI or other patient
image.
[0149] The stimulation element, such as one or more stimulation
elements 150 of stimulator 100 of FIG. 1, can comprise an
electrical stimulation element such as an electrode or a magnet
such as an electromagnet. Alternatively or additionally, the
stimulation element can comprise an optical stimulation element,
such as a visible light element; an infrared light element; and
combinations of these. Alternatively or additionally, the
stimulation element can comprise a chemical stimulation element,
such as a drug or other agent delivery assembly. The drug delivery
assembly can be configured to deliver one or more of: biologically
active molecules; neurotransmitters; and neurotrophic factors. The
stimulation element can deliver one or more drugs or pharmaceutical
agents, and delivery rate or drug concentration can be determined
based on patient tolerance, such as a tolerance determined in a
titration procedure performed using diagnostic tool 300 of FIG. 1.
In a particular embodiment, the stimulation element is constructed
and arranged to deliver a cholinesterase inhibitor. In another
particular embodiment, an electrode and a second stimulation
element is included. The second stimulation element can comprise an
element selected from the group consisting of: a second electrode;
a magnet; an optical element; a chemical or other agent delivery
assembly; and combinations of these.
[0150] In STEP 540, one more diagnostic tests can be performed,
such as using diagnostic tool 300 of FIG. 1 to gather diagnostic
data 305, as described hereabove. The diagnostic data collected can
be collected during stimulation with one or more test stimulation
parameters, such as test stimulation parameters 106 described
hereabove. Diagnostic tool 300 can be used to reposition one or
more stimulation elements, such as a repositioning performed during
the implantation procedure or during a subsequent surgical or
minimally invasive procedure. This repositioning can be based on
maximizing a desirable patient effect, such as maximizing recalled
memory or memories. Alternatively or additionally, the
repositioning can be based on minimizing an adverse event, such as
to minimize chest pain; undesired EKG signal or signals; undesired
EEG signal or signals; labored breathing; twitching; undesired
heart rate; undesired blood pressure; and combinations of these.
Alternatively or additionally, the repositioning can be based on
minimizing a neurological condition of the patient, such as a level
of one or more of: paranoia; psychosis; anxiety; depression; and
confusion.
[0151] Diagnostic data 305 can be gathered prior to, during or
after implantation of one or more portions of the stimulation
system, such as diagnostic data gathered at least two weeks after
implantation of a stimulator portion. During or after implantation
of the implanted stimulator portion, a decision can be made to
adjust at least one stimulation parameter based on the diagnostic
data 305. The adjusted parameter can be a stimulation parameter
selected from the group consisting of: voltage level such as an
average voltage level, rms voltage level and/or a peak voltage
level; current level such as an average current level, rms current
level and/or a peak current level; power level such as an average
power level, rms power level and/or a peak power level; frequency
of stimulation signal; series of frequencies of the stimulation
signal; phase of stimulation signal; pulse width modulation ratio;
signal pulse width; current density such as current density applied
to tissue; single electrode selected to receive stimulation energy;
set of electrodes selected to receive monopolar and/or bipolar
stimulation energy; agent delivery rate; physiologic concentration;
power of light delivered to tissue; frequency of light delivered to
tissue; a modulation parameter of light delivered to tissue;
amplitude of sound delivered to tissue; frequency of sound
delivered to tissue; a modulation parameter of sound delivered to
tissue; mass of agent delivered to tissue; volume of agent
delivered to tissue; concentration of agent delivered to tissue;
delivery rate of agent delivered to tissue; and combinations of
these. Diagnostic data 305 can be used to set initial stimulation
parameters and/or to modify existing stimulation parameters.
[0152] The implantation procedure can include a calibration or
titration procedure, such as procedures which use a diagnostic tool
of the present inventive concepts to optimize or otherwise modify
one or more stimulation parameters (e.g. one or more test
stimulation parameters or treatment stimulation parameters) such as
one or more stimulation parameters selected from the group
consisting of: an electromagnetic energy delivery parameter such as
voltage or current delivered; a magnetic energy delivery parameter
such as field strength or field orientation; a light delivery
parameter such as wavelength or magnitude of light delivered; a
sound delivery parameter such as frequency or amplitude of a
delivered sound wave; a chemical delivery parameter such as a
concentration of a drug or other agent delivered or a rate of an
agent delivered; and combinations of these. If successful
calibration or titration cannot be achieved, the implanted
stimulator portion can be removed and the procedure abandoned.
Alternatively, if a particular adverse event occurs, the implanted
stimulator portion can be explanted. Typical adverse events causing
explantation can include but are not limited to: chest pain;
labored breathing; twitching; unacceptable EKG signal or
combination of signals; unacceptable EEG signal or combination of
signals; undesired heart rate; undesired blood pressure; and
combinations of these. Alternatively or additionally, typical
adverse events causing explantation can be an unacceptable
neurological state such as an unacceptable level of one or more of:
paranoia; psychosis; anxiety; depression; and confusion.
[0153] STEP 540 can include multiple diagnostic tests performed by
one or more diagnostic tools of the present inventive concepts,
such as the one or more diagnostic tools 300 described in reference
to FIG. 1 hereabove. The diagnostic procedure can include a series
of diagnostic tests performed relatively continuously. The
diagnostic procedure can include confirming electrode placement via
an impedance measurement, for example during and/or after an
implantation step. The diagnostic procedure can include measuring
toxicity at one or more patient locations, and a stimulation
parameter can be adjusted if a measured toxicity exceeds a
threshold. The diagnostic procedure can include a patient memory
test that produces results, and a stimulation parameter can be
adjusted if the results exceed a threshold. The diagnostic
procedure can include a learning task such as a task selected from
the group consisting of: a memory task; a cognitive task; a motor
task; a standardized test such as a full or partial ADAS-Cog or
California Verbal Learning test; and combinations of these. Based
on the outcome from any of the above described diagnostic
procedures, at least one stimulation parameter can be adjusted
(e.g. a test stimulation parameter and/or a treatment stimulation
parameter), for example an adjustment of a parameter selected from
the group consisting of: voltage level; current level; current
density level; a duty cycle parameter such as a pulse width
duration; an energy delivery frequency; and combinations of
these.
[0154] STEP 540 can include sensing a characteristic indicative of
the extent of the cognitive disorder and generating a sensor signal
and regulating the operation of the stimulator in response to the
sensor signal. In some embodiments, sensing a characteristic
indicative of the extent of the cognitive disorder and generating a
sensor signal can comprise detecting a neurochemical characteristic
of the cognitive disorder, for example the signal may represent a
neurochemical characteristic selected from the group consisting of:
neurotransmitter level, pH concentration, ion concentration,
lactate level, cerebral blood flow, glucose utilization, and oxygen
extraction. In some embodiments, sensing a characteristic
indicative of the extent of the cognitive disorder and generating a
sensor signal can comprise detecting an electrophysiological
characteristic of the cognitive disorder, for example an
electrophysiological characteristic is selected from the group
consisting of: the activity of one or more neurons, collectively or
singly; local field potentials; event related potentials (ERPs); a
characteristic collected by an electroencephalogram; a
characteristic collected with MagnetoEncephalography (MEG); a
characteristic collected by an electrocorticogram; and combinations
of these.
[0155] STEP 540 can include sensing a characteristic indicative of
the extent of the cognitive disorder, generating a sensor signal,
and, if the sensor signal is outside of a predetermined threshold,
treating the cognitive disorder by initiating stimulation therapy
by the stimulator. STEP 540 can include determining the threshold
of one or more stimulation parameters (i.e. the "stimulation
threshold" as described herein) associated with an adverse event,
such as an adverse event that occurs during continuous or
intermittent adjustment of one or more stimulation parameters as
described in reference to FIG. 3 herebelow. STEP 540 can include
determining the stimulation threshold of one or more stimulation
parameters associated with onset of a therapeutic benefit to the
patient, such as a recalled memory event or an improved memory test
score.
[0156] In some embodiments, multiple portions of brain tissue are
stimulated sequentially, such as by sequentially stimulating a set
of multiple electrodes. For example, a lead comprising a set of
multiple electrodes can be sequentially stimulated in order to
identify one or more electrodes that avoid an adverse event and/or
provide enhanced therapeutic benefit to the patient. In these
embodiments, two or more electrodes can be stimulated with bipolar
stimulation energy.
[0157] STEP 550 comprises setting one or more treatment stimulation
parameters (e.g. treatment stimulation parameters 107 of FIG. 1
described hereabove) based on diagnostic data 305 collected during
STEP 540 or other diagnostic data collected by a diagnostic tool of
the present inventive concepts. In some embodiments, the treatment
stimulation parameters approximate one or more test stimulation
parameters at which a desirable result was achieved, such as a
desired therapeutic benefit. In some embodiments, the treatment
stimulation parameters are a safety margin below a level at which a
test stimulation parameter resulted in an adverse event, as has
been described in detail in reference to FIG. 1 hereabove.
[0158] One or more portions of STEP 540 can be performed prior to
STEP 520, prior to STEP 530 and/or after STEP 550. STEP 540 can be
performed multiple times, such as one or more times prior to STEP
520, one or more times after STEP 520 and before STEP 530, one or
more times after STEP 530 and before STEP 550, and/or one or more
times after STEP 550. In some embodiments, STEPs 520 and 550 are
performed multiple times. In some embodiments, multiple
performances of STEP 540 are performed (e.g. multiple productions
of diagnostic data 305 at multiple test stimulation parameters
106), and the collective diagnostic data 305 is used to produce a
set of treatment stimulation parameters 107 set in a subsequent
step 550. In some embodiments, multiple performances of STEP 540
are performed and each result in a STEP 550 being performed in
which one or more treatment stimulation parameters 107 are
initiated and/or modified.
[0159] Referring now to FIG. 3, a flow chart of a series of steps
for performing STEP 540 of FIG. 2 is illustrated, consistent with
the present inventive concepts. STEPs 541 through 546 of FIG. 3 can
be performed using one or more components of system 10 of FIG. 1 as
described hereabove. In STEP 541, a set of test stimulation
parameters 106 are programmed into a stimulation device (e.g. a
first set of test stimulation parameters 106' programmed into
stimulator 100 using controller 200 as described in reference to
FIG. 1). In STEP 542, one or more portions of brain tissue of a
patient (e.g. tissue of brain B of FIG. 1) are stimulated using the
test stimulation parameters 106. In STEP 543, diagnostic data 305
is gathered with one or more diagnostic tools (e.g. diagnostic data
305 gathered by diagnostic tool 300 of FIG. 1) during stimulation
with the test stimulation parameters 106. In STEP 544, a
determination of testing completeness is performed. If testing is
not complete, STEP 547 is performed in which one or more of the
test stimulation parameters 106 are adjusted (e.g. a second set of
test stimulation parameters 106'' programmed into stimulator 100
using controller 200). Subsequently, STEP 542 is performed again,
stimulating brain B tissue with the adjusted test stimulation
parameters 106. STEP 543 is also performed again, gathering new
diagnostic data 305 at the adjusted test stimulation parameters
106. STEP 544 is performed again, determining test completeness. If
test is not complete, STEPs 547, 542, 543 and 544 are continuously
repeated until testing is complete.
[0160] In some embodiments, repeated stimulation with initial and
adjusted test stimulation parameters 106 includes incremental
increases or decreases of a test stimulation parameter 106 such a
series of increases in stimulation voltage and/or current as
described hereabove. In some embodiments, a first test stimulation
parameter 106 comprises a voltage level below 3.0 Volts, and a
second and subsequent test stimulation parameters 106 comprise
values correlating to sequentially increasing the voltage (e.g. in
0.1, 0.2, 0.3, 0.4 or 0.5 Volt increments) until an adverse event
and/or a therapeutic benefit is recorded by a diagnostic device of
the present inventive concepts. In some embodiments, the test
stimulation parameter 106 used does not exceed a maximum, such as a
maximum less than or equal to approximately 10.0 Volts, 9.0 Volts,
8.0 Volts or 7.0 volts. In some embodiments, the voltage or other
test stimulation parameter 106 level is increased slowly, such as
an increment made in time intervals of approximately at least 0.5
seconds, 2.0 seconds, 5.0 seconds, 10.0 seconds or 30.0
seconds.
[0161] In some embodiments, a set of test stimulation parameters
106 used in multiple steps 542 include at least one test
stimulation parameter 106 in which no stimulation is performed
(e.g. a test stimulation parameter 106 of 0.0 Volts). In these
embodiments, a therapeutic benefit of stimulation can be confirmed
(e.g. by the absence of the benefit when no stimulation was given,
such as when the diagnostic device comprises a memory test tool as
described herein wherein a higher score is achieved with one set of
test stimulation parameters 106).
[0162] After testing completeness has been confirmed in STEP 544,
STEP 545 is performed in which an assessment of the diagnostic data
305 produced by the one or more diagnostic tools 300 is assessed to
determine an optimized set of one or more treatment stimulation
parameters to be used to stimulate the brain tissue of the
patient.
[0163] In STEP 550, the optimized set of treatment stimulation
parameters 107 are programmed into the stimulation device, such as
is described in reference to STEP 550 of FIG. 2 hereabove. In some
embodiments, the treatment stimulation parameters 107 are a safety
margin below a level at which a test stimulation parameter 106
resulted in an adverse event, as has been described in detail in
reference to FIG. 1 hereabove.
[0164] In some embodiments, a first series of STEPs 542 through 547
are performed with a first set of test stimulation parameters 106
during a first time period to gather a first set of diagnostic data
305 with a diagnostic tool 300 of the present inventive concepts,
and a second series of STEPs 542 through 547 are performed with a
second set of test stimulation parameters 106 during a second time
period to gather a second set of diagnostic data 305. The treatment
stimulation parameters 107 can be based on the first set of test
stimulation parameters 106 and/or the second set of test
stimulation parameters 106, such as when the chosen set of
treatment stimulation parameters 107 avoids an adverse event and/or
causes a therapeutic benefit to the patient or other desired event.
Accordingly, a third and additional set of test stimulation
parameters 106 can be delivered in a third and additional time
periods. The various time periods can be similar or dissimilar in
length of time. In some embodiments, one or more time periods
comprise a length of time less than 24 hours, such as less than 6
hours, less than 3 hours, less than 1 hour, less than 30 minutes,
less than 15 minutes, less than 10 minutes, less than 5 minutes or
less than 2 minutes. Any or all of the test stimulation parameters
106 can be based on diagnostic data 305 gathered by a diagnostic
tool 300 of the present inventive concepts during a previous test
or treatment stimulation.
[0165] Referring now to FIG. 4, a schematic view of an electrical
stimulation device is illustrated, consistent with the present
inventive concepts. Stimulation device 100 delivers electrical
stimulation energy including a stimulus pulse frequency that is
controlled by programming a value to a frequency generator 412
(e.g. a programmable frequency generator) using bus 402. The
frequency generator 412 provides an interrupt signal to
microprocessor 410 through an interrupt line 401 when each stimulus
pulse is to be generated. The programmable frequency generator 412
communicates with a pulse width control module 414 via pathway 404.
The frequency generator 412 can be implemented by a commercial
device model CDP1878 sold by Harris Corporation. The amplitude for
each stimulus pulse is programmed to a digital to analog converter
416 using bus 402. The analog output is conveyed through a
conductor 403 to an output driver circuit 418 to control stimulus
amplitude.
[0166] Microprocessor 410 also programs pulse width control module
414 using bus 402. The pulse width control module 414 provides an
enabling pulse of duration equal to the pulse width via a conductor
405. Pulses with the selected characteristics are then delivered
from stimulation device 100 through cable 406 to stimulation
element 150. Stimulation element 150, typically comprising one or
more electrodes as are described hereabove, can be positioned to
stimulate the fornix and/or other regions of the brain or other
body tissue. At the time that all or a portion of stimulation
device 100 is implanted or otherwise positioned, a clinician can
program certain key parameters into the memory 422 of stimulation
device 100, such as via telemetry from an external controller, such
as controller 200 described in reference to FIG. 1 hereabove. These
parameters can be updated subsequently as needed, such as to modify
one or more test or treatment stimulation parameters based on
diagnostic data produced by a diagnostic device (e.g. diagnostic
data 305 produced by diagnostic tool 300 of FIG. 1). Battery 411
can provide electrical power to one or more components of
stimulation device 100 described herein.
[0167] Stimulation element 150 can comprise one or more deep brain
stimulation electrodes, such as electrodes model 3387 produced by
Medtronic of Minneapolis, Minn. These electrodes can be bilaterally
implanted such that the tips of the electrodes are positioned in a
region where cells can be recorded during micro-recording mapping.
Alternatively, a single electrode can be implanted unilaterally.
Energy can be applied at a frequency of 2 Hz to 1000 Hz, such as at
a frequency of approximately 130 Hz. Energy can be delivered at a
constant or varied pulse amplitude, such as at a constant pulse
amplitude of approximately 500 .mu.A. Energy can be delivered at a
voltage between 0.1 and 10 Volts, such as between 1 Volt and 6
Volts, such as at a voltage of approximately 3 Volts. Energy
delivery can be given in a series of on and off times, such as with
an on-time of approximately 30 .mu.seconds to 200 .mu.seconds, such
as with an on time of approximately 90 .mu.seconds. The duration of
energy delivery can range from 30 minutes to 120 minutes, such as a
duration of approximately 60 minutes, which can be repeated at
regular or irregular time intervals.
[0168] The embodiments of the present inventive concepts can be
configured as open-loop systems. The microcomputer algorithm
programmed by the clinician sets the stimulation parameters of the
stimulation device 100. In open-loop embodiments, this algorithm
can change one or more parameter values over time, but does so
independent of any changes in symptoms or other physiologic changes
the patient can be experiencing. Alternatively, a closed-loop
system discussed below which incorporates a sensor 430 to provide
feedback can be used to provide enhanced results. Sensor 430 (e.g.
an implanted or external sensor) can be used with a closed loop
feedback system in order to automatically or semi-automatically
determine the level of stimulation necessary to achieve the desired
level of improved cognitive function and/or to avoid an adverse
event. In closed-loop embodiments, microprocessor 410 can execute
an algorithm in order to provide stimulation with closed loop
feedback control. Such an algorithm can analyze a sensed signal
from sensor 430 and deliver stimulation therapy (e.g. delivery or
electrical, magnetic, light, sound and/or chemical treatment
therapy) based on the sensed signal. Adjustments can be made to one
or more treatment stimulation parameters when the signal falls
within or outside predetermined values or windows, for example,
predetermined levels of BDNF and other neurotrophins (e.g., NGF,
CNTF, FGF, EGF, NT-3) and corticosteroids. Closed loop applications
can be driven by diagnostic data, such as diagnostic data 305
produced by diagnostic tool 300 described in reference to FIG. 1
hereabove.
[0169] For example, in some embodiments, the patient can engage in
a specified cognitive task, wherein the system measures one or more
characteristics to determine if the levels sensed by sensor 430 are
at expected thresholds. If one or more of the sensed
characteristics are outside a predetermined threshold, the system
can initiate and/or modify one or more treatment stimulation
parameters, such as to enhance or otherwise improve cognitive
function.
[0170] In some embodiments, the system can be continuously
providing closed-loop feedback control. In other embodiments, the
system can intermittently operate in closed-loop feedback control,
such as based on a time of day (e.g., during hours that the patient
is awake) or based on a cognitive task (e.g., when the patient is
working). In yet other embodiments, the system can be switchable
between open-loop and closed-loop by operator control,
automatically and/or manually (e.g. manually via a handheld
controller).
[0171] In some embodiments, stimulation therapy can be provided in
relation to learning a task. For example, electrical stimulation
and/or drug delivery can be applied before, after and/or during the
performance of a memory, cognitive or motor task to facilitate the
acquisition of learning or consolidation of the task. In so doing,
the rate of memory acquisition and learning can be accelerated and
enhanced in magnitude. For example, electrical stimulation and/or
drug delivery can be provided before, during, and/or after periods
when the patient is learning a new language or playing a new
instrument. Such therapy can be useful during the encoding,
consolidation and/or retrieval phases of memory. The
neuromodulation intervention, brain stimulation or drug delivery
can occur before, after or simultaneously to the memory, cognitive
of motor skill task.
[0172] In another aspect of the invention, stimulation therapy can
be utilized to enhance neurogenesis as a method of improving
cognitive function. Techniques for enhancing neurogenesis through
treatment therapy are disclosed in U.S. Patents "Cognitive Function
Within A Human Brain", U.S. Ser. No. 11/303,293; "Inducing
Neurogenesis Within A Human Brain", U.S. Ser. No. 11/303,292; and
"Regulation of Neurotrophins", U.S. Ser. No. 11/303,619; as well as
U.S. Patent Application "Method Of Treating Cognitive Disorders
Using Neuromodulation", U.S. Ser. No. 11/364,977; the contents of
which are each incorporated herein by reference in their
entirety.
[0173] Referring back to FIG. 4, the system can optionally utilize
closed-loop feedback control having an analog to digital (A-to-D)
converter 424 coupled to sensor 430 via pathways 431 and 432.
Output of the A-to-D converter 424 is connected to microprocessor
410 through peripheral bus 402 including address, data and control
lines. Microprocessor 410 processes sensor 430 data in different
ways depending on the type of transducer in use and regulates
delivery, via a control algorithm, of stimulation based on the
sensed signal. For example, when the signal on sensor 430 exceeds a
level programmed by the clinician and stored in a memory 422,
increasing amounts of stimulation can be applied through an output
driver circuit 418. In the case of electrical stimulation, a
parameter of the stimulation can be adjusted such as amplitude,
pulse width and/or frequency.
[0174] Parameters which can be sensed include the activity of
single neurons as detected with microelectrode recording
techniques, local field potentials (LFPs), and event related
potentials (ERPs), for example in response to a memory task or
sensory stimulus and electroencephalogram or electrocorticogram.
For example, U.S. Pat. No. 6,227,203 provides examples of various
types of sensors that can be used to detect a symptom or a
condition of a cognitive disorder and responsively generate a
neurological signal. In an embodiment, a neurochemical
characteristic of the cognitive function can be sensed,
additionally or alternatively. For example, sensing of local levels
of neurotransmitters (e.g. glutamate, GABA, Aspartate), local pH or
ion concentration, lactate levels, local cerebral blood flow,
glucose utilization or oxygen extraction can also be used as the
input component of a closed loop system. These measures can be
taken at rest or in response to a specific memory or cognitive task
or in response to a specific sensory or motor stimulus. In another
embodiment, an electro-physiological characteristic of the
cognitive function can be sensed by sensor 430. The information
contained within the neuronal firing spike train, including spike
amplitude, frequency of action potentials, signal to noise ratio,
the spatial and temporal features and the pattern of neuronal
firing, oscillation behavior and inter-neuronal correlated activity
can be used to deliver therapies on a contingency basis in a closed
loop system. Moreover, treatment therapy delivered can be immediate
or delayed, diurnal, constant or intermittent depending on
contingencies as defined by the closed loop system.
[0175] The foregoing description and accompanying drawings set
forth a number of examples of representative embodiments at the
present time. Various modifications, additions and alternative
designs will become apparent to those skilled in the art in light
of the foregoing teachings without departing from the spirit
hereof, or exceeding the scope hereof, which is indicated by the
following claims rather than by the foregoing description. All
changes and variations that fall within the meaning and range of
equivalency of the claims are to be embraced within their
scope.
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