United States Patent [19]
`Rise et al.
`
`|||||||||||||||||||||||
`5,716,377
`Feb. 10, 1998
`
`US005716377A
`[11] Patent Number:
`[45] Date of Patent:
`
`[54] METHOD OF TREATING MOVEMENT
`DISORDERS BY BRAIN STIMULATION
`
`[75] Inventors: Mark T. Rise, Monticello; Gary W.
`King, Fridley, both of Minn.
`[73] Assignee: Medtronic, Inc., Minneapolis, Minn.
`
`van Horne et al., “Multichannel Semiconductor—Based Elec
`trodes for In Vivo Electrochemical and Electrophysiological
`Studies in Rat CNS”, Neuroscience Letters, 120, pp.
`249–252 (1990).
`Alexander et al., “Basal Ganglia–Thalamocortical Circuits:
`Parallel Substrates for Motor, Oculomotor, “Prefrontal” and
`‘Limbic' Functions”, Progress in Brain Research, vol. 85:
`119–146 (1990).
`Bergman et al., “Reversal of Experimental Parkinsonism by
`[21] Appl. No.: 637,366
`Lesions of the Subthalamic Nucleus”, Science, vol. 249:
`[22] Filed:
`Apr. 25, 1996
`1436–1438 (Sep. 21, 1990).
`Benabid et al., “Long term Suppression of Tremor by
`[51] Int. Cl* … A61N 1/00
`Cchronic Stimulation of the Ventral Intermediate Thalamic
`[52] U.S. Cl. … 607/2
`Nucleus”. The Lancet, vol. 337: 403–406 (Feb. 16, 1991).
`[58] Field of Search .................................. 607/1. 2, 3, 43.
`Limousin et al., “Effect on Parkinsonian Signs and Symp
`607/45, 46, 6, 72
`toms of Bilateal Subthalamic Nucleus Stimulation”. The
`Lancet, vol. 345: 91–95 (Jan. 14, 1995).
`Benabid et al., “Chronic Electrical Stimulation of the Ven
`tralis Intermedius Nucleus of the Thalamus as a Treatment
`of Movement Disorders”. J. Neurosurg., vol. 84; pp.
`203—214 (Feb. 1996).
`Primary Examiner—William E. Kamm
`Assistant Examiner—George R. Evanisko
`Attorney, Agent, or Firm—Banner & Witcoff. Ltd.
`[57]
`ABSTRACT
`Techniques for stimulating the brain to treat movement
`disorders resulting in abnormal motor behavior by means of
`an implantable signal generator and electrode. A sensor is
`used to detect the symptoms resulting from the motion
`disorder. A microprocessor algorithm analyzes the output
`from the sensor in order to regulate the stimulation delivered
`to the brain.
`
`[56]
`
`References Cited
`U.S. PATENT DOCUMENTS
`3,850,161 11/1974 Liss.
`4,702,254 10/1987 Zabara.
`4,867,164 9/1989 Zabara.
`5,025,807
`6/1991 Zabara .
`5,293,879 3/1994 Wonk et al. .
`OTHER PUBLICATIONS
`Andy “Thalemic Stimulation for Control of Movement
`Disorders”. Applied Nucrophysiology, Dec. 83 pp. 107–111.
`Benabid et al. “Vim and STN stimulation in Parkinsons
`Disease” Abstracts of the Intl Congress of Movement Dis
`orders, 1994 paper.
`Capellos—Lefebure D. et al “Chronic thalamic stimulation
`improves tremors and levodope induced dyskinesics in
`Parkinson’s disease” J Neurol Neurosurg Psychietry, 1993,
`J6: 268–73.
`
`
`
`18 Claims, 8 Drawing Sheets
`
`FITBIT, INC. v. LOGANTREE LP
`Ex. 1022 / Page 1 of 15
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`

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`U.S. Patent
`U.S. Patent
`
`Feb. 10, 1998
`Feb. 10, 1998
`
`Sheet 1 of 8
`Sheet 1 of 8
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`5,716,377
`5,716,377
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`
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`Ex. 1022 / Page 2 of 15
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`

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`U.S. Patent
`U.S. Patent
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`Feb. 10, 1998
`Feb. 10, 1998
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`Sheet 2 of 8
`Sheet 2 of 8
`
`5,716,377
`5,716,377
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`
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`Ex. 1022 / Page 3 of 15
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`

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`U.S. Patent
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`Feb. 10, 1998
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`Sheet 3 of 8
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`5,716,377
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`Fig. 3
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`MICRO
`PROCESSOR
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`PROGRAMMABLE
`FREQUENCY
`GENERATOR
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`PULSE
`WIDTH
`CONTROL
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`22
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`D gºal
`ANALOG
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`OUTPUT
`DRIVER
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`229
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`MEMORY
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`224
`204
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`206
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`134 – 130
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`135
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`Ex. 1022 / Page 4 of 15
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`

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`U.S. Patent
`
`Feb. 10, 1998
`Sheet 4 of 8
`Fig. 4
`400
`
`5,716,377
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`READ PARAMETERS
`(1)BLOCK OR INCREASE NEURAL ACTIVITY AT
`STIMULATION SITE
`(2) INCREASE IN SENSOR ACTIVITY = INCREASE OR
`DECREASE IN STIMULATION TARGET ACTIVITY
`(3) PULSE WIDTH MINIMUM AND MAXIMUM
`(4) AMPLITUDE MINIMUM AND MAXIMUM
`(5) FREQUENCY MINIMUM AND MAXIMUM
`(6) PRIORITY OF PARAMETER CHANGES
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`406
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`RESET
`TIMER
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`410
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`READ
`FEEDBACK
`SENSOR
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`CHANGE
`PARAMETERS
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`414
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`YES
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`PARAMETER
`CHANGE
`NEEDED?
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`TIMER
`ELAPSED?
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`REDUCE
`PARAMETERS
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`Ex. 1022 / Page 5 of 15
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`U.S. Patent
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`Feb. 10, 1998
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`Sheet 5 of 8
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`5,716,377
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`Fig. 5
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`PROGRAMMED
`TO BLOCK NEURAL ACTIVITY?
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`NO
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`YES
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`READ SENSOR FEEDBACK VALUE
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`STIMULATION
`TARGET ACTIVITY
`TOO HIGH
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`YES
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`EXCEEDS
`MAXIMUM
`FREQUENCYP
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`423A
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`|NCREASE FREQUENCY
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`Ex. 1022 / Page 6 of 15
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`U.S. Patent
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`Feb. 10, 1998
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`Sheet 6 of 8
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`5,716,377
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`Fig. 6
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`YES
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`EXCEEDS
`MAXIMUM
`PULSE
`WIDTH 7
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`INCREASE PULSE WIDTH
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`EXCEEDS
`MAXIMUM
`AMPLITUDE7
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`NO
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`SET CLINIC [AN
`NOTIFICATION
`MESSAGE
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`Ex. 1022 / Page 7 of 15
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`U.S. Patent
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`Feb. 10, 1998
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`Sheet 7 of 8
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`5,716,377
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`420A
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`Fig. 7
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`430
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`SET PROGRAMMED FREQUENCY VALUE
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`READ FEEDBACK SENSOR VALUE
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`431
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`STIMULATIONN?”
`TARGET
`ACTIVITY
`TOO LOW2
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`EXCEEDS
`MAXIMUM
`AMPLITUDE7
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`YES
`
`434
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`INCREASE AMPLITUDE
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`433A
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`Ex. 1022 / Page 8 of 15
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`U.S. Patent
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`Feb. 10, 1998
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`Sheet 8 of 8
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`5,716,377
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`Fig. 8
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`EXCEEDS
`MAXIMUM
`PULSE WIDTH2
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`YES
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`INCREASE PULSE WIDTH
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`437
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`SET CLINIC IAN INDICATOR
`MESSAGE
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`Ex. 1022 / Page 9 of 15
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`

`
`1
`METHOD OF TREATING MOVEMENT
`DISORDERS BY BRAIN STIMULATION
`
`5,716.377
`
`2
`Neurosurgeons have been able to diminish the symptoms
`of the foregoing movement disorders by lesioning certain
`brain areas. In addition, it has been demonstrated that Deep
`Brain Stimulation (DBS) at high frequencies (100 Hz or
`higher) of certain brain structures can alleviate, diminish, or
`completely stop symptoms of tremor, rigidity, akinesia or
`hemiballism. Published targets of stimulation include the
`VIM (ventral intermediate thalamus), subthalamic nucleus
`and internal globus pallidus.
`It is believed that many symptoms of the foregoing
`motion disorders are due to dysfunction of the basal ganglia
`or thalamus. The dysfunction can result in overactivity of the
`output neurons of the ganglia creating excessive inhibition
`of the thalamus or underactivity of the ganglia resulting in
`too little inhibition of the thalamus. If there is too little
`output activity from the basal ganglia or too little inhibition
`of the thalamus, a condition such as Ballism or Dystonia will
`result. If there is too much output activity from the basal
`ganglia (too much inhibition), a condition such as Hypoki
`nesia will result.
`SUMMARY OF THE INVENTION
`A preferred form of the invention can treat a movement
`disorder resulting in abnormal motor response by means of
`an implantable signal generator and an implantable electrode
`having a proximal end coupled to the signal generator and
`having a stimulation portion for therapeutically stimulating
`the brain. The electrode is implanted in the brain so that the
`stimulation portion lies adjacent to a predetermined site in
`the basal ganglia or thalamus of the brain. The signal
`generator is operated to pulse the electrode at a predeter
`mined rate and amplitude. By using the foregoing method,
`the symptoms of hypokinetic disorders, such as Akinesia,
`Bradykinesia or Rigidity, and hyperkinetic disorders, such as
`Ballism, Hemiballism, Choreiform. Torticollis. Spasticity or
`Dystonia can be alleviated. According to one embodiment of
`the invention, the stimulation can decrease excitement of the
`thalamus or increase inhibition of the thalamus. According
`to another embodiment of the invention, the stimulation can
`increase excitement of the thalamus or decrease inhibition of
`the thalamus.
`Another form of the invention uses a sensor in combina
`tion with a signal generator and a stimulating electrode to
`treat a movement disorder resulting in abnormal motor
`behavior. In this form of the invention, the sensor generates
`a sensor signal relating to the extent of the abnormal motor
`behavior. Control means responsive to the sensor signal
`regulate the signal generator so that the stimulation is
`increased in response to an increase in the abnormal motor
`behavior and is decreased in response to a decrease in the
`abnormal motor behavior.
`By using the foregoing techniques, the symptoms of
`hypokinetic disorders, such as akinesia, bradykinesia or
`rigidity, and hyperkinetic disorders, such as ballism or
`hemiballism, chorea, athetosis, spasticity, or dystonia can be
`alleviated.
`BRIEF DESCRIPTION OF THE DRAWINGS
`These and other advantages and features of the invention
`will become apparent upon reading the following detailed
`description and referring to the accompanying drawings in
`which like numbers refer to like parts throughout and in
`which:
`FIG. 1 is a diagrammatic illustration of an electrode
`implanted in a brain according to a preferred embodiment of
`the present invention and a signal generator coupled to the
`electrode;
`
`BACKGROUND OF THE INVENTION
`1. Field of the Invention
`This invention relates to brain stimulation techniques, and
`more particularly relates to such techniques for treating
`movement disorders.
`2. Description of Related Art
`Patients with neurodegenerative diseases or trauma like
`cerebral infarct or spinal cord injury can have a variety of
`movement and muscle control problems, like resting,
`postural, intention or action tremor; dystonia (improper
`muscle tone, myoclonus); spasticity (undesirable
`movements, or muscle co-contraction); dyskinesia (poorly
`executed movements) or involuntary movements like
`ballismus, choreiform movements and torticollis
`(inappropriate movements or limb control). Many of these
`problems can be called hyperkinesia. Although they can be
`chronic, or worse, progressive, they also may have times of
`relative remission. Such problems are found, at certain
`stages, for patients with Parkinson’s disease, multiple
`sclerosis, cerebral palsy, secondary to deafferentation pain,
`post stroke, post apoplexy or anoxia, post head or spinal
`trauma, post poisoning, cerebellar disease, etc. Dyskinesia
`also may result from long term usage of L-dopa, or
`Levodopa, for Parkinson's patients, or other drugs.
`Spasticity is defined as a state of excessive muscular tonus
`(hypertonus) and increased spinal reflexes. This condition
`exists when the corticospinal pathways have been disrupted.
`Disruption can occur as a result of stroke causing injury to
`the fibers as they pass through the internal capsule, a
`degenerative disorder or physical trauma to the cortex or
`spinal cord. Loss of this pathway leads to a lack of inhibition
`of the lower motorneurons which then are more active and
`responsive to reflexes. In some cases injury to the premotor
`cortex disrupts the output of the primary motor cortex
`leading to the similar phenomena.
`One form of the Dyskinesia is known as Ballism which
`typically results in violent flinging movements of the limbs.
`The movements often affect only one side of the body, in
`which case the disorder is known as Hemiballism.
`In patients suffering from essential tremor or tremor due
`to Parkinson's Disease, the predominant symptom of the
`disordered movement is tremor. Tremor is often subdivided
`on the basis of whether the trembling of the limb occurs
`when the limb is at rest or when muscular contraction is
`occurring.
`Besides being caused by degenerative illness or head
`injury, tremor can be of unknown origin. One syndrome of
`idopathic tremor is referred to as essential tremor.
`Patients with neurodegenerative diseases or trauma to the
`basal ganglia like cerebral infarct can have a variety of
`movement and muscle control problems, like akinesia, rigid
`ity or bradykinesia. These motor disorders may be called
`hypokinetic problems, the inability to move. These problems
`can be chronic, or worse, progressive, but they also may
`have times of relative remission, especially when drugs are
`effective. Such problems are common, at certain stages, for
`patients with Parkinson's disease, multiple sclerosis, cere
`bral palsy, secondary to deafferentation pain, post stroke,
`post apoplexy or anoxia, post head or spinal trauma, post
`poisoning, cerebellar disease, etc. Dyskinesia is often a
`side-effect from medications used for certain symptoms (like
`tremor, akinesia, rigidity), especially L-dopa or Levodopa.
`
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`5,716,377
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`3
`FIG. 2 is a diagrammatic illustration of a portion of the
`nervous system of the human body in which a preferred form
`of motion sensor, signal generator and electrode have been
`implanted;
`FIG. 3 is a schematic block diagram of a microprocessor
`and related circuitry used in the preferred embodiment of the
`invention; and
`FIGS. 4–8 are flow charts illustrating a preferred form of
`a microprocessor program for generating stimulation pulses
`to be administered to the brain.
`
`DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`Referring to FIG. 1. a system or device 10 made in
`accordance with the preferred embodiment may be
`implanted below the skin of a patient. A lead 22A is
`positioned to stimulate a specific site in a brain (B). Device
`10 may take the form of a modified signal generator Model
`7424 manufactured by Medtronic, Inc. under the trademark
`Itrel II which is incorporated by reference. Lead 22A may
`take the form of any of the leads sold with the Model 7424.
`for stimulating the brain, and is coupled to device 10 by a
`conventional conductor 22.
`The distal end of lead 22A terminates in four stimulation
`electrodes generally designated 115 implanted into a portion
`of the basal ganglia of the brain by conventional stereotactic
`surgical techniques. However, other numbers of electrodes.
`such as two or six, may be used for various applications.
`Each of the four electrodes is individually connected to
`device 10 through lead 22A and conductor 22. Lead 22A is
`surgically implanted through a hole in the skull 123 and
`conductor 22 is implanted between the skull and the scalp
`125 as shown in FIG. 1. Conductor 22 is joined to implanted
`device 10 in the manner shown. Referring to FIG. 2. device
`10 is implanted in a human body 120 in the location shown.
`Body 120 includes arms 122 and 123. Alternatively, device
`10 may be implanted in the abdomen.
`Conductor 22 may be divided into twin leads 22A and
`22B that are implanted into the brain bilaterally as shown.
`Alternatively, lead 22B may be supplied with stimulating
`pulses from a separate conductor and signal generator. Leads
`22A and 22B could be 1) two electrodes in two separate
`nuclei that potentiate each others effects or 2) nuclei with
`opposite effects with the stimulation being used to fine tune
`the response through opposing forces.
`A sensor 130 is attached to or implanted into a portion of
`a patient's body suitable for detecting symptoms of the
`motion disorder being treated, such as a motor response or
`motor behavior. In this specification and claims, motor
`behavior includes motor response. Sensor 130 is adapted to
`sense an attribute of the symptom to be controlled or an
`important related symptom. For motion disorders that result
`in abnormal movement of an arm, such as arm 122, sensor
`130 may be a motion detector implanted in arm 122 as
`shown. For example, sensor 130 may sense three
`dimensional or two-dimensional motion (linear rotational or
`joint motion), such as by an accelerometer. One such sensor
`suitable for use with the present invention is described in
`U.S. Pat. No. 5.293.879 (Vonk). Another suitable acceler
`ometer is found in pacemakers manufactured by Medtronic,
`Inc. and described in patent application Ser. No. 08/399,072
`filed Mar. 8, 1995, in the names of James Sikorski and Larry
`R. Larson and entitled “Package Integrated Accelerometer”.
`Sensor 130 also may be placed in device 10 in order to detect
`abnormal movement resulting from the motion disorder
`being treated.
`
`4
`Sensor 130 also may be capable of detecting gravity
`direction or motion relative to some object (e.g., a magnet)
`either implanted or fixed nearby. Sensor 130 also may take
`the form of a device capable of detecting force in muscles or
`at joints, or pressure.
`Sensor 130 may detect muscle EMG in one, two or more
`muscles, or in reciprocal muscles at one joint. For such
`detection, sensor 130 may take the form of a recording
`electrode inserted into the muscle of interest.
`Brain EEG (e.g., motor cortex potentials recorded above
`the motor neurons controlling specific muscle groups) also
`may be detected by sensor 130.
`Yet another form of sensor 130 would include a device
`capable of detecting nerve compound action potentials (e.g.,
`either sensory afferent information from muscle or skin
`receptors or efferent motor potentials controlling a muscle of
`interest).
`For certain types of patients, sensor 130 may take the
`form of device detecting the posture of the patient.
`Sensor 130 also may take the form of a device capable of
`detecting nerve cell or axon activity that is related to the
`pathways at the cause of the symptom, or that reflects
`sensations which are elicited by the symptom. Such a sensor
`may be located deep in the brain. For such detecting, sensor
`130 may take the form of an electrode inserted into the
`internal capsule of the brain, or other locations that are part
`of the basal ganglia. Signals that are received by the sensor
`may by amplified before transmission to circuitry contained
`within device 10.
`Sensor 130 may take the form of a transducer consisting
`of an electrode with an ion selective coating applied which
`is capable of directly transducing the amount of a particular
`transmitter substance or its breakdown by-products found in
`the interstitial space of a region of the brain such as the
`ventral lateral thalamus. The level of the interstitial trans
`mitter substance is an indicator of the relative activity of the
`brain region. An example of this type of transducer is
`described in the paper “Multichannel semiconductor-based
`electrodes for in vivo electrochemical and electrophysi
`ological studies in rat CNS” by Craig G. van Horne, Spencer
`Bement, Barry J. Hoffer, and Greg A. Gerhardt, published in
`Neuroscience Letters, 120 (1990) 249–252.
`For tremor, the relative motion of a joint or limb or muscle
`EMG may be productively sensed. Sensing electrical activ
`ity of neurons in various locations of the motor circuitry also
`is helpful. Recording the electrical activity in the thalamus
`or cerebellum will reveal a characteristic oscillating electri
`cal activity when tremor is present.
`For Ballism. Hemiballism or tremor, sensor 130 may take
`the form of an accelerometer detecting relative motion of a
`joint and limb or muscle EMG.
`For Dystonia, sensor 130 may take the form of a device
`for detecting relative motion of a joint or limb or muscle
`EMG.
`Referring to FIGS. 2 and 3, the output of sensor 130 is
`coupled by cable 132, comprising conductors 134 and 135,
`to the input of an analog to digital converter 206 within
`device 10. Alternatively, the output of an external sensor
`would communicate with the implanted pulse generator
`through a telemetry downlink.
`The remainder of the components shown in FIG. 3 are
`included in device 10. The output of the analog to digital
`converter 206 is connected to a microprocessor 200 through
`a peripheral bus 202 including address. data and control
`lines. Microprocessor 200 processes the sensor data in
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`5
`different ways depending on the type of transducer in use.
`When the signal on sensor 130 exceeds a level programmed
`by the clinician and stored in a memory 204, increasing
`amounts of stimulation will be applied through an output
`driver 224.
`The stimulus pulse frequency is controlled by program
`ming a value to a programmable frequency generator 208
`using bus 202. The programmable frequency generator
`provides an interrupt signal to microprocessor 200 through
`an interrupt line 210 when each stimulus pulse is to be
`generated. The frequency generator may be implemented by
`model CDP1878 sold by Harris Corporation.
`The amplitude for each stimulus pulse is programmed to
`a digital to analog converter 218 using bus 202. The analog
`output is conveyed through a conductor 220 to an output
`driver circuit 224 to control stimulus amplitude.
`Microprocessor 200 also programs a pulse width control
`module 214 using bus 202. The pulse width control provides
`an enabling pulse of duration equal to the pulse width via a
`conductor 216. Pulses with the selected characteristics are
`then delivered from device 10 through cable 22 and lead 22A
`to the basal ganglia, thalamus or other region of the brain.
`Microprocessor 200 executes an algorithm shown in
`FIGS. 4–8 in order to provide stimulation with closed loop
`feedback control. At the time the stimulation device 10 is
`implanted, the clinician programs certain key parameters
`into the memory of the implanted device via telemetry.
`These parameters may be updated subsequently as needed.
`Step 400 in FIG. 4 indicates the process of first choosing
`whether the neural activity at the stimulation site is to be
`blocked or facilitated (step 400(1)) and whether the sensor
`location is one for which an increase in the neural activity at
`that location is equivalent to an increase in neural activity at
`the stimulation target or vice versa (step 400(2)). Next the
`clinician must program the range of values for pulse width
`(step 400(3)), amplitude (step 400(4)) and frequency (step
`400(5)) which device 10 may use to optimize the therapy.
`The clinician may also choose the order in which the
`parameter changes are made (step 400(6)). Alternatively, the
`clinician may elect to use default values.
`The algorithm for selecting parameters is different
`depending on whether the clinician has chosen to block the
`neural activity at the stimulation target or facilitate the
`neural activity. FIG. 4 details steps of the algorithm to make
`parameter changes.
`The algorithm uses the clinician programmed indication
`of whether the neurons at the particular location of the
`stimulating electrode are to be facilitated or blocked in order
`to reduce the neural activity in the subthalamic nucleus to
`decide which path of the parameter selection algorithm to
`follow (step 420. FIG. 5). If the neuronal activity is to be
`blocked, device 10 first reads the feedback sensor 130 in step
`421. If the sensor values indicate the activity in the
`glutamatergic neurons is too high (step 422), the algorithm
`in this embodiment first increases the frequency of stimu
`lation in step 424 provided this increase does not exceed the
`preset maximum value set by the physician. Step 423 checks
`for this condition. If the frequency parameter is not at the
`maximum, the algorithm returns to step 421 through path
`421A to monitor the feedback signal from sensor 130. If the
`frequency parameter is at the maximum, the algorithm next
`increases the pulse width in step 26 (FIG. 6). again with the
`restriction that this parameter has not exceeded the maxi
`mum value as checked for in step 425 through path 423A.
`Not having reached maximum pulse width, the algorithm
`returns to step 421 to monitor the feedback signal from
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`sensor 130. Should the maximum pulse width have been
`reached, the algorithm next increases amplitude in a like
`manner as shown in steps 427 and 428. In the event that all
`parameters reach the maximum, a notification message is set
`in step 429 to be sent by telemetry to the clinician indicating
`that device 10 is unable to reduce neural activity to the
`desired level.
`If, on the other hand, the stimulation electrode is placed
`in a location which the clinician would like to activate in
`order to increase an inhibition of the subthalamic nucleus,
`the algorithm would follow a different sequence of events.
`In the preferred embodiment, the frequency parameter
`would be fixed at a value chosen by the clinician to facilitate
`neuronal activity in step 430 (FIG. 7) through path 420A. In
`steps 431 and 432 the algorithm uses the values of the
`feedback sensor to determine if neuronal activity is being
`adequately controlled. In this case, inadequate control indi
`cates that the neuronal activity of the stimulation target is too
`low. Neuronal activity is increased by first increasing stimu
`lation amplitude (step 434) provided it doesn't exceed the
`programmed maximum value checked for in step 433. When
`maximum amplitude is reached, the algorithm increases
`pulse width to its maximum value in steps 435 and 436 (FIG.
`8). A lack of adequate reduction of neuronal activity in the
`subthalamic nucleus, even though maximum parameters are
`used, is indicated to the clinician in step 437. After steps 434.
`436 and 437, the algorithm returns to step 431 through path
`431A, and the feedback sensor again is read.
`It is desirable to reduce parameter values to the minimum
`level needed to establish the appropriate level of neuronal
`activity in the subthalamic nucleus. Superimposed on the
`algorithm just described is an additional algorithm to read
`just all the parameter levels downward as far as possible. In
`FIG. 4, steps 410 through 415 constitute the method to do
`this. When parameters are changed, a timer is reset in step
`415. If there is no need to change any stimulus parameters
`before the timer has counted out, then it may be possible due
`to changes in neuronal activity to reduce the parameter
`values and still maintain appropriate levels of neuronal
`activity in the target neurons. At the end of the programmed
`time interval, device 10 tries reducing a parameter in step
`413 to determine if control is maintained. If it is, the various
`parameter values will be ratcheted down until such time as
`the sensor values again indicate a need to increase them.
`While the algorithms in FIG.4 follow the order of parameter
`selection indicated, other sequences may be programmed by
`the clinician.
`The present invention may be implemented by providing
`pulses to lead 22A having amplitudes of 0.1 to 20 volts,
`pulse widths varying from 0.02 to 1.5 milliseconds, and
`repetition rates varying from 2 to 2500 Hz. The appropriate
`stimulation pulses are generated by device 10 based on the
`computer algorithm shown in FIGS. 4–8 that read the output
`of converter 140 and makes the appropriate analysis.
`For some types of motion disorders, a microprocessor and
`analog to digital converter will not be necessary. The output
`from sensor 130 can be filtered by an appropriate electronic
`filter in order to provide a control signal for device 10.
`The type of stimulation administered by device 10 to the
`brain depends on the specific location at which the elec
`trodes 115 of lead 22A are surgically implanted. The appro
`priate stimulation for the portion of the basal ganglia or
`thalamus in which lead 22A terminates. together with the
`effect of the stimulation on that portion of the brain for
`hyperkinetic motion disorders is provided in the following
`Table I:
`
`Ex. 1022 / Page 12 of 15
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`

`
`7
`
`TABLE I
`
`5,716.377
`
`8
`
`EFFECT
`
`STIMULUS TYPE
`
`LOCATION
`
`DECREASE EXCITATION HIGH FREQ. BLOCKING VLTHALAMUS
`OF VL THALAMLUS
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ. ACTIVATING Pallido-thalamic axons (AL
`OF WL THALAMUS
`STIMULATION
`and LT)
`INCREASE EXCITATION LOW FREQ. ACTIVATING GPi/SNr
`OF GPi?sNr
`STIMULATION
`INCREASE EXCITATION LOW FREQ. ACTIVATING Subthalamic to pallidal fiber
`OF GPWSNr
`STIMULATION
`tracts
`DECREASE INHIBITION
`HIGH FREQ BLOCKING
`Neostriatum
`OF GPi?sNr
`STIMULATION
`INCREASE EXCITATION LOW FREQ
`OF STN
`STIMULATION
`DECREASE INHIBITION
`HIGH FREQ. BLOCKING GPe
`OF STN
`STIMULATION
`DECREASE EXCITATION HIGH FREQ. BLOCKING GPe
`OF GPe
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ
`OF GPe
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ
`OF GPe
`STIMULATION
`
`Neostriatum
`
`Putamen to Gpe fibers (i.e.,
`border of nucleus)
`
`STN Nucleus
`
`The appropriate stimulation for use in connection with the
`portion of the basal ganglia or thalamus in which lead 22A
`terminates, together with the effect of the stimulation on that 2s
`portion of the brain for hypokinetic motion disorders is
`provided in the following Table II:
`TABLE II
`
`EFFECT
`
`STIMULUS TYPE
`
`LOCATION
`
`VL THALAMUS
`
`INCREASE EXCITATION LOW FREQ.
`OF VL THALAMUS
`STIMULATION
`DECREASE INHIBITION
`HIGH FREQ. BLOCKING GPi?sNr
`OF VL THALAMUS
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ.
`Striatopallidal fiber pathway
`OF GPWSNr
`STIMULATION
`INCREASE INHIBITION
`Low FREQ.
`OF GPWSNr
`STIMULATION
`DECREASE EXCITATION HIGH FREQ. BLOCKING GPI/SNR
`OF GPWSNr
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ.
`GPe TO STN fiber pathway
`OF STN
`STIMULATION
`INCREASE INHIBITION
`LOW FREQ.
`OF STN
`STIMULATION
`DECREASE EXCITATION HIGH FREQ, BLOCKING STN
`OF STN
`STIMULATION
`INCREASE EXCITATION LOW FREQ. ACTIVATING GPe
`OF GPe
`STIMULATION
`DECREASE INHIBITION
`HIGH FREQ. BLOCKING Neostriatum
`OF GPe
`STIMULATION
`INCREASE INHIBITION LOW FREQ, ACTIVATING Striatopallidal fiber pathways
`OF GP:/SNT
`STIMULATION
`
`Neostriatum
`
`GPE
`
`In the foregoing tables I and II, VL Thalamus means
`ventrolateral thalamus; GPi means internal segment of glo
`bus pallidus; SNr means substantia nigra pars reticulata,
`STN means subthalamic nucleus; and GPe means external
`segment of globus pallidus; LT means lenticulo–thalamic
`fiber pathway and AL means ansa lenticularis.
`
`TABLE III
`
`MEDIAL-
`LATERAL
`55 BRAIN REGION DIMENSION
`
`ANTERIOR
`DORSAL-
`POSTERIOR
`VENTRAL
`DIMENSION DIMENSION
`
`VL Thalamus
`GPi
`SNr
`STN
`60 GPe
`Striatum
`
`0.7 to 1.8
`0.5 to 2.0
`0.5 to 1.5
`0.5 to 2.0
`1.6 to 2.7
`
`1.5 to -0.2
`0.5 to —0.7
`–0.6 to -1.5
`0.0 to -1.0
`1.0 to -1.0
`
`0.0 to -1.0
`0.7 to 2.0
`0.7 to -0.7
`0.6 to -1.0
`2.0 to -1.0
`
`Caudate
`Putamen
`
`0.5 to 2.0
`1.2 to 3.3
`
`1.5 to 3.0
`1.5 to -1.0
`
`15 to 3.0
`2.5 to -1.2
`
`Typical stereotaxic coordinates for the portions of a
`normal brain described in Tables I and II are identified in the
`following Table III:
`
`65
`
`In the foregoing table: the medial-lateral dimensions are
`relative to midline of the brain; the anterior-posterior dimen
`
`Ex. 1022 / Page 13 of 15
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`25
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`35
`
`20
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`9
`sions are relative to the midpoint between the anterior
`commissure and posterior commissure with negative indi
`cating the posterior direction; the dorsal-ventral dimensions
`are relative to a line connecting the midpoints of the anterior
`and posterior commissures with negative being ventral to the
`line; all dimension are in centimeters.
`Microprocessor 200 within device 10 can be programmed
`so that the desired stimulation can be delivered to the
`specific brain sites described in Tables I and II. Alternatively,
`sensor 130 can be used with a closed loop feedback system
`in order to automatically determine the type of stimulation
`necessary to alleviate motor disorder symptoms as described
`in connection with FIGS. 4 and 5.
`By using the foregoing techniques, motor disorders can be
`controlled with a degree of accuracy previously unattain
`able.
`Those skilled in that art will recognize that the preferred
`embodiments may be altered or amended without departing
`from the true spirit and scope of the invention, as defined in
`the accompanying claims.
`We claim:
`1. A method of therapeutically treating a movement
`disorder resulting in abnormal motor behavior by means of
`a signal generator and an implantable electrode having a
`proximal end and a stimulation portion comprising the steps
`of:
`surgically implanting said electrode in a brain of a patient
`so that the stimulation portion lies in communication
`with a predetermined treatment site in the brain, said
`predetermined treatment site being selected from the
`group consisting of the pallido—thalamic axons (AL),
`the lenticulo-thalamic fiber pathway (LT), substantia
`migra pars reticulata (SNI), external segment of globus
`pallidus (GPe), subthalamic to pallidal fiber tracts,
`putamen, and putamen to GPe fibers;
`coupling said proximal end of said electrode to said signal
`generator; and
`operating said signal generator to stimulate said prede
`termined treatment site in the brain,
`whereby the symptoms of said movement disorder are
`reduced.
`2. A method, as claimed in claim 1, wherein said move
`ment disorder is a hyperkinetic disorder and wherein said
`45
`stimulation is selected to reduce thalamic output.
`.
`3. A method, as claimed in claim 2, wherein said hyper
`kinetic disorder comprises dystonia, ballism, hemiballism,
`chorea, athetosis, torticollis, or spasticity.
`4. A method, as claimed in claim 2, wherein said stimu
`lation is selected to decrease excitement of the thalamus or