US20050033379A1 - Method of treating depression, mood disorders and anxiety disorders using neuromodulation - Google Patents

Method of treating depression, mood disorders and anxiety disorders using neuromodulation Download PDF

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US20050033379A1
US20050033379A1 US10/872,271 US87227104A US2005033379A1 US 20050033379 A1 US20050033379 A1 US 20050033379A1 US 87227104 A US87227104 A US 87227104A US 2005033379 A1 US2005033379 A1 US 2005033379A1
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stimulation
area
mood
lead
electrical
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US10/872,271
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Andres Lozano
Helen Mayberg
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Advanced Neuromodulation Systems Inc
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Advanced Neuromodulation Systems Inc
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61MDEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142Pressure infusion, e.g. using pumps
    • A61M5/14244Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body
    • A61M5/14276Pressure infusion, e.g. using pumps adapted to be carried by the patient, e.g. portable on the body specially adapted for implantation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4848Monitoring or testing the effects of treatment, e.g. of medication
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/02Details
    • A61N1/04Electrodes
    • A61N1/05Electrodes for implantation or insertion into the body, e.g. heart electrode
    • A61N1/0526Head electrodes
    • A61N1/0529Electrodes for brain stimulation
    • A61N1/0534Electrodes for deep brain stimulation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/3606Implantable neurostimulators for stimulating central or peripheral nerve system adapted for a particular treatment
    • A61N1/36082Cognitive or psychiatric applications, e.g. dementia or Alzheimer's disease
    • A61N1/36096Mood disorders, e.g. depression, anxiety or panic disorder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61NELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00Electrotherapy; Circuits therefor
    • A61N1/18Applying electric currents by contact electrodes
    • A61N1/32Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/3605Implantable neurostimulators for stimulating central or peripheral nerve system
    • A61N1/36128Control systems
    • A61N1/36146Control systems specified by the stimulation parameters
    • A61N1/36182Direction of the electrical field, e.g. with sleeve around stimulating electrode
    • A61N1/36185Selection of the electrode configuration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants

Definitions

  • This invention relates to nervous tissue stimulation for treating depression, anxiety disorders and mood disorders, and more particularly to modulating nervous tissue at a predetermined stimulation site in brain tissue.
  • electrical stimulation for treating neurological disease, including such disorders as movement disorders including Parkinson's disease, essential tremor, dystonia, and chronic pain, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over lesioning since lesioning destroys the nervous system tissue. In many instances, the preferred effect is to modulate neuronal activity. Electrical stimulation permits such modulation of the target neural structures and, equally importantly, does not require the destruction of nervous tissue.
  • electrical stimulation procedures include electroconvulsive therapy (ECT), repetitive transcranial (rTMS) magnetic stimulation and vagal nerve stimulation (VNS).
  • DBS Deep brain stimulation
  • U.S. Pat. No. 6,016,449 and U.S. Pat. No. 6,176,242 disclose a system for the electrical stimulation of areas in the brain for the treatment of certain neurological diseases such as epilepsy, migraine headaches and Parkinson's disease.
  • Electrodes placed on the scalp.
  • Other devices require significant surgical procedures for placement of electrodes, catheters, leads, and/or processing units. These devices may also require an external apparatus that needs to be strapped or otherwise affixed to the skin.
  • the present invention relates to electrical and/or chemical stimulation applied to areas of the brain not considered in the prior art to play a role in depression.
  • the invention uses electrical stimulation and/or chemical stimulation (i.e., one or more pharmaceuticals) to treat depression.
  • electrical stimulation i.e., one or more pharmaceuticals
  • magnetic stimulation can also be used, such as transcranial magnetic stimulation (“TMS”).
  • TMS transcranial magnetic stimulation
  • the stimulation modulates areas of the brain that exhibit altered activity in patients relative to psychiatrically normal control subjects, thereby treating or preventing affective disorders, for example depression and/or anxiety disorders.
  • Such stimulation is likely to be produced by electrical stimulation, an excitatory neurotransmitter agonist(s) (i.e., norepinephrine), an inhibitory neurotransmitter antagonist(s), and/or a medication that increases the level of an excitatory neurotransmitter (i.e., flouxetine (Prozac®), trazodone).
  • an excitatory neurotransmitter agonist(s) i.e., norepinephrine
  • an inhibitory neurotransmitter antagonist(s) i.e., a medication that increases the level of an excitatory neurotransmitter
  • a medication that increases the level of an excitatory neurotransmitter i.e., flouxetine (Prozac®), trazodone.
  • One embodiment of the present invention utilizes neurosurgical intervention to modulate the pathological activity of a subcallosal area in patients suffering from depression or other affective disorders.
  • Such interventions include, applying electrical stimulation, herein termed “deep brain stimulation” or DBS, as is currently practiced to treat a number of disorders like Parkinson's disease.
  • DBS deep brain stimulation
  • Other stimulations can include chemical stimulation such as through the use of pharmaceutical or drug pumps, for example local delivery of neuroactive substances to disrupt or block the pathological activity stemming from or coursing through this area.
  • stimulation i.e., electrical, magnetic and/or chemical modulates the gray matter and white matter tracts in a subcallosal area, as well as the white matter tracts that are associated with the subcallosal area (such as the white matter tracts that lead to and from the subcallosal area or that are adjacent to the subcallosal area), which in turn modulates the limbic system.
  • other stimulations may comprise magnetic stimulation and/or transplantation of cells.
  • Certain embodiments of the present invention involve a method that comprises surgically implanting a device or stimulation system in communication with a predetermined site, for example a subcallosal area.
  • the device or stimulation system is operated to stimulate the predetermined site thereby treating the mood and/or anxiety disorder.
  • the device or stimulation system may include a probe, for example, an electrode assembly (i.e., electrical stimulation lead), pharmaceutical-delivery assembly (i.e., catheters) or combinations of these (i.e., a catheter having at least one electrical stimulation lead) and/or a signal generator or signal source (i.e., electrical signal source, chemical signal source (i.e., pharmaceutical delivery pump) or magnetic signal source).
  • an electrode assembly i.e., electrical stimulation lead
  • pharmaceutical-delivery assembly i.e., catheters
  • combinations of these i.e., a catheter having at least one electrical stimulation lead
  • a signal generator or signal source i.e., electrical signal source, chemical signal source (i.e., pharmaceutical delivery pump) or magnetic
  • the probe may be coupled to the electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site.
  • the probe and the signal generator or source can be incorporated together, wherein the signal generator and probe are formed into a unitary or single unit, such unit may comprise, one, two or more electrodes.
  • These devices are known in the art as microstimulators, for example, BionTM which is manufactured by Advanced Bionics Corporation.
  • the predetermined site is a subcallosal area.
  • a subcallosal area includes, but is not limited to subgenual cingulate area, subcallosal gyrus area, ventral/medial prefrontal cortex area, ventral/medial white matter, Brodmann area 24 , Brodmann area 25 , and/or Brodmann area 10 .
  • the predetermined site is a subgenual cingulate area, more preferably Brodmann area 25 , Brodmann area 24 or Brodmann area 10 .
  • Stimulation of a subcallosal area includes stimulation of the gray matter and white matter tracts associated with the subcallosal area that results in an alleviation or modulation of the mood and/or anxiety disorder.
  • Associated white matter tracts includes the surrounding or adjacent white matter tracts leading to or from a subcallosal area or white matter tracts that are contiguous with the subcallosal area.
  • Modulating the subcallosal area via electrical and/or chemical stimulation (i.e., pharmaceutical) and/or magnetic stimulation can result in increasing, decreasing, masking, altering, overriding or restoring neuronal activity resulting in treatment of the mood and/or anxiety disorder.
  • stimulation of a subcallosal area may result in modulation of neuronal activity of other areas of the brain, for example, Brodmann area, 24 , Brodmann area 25 , Brodmann area 10 , Brodmann area 9 , the hypothalamus and the brain stem.
  • Another embodiment of the present invention comprises a method of treating the mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; the stimulation lead is coupled to or in communication with a signal generator; and an electrical signal is generated using the signal generator to modulate the predetermined site thereby treating the mood and/or anxiety disorder.
  • the mood disorder is selected from the group consisting of major depressive disorder, bipolar disorder, and dysthymic disorder.
  • the anxiety disorder is selected from the group consisting of panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorder.
  • the method can comprise the steps of: surgically implanting a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with the predetermined stimulation site; and operating the pump to discharge the pharmaceutical through the discharge portion of the catheter into the stimulation site thereby treating the mood and/or anxiety disorder.
  • the pharmaceutical is selected from the group consisting of inhibitory neurotransmitter agonist, an excitatory neurotransmitter antagonist, an agent that increases the level of an inhibitory neurotransmitter, an agent that decrease the level of an excitatory neurotransmitter, and a local anesthetic agent. It is envisioned that chemical stimulation or pharmaceutical infusion can be preformed independently of electrical stimulation and/or in combination with electrical stimulation.
  • Another embodiment of the present invention is a method of treating a mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; surgically implanting a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with a predetermined infusion site; and coupling the proximal end of the lead to a signal generator; generating an electrical signal with the signal generator to modulate the predetermined site; and operating the pump to discharge the pharmaceutical through the discharge portion of the catheter into the infusion site thereby treating the mood and/or anxiety disorder.
  • the therapeutic system comprises an electrical stimulation lead that is implanted into the subject's brain.
  • the electrical stimulation lead comprises at least one electrode that is in communication with a predetermined site and delivers electrical signals to the predetermined site in response to received signals; and a signal generator that generates signals for transmission to the electrodes of the lead resulting in delivery of electrical signals to predetermined site thereby treating the mood and/or anxiety disorder.
  • the electrical stimulation lead may comprise one electrode or a plurality of electrodes in or around the target area.
  • the signal generator is implanted in the subject's body.
  • a therapeutic system is a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with a predetermined stimulation site; and a pump to discharge the pharmaceutical through the discharge portion of the catheter into the predetermined stimulation site thereby treating the mood and/or anxiety disorder.
  • another therapeutic system comprises a device that is surgically implanted into the subject such that the device is in communication with a predetermined site, for example a subcallosal area.
  • An exemplary device includes a microstimulator (i.e., BionTM manufactured by Advanced Bionics Corporation) in which the device contains a generating portion and at least one electrode in a single unit.
  • a lead assembly is associated with at least one electrode of the microstimulator such that the lead can stimulate the predetermined site not in direct contact with the microstimulator.
  • Other therapeutic systems include a probe that is in communication with the predetermined site and a device that stimulates the probe thereby treating the mood and/or anxiety disorder.
  • the probe can be, for example, an electrode assembly (i.e., electrical stimulation lead), pharmaceutical-delivery assembly (i.e., catheters) or combinations of these (i.e., a catheter having at least one electrical stimulation lead).
  • the probe is coupled to the device, for example, electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site.
  • FIGS. 1A and 1B illustrate example electrical stimulation systems.
  • FIGS. 2A-2D illustrate example electrical stimulation leads that may be used in the present invention.
  • FIG. 3 is a coronal (front vertical) section of a human brain showing arrows directed to target areas.
  • FIG. 4 is a flowchart describing the general procedure.
  • FIGS. 5A and 5B shows a graphical analysis of scores based upon the Hamilton Rating Scale for Depression after deep brain stimulation treatment.
  • FIGS. 6A-6E show scans through various planes of the brain.
  • FIG. 6A shows a T 1 MRI in the horizontal plane showing the tips (at arrows) on the implanted lead 4 contact electrodes positioned anterior to the anterior commissure (AC), approximately 7 mm from the midline and below the plane of the inter-commissural line, in a patient with depression.
  • FIG. 6B shows an axial T 1 MRI in the horizontal plane of a patient with depression implanted with chronic deep brain stimulating electrodes to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25 /Brodmann area 24 .
  • FIG. 6C shows a Sagittal T 1 weighted MRI, vertical through the nose, showing an implanted chronic deep brain stimulating electrode with 4 contacts to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25 /Brodmann area 24 .
  • the central dot shows a contact area.
  • FIG. 6D shows a T 1 weighted MRI Coronal view of a patient having scans of FIGS. 6A and 6B showing right and left electrodes in the plane of the brain corresponding to the Wegebrand and Warren atlas section plate 3 shown in FIG. 3 .
  • the central dot is the midline.
  • FIG. 6E shows T 1 weighted MRI images of a second patient with bilateral electrodes implanted to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25 /Brodmann area 24 .
  • cognate disorders refers to a group of disorders that are commonly associated with co-morbidity of depression and anxiety symptoms.
  • anxiety refers to an uncomfortable and unjustified sense of apprehension that may be diffuse and unfocused and is often accompanied by physiological symptoms.
  • anxiety disorder refers to or connotes significant distress and dysfunction due to feelings of apprehension, guilt, fear, etc.
  • Anxiety disorders include, but are not limited to panic disorders, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorders.
  • Brodmann area 25 refers to the defined area of Brodmann area 25 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 25 and/or white matter tracts that are contiguous with Brodmann area 25 .
  • the surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 25 .
  • Brodmann area 24 refers to the defined area of Brodmann area 24 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 24 and/or white matter tracts that are contiguous with Brodmann area 24 .
  • the surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 24 .
  • Brodmann area 9 refers to the defined area of Brodmann area 9 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 9 and/or white matter tracts that are contiguous with Brodmann area 9 .
  • the surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 9 .
  • Brodmann area 10 refers to the defined area of Brodmann area 10 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 10 and/or white matter tracts that are contiguous with Brodmann area 10 .
  • the surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 10 .
  • depression refers to a morbid sadness, dejection, or melancholy.
  • the term “in communication” refers to one or more electrical stimulation leads and/or catheters being adjacent, in the general vicinity, in close proximity, or directly next to, or in direct contact or directly in the predetermined stimulation site.
  • the one or more electrical stimulation leads and/or catheters are “in communication” with the predetermined site of the brain if the stimulation results in a modulation of neuronal activity associated with a site.
  • “in communication” with brain tissue encompasses surrounding or adjacent white matter tracts or fibers leading to and from the brain tissue and/or white matter tracts or fibers that are contiguous with the brain tissue.
  • limbic system encompasses the amygdala, hippocampus, septum, cingulate gyrus, cingulate cortex, hypothalamus, epithalamus, anterior thalamus, mammillary bodies, and fornix.
  • the limbic system has connections throughout the brain, more particularly with the primary sensory cortices, including the rhinencephalon for smell, the autonomic nervous system via the hypothalamus, and memory areas. Yet further, the limbic system is involved in mood, emotion and thought.
  • mania or “manic” refers to a disordered mental state of extreme excitement.
  • misod refers to an internal emotional state of a person.
  • the term “mood disorder” is typically characterized by pervasive, prolonged, and disabling exaggerations of mood and affect that are associated with behavioral, physiologic, cognitive, neurochemical and psychomotor dysfunctions.
  • the major mood disorders include, but are not limited to major depressive disorder (also known as unipolar disorder), bipolar disorder (also known as manic depressive illness or bipolar depression), dysthymic disorder.
  • Other mood disorders may include, but are not limited to major depressive disorder, psychotic; major depressive disorder, melancholic; major depressive disorder, seasonal pattern; postpartum depression; brief recurrent depression; late luteal phase dysphoric disorder (premenstrual dysphoria); and cyclothymic disorder.
  • modulate refers to the ability to regulate positively or negatively neuronal activity.
  • modulate can be used to refer to an increase, decrease, masking, altering, overriding or restoring neuronal activity. Modulation of neuronal activity affects psychological and/or psychiatric activity of a subject.
  • neuron refers to a neuron which is a morphologic and functional unit of the brain, spinal column, and peripheral nerves.
  • the term “pharmaceutical” refers to a chemical or agent that is used as a drug.
  • the term pharmaceutical and drug are interchangeable.
  • stimulation refers to electrical, chemical, and/or magnetic stimulation that modulates the predetermined sites in the brain.
  • subcallosal area includes the medial gray matter and white matter under the corpus callosum, as well as the white matter tracts that are associated with the subcallosal area.
  • Associated white matter tracts includes the surrounding or adjacent white matter tracts leading to or from a subcallosal area or white matter tracts that are contiguous with the subcallosal area.
  • the subcallosal area includes the following gray matter and the white matter tracts, as well as the white matter tracts that are associated with or leading to or from the following areas: subgenual cingulate area, subcallosal gyrus area, ventral/medial prefrontal cortex area, ventral/medial white matter, Brodmann area 24 , Brodmann area 25 , and/or Brodmann area 10 .
  • the surrounding or adjacent white matter tracts can include up to approximately a 1 cm radius of the subcallosal area.
  • the term “subgenual cingulate area” includes the gray matter and white matter tracts associated with the subgenual cingulate area, the white matter tracts that surround or adjacent to the subgenual cingulate area, or the white matter tracts that lead to or from the subgenual cingulate area.
  • the subgenual cingulate area includes Brodmann area 10 , Brodmann area 24 and Brodmann area 25 .
  • the surrounding or adjacent white matter can include up to approximately a 1 cm radius of the subgenual cingulate area.
  • beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable.
  • a treatment may improve the disease condition, but may not be a complete cure for the disease.
  • FIGS. 1A and 1B illustrate example electrical stimulation systems or devices 10 used to provide deep brain stimulation.
  • Stimulation system 10 generates and applies a stimulus to a target area of the brain, for example, a target area of a subcallosal area, more particularly, a subgenual cingulate area. Still further, the target area can comprise Brodmann area 25 , Brodmann area 24 and/or Brodmann area 10 .
  • stimulation system 10 includes an implantable electrical stimulation source 12 and an implantable electrical stimulation lead 14 for applying the stimulation signal to the target brain tissue. In operation, both of these primary components are implanted in the person's body. Stimulation source 12 is coupled to a connecting portion 16 of electrical stimulation lead 14 .
  • Stimulation source 12 controls the electrical signals transmitted to electrodes 18 located on a stimulating portion 20 of electrical stimulation lead 14 , located adjacent the target brain tissue, according to suitable signal parameters (i.e., duration, intensity, frequency, etc.).
  • suitable signal parameters i.e., duration, intensity, frequency, etc.
  • a doctor, the patient, or another user of stimulation source may directly or indirectly input signal parameters for controlling the nature of the electrical stimulation provided.
  • Another exemplary stimulation system or device includes a microstimulator (i.e., BionTM, manufactured by Advanced Bionics Corporation) in which the device contains a signal generating portion and at least one electrode in a the same unit or single unit, as defined in U.S. Pat. Nos. 6,051,017; 6,735,475 and 6,735,474, each of which are incorporated herein in its entirety.
  • a lead assembly is associated with at least one electrode of the microstimulator such that the lead can stimulate the predetermined site not in contact with the micro stimulator.
  • stimulation source 12 includes an implantable pulse generator (IPG).
  • IPG implantable pulse generator
  • Any commercially available implantable pulse generator can be used in the present invention, as well as a modified version of any commercially available pulse generator.
  • An exemplary IPG is one that is manufactured by Advanced Neuromodulation Systems, Inc., such as the Genesis® System, part numbers 3604, 3608, 3609, and 3644.
  • FIG. 1B shows stimulation source 12 including an implantable wireless receiver.
  • An example of a wireless receiver may be one manufactured by Advanced Neuromodulation Systems, Inc., such as the Renew® System, part numbers 3408 and 3416.
  • the wireless receiver is capable of receiving wireless signals from a wireless transmitter 22 located external to the person's body.
  • the wireless signals are represented in FIG. 1B by wireless link symbol 24 .
  • a doctor, the patient, or another user of stimulation source 12 may use a controller 26 located external to the person's body to provide control signals for operation of stimulation source 12 .
  • Controller 26 provides the control signals to wireless transmitter 22
  • wireless transmitter 22 transmits the control signals and power to the wireless receiver of stimulation source 12
  • stimulation source 12 uses the control signals to vary the signal parameters of electrical signals transmitted through electrical stimulation lead 14 to the stimulation site.
  • An example wireless transmitter may be one manufactured by Advanced Neuromodulation Systems, Inc., such as the Renew® System, part numbers 3508 and 3516.
  • FIGS. 2A through 2D illustrate example electrical stimulation leads 14 that may be used to provide electrical stimulation to an area of the brain, however, one of skill in the art is aware that any electrical lead may be used in the present invention.
  • each of the one or more leads 14 incorporated in stimulation system 10 includes one or more electrodes 18 adapted to be positioned near the target brain tissue and used to deliver electrical stimulation energy to the target brain tissue in response to electrical signals received from stimulation source 12 .
  • a percutaneous lead 14 such as example leads shown in FIG. 2A-2D , includes one or more circumferential electrodes 18 spaced apart from one another along the length of lead 14 . Circumferential electrodes 18 emit electrical stimulation energy generally radially in all directions.
  • patients who are to have an electrical stimulation lead or electrode implanted into the brain generally, first have a stereotactic head frame, such as the Leksell, CRW, or Compass, mounted to the patient's skull by fixed screws.
  • a stereotactic head frame such as the Leksell, CRW, or Compass
  • frameless techniques may also be used.
  • the patient typically undergoes a series of magnetic resonance imaging sessions, during which a series of two dimensional slice images of the patient's brain are built up into a quasi—three dimensional map in virtual space. This map is then correlated to the three dimensional stereotactic frame of reference in the real surgical field.
  • both the instruments and the patient must be situated in correspondence to the virtual map.
  • the current way to do this is to rigidly mount the head frame to the surgical table. Subsequently, a series of reference points are established to relative aspects of the frame and the patient's skull, so that either a person or a computer software system can adjust and calculate the correlation between the real world of the patient's head and the virtual space model of the patient's MRI scans.
  • the surgeon is able to target any region within the stereotactic space of the brain with precision (i.e., within 1 mm).
  • Initial anatomical target localization is achieved either directly using the MRI images, or indirectly using interactive anatomical atlas programs that map the atlas image onto the stereotactic image of the brain. As is described in greater detail below, the anatomical targets may be stimulated directly or affected through stimulation in another region of the brain.
  • this shows the position of the subcallosal area having coordinates derived from the Heidelbergenbrand and Wahren Atlas plate 3 coronal section through the brain are 6-7 mm from the midline (range 2-14 mm), 29 mm anterior to the mid-commissural point range (20-40) and 5mm (range 0-10 mm) below the intra-commissural line.
  • arrow 1 points to the subgenual cingulate area, more particularly Brodmann area 25 ;
  • arrow 2 points to the gyrus rectus area;
  • arrow 3 points to the subcaudate area;
  • arrow 4 points to the orbitofrontal area.
  • the electrical stimulation lead 14 can be positioned in the brain.
  • an insertion cannula for electrical stimulation lead 14 is inserted through the burr hole into the brain, but a cannula is not required.
  • a hollow needle may provide the cannula.
  • the cannula and electrical stimulation lead 14 may be inserted together or lead 14 may be inserted through the cannula after the cannula has been inserted.
  • an electrical stimulation lead such as lead 14
  • the lead is uncoupled from any stereotactic equipment present, and the cannula and stereotactic equipment are removed.
  • the cannula may be removed before, during, or after removal of the stereotactic equipment.
  • Connecting portion 16 of electrical stimulation lead 14 is laid substantially flat along the skull.
  • any burr hole cover seated in the burr hole may be used to secure electrical stimulation lead 14 in position and possibly to help prevent leakage from the burr hole and entry of contaminants into the burr hole.
  • Example burr hole covers that may be appropriate in certain embodiments are illustrated and described in co-pending U.S. Application Nos.
  • connecting portion 16 of lead 14 extends from the lead insertion site to the implant site at which stimulation source 12 is implanted.
  • the implant site is typically a subcutaneous pocket formed to receive and house stimulation source 12 .
  • the implant site is usually positioned a distance away from the insertion site, such as near the chest, below the clavicle or alternatively near the buttocks or another place in the torso area.
  • the present invention contemplates two or more steps taking place substantially simultaneously or in a different order.
  • the present invention contemplates using methods with additional steps, fewer steps, or different steps, so long as the steps remain appropriate for implanting an example stimulation system into a person for electrical stimulation of the person's brain.
  • a drug delivery system independent of or in combination with electrical stimulation of the brain.
  • Drug delivery may be used independent of or in combination with a lead/electrode to provide electrical stimulation and chemical stimulation.
  • the drug delivery catheter is implanted such that the proximal end of the catheter is coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical or drug.
  • Implantation of the catheter can be achieved by combining data from a number of sources including CT, MRI or conventional and/or magnetic resonance angiography into the stereotactic targeting model.
  • implantation of the catheter can be achieved using similar techniques as discussed above for implantation of electrical leads, which is incorporated herein.
  • the distal portion of the catheter can have multiple orifices to maximize delivery of the pharmaceutical while minimizing mechanical occlusion.
  • the proximal portion of the catheter can be connected directly to a pump or via a metal, plastic, or other hollow connector, to an extending catheter.
  • infusion pump Any type of infusion pump can be used in the present invention.
  • active pumping devices or so-called peristaltic pumps are described in U.S. Pat. Nos. 4,692,147, 5,840,069, and 6,036,459, which are incorporated herein by reference in their entirety.
  • Peristaltic pumps are used to provide a metered amount of a drug in response to an electronic pulse generated by control circuitry associated within the device.
  • An example of a commercially available peristaltic pump is SynchroMed® implantable pump from Medtronic, Inc., Minneapolis, Minn.
  • Other pumps that may be used in the present invention include accumulator-type pumps, for example certain external infusion pumps from Minimed, Inc., Northridge, Calif. and Infusaid® implantable pump from Strato/Infusaid, Inc., Norwood, Mass.
  • Passive pumping mechanisms can be used to release an agent in a constant flow or intermittently or in a bolus release.
  • Passive type pumps include, for example, but are not limited to gas-driven pumps described in U.S. Pat. Nos. 3,731,681 and 3,951,147; and drive-spring diaphragm pumps described in U.S. Pat. Nos. 4,772,263, 6,666,845, 6,620,151 which are incorporated by reference in its entirety.
  • a catheter having electrical leads may be used, similar to the ones described in U.S. Pat. Nos. 6,176,242; 5,423,877; 5,458,631 and 5,119,832, each of which are incorporated herein by reference in its entirety.
  • Subjects to be treated using the present invention can be selected, identified and/or diagnosed based upon the accumulation of physical, chemical, and historical behavioral data on each patient.
  • One of skill in the art is able to perform the appropriate examinations to accumulate such data.
  • One type of examination can include neurological examinations, which can include mental status evaluations, which can further include a psychiatric assessment.
  • Other types of examinations can include, but are not limited to, motor examination, cranial nerve examination, and neuropsychological tests (i.e., Minnesota Multiphasic Personality Inventory, Beck Depression Inventory, or Hamilton Rating Scale for Depression).
  • imaging techniques can be used to determine normal and abnormal brain function that can result in disorders.
  • Functional brain imaging allows for localization of specific normal and abnormal functioning of the nervous system. This includes electrical methods such as electroencephalography (EEG), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), as well as metabolic and blood flow studies such as functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) which can be utilized to localize brain function and dysfunction.
  • EEG electroencephalography
  • MEG magnetoencephalography
  • SPECT single photon emission computed tomography
  • metabolic and blood flow studies such as functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) which can be utilized to localize brain function and dysfunction.
  • fMRI functional magnetic resonance imaging
  • PET positron emission tomography
  • EEG electroencephalography
  • MEG magnetoencephalography
  • fMRI functional magnetic resonance imaging
  • PET positron emission tomography
  • the present invention relates to modulation of neuronal activity to affect psychological or psychiatric activity and/or mental activity.
  • the present invention finds particular application in the modulation of neuronal function or processing to effect a functional outcome.
  • the modulation of neuronal function is particularly useful with regard to the prevention, treatment, or amelioration of psychiatric, psychological, conscious state, behavioral, mood, and thought activity (unless otherwise indicated these will be collectively referred to herein as “psychological activity” or “psychiatric activity” or “mental activity”).
  • psychological activity or “psychiatric activity” or “mental activity”.
  • a pathological or undesirable condition associated with the activity reference may be made to “psychiatric disorder” or “psychological disorder” instead of psychiatric or psychological activity.
  • a disorder such as a mood disorder (i.e., major depressive disorder, bipolar disorder, and dysthymic disorder) or an anxiety disorder (i.e., panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorder)
  • a mood disorder i.e., major depressive disorder, bipolar disorder, and dysthymic disorder
  • an anxiety disorder i.e., panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorder
  • Psychiatric activity that may be modulated can include, but not be limited to, normal functions such as alertness, conscious state, drive, fear, anger, anxiety, euphoria, sadness, and the fight or flight response.
  • the present invention finds particular utility in its application to human psychological or psychiatric activity/disorder.
  • the present invention is applicable to other animals which exhibit behavior that is modulated by the brain. This may include, for example, rodents, primates, canines, felines, elephants, dolphins, etc. Utilizing the various embodiments of the present invention, one skilled in the art may be able to modulate the functional outcome of the brain to achieve a desirable result.
  • the probe can be a stimulation lead or electrode assembly or drug-delivery catheter, or any combination thereof.
  • the electrode assembly may be one electrode, multiple electrodes, or an array of electrodes in or around the target area.
  • the proximal end of the probe can be coupled to a device, such as an electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site.
  • the probe can be incorporated into the device such that the probe and the signal generating device are a single unit.
  • Certain embodiments of the present invention involve a method of treating a mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; coupling the proximal end of the lead to a signal generator; and generating an electrical signal with the signal generator to modulate the predetermined site thereby treating the mood and/or anxiety disorder.
  • neuromodulation of the predetermined site of the present invention can be achieved using magnetic stimulation.
  • One such system that can be employed and that is well known in the art is described in U.S. Pat. No. 6,425,852, which is incorporated herein by reference in its entirety.
  • the therapeutic system or deep brain stimulation system of the present invention is surgically implanted as described in the above sections.
  • One of skill in the art is cognizant that a variety of electrodes or electrical stimulation leads may be utilized in the present invention. It is desirable to use an electrode or lead that contacts or conforms to the target site for optimal delivery of electrical stimulation.
  • One such example is a single multi contact electrode with eight contacts separated by 21 ⁇ 2 mm each contract would have a span of approximately 2 mm.
  • Another example is an electrode with two 1 cm contacts with a 2 mm intervening gap.
  • another example of an electrode that can be used in the present invention is a 2 or 3 branched electrode/catheter to cover the predetermined site or target site.
  • Each one of these three pronged catheters/electrodes have four contacts 1-2 mm contacts with a center to center separation of 2 of 2.5 mm and a span of 1.5 mm. Similar designs with catheters to infuse drugs with single outlet pore at the extremities of these types of catheters or along their shaft may also be designed and used in the present invention.
  • the present invention extends to methods of transplanting cells into a predetermined site to treat mood and/or anxiety disorders. It is envisioned that the transplanted cells can replace damaged, degenerating or dead neuronal cells, deliver a biologically active molecule to the predetermined site or to ameliorate a condition and/or to enhance or stimulate existing neuronal cells. Such transplantation methods are described in U.S. Application No. US20040092010, which is incorporated herein by reference in its entirety.
  • Cells that can be transplanted can be obtained from stem cell lines (i.e., embryonic stem cells, non-embryonic stem cells, etc.) and/or brain biopsies, including tumor biopsies, autopsies and from animal donors. (See U.S. Application No. US20040092010; U.S. Pat. Nos. 5,735,505 and 6,251,669; Temple, Nature Reviews 2:513-520 (2000); Bjorklund and Lindvall, Nat. Neurosci. 3:537-544 (2000)), each of which is incorporated herein by reference in its entirety). Brain stem cells can then be isolated (concentrated) from non-stem cells based on specific “marker” proteins present on their surface. In one such embodiment, a fluorescent antibody specific for such a marker can be used to isolate the stem cells using fluorescent cell sorting (FACS). In another embodiment an antibody affinity column can be employed. Alternatively, distinctive morphological characteristics can be employed.
  • FACS fluorescent cell sorting
  • the predetermined site or target area is a subcallosal area, more preferably, the subgenual cingulate area, and more preferably Brodmann area 25 /Brodmann area 24 .
  • Stimulation of a subcallosal area i.e., subgenual cingulate area or Brodmann area 25 /Brodmann area 24
  • the surrounding or adjacent white matter tracts leading to or from the subcallosal area or white matter tracts that are contiguous with the subcallosal area results in changes that alleviate or improve the mood and/or anxiety disorder of the subject.
  • modulating a subcallosal area can result in increasing, decreasing, masking, altering, overriding or restoring neuronal activity resulting in treatment of the mood and/or anxiety disorder.
  • Yet further stimulation of a subgenual cingulate area, more particularly Brodmann area 25 results in modulation of neuronal activity of other areas of the brain, for example, Brodmann area 9 , Brodmann area 10 , Brodmann area 24 , the hypothalamus, and the brain stem.
  • the predetermined site or target area is stimulated in an effective amount or effective treatment regimen to decrease, reduce, modulate or abrogate the mood and/or anxiety disorder.
  • a subject is administered a therapeutically effective stimulation so that the subject has an improvement in the parameters relating to the affective disorder including subjective measures such as, for example, neurological examinations and neuropsychological tests (i.e., Minnesota Multiphasic Personality Inventory, Beck Depression Inventory, Mini-Mental Status Examination (MMSE), Hamilton Rating Scale for Depression, Wisconsin Card Sorting Test (WCST), Tower of London, Stroop task, MADRAS, CGI, N-BAC, or Yale-Brown Obsessive Compulsive score (Y-BOCS)), motor examination, and cranial nerve examination, and objective measures including use of additional psychiatric medications, such as anti-depressants, or other alterations in cerebral blood flow or metabolism and/or neurochemistry.
  • the improvement is any observable or measurable improvement.
  • Treatment regimens may vary as well, and often depend on the health and age of the patient. Obviously, certain types of disease will require more aggressive treatment, while at the same time, certain patients cannot tolerate more taxing regimens. The clinician will be best suited to make such decisions based on the known subject's history.
  • the target site is stimulated using stimulation parameters such as, pulse width of about 1 to about 500 microseconds, more preferable, about 1 to about 90 microseconds; frequency of about 1 to about 300 Hz, more preferably, about 100 to about 185 Hz; and voltage of about 0.5 to about 10 volts, more preferably about 1 to about 10 volts.
  • stimulation parameters such as, pulse width of about 1 to about 500 microseconds, more preferable, about 1 to about 90 microseconds; frequency of about 1 to about 300 Hz, more preferably, about 100 to about 185 Hz; and voltage of about 0.5 to about 10 volts, more preferably about 1 to about 10 volts.
  • stimulation parameters such as, pulse width of about 1 to about 500 microseconds, more preferable, about 1 to about 90 microseconds; frequency of about 1 to about 300 Hz, more preferably, about 100 to about 185 Hz; and voltage of about 0.5 to about 10 volts, more preferably about 1 to about 10 volts.
  • stimulation of a subcallosal area and/or the adjacent white matter modulates other targets in the limbic-cortical circuit or pathway thereby improving any dysfunctional limbic-cortical circuits resulting in an improvement or alleviation or providing remission of depression and/or anxiety in the treated subjects.
  • Other such improvements can be sensations of calm, tranquility, peacefulness, increased energy and alertness, improved mood, improvement in attention and thinking, improvement in motor speed, improvement in mental speed and in spontaneity of speech, improved sleep, improved appetite, improved limbic behavior, increased motivation, decreases in anxiety, decreases in repetitive behavior, impulses, obsessions, etc.
  • beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether objective or subjective.
  • FIG. 4 summarizes the general procedure of the present invention. Any of the above described methods can be used to identify a subject or diagnose a subject that suffers from an affective disorder ( 100 ). Once the subject is identified, a stimulation device is implanted ( 200 ) into the subject such that the subcallosal area of the subject's brain is stimulated ( 300 ). After the target area has been stimulated (i.e., electrical, chemical or magnetic stimulation), the subject is evaluated to determine the change in the affective disorder.
  • the target area i.e., electrical, chemical or magnetic stimulation
  • the present invention is not bound by the described methods or devices and that any method or device that would result in neuromodulation of the subcallosal area could be used in the present invention.
  • an implantable signal generator and electrical stimulating lead and an implantable pump and catheter(s) are used to deliver electrical stimulation and/or one or more stimulating drugs to the above mentioned areas as a treatment for mood and/or anxiety disorders.
  • stimulating drugs comprise medications, anesthetic agents, synthetic or natural peptides or hormones, neurotransmitters, cytokines and other intracellular and intercellular chemical signals and messengers, and the like.
  • certain neurotransmitters, hormones, and other drugs are excitatory for some tissues, yet are inhibitory to other tissues. Therefore, where, herein, a drug is referred to as an “excitatory” drug, this means that the drug is acting in an excitatory manner, although it may act in an inhibitory manner in other circumstances and/or locations.
  • an “inhibitory” drug is mentioned, this drug is acting in an inhibitory manner, although in other circumstances and/or locations, it may be an “excitatory” drug.
  • stimulation of an area herein includes stimulation of cell bodies and axons in the area.
  • excitatory neurotransmitter agonists i.e., norepinephrine, epinephrine, glutamate, acetylcholine, serotonin, dopamine
  • agonists thereof and agents that act to increase levels of an excitatory neurotransmitter(s) (i.e., edrophonium; Mestinon; trazodone; SSRIs (i.e., flouxetine, paroxetine, sertraline, citalopram and fluvoxamine); tricyclic antidepressants (i.e., imipramine, amitriptyline, doxepin, desipramine, trimipramine and nortriptyline), monoamine oxidase inhibitors (i.e., phenelzine, tranylcypromine, isocarboxasid)), generally have an excitatory effect on neural tissue, while inhibitory neurotransmitters (i.e., dopamine,
  • antagonists of inhibitory neurotransmitters i.e., bicuculline
  • agents that act to decrease levels of an inhibitory neurotransmitter(s) have been demonstrated to excite neural tissue, leading to increased neural activity.
  • excitatory neurotransmitter antagonists i.e., prazosin, and metoprolol
  • agents that decrease levels of excitatory neurotransmitters may inhibit neural activity.
  • lithium salts and anesthetics i.e., lidocane
  • lidocane lithium salts and anesthetics
  • H17 Hamilton 17 scale
  • a stereotactic frame was first placed on the patient's head, followed by acquisition of an MRI (Magnetic Resonance Imaging) scan to localize the target region. Patients were then taken to the operating room where, under local anesthesia, two burr holes were placed behind the hairline. Stereotactic coordinates were derived from the pre-op MRI. The coordinates of this target derived from the Wennenbrand and Wahren Atlas plate 3 ( FIG. 3 ) were 6-7 mm from the midline (range 2-14 mm), 29 mm anterior to the mid-commissural point range 20-40) and 5mm (range 0-10 mm) below the intra-commissural line.
  • two multi contact electrodes were delivered, one in each hemisphere.
  • the electrodes were connected to a stimulating pulse generator.
  • each electrode contact was stimulated and acute changes in behavior was assessed using self report and mood rating scales, such as POMS, PANAS, sadness, anxiety and general well being, self-report, and mood, motor and cognitive scales, such as, finger tapping, verbal fluency.
  • self report and mood rating scales such as POMS, PANAS, sadness, anxiety and general well being, self-report, and mood, motor and cognitive scales, such as, finger tapping, verbal fluency.
  • Patients returned for generator device programming There were several parameters that were tested, namely, which electrode contact was to be stimulated, the polarity of stimulation, the frequency and pulse width of stimulation, etc.
  • Electrode programming was done on an outpatient basis and involved a series of trials over the course of a week. Electrode contacts that produced acute behavioral changes or fMRI signal changes in the subgenual cingulate area (Brodmann area 25 ) were tried first. Once basic parameters were set, adjustments were made periodically until a stable program was established.
  • test battery was designed to differentiate dorsolateral, superior medial, and ventrolateral/orbital frontal behaviors which was differently affected by activation or disruption of the target areas with electrical stimulation. Serial testing allowed differentiation between early surgical effects, chronic stimulation effects, and correlations with mood change.
  • FIG. 5A and FIG. 5B show the results of the Hamilton Scale Scores after 6 months of stimulation for the first five subjects.
  • Brodmann area 25 leads to changes in the activity of Brodmann area 25 , the dorsal/lateral frontal lobe (Brodmann areas 9 and 6 ), dorsal/medial frontal lobe (Brodmann areas 9 and 10 ), anterior cingulate area (Brodmann area 24 ), orbital frontal cortex (Brodmann areas 10 and 11 ), the hypothalamus, brain stem and other target areas such as upstream, downstream or remote cortical and subcortical regions.
  • fMRI scans were performed during successive stimulation of each electrode contact. fMRI was used as an additional means of mapping the differences in activity of the electrodes. fMRI was not required because the optimal electrode was determined based upon clinical observations during the operation and operatively, as described above.
  • Imaging was performed on a 1.5T scanner using methods proven safe for patients with implanted electrodes and delivery catheters ( FIG. 6A-6E ).
  • Whole brain samples using spiral acquisition were repeated every 3.52 seconds.
  • One cycle was 120 seconds of stimulation and 120 seconds rest.
  • a block of 4 cycles was acquired for the best and worst contact pairs within each hemisphere based on behavior changes in the operating room and post-operatively.
  • the electrodes were activated using a transcutaneous lead connected to a pulse generator outside the imaging room.
  • Analyses addressed differences ON vs OFF for each contact and changes over multiple cycles.

Abstract

The present invention involves a method and a system for using electrical stimulation and/or chemical stimulation to treat depression. More particularly, the method comprises surgically implanting an electrical stimulation lead and/or catheter that is in communication with a predetermined site which is coupled to a signal generator and/or infusion pump that release either an electrical signal and/or a pharmaceutical resulting in stimulation of the predetermined site thereby treating the mood and/or anxiety.

Description

    CROSS-REFERENCE TO RELATED APPLICATIONS
  • This application claims priority to U.S. Provisional Application Nos. 60/511,268 filed Oct. 15, 2003 and 60/550,164 filed Mar. 4, 2004 and Canadian Application No. 2,432,810 filed Jun. 19, 2003, each of which is incorporated herein by reference in its entirety.
  • TECHNICAL FIELD
  • This invention relates to nervous tissue stimulation for treating depression, anxiety disorders and mood disorders, and more particularly to modulating nervous tissue at a predetermined stimulation site in brain tissue.
  • BACKGROUND OF THE INVENTION
  • Recent estimates indicate that more than 19 million Americans over the age of 18 years experience a depressive illness each year. The American Psychiatric Association recognizes several types of clinical depression, including Mild Depression (Dysthymia), Major Depression, and Bipolar Disorder (Manic-Depression). Major Depression is defined by a constellation of chronic symptoms that include sleep problems, appetite problems, anhedonia or lack of energy, feelings of worthlessness or hopelessness, difficulty concentrating, and suicidal thoughts. Approximately 9.2 million Americans suffer from Major Depression, and approximately 15 percent of all people who suffer from Major Depression take their own lives. Bipolar Disorder involves major depressive episodes alternating with high-energy periods of rash behavior, poor judgment, and grand delusions. An estimated one percent of the American population experiences Bipolar Disorder annually.
  • Significant advances in the treatment of depression have been made in the past decade. Since the introduction of selective serotonin reuptake inhibitors (SSRIs), i.e., Prozac®, many patients have been effectively treated with anti-depressant medication. New medications to treat depression are introduced almost every year, and research in this area is ongoing. However, an estimated 10 to 30 percent of depressed patients taking an anti-depressant are partially or totally resistant to the treatment. Those who suffer from treatment-resistant depression have almost no alternatives. Thus, there is a need to develop alternative treatments for these patients.
  • The use of electrical stimulation for treating neurological disease, including such disorders as movement disorders including Parkinson's disease, essential tremor, dystonia, and chronic pain, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over lesioning since lesioning destroys the nervous system tissue. In many instances, the preferred effect is to modulate neuronal activity. Electrical stimulation permits such modulation of the target neural structures and, equally importantly, does not require the destruction of nervous tissue. Such electrical stimulation procedures include electroconvulsive therapy (ECT), repetitive transcranial (rTMS) magnetic stimulation and vagal nerve stimulation (VNS).
  • Efforts have been made to treat psychiatric disorders with peripheral/cranial nerve stimulation. Recently, partial benefits with vagus nerve stimulation in patients with depression have been described in U.S. Pat. No. 5,299,569. Another example of electrical stimulation to treat depression is described in U.S. Pat. No. 5,470,846, which discloses the use of transcranial pulsed magnetic fields to treat depression. Yet further, U.S. Pat. No. 5,263,480 describes that stimulation of the vagus nerve may control depression and compulsive eating disorders and U.S. Pat. No. 5,540,734 teaches stimulation of the trigeminal or glossopharyngeal nerves for psychiatric illness, such as depression.
  • Deep brain stimulation (DBS) has been applied to the treatment of central pain syndromes and movement disorders, and it is currently being explored as a therapy for epilepsy. For instance, U.S. Pat. No. 6,016,449 and U.S. Pat. No. 6,176,242 disclose a system for the electrical stimulation of areas in the brain for the treatment of certain neurological diseases such as epilepsy, migraine headaches and Parkinson's disease.
  • Various electrical stimulation and/or drug infusion devices have been proposed for treating neurological disorders. Some devices stimulate through the skin, such as electrodes placed on the scalp. Other devices require significant surgical procedures for placement of electrodes, catheters, leads, and/or processing units. These devices may also require an external apparatus that needs to be strapped or otherwise affixed to the skin.
  • However, despite the aforesaid available treatments, there are patients with major depression that remain treatment refractory and chronically disabled. For these severely ill and disabled patients, novel therapies are required.
  • BRIEF SUMMARY OF THE INVENTION
  • The present invention relates to electrical and/or chemical stimulation applied to areas of the brain not considered in the prior art to play a role in depression. In certain embodiments, the invention uses electrical stimulation and/or chemical stimulation (i.e., one or more pharmaceuticals) to treat depression. In addition to electrical and/or chemical stimulation, magnetic stimulation can also be used, such as transcranial magnetic stimulation (“TMS”). According to one embodiment of the invention, the stimulation modulates areas of the brain that exhibit altered activity in patients relative to psychiatrically normal control subjects, thereby treating or preventing affective disorders, for example depression and/or anxiety disorders. Such stimulation is likely to be produced by electrical stimulation, an excitatory neurotransmitter agonist(s) (i.e., norepinephrine), an inhibitory neurotransmitter antagonist(s), and/or a medication that increases the level of an excitatory neurotransmitter (i.e., flouxetine (Prozac®), trazodone).
  • One embodiment of the present invention utilizes neurosurgical intervention to modulate the pathological activity of a subcallosal area in patients suffering from depression or other affective disorders. Such interventions include, applying electrical stimulation, herein termed “deep brain stimulation” or DBS, as is currently practiced to treat a number of disorders like Parkinson's disease. Other stimulations can include chemical stimulation such as through the use of pharmaceutical or drug pumps, for example local delivery of neuroactive substances to disrupt or block the pathological activity stemming from or coursing through this area. It is envisioned that such stimulation (i.e., electrical, magnetic and/or chemical) modulates the gray matter and white matter tracts in a subcallosal area, as well as the white matter tracts that are associated with the subcallosal area (such as the white matter tracts that lead to and from the subcallosal area or that are adjacent to the subcallosal area), which in turn modulates the limbic system. Still further, other stimulations may comprise magnetic stimulation and/or transplantation of cells.
  • Certain embodiments of the present invention involve a method that comprises surgically implanting a device or stimulation system in communication with a predetermined site, for example a subcallosal area. The device or stimulation system is operated to stimulate the predetermined site thereby treating the mood and/or anxiety disorder. The device or stimulation system may include a probe, for example, an electrode assembly (i.e., electrical stimulation lead), pharmaceutical-delivery assembly (i.e., catheters) or combinations of these (i.e., a catheter having at least one electrical stimulation lead) and/or a signal generator or signal source (i.e., electrical signal source, chemical signal source (i.e., pharmaceutical delivery pump) or magnetic signal source). The probe may be coupled to the electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site. Yet further, the probe and the signal generator or source can be incorporated together, wherein the signal generator and probe are formed into a unitary or single unit, such unit may comprise, one, two or more electrodes. These devices are known in the art as microstimulators, for example, Bion™ which is manufactured by Advanced Bionics Corporation.
  • It is envisioned that the predetermined site is a subcallosal area. A subcallosal area includes, but is not limited to subgenual cingulate area, subcallosal gyrus area, ventral/medial prefrontal cortex area, ventral/medial white matter, Brodmann area 24, Brodmann area 25, and/or Brodmann area 10. More specifically, the predetermined site is a subgenual cingulate area, more preferably Brodmann area 25, Brodmann area 24 or Brodmann area 10.
  • Stimulation of a subcallosal area includes stimulation of the gray matter and white matter tracts associated with the subcallosal area that results in an alleviation or modulation of the mood and/or anxiety disorder. Associated white matter tracts includes the surrounding or adjacent white matter tracts leading to or from a subcallosal area or white matter tracts that are contiguous with the subcallosal area. Modulating the subcallosal area via electrical and/or chemical stimulation (i.e., pharmaceutical) and/or magnetic stimulation can result in increasing, decreasing, masking, altering, overriding or restoring neuronal activity resulting in treatment of the mood and/or anxiety disorder. Yet further, stimulation of a subcallosal area may result in modulation of neuronal activity of other areas of the brain, for example, Brodmann area, 24, Brodmann area 25, Brodmann area 10, Brodmann area 9, the hypothalamus and the brain stem.
  • Another embodiment of the present invention comprises a method of treating the mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; the stimulation lead is coupled to or in communication with a signal generator; and an electrical signal is generated using the signal generator to modulate the predetermined site thereby treating the mood and/or anxiety disorder. The mood disorder is selected from the group consisting of major depressive disorder, bipolar disorder, and dysthymic disorder. The anxiety disorder is selected from the group consisting of panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorder.
  • In further embodiments, the method can comprise the steps of: surgically implanting a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with the predetermined stimulation site; and operating the pump to discharge the pharmaceutical through the discharge portion of the catheter into the stimulation site thereby treating the mood and/or anxiety disorder. The pharmaceutical is selected from the group consisting of inhibitory neurotransmitter agonist, an excitatory neurotransmitter antagonist, an agent that increases the level of an inhibitory neurotransmitter, an agent that decrease the level of an excitatory neurotransmitter, and a local anesthetic agent. It is envisioned that chemical stimulation or pharmaceutical infusion can be preformed independently of electrical stimulation and/or in combination with electrical stimulation.
  • Another embodiment of the present invention is a method of treating a mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; surgically implanting a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with a predetermined infusion site; and coupling the proximal end of the lead to a signal generator; generating an electrical signal with the signal generator to modulate the predetermined site; and operating the pump to discharge the pharmaceutical through the discharge portion of the catheter into the infusion site thereby treating the mood and/or anxiety disorder.
  • Other embodiments of the present invention include a system for treating subjects with mood and/or anxiety disorders. The therapeutic system comprises an electrical stimulation lead that is implanted into the subject's brain. The electrical stimulation lead comprises at least one electrode that is in communication with a predetermined site and delivers electrical signals to the predetermined site in response to received signals; and a signal generator that generates signals for transmission to the electrodes of the lead resulting in delivery of electrical signals to predetermined site thereby treating the mood and/or anxiety disorder. The electrical stimulation lead may comprise one electrode or a plurality of electrodes in or around the target area. Still further, the signal generator is implanted in the subject's body.
  • Another example of a therapeutic system is a catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical, wherein after implantation the discharge portion of the catheter is in communication with a predetermined stimulation site; and a pump to discharge the pharmaceutical through the discharge portion of the catheter into the predetermined stimulation site thereby treating the mood and/or anxiety disorder.
  • Still further, another therapeutic system comprises a device that is surgically implanted into the subject such that the device is in communication with a predetermined site, for example a subcallosal area. An exemplary device includes a microstimulator (i.e., Bion™ manufactured by Advanced Bionics Corporation) in which the device contains a generating portion and at least one electrode in a single unit. In further embodiments, a lead assembly is associated with at least one electrode of the microstimulator such that the lead can stimulate the predetermined site not in direct contact with the microstimulator.
  • Other therapeutic systems include a probe that is in communication with the predetermined site and a device that stimulates the probe thereby treating the mood and/or anxiety disorder. The probe can be, for example, an electrode assembly (i.e., electrical stimulation lead), pharmaceutical-delivery assembly (i.e., catheters) or combinations of these (i.e., a catheter having at least one electrical stimulation lead). The probe is coupled to the device, for example, electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site.
  • The foregoing has outlined rather broadly the features and technical advantages of the present invention in order that the detailed description of the invention that follows may be better understood. Additional features and advantages of the invention will be described hereinafter which form the subject of the claims of the invention. It should be appreciated that the conception and specific embodiment disclosed may be readily utilized as a basis for modifying or designing other structures for carrying out the same purposes of the present invention. It should also be realized that such equivalent constructions do not depart from the invention as set forth in the appended claims. The novel features which are believed to be characteristic of the invention, both as to its organization and method of operation, together with further objects and advantages will be better understood from the following description when considered in connection with the accompanying figures. It is to be expressly understood, however, that each of the figures is provided for the purpose of illustration and description only and is not intended as a definition of the limits of the present invention.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • For a more complete understanding of the present invention, reference is now made to the following descriptions taken in conjunction with the accompanying drawings.
  • FIGS. 1A and 1B illustrate example electrical stimulation systems.
  • FIGS. 2A-2D illustrate example electrical stimulation leads that may be used in the present invention.
  • FIG. 3 is a coronal (front vertical) section of a human brain showing arrows directed to target areas.
  • FIG. 4 is a flowchart describing the general procedure.
  • FIGS. 5A and 5B shows a graphical analysis of scores based upon the Hamilton Rating Scale for Depression after deep brain stimulation treatment.
  • FIGS. 6A-6E show scans through various planes of the brain. FIG. 6A shows a T1 MRI in the horizontal plane showing the tips (at arrows) on the implanted lead 4 contact electrodes positioned anterior to the anterior commissure (AC), approximately 7 mm from the midline and below the plane of the inter-commissural line, in a patient with depression. FIG. 6B shows an axial T1 MRI in the horizontal plane of a patient with depression implanted with chronic deep brain stimulating electrodes to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25/Brodmann area 24. FIG. 6C shows a Sagittal T1 weighted MRI, vertical through the nose, showing an implanted chronic deep brain stimulating electrode with 4 contacts to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25/Brodmann area 24. The central dot shows a contact area. FIG. 6D shows a T1 weighted MRI Coronal view of a patient having scans of FIGS. 6A and 6B showing right and left electrodes in the plane of the brain corresponding to the Schaltebrand and Warren atlas section plate 3 shown in FIG. 3. The central dot is the midline. FIG. 6E shows T1 weighted MRI images of a second patient with bilateral electrodes implanted to stimulate subcallosal white matter and adjacent cortex including subgenual cingulate gyrus, particularly Brodmann area 25/Brodmann area 24.
  • DETAILED DESCRIPTION OF THE INVENTION
  • It is readily apparent to one skilled in the art that various embodiments and modifications can be made to the invention disclosed in this Application without departing from the scope and spirit of the invention.
  • I. Definitions
  • As used herein, the use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” Still further, the terms “having”, “including”, “containing” and “comprising” are interchangeable and one of skill in the art is cognizant that these terms are open ended terms.
  • As used herein the term “affective disorders” refers to a group of disorders that are commonly associated with co-morbidity of depression and anxiety symptoms.
  • As used herein the term “anxiety” refers to an uncomfortable and unjustified sense of apprehension that may be diffuse and unfocused and is often accompanied by physiological symptoms.
  • As used herein the term “anxiety disorder” refers to or connotes significant distress and dysfunction due to feelings of apprehension, guilt, fear, etc. Anxiety disorders include, but are not limited to panic disorders, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorders.
  • As used herein, the term “Brodmann area 25” refers to the defined area of Brodmann area 25 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 25 and/or white matter tracts that are contiguous with Brodmann area 25. The surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 25.
  • As used herein, the term “Brodmann area 24” refers to the defined area of Brodmann area 24 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 24 and/or white matter tracts that are contiguous with Brodmann area 24. The surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 24.
  • As used herein, the term “Brodmann area 9” refers to the defined area of Brodmann area 9 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 9 and/or white matter tracts that are contiguous with Brodmann area 9. The surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 9.
  • As used herein, the term “Brodmann area 10” refers to the defined area of Brodmann area 10 as known by one of skill in the art, as well as the surrounding or adjacent white matter tracts leading to and from Brodmann area 10 and/or white matter tracts that are contiguous with Brodmann area 10. The surrounding or adjacent white matter can include up to approximately a 1 cm radius of Brodmann area 10.
  • As used herein the term “depression” refers to a morbid sadness, dejection, or melancholy.
  • As used herein, the term “in communication” refers to one or more electrical stimulation leads and/or catheters being adjacent, in the general vicinity, in close proximity, or directly next to, or in direct contact or directly in the predetermined stimulation site. Thus, one of skill in the art understands that the one or more electrical stimulation leads and/or catheters are “in communication” with the predetermined site of the brain if the stimulation results in a modulation of neuronal activity associated with a site. Still further, “in communication” with brain tissue encompasses surrounding or adjacent white matter tracts or fibers leading to and from the brain tissue and/or white matter tracts or fibers that are contiguous with the brain tissue.
  • As used herein the term “limbic system” encompasses the amygdala, hippocampus, septum, cingulate gyrus, cingulate cortex, hypothalamus, epithalamus, anterior thalamus, mammillary bodies, and fornix. The limbic system has connections throughout the brain, more particularly with the primary sensory cortices, including the rhinencephalon for smell, the autonomic nervous system via the hypothalamus, and memory areas. Yet further, the limbic system is involved in mood, emotion and thought.
  • As used herein the term “mania” or “manic” refers to a disordered mental state of extreme excitement.
  • As used herein the term “mood” refers to an internal emotional state of a person.
  • As used herein the term “mood disorder” is typically characterized by pervasive, prolonged, and disabling exaggerations of mood and affect that are associated with behavioral, physiologic, cognitive, neurochemical and psychomotor dysfunctions. The major mood disorders include, but are not limited to major depressive disorder (also known as unipolar disorder), bipolar disorder (also known as manic depressive illness or bipolar depression), dysthymic disorder. Other mood disorders may include, but are not limited to major depressive disorder, psychotic; major depressive disorder, melancholic; major depressive disorder, seasonal pattern; postpartum depression; brief recurrent depression; late luteal phase dysphoric disorder (premenstrual dysphoria); and cyclothymic disorder.
  • As used herein the term “modulate” refers to the ability to regulate positively or negatively neuronal activity. Thus, the term modulate can be used to refer to an increase, decrease, masking, altering, overriding or restoring neuronal activity. Modulation of neuronal activity affects psychological and/or psychiatric activity of a subject.
  • As used herein, the term “neuronal” refers to a neuron which is a morphologic and functional unit of the brain, spinal column, and peripheral nerves.
  • As used herein, the term “pharmaceutical” refers to a chemical or agent that is used as a drug. Thus, the term pharmaceutical and drug are interchangeable.
  • As used herein, the term “stimulate” or “stimulation” refers to electrical, chemical, and/or magnetic stimulation that modulates the predetermined sites in the brain.
  • As used herein, the term “subcallosal area” includes the medial gray matter and white matter under the corpus callosum, as well as the white matter tracts that are associated with the subcallosal area. Associated white matter tracts includes the surrounding or adjacent white matter tracts leading to or from a subcallosal area or white matter tracts that are contiguous with the subcallosal area. For the purposes of the present invention, the subcallosal area includes the following gray matter and the white matter tracts, as well as the white matter tracts that are associated with or leading to or from the following areas: subgenual cingulate area, subcallosal gyrus area, ventral/medial prefrontal cortex area, ventral/medial white matter, Brodmann area 24, Brodmann area 25, and/or Brodmann area 10. The surrounding or adjacent white matter tracts can include up to approximately a 1 cm radius of the subcallosal area.
  • As used herein, the term “subgenual cingulate area” includes the gray matter and white matter tracts associated with the subgenual cingulate area, the white matter tracts that surround or adjacent to the subgenual cingulate area, or the white matter tracts that lead to or from the subgenual cingulate area. The subgenual cingulate area includes Brodmann area 10, Brodmann area 24 and Brodmann area 25. The surrounding or adjacent white matter can include up to approximately a 1 cm radius of the subgenual cingulate area.
  • As used herein, the term “treating” and “treatment” refers to modulating certain areas of the brain so that the subject has an improvement in the disease, for example, beneficial or desired clinical results. For purposes of this invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether detectable or undetectable. One of skill in the art realizes that a treatment may improve the disease condition, but may not be a complete cure for the disease.
  • II. Electrical Stimulation Devices
  • FIGS. 1A and 1B illustrate example electrical stimulation systems or devices 10 used to provide deep brain stimulation. Stimulation system 10 generates and applies a stimulus to a target area of the brain, for example, a target area of a subcallosal area, more particularly, a subgenual cingulate area. Still further, the target area can comprise Brodmann area 25, Brodmann area 24 and/or Brodmann area 10. In general terms, stimulation system 10 includes an implantable electrical stimulation source 12 and an implantable electrical stimulation lead 14 for applying the stimulation signal to the target brain tissue. In operation, both of these primary components are implanted in the person's body. Stimulation source 12 is coupled to a connecting portion 16 of electrical stimulation lead 14. Stimulation source 12 controls the electrical signals transmitted to electrodes 18 located on a stimulating portion 20 of electrical stimulation lead 14, located adjacent the target brain tissue, according to suitable signal parameters (i.e., duration, intensity, frequency, etc.). A doctor, the patient, or another user of stimulation source may directly or indirectly input signal parameters for controlling the nature of the electrical stimulation provided.
  • Another exemplary stimulation system or device includes a microstimulator (i.e., Bion™, manufactured by Advanced Bionics Corporation) in which the device contains a signal generating portion and at least one electrode in a the same unit or single unit, as defined in U.S. Pat. Nos. 6,051,017; 6,735,475 and 6,735,474, each of which are incorporated herein in its entirety. In further embodiments, a lead assembly is associated with at least one electrode of the microstimulator such that the lead can stimulate the predetermined site not in contact with the micro stimulator.
  • In one embodiment, as shown in FIG. 1A, stimulation source 12 includes an implantable pulse generator (IPG). One of skill in the art is aware that any commercially available implantable pulse generator can be used in the present invention, as well as a modified version of any commercially available pulse generator. Thus, one of skill in the art would be able to modify an IPG to achieve the desired results. An exemplary IPG is one that is manufactured by Advanced Neuromodulation Systems, Inc., such as the Genesis® System, part numbers 3604, 3608, 3609, and 3644. Another example of an IPG is shown in FIG. 1B, which shows stimulation source 12 including an implantable wireless receiver. An example of a wireless receiver may be one manufactured by Advanced Neuromodulation Systems, Inc., such as the Renew® System, part numbers 3408 and 3416. The wireless receiver is capable of receiving wireless signals from a wireless transmitter 22 located external to the person's body. The wireless signals are represented in FIG. 1B by wireless link symbol 24. A doctor, the patient, or another user of stimulation source 12 may use a controller 26 located external to the person's body to provide control signals for operation of stimulation source 12. Controller 26 provides the control signals to wireless transmitter 22, wireless transmitter 22 transmits the control signals and power to the wireless receiver of stimulation source 12, and stimulation source 12 uses the control signals to vary the signal parameters of electrical signals transmitted through electrical stimulation lead 14 to the stimulation site. An example wireless transmitter may be one manufactured by Advanced Neuromodulation Systems, Inc., such as the Renew® System, part numbers 3508 and 3516.
  • FIGS. 2A through 2D illustrate example electrical stimulation leads 14 that may be used to provide electrical stimulation to an area of the brain, however, one of skill in the art is aware that any electrical lead may be used in the present invention. As described above, each of the one or more leads 14 incorporated in stimulation system 10 includes one or more electrodes 18 adapted to be positioned near the target brain tissue and used to deliver electrical stimulation energy to the target brain tissue in response to electrical signals received from stimulation source 12. A percutaneous lead 14, such as example leads shown in FIG. 2A-2D, includes one or more circumferential electrodes 18 spaced apart from one another along the length of lead 14. Circumferential electrodes 18 emit electrical stimulation energy generally radially in all directions.
  • III. Implantation of Electrical Stimulation Devices
  • While not being bound by the description of a particular procedure, patients who are to have an electrical stimulation lead or electrode implanted into the brain, generally, first have a stereotactic head frame, such as the Leksell, CRW, or Compass, mounted to the patient's skull by fixed screws. However, frameless techniques may also be used. Subsequent to the mounting of the frame, the patient typically undergoes a series of magnetic resonance imaging sessions, during which a series of two dimensional slice images of the patient's brain are built up into a quasi—three dimensional map in virtual space. This map is then correlated to the three dimensional stereotactic frame of reference in the real surgical field. In order to align these two coordinate frames, both the instruments and the patient must be situated in correspondence to the virtual map. The current way to do this is to rigidly mount the head frame to the surgical table. Subsequently, a series of reference points are established to relative aspects of the frame and the patient's skull, so that either a person or a computer software system can adjust and calculate the correlation between the real world of the patient's head and the virtual space model of the patient's MRI scans. The surgeon is able to target any region within the stereotactic space of the brain with precision (i.e., within 1 mm). Initial anatomical target localization is achieved either directly using the MRI images, or indirectly using interactive anatomical atlas programs that map the atlas image onto the stereotactic image of the brain. As is described in greater detail below, the anatomical targets may be stimulated directly or affected through stimulation in another region of the brain.
  • With reference to FIG. 3, this shows the position of the subcallosal area having coordinates derived from the Schaltenbrand and Wahren Atlas plate 3 coronal section through the brain are 6-7 mm from the midline (range 2-14 mm), 29 mm anterior to the mid-commissural point range (20-40) and 5mm (range 0-10 mm) below the intra-commissural line. Referring to FIG. 3, arrow 1 points to the subgenual cingulate area, more particularly Brodmann area 25; arrow 2 points to the gyrus rectus area; arrow 3 points to the subcaudate area; and arrow 4 points to the orbitofrontal area.
  • Based upon the coordinates derived or described above, the electrical stimulation lead 14 can be positioned in the brain. Typically, an insertion cannula for electrical stimulation lead 14 is inserted through the burr hole into the brain, but a cannula is not required. For example, a hollow needle may provide the cannula. The cannula and electrical stimulation lead 14 may be inserted together or lead 14 may be inserted through the cannula after the cannula has been inserted.
  • Once an electrical stimulation lead, such as lead 14, has been positioned in the brain, the lead is uncoupled from any stereotactic equipment present, and the cannula and stereotactic equipment are removed. Where stereotactic equipment is used, the cannula may be removed before, during, or after removal of the stereotactic equipment. Connecting portion 16 of electrical stimulation lead 14 is laid substantially flat along the skull. Where appropriate, any burr hole cover seated in the burr hole may be used to secure electrical stimulation lead 14 in position and possibly to help prevent leakage from the burr hole and entry of contaminants into the burr hole. Example burr hole covers that may be appropriate in certain embodiments are illustrated and described in co-pending U.S. Application Nos. 60/528,604 and 60/528,689, both filed Dec. 11, 2003 and entitled “Electrical Stimulation System and Associated Apparatus for Securing an Electrical Stimulation Lead in Position in a Person's Brain”, each of which are incorporated herein in its entirety.
  • Once electrical stimulation lead 14 has been inserted and secured, connecting portion 16 of lead 14 extends from the lead insertion site to the implant site at which stimulation source 12 is implanted. The implant site is typically a subcutaneous pocket formed to receive and house stimulation source 12. The implant site is usually positioned a distance away from the insertion site, such as near the chest, below the clavicle or alternatively near the buttocks or another place in the torso area. Once all appropriate components of stimulation system are implanted, these components may be subject to mechanical forces and movement in response to movement of the person's body. A doctor, the patient, or another user of stimulation source may directly or indirectly input signal parameters for controlling the nature of the electrical stimulation provided.
  • Although example steps are illustrated and described, the present invention contemplates two or more steps taking place substantially simultaneously or in a different order. In addition, the present invention contemplates using methods with additional steps, fewer steps, or different steps, so long as the steps remain appropriate for implanting an example stimulation system into a person for electrical stimulation of the person's brain.
  • IV. Infusion pumps
  • In further embodiments, it may be desirable to use a drug delivery system independent of or in combination with electrical stimulation of the brain. Drug delivery may be used independent of or in combination with a lead/electrode to provide electrical stimulation and chemical stimulation. When used, the drug delivery catheter is implanted such that the proximal end of the catheter is coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical or drug. Implantation of the catheter can be achieved by combining data from a number of sources including CT, MRI or conventional and/or magnetic resonance angiography into the stereotactic targeting model. Thus, without being bound to a specific procedure, implantation of the catheter can be achieved using similar techniques as discussed above for implantation of electrical leads, which is incorporated herein. The distal portion of the catheter can have multiple orifices to maximize delivery of the pharmaceutical while minimizing mechanical occlusion. The proximal portion of the catheter can be connected directly to a pump or via a metal, plastic, or other hollow connector, to an extending catheter.
  • Any type of infusion pump can be used in the present invention. For example, “active pumping” devices or so-called peristaltic pumps are described in U.S. Pat. Nos. 4,692,147, 5,840,069, and 6,036,459, which are incorporated herein by reference in their entirety. Peristaltic pumps are used to provide a metered amount of a drug in response to an electronic pulse generated by control circuitry associated within the device. An example of a commercially available peristaltic pump is SynchroMed® implantable pump from Medtronic, Inc., Minneapolis, Minn.
  • Other pumps that may be used in the present invention include accumulator-type pumps, for example certain external infusion pumps from Minimed, Inc., Northridge, Calif. and Infusaid® implantable pump from Strato/Infusaid, Inc., Norwood, Mass. Passive pumping mechanisms can be used to release an agent in a constant flow or intermittently or in a bolus release. Passive type pumps include, for example, but are not limited to gas-driven pumps described in U.S. Pat. Nos. 3,731,681 and 3,951,147; and drive-spring diaphragm pumps described in U.S. Pat. Nos. 4,772,263, 6,666,845, 6,620,151 which are incorporated by reference in its entirety. Pumps of this type are commercially available, for example, Model 3000® from Arrow International, Reading, Penn. and IsoMed® from Medtronic, Inc., Minneapolis, Minn.; AccuRx® pump from Advanced Neuromodulation Systems, Inc., Plano, Tex.
  • Instances in which chemical and electrical stimulation will be administered to the subject, a catheter having electrical leads may be used, similar to the ones described in U.S. Pat. Nos. 6,176,242; 5,423,877; 5,458,631 and 5,119,832, each of which are incorporated herein by reference in its entirety.
  • V. Identifying a Subject with an Affective Disorder
  • Subjects to be treated using the present invention can be selected, identified and/or diagnosed based upon the accumulation of physical, chemical, and historical behavioral data on each patient. One of skill in the art is able to perform the appropriate examinations to accumulate such data. One type of examination can include neurological examinations, which can include mental status evaluations, which can further include a psychiatric assessment. Other types of examinations can include, but are not limited to, motor examination, cranial nerve examination, and neuropsychological tests (i.e., Minnesota Multiphasic Personality Inventory, Beck Depression Inventory, or Hamilton Rating Scale for Depression).
  • In addition to the above examinations, imaging techniques can be used to determine normal and abnormal brain function that can result in disorders. Functional brain imaging allows for localization of specific normal and abnormal functioning of the nervous system. This includes electrical methods such as electroencephalography (EEG), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), as well as metabolic and blood flow studies such as functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) which can be utilized to localize brain function and dysfunction.
  • VI. Treatment of an Affective Disorder
  • Initially, there is an impetus to treat psychiatric disorders with direct modulation of activity in that portion of the brain causing the pathological behavior. In this regard, there have been a large number of anatomical studies that have helped to identify the neural structures and their precise connections which are implicated in psychiatric activity/disorders. These are the structures that are functioning abnormally and manifesting in psychiatric/behavioral/addiction disorders. Numerous anatomical studies from autopsies, animal studies, and imaging such as computerized tomography (CT) scans, and magnetic resonance imaging (MRI) scans have demonstrated the role of these structures and their connections in psychiatric activity/disorders. In addition to these anatomical studies, a number of physiological techniques and diagnostic tools are used to determine the physiological aberrations underlying these disorders. This includes electrical methods such as electroencephalography (EEG), magnetoencephalography (MEG), as well as metabolic and blood flow studies such as functional magnetic resonance imaging (fMRI), and positron emission tomography (PET). The combination of the anatomical and physiological studies have provided increased insight into our understanding of the structures which are involved in the normal functioning or activity of the brain and the abnormal functioning manifesting in psychiatric, behavioral and addiction disorders.
  • Accordingly, the present invention relates to modulation of neuronal activity to affect psychological or psychiatric activity and/or mental activity. The present invention finds particular application in the modulation of neuronal function or processing to effect a functional outcome. The modulation of neuronal function is particularly useful with regard to the prevention, treatment, or amelioration of psychiatric, psychological, conscious state, behavioral, mood, and thought activity (unless otherwise indicated these will be collectively referred to herein as “psychological activity” or “psychiatric activity” or “mental activity”). When referring to a pathological or undesirable condition associated with the activity, reference may be made to “psychiatric disorder” or “psychological disorder” instead of psychiatric or psychological activity. Although the activity to be modulated usually manifests itself in the form of a disorder such as a mood disorder (i.e., major depressive disorder, bipolar disorder, and dysthymic disorder) or an anxiety disorder (i.e., panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder and phobic disorder), it is to be appreciated that the invention may also find application in conjunction with enhancing or diminishing any neurological or psychiatric function, not just an abnormality or disorder. Psychiatric activity that may be modulated can include, but not be limited to, normal functions such as alertness, conscious state, drive, fear, anger, anxiety, euphoria, sadness, and the fight or flight response.
  • The present invention finds particular utility in its application to human psychological or psychiatric activity/disorder. However, it is also to be appreciated that the present invention is applicable to other animals which exhibit behavior that is modulated by the brain. This may include, for example, rodents, primates, canines, felines, elephants, dolphins, etc. Utilizing the various embodiments of the present invention, one skilled in the art may be able to modulate the functional outcome of the brain to achieve a desirable result.
  • One technique that offers the ability to affect neuronal function is the delivery of electrical, chemical, and/or magnetic stimulation for neuromodulation directly to target tissues via an implanted device having a probe. The probe can be a stimulation lead or electrode assembly or drug-delivery catheter, or any combination thereof. The electrode assembly may be one electrode, multiple electrodes, or an array of electrodes in or around the target area. The proximal end of the probe can be coupled to a device, such as an electrical signal source, pharmaceutical delivery pump, or both which, in turn, is operated to stimulate the predetermined treatment site. In certain embodiments, the probe can be incorporated into the device such that the probe and the signal generating device are a single unit.
  • Certain embodiments of the present invention involve a method of treating a mood and/or anxiety disorder comprising the steps of: surgically implanting an electrical stimulation lead having a proximal end and a stimulation portion, wherein after implantation the stimulation portion is in communication with a predetermined site; coupling the proximal end of the lead to a signal generator; and generating an electrical signal with the signal generator to modulate the predetermined site thereby treating the mood and/or anxiety disorder.
  • In further embodiments, neuromodulation of the predetermined site of the present invention can be achieved using magnetic stimulation. One such system that can be employed and that is well known in the art is described in U.S. Pat. No. 6,425,852, which is incorporated herein by reference in its entirety.
  • The therapeutic system or deep brain stimulation system of the present invention is surgically implanted as described in the above sections. One of skill in the art is cognizant that a variety of electrodes or electrical stimulation leads may be utilized in the present invention. It is desirable to use an electrode or lead that contacts or conforms to the target site for optimal delivery of electrical stimulation. One such example, is a single multi contact electrode with eight contacts separated by 2½ mm each contract would have a span of approximately 2 mm. Another example is an electrode with two 1 cm contacts with a 2 mm intervening gap. Yet further, another example of an electrode that can be used in the present invention is a 2 or 3 branched electrode/catheter to cover the predetermined site or target site. Each one of these three pronged catheters/electrodes have four contacts 1-2 mm contacts with a center to center separation of 2 of 2.5 mm and a span of 1.5 mm. Similar designs with catheters to infuse drugs with single outlet pore at the extremities of these types of catheters or along their shaft may also be designed and used in the present invention.
  • Still further, the present invention extends to methods of transplanting cells into a predetermined site to treat mood and/or anxiety disorders. It is envisioned that the transplanted cells can replace damaged, degenerating or dead neuronal cells, deliver a biologically active molecule to the predetermined site or to ameliorate a condition and/or to enhance or stimulate existing neuronal cells. Such transplantation methods are described in U.S. Application No. US20040092010, which is incorporated herein by reference in its entirety.
  • Cells that can be transplanted can be obtained from stem cell lines (i.e., embryonic stem cells, non-embryonic stem cells, etc.) and/or brain biopsies, including tumor biopsies, autopsies and from animal donors. (See U.S. Application No. US20040092010; U.S. Pat. Nos. 5,735,505 and 6,251,669; Temple, Nature Reviews 2:513-520 (2000); Bjorklund and Lindvall, Nat. Neurosci. 3:537-544 (2000)), each of which is incorporated herein by reference in its entirety). Brain stem cells can then be isolated (concentrated) from non-stem cells based on specific “marker” proteins present on their surface. In one such embodiment, a fluorescent antibody specific for such a marker can be used to isolate the stem cells using fluorescent cell sorting (FACS). In another embodiment an antibody affinity column can be employed. Alternatively, distinctive morphological characteristics can be employed.
  • The predetermined site or target area is a subcallosal area, more preferably, the subgenual cingulate area, and more preferably Brodmann area 25/Brodmann area 24. Stimulation of a subcallosal area (i.e., subgenual cingulate area or Brodmann area 25/Brodmann area 24) and/or the surrounding or adjacent white matter tracts leading to or from the subcallosal area or white matter tracts that are contiguous with the subcallosal area results in changes that alleviate or improve the mood and/or anxiety disorder of the subject. It is contemplated that modulating a subcallosal area, more particularly a subgenual cingulate area, can result in increasing, decreasing, masking, altering, overriding or restoring neuronal activity resulting in treatment of the mood and/or anxiety disorder. Yet further stimulation of a subgenual cingulate area, more particularly Brodmann area 25, results in modulation of neuronal activity of other areas of the brain, for example, Brodmann area 9, Brodmann area 10, Brodmann area 24, the hypothalamus, and the brain stem.
  • Using the therapeutic stimulation system of the present invention, the predetermined site or target area is stimulated in an effective amount or effective treatment regimen to decrease, reduce, modulate or abrogate the mood and/or anxiety disorder. Thus, a subject is administered a therapeutically effective stimulation so that the subject has an improvement in the parameters relating to the affective disorder including subjective measures such as, for example, neurological examinations and neuropsychological tests (i.e., Minnesota Multiphasic Personality Inventory, Beck Depression Inventory, Mini-Mental Status Examination (MMSE), Hamilton Rating Scale for Depression, Wisconsin Card Sorting Test (WCST), Tower of London, Stroop task, MADRAS, CGI, N-BAC, or Yale-Brown Obsessive Compulsive score (Y-BOCS)), motor examination, and cranial nerve examination, and objective measures including use of additional psychiatric medications, such as anti-depressants, or other alterations in cerebral blood flow or metabolism and/or neurochemistry. The improvement is any observable or measurable improvement. Thus, one of skill in the art realizes that a treatment may improve the patient condition, but may not be a complete cure of the disease.
  • Treatment regimens may vary as well, and often depend on the health and age of the patient. Obviously, certain types of disease will require more aggressive treatment, while at the same time, certain patients cannot tolerate more taxing regimens. The clinician will be best suited to make such decisions based on the known subject's history.
  • According to one embodiment of the present invention, the target site is stimulated using stimulation parameters such as, pulse width of about 1 to about 500 microseconds, more preferable, about 1 to about 90 microseconds; frequency of about 1 to about 300 Hz, more preferably, about 100 to about 185 Hz; and voltage of about 0.5 to about 10 volts, more preferably about 1 to about 10 volts. It is known in the art that the range for the stimulation parameters may be greater or smaller depending on the particular patient needs and can be determined by the physician. Other parameters that can be considered may include the type of stimulation for example, but not limited to acute stimulation, subacute stimulation, and/or chronic stimulation.
  • It is envisioned that stimulation of a subcallosal area and/or the adjacent white matter modulates other targets in the limbic-cortical circuit or pathway thereby improving any dysfunctional limbic-cortical circuits resulting in an improvement or alleviation or providing remission of depression and/or anxiety in the treated subjects. Other such improvements can be sensations of calm, tranquility, peacefulness, increased energy and alertness, improved mood, improvement in attention and thinking, improvement in motor speed, improvement in mental speed and in spontaneity of speech, improved sleep, improved appetite, improved limbic behavior, increased motivation, decreases in anxiety, decreases in repetitive behavior, impulses, obsessions, etc.
  • For purposes of this invention, beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, and remission (whether partial or total), whether objective or subjective.
  • FIG. 4 summarizes the general procedure of the present invention. Any of the above described methods can be used to identify a subject or diagnose a subject that suffers from an affective disorder (100). Once the subject is identified, a stimulation device is implanted (200) into the subject such that the subcallosal area of the subject's brain is stimulated (300). After the target area has been stimulated (i.e., electrical, chemical or magnetic stimulation), the subject is evaluated to determine the change in the affective disorder. One of skill in the art realizes that the present invention is not bound by the described methods or devices and that any method or device that would result in neuromodulation of the subcallosal area could be used in the present invention.
  • VII. Combination Treatment
  • In order to increase the effectiveness of the electrical stimulation method of the present invention, it may be desirable to combine electrical stimulation with chemical stimulation to treat the mood and/or anxiety disease.
  • In one preferred alternative, an implantable signal generator and electrical stimulating lead and an implantable pump and catheter(s) are used to deliver electrical stimulation and/or one or more stimulating drugs to the above mentioned areas as a treatment for mood and/or anxiety disorders.
  • Herein, stimulating drugs comprise medications, anesthetic agents, synthetic or natural peptides or hormones, neurotransmitters, cytokines and other intracellular and intercellular chemical signals and messengers, and the like. In addition, certain neurotransmitters, hormones, and other drugs are excitatory for some tissues, yet are inhibitory to other tissues. Therefore, where, herein, a drug is referred to as an “excitatory” drug, this means that the drug is acting in an excitatory manner, although it may act in an inhibitory manner in other circumstances and/or locations. Similarly, where an “inhibitory” drug is mentioned, this drug is acting in an inhibitory manner, although in other circumstances and/or locations, it may be an “excitatory” drug. In addition, stimulation of an area herein includes stimulation of cell bodies and axons in the area.
  • Similarly, excitatory neurotransmitter agonists (i.e., norepinephrine, epinephrine, glutamate, acetylcholine, serotonin, dopamine), agonists thereof, and agents that act to increase levels of an excitatory neurotransmitter(s) (i.e., edrophonium; Mestinon; trazodone; SSRIs (i.e., flouxetine, paroxetine, sertraline, citalopram and fluvoxamine); tricyclic antidepressants (i.e., imipramine, amitriptyline, doxepin, desipramine, trimipramine and nortriptyline), monoamine oxidase inhibitors (i.e., phenelzine, tranylcypromine, isocarboxasid)), generally have an excitatory effect on neural tissue, while inhibitory neurotransmitters (i.e., dopamine, glycine, and gamma-aminobutyric acid (GABA)), agonists thereof, and agents that act to increase levels of an inhibitory neurotransmitter(s) generally have an inhibitory effect. (Dopamine acts as an excitatory neurotransmitter in some locations and circumstances, and as an inhibitory neurotransmitter in other locations and circumstances.) However, antagonists of inhibitory neurotransmitters (i.e., bicuculline) and agents that act to decrease levels of an inhibitory neurotransmitter(s) have been demonstrated to excite neural tissue, leading to increased neural activity. Similarly, excitatory neurotransmitter antagonists (i.e., prazosin, and metoprolol) and agents that decrease levels of excitatory neurotransmitters may inhibit neural activity. Yet further, lithium salts and anesthetics (i.e., lidocane) may also be used in combination with electrical stimulation.
  • VIII. EXAMPLES
  • The following examples are included to demonstrate preferred embodiments, more particularly methods and procedures, of the invention. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the invention, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the invention.
  • Example 1 Patient Selection
  • Five patients were selected for electrical stimulation of the brain. Patients were selected based upon various demographics, family history of depression (FHx), age of onset, episodes of depression per year, the medications, other therapies, and the Hamilton rating score, as shown in Table 1. (Note “Dur yr” means duration in years).
  • As is known in the art, a score above 7 on the Hamilton 17 scale (“H17”) is an indication of depression. A 50% change in the H17 scale score of from the initial baseline score is considered a clinical response, while a score of less than 7 is considered clinical remission.
    TABLE 1
    Patient Demographic
    Age Dur Epi
    PT Sex Age FHx onset Yr Yr Meds ECT CBT IPT H17 dx
    A F 48 Y 18 20 2.5 1,2,4 N N Y 29 UP
    B F 45 Y 21 24 6 1,2,3,5 Y Y Y 27 UP
    C M 37 Y 20 17 10 1,2 Y Y Y 26 UP
    D M 48 Y 36 12 5 1,2,5 Y Y Y 24 UP
    E M 59 N 45 15 3 1,2,3 Y N Y 20 BPII
    Mean 47 28 18 5 25

    Meds: 1 = SSRI,

    2 = bupropion,

    3 = atypical antipsychotics,

    4 = stimulates,

    5 = other (benzo, and anticonvulsants).
  • Example 2 Surgical Procedure
  • Under local anesthesia, a stereotactic frame was first placed on the patient's head, followed by acquisition of an MRI (Magnetic Resonance Imaging) scan to localize the target region. Patients were then taken to the operating room where, under local anesthesia, two burr holes were placed behind the hairline. Stereotactic coordinates were derived from the pre-op MRI. The coordinates of this target derived from the Schaltenbrand and Wahren Atlas plate 3 (FIG. 3) were 6-7 mm from the midline (range 2-14 mm), 29 mm anterior to the mid-commissural point range 20-40) and 5mm (range 0-10 mm) below the intra-commissural line.
  • Once the target sites were identified, two multi contact electrodes were delivered, one in each hemisphere. The electrodes were connected to a stimulating pulse generator.
  • With the patient's participation, each electrode contact was stimulated and acute changes in behavior was assessed using self report and mood rating scales, such as POMS, PANAS, sadness, anxiety and general well being, self-report, and mood, motor and cognitive scales, such as, finger tapping, verbal fluency. As either positive or negative changes in mood might occur, the relationship between the specific stimulation site and the resulting behavior was carefully documented. Following a testing session to help in optimal target selection and adjustment of the position of the electrode contacts, the incisions were closed and patients taken to the intensive care unit for recovery from surgery.
  • At anytime after the surgery for implantation of the electrodes, patients underwent a second procedure (˜45 mins under general anesthesia) to connect the electrodes to a self contained subcutaneous generator device placed below the clavicle and connected to the electrodes in the head. After 2-3 days, the patients was discharged home on their regular antidepressant regime with the stimulator turned OFF.
  • Example 3 Outpatient Programming and Clinical Follow-Up
  • Patients returned for generator device programming. There were several parameters that were tested, namely, which electrode contact was to be stimulated, the polarity of stimulation, the frequency and pulse width of stimulation, etc.
  • The electrode programming was done on an outpatient basis and involved a series of trials over the course of a week. Electrode contacts that produced acute behavioral changes or fMRI signal changes in the subgenual cingulate area (Brodmann area 25) were tried first. Once basic parameters were set, adjustments were made periodically until a stable program was established.
  • Once final stimulation parameters were established, psychiatric symptoms were monitored on a monthly basis. Clinical ratings were quantified using Beck, Hamilton, CGI, and Quality of Life Scales and Serial Neuropsychological Testing. Serial Neuropsychological Testing and PET studies were performed at 8 weeks and 6 months. General cognitive performance and detailed frontal lobe functioning was assessed. The test battery was designed to differentiate dorsolateral, superior medial, and ventrolateral/orbital frontal behaviors which was differently affected by activation or disruption of the target areas with electrical stimulation. Serial testing allowed differentiation between early surgical effects, chronic stimulation effects, and correlations with mood change.
  • FIG. 5A and FIG. 5B show the results of the Hamilton Scale Scores after 6 months of stimulation for the first five subjects.
  • Thus, stimulation in a subcallosal white matter area in the vicinity of Brodmann area 25 leads to changes in the activity of Brodmann area 25, the dorsal/lateral frontal lobe (Brodmann areas 9 and 6), dorsal/medial frontal lobe (Brodmann areas 9 and 10), anterior cingulate area (Brodmann area 24), orbital frontal cortex (Brodmann areas 10 and 11), the hypothalamus, brain stem and other target areas such as upstream, downstream or remote cortical and subcortical regions.
  • Example 4 Mapping Using fMRI
  • Within 1-5 days of the initial electrode surgery, fMRI scans were performed during successive stimulation of each electrode contact. fMRI was used as an additional means of mapping the differences in activity of the electrodes. fMRI was not required because the optimal electrode was determined based upon clinical observations during the operation and operatively, as described above.
  • This procedure was used to further define the differential projection fields mediating acute changes in behavior initiated by a particular stimulation site. Even without acute changes in behavior, these maps allowed discrimination of subtle differences in pathways served by stimulation of different white matter tracts within the stimulation field of each electrode. These results were also useful in guiding selection of the optimal site for chronic stimulation, particularly if changes with some but not all electrodes were seen in the target subgenual cingulate area.
  • Imaging was performed on a 1.5T scanner using methods proven safe for patients with implanted electrodes and delivery catheters (FIG. 6A-6E). Whole brain samples using spiral acquisition were repeated every 3.52 seconds. One cycle was 120 seconds of stimulation and 120 seconds rest. A block of 4 cycles was acquired for the best and worst contact pairs within each hemisphere based on behavior changes in the operating room and post-operatively. The electrodes were activated using a transcutaneous lead connected to a pulse generator outside the imaging room. Patients rated mood (pos/neg) on a 1-5 scale by button push and auditory prompt following each cycle. Analyses addressed differences ON vs OFF for each contact and changes over multiple cycles.
  • References
  • All patents and publications mentioned in the specifications are indicative of the levels of those skilled in the art to which the invention pertains. All patents and publications are herein incorporated by reference to the same extent as if each individual publication was specifically and individually indicated to be incorporated by reference.
    • Bjorklund and Lindvall, Nat. Neurosci. 3:537-544 (2000)
    • Drevets et al., Nature 386:824-7, 1997.
    • Ebmeier et al., Br J Psychiatry, 170:77-81, 1997.
    • Galynker et al., J Nucl Med., 39:608-12, 1998.
    • Temple, Nature Reviews 2:513-520 (2000)
    • U.S. Pat. No. 3,731,681
    • U.S. Pat. No. 3,951,147
    • U.S. Pat. No. 4,692,147
    • U.S. Pat. No. 4,772,263
    • U.S. Pat. No. 5,119,832
    • U.S. Pat. No. 5,263,480
    • U.S. Pat. No. 5,299,569
    • U.S. Pat. No. 5,423,877
    • U.S. Pat. No. 5,458,631
    • U.S. Pat. No. 5,470,846
    • U.S. Pat. No. 5,540,734
    • U.S. Pat. No. 5,735,505
    • U.S. Pat. No. 5,840,069
    • U.S. Pat. No. 6,016,449
    • U.S. Pat. No. 6,036,459
    • U.S. Pat. No. 6,051,017
    • U.S. Pat. No. 6,176,242
    • U.S. Pat. No. 6,251,669
    • U.S. Pat. No. 6,425,852
    • U.S. Pat. No. 6,609,031
    • U.S. Pat. No. 6,620,151
    • U.S. Pat. No. 6,666,845
    • U.S. Pat. No. 6,735,474
    • U.S. Pat. No. 6,735,475
    • U.S. Publication No. US20040092010
  • Although the present invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the invention as defined by the appended claims. Moreover, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. As one will readily appreciate from the disclosure, processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

Claims (28)

1. A system for treating a mood and/or anxiety disorder comprising:
a probe having a stimulation portion in communication with a subcallosal area; and
a device to stimulate the probe thereby stimulating the subcallosal area and treating the mood and/or anxiety disorder.
2. The system of claim 1, wherein the probe is coupled to the device.
3. The system of claim 1, wherein the probe is incorporated within the device.
4. The system of claim 1, wherein the device is an electrical signal source or a pharmaceutical delivery pump.
5. The system of claim 1, wherein the device is a combination of an electrical signal source and a pharmaceutical delivery pump.
6. The system of claim 1, wherein the probe is an electrical stimulation lead.
7. The system of claim 1, wherein the probe is a pharmaceutical catheter.
8. The system of claim 6, wherein the lead comprises a plurality of electrodes.
9. The system of claim 7, wherein the catheter comprises at least one electrode.
10. The system of claim 1, wherein the stimulation is electrical.
11. The system of claim 1, wherein the stimulation is chemical.
12. The system of claim 1, wherein the stimulation is magnetic.
13. A microstimulator for treating subjects with mood and/or anxiety disorders comprising:
an electrical stimulation lead having a stimulation portion in communication with a subcallosal area; and
an electrical signal generating portion to stimulate the probe thereby stimulating the subcallosal area and treating the mood and/or anxiety disorder, wherein the lead and the generating portion are combined in one unit.
14. The system of claim 13, wherein the generating portion further comprising a pharmaceutical delivery pump.
15. The system of claim 13, wherein the lead comprises a plurality of electrodes.
16. The system of claim 14, wherein the lead further comprises a catheter.
17. A system for treating subjects with mood and/or anxiety disorders comprising:
an electrical stimulation lead that is implanted into the subject's brain, the lead comprises at least one electrode that is in communication with a subcallosal area and delivers an electrical signal to the subcallosal area in response to the received signal; and
a signal generator that generates the electrical signal for transmission to the at least one electrode of the lead resulting in delivery of the electrical signals to subcallosal area thereby treating the mood and/or anxiety disorder.
18. The system of claim 17, wherein the lead comprises a plurality of electrodes.
19. The system of claim 17, wherein the signal generator is implanted in the subject's body.
20. The system of claim 17 further comprising:
a catheter that is implanted into a subject's brain, the catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical is in communication with the subcallosal area and a pump to discharge the pharmaceutical through the discharge portion of the catheter into the predetermined site thereby chemically stimulating the subcallosal area and treating the mood and/or anxiety disorder.
21. A system for treating subjects with mood and/or anxiety disorders comprising:
an electrical stimulation lead that is implanted into the subject's brain, the lead comprises at least one electrode that is in communication with Brodmann area 25 and delivers an electrical signal to Brodmann area 25 in response to the received signal; and
a signal generator that generates the electrical signal for transmission to the at least one electrode of the lead resulting in delivery of the electrical signals to Brodmann area 25 thereby treating the mood and/or anxiety disorder.
22. A system for treating subjects with mood and/or anxiety disorder comprising:
a catheter that is implanted into a subject's brain, the catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical is in communication with a subcallosal area; and
a pump to discharge the pharmaceutical through the discharge portion of the catheter into the predetermined site thereby chemically stimulating the subcallosal area and treating the mood and/or anxiety disorder.
23. The system of claim 22, wherein the catheter further comprises an electrical stimulation lead having at least one electrode.
24. The system of claim 23 further comprising a signal generator that generates signals for transmission to the electrode of the lead resulting in delivery of electrical signals to the subcallosal thereby treating the mood and/or anxiety disorder.
25. A system for treating subjects with mood disorder and/or anxiety disorder comprising:
an electrical stimulation lead that is implanted into the subject's brain, the lead comprises at least one electrode that is in communication with a subcallosal area and delivers electrical signals to the predetermined site in response to received signals;
a signal generator that generates signals for transmission to the electrode of the lead resulting in delivery of electrical signals to the subcallosal area;
a catheter that is implanted into the subject's brain, the catheter having a proximal end coupled to a pump and a discharge portion for infusing a dosage of a pharmaceutical is in communication with the subcallosal area; and
a pump to discharge the pharmaceutical through the discharge portion of the catheter into the subcallosal area;
wherein stimulation of subcallosal area treats the mood and/or anxiety disorder.
26. The system of claim 25, wherein the lead comprises a plurality of electrodes.
27. The system of claim 25, wherein the signal generator is implanted in the subject's body.
28. The system of claim 25, wherein the pump is implanted in the subject's body.
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Cited By (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050027284A1 (en) * 2003-06-19 2005-02-03 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20050154425A1 (en) * 2004-08-19 2005-07-14 Boveja Birinder R. Method and system to provide therapy for neuropsychiatric disorders and cognitive impairments using gradient magnetic pulses to the brain and pulsed electrical stimulation to vagus nerve(s)
WO2005065768A1 (en) * 2003-12-30 2005-07-21 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
US20060058856A1 (en) * 2004-09-14 2006-03-16 Neuropace, Inc. Responsive therapy for psychiatric disorders
US20060064138A1 (en) * 2004-04-30 2006-03-23 Francisco Velasco Method of treating mood disorders and/or anxiety disorders by brain stimulation
US20060212090A1 (en) * 2005-03-01 2006-09-21 Functional Neuroscience Inc. Method of treating cognitive disorders using neuromodulation
US20060212091A1 (en) * 2005-03-01 2006-09-21 Functional Neuroscience Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20070032834A1 (en) * 2000-07-13 2007-02-08 Northstar Neuroscience, Inc. Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US20070088403A1 (en) * 2005-10-19 2007-04-19 Allen Wyler Methods and systems for establishing parameters for neural stimulation
US20070100398A1 (en) * 2005-10-19 2007-05-03 Northstar Neuroscience, Inc. Neural stimulation system and optical monitoring systems and methods
US20070173901A1 (en) * 2006-01-24 2007-07-26 Reeve Helen L Method and device for detecting and treating depression
US20070179558A1 (en) * 2006-01-30 2007-08-02 Gliner Bradford E Systems and methods for varying electromagnetic and adjunctive neural therapies
US20070233193A1 (en) * 2006-03-29 2007-10-04 Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US20070255351A1 (en) * 2006-04-28 2007-11-01 Cyberonics, Inc. Threshold optimization for tissue stimulation therapy
WO2008003318A1 (en) * 2006-07-05 2008-01-10 Aarhus Universitet A research model system and a method for using electrical stimulation and/ chemical stimulation to induce depressive illness in research animals
US20080103548A1 (en) * 2006-08-02 2008-05-01 Northstar Neuroscience, Inc. Methods for treating neurological disorders, including neuropsychiatric and neuropsychological disorders, and associated systems
US20080183074A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Method and apparatus for coordinated display of anatomical and neuromonitoring information
US20080183190A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated surgical navigational and neuromonitoring system having automated surgical assistance and control
US20080183068A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated Visualization of Surgical Navigational and Neural Monitoring Information
US20080183188A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated Surgical Navigational and Neuromonitoring System
US20080183189A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Surgical navigational and neuromonitoring instrument
US20080269839A1 (en) * 2007-04-27 2008-10-30 Armstrong Randolph K Dosing Limitation for an Implantable Medical Device
US20090149898A1 (en) * 2007-12-07 2009-06-11 Northstar Neuroscience, Inc. Systems and Methods for Providing Targeted Neural Stimulation Therapy to Address Neurological Disorders, Including Neuropyschiatric and Neuropyschological Disorders
US20090210018A1 (en) * 2008-02-15 2009-08-20 Lozano Andres M Method for treating neurological /psychiatric disorders with stimulation to the subcaudate area of the brain
US20090264956A1 (en) * 2008-04-18 2009-10-22 Medtronic, Inc. Psychiatric disorder therapy control
US20090264967A1 (en) * 2008-04-18 2009-10-22 Medtronic, Inc. Timing therapy evaluation trials
US20090320844A1 (en) * 2006-08-04 2009-12-31 Nielsen Joergen Groenlund Method to compensate for the effect of recirculation of inert blood soluble gas on the determination of pulmonary blood flow in repeated inert gas rebreathing tests
US20100036453A1 (en) * 2008-08-05 2010-02-11 Northstar Neuroscience, Inc. Techniques for selecting signal delivery sites and other parameters for treating depression and other neurological disorders, and associated systems and methods
US20100057159A1 (en) * 2008-04-30 2010-03-04 Lozano Andres M Methods for targeting deep brain sites to treat mood and/or anxiety disorders
US7684866B2 (en) 2003-08-01 2010-03-23 Advanced Neuromodulation Systems, Inc. Apparatus and methods for applying neural stimulation to a patient
US20100100151A1 (en) * 2008-10-20 2010-04-22 Terry Jr Reese S Neurostimulation with signal duration determined by a cardiac cycle
US20100106217A1 (en) * 2008-10-24 2010-04-29 Colborn John C Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US20100191304A1 (en) * 2009-01-23 2010-07-29 Scott Timothy L Implantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation
US20100204751A1 (en) * 2009-02-11 2010-08-12 University Of Maryland, Baltimore Methods for Treating Central Pain Syndrome and Other Pain Related Pathologies
US7801601B2 (en) 2006-01-27 2010-09-21 Cyberonics, Inc. Controlling neuromodulation using stimulus modalities
US20100274308A1 (en) * 2009-04-24 2010-10-28 Scott Timothy L Use of cardiac parameters in methods and systems for treating a chronic medical condition
US7869867B2 (en) 2006-10-27 2011-01-11 Cyberonics, Inc. Implantable neurostimulator with refractory stimulation
US8204603B2 (en) 2008-04-25 2012-06-19 Cyberonics, Inc. Blocking exogenous action potentials by an implantable medical device
US8337404B2 (en) 2010-10-01 2012-12-25 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8382667B2 (en) 2010-10-01 2013-02-26 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8452387B2 (en) 2010-09-16 2013-05-28 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8565867B2 (en) 2005-01-28 2013-10-22 Cyberonics, Inc. Changeable electrode polarity stimulation by an implantable medical device
US8562536B2 (en) 2010-04-29 2013-10-22 Flint Hills Scientific, Llc Algorithm for detecting a seizure from cardiac data
WO2013172981A1 (en) * 2012-05-16 2013-11-21 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
US8641646B2 (en) 2010-07-30 2014-02-04 Cyberonics, Inc. Seizure detection using coordinate data
US8649871B2 (en) 2010-04-29 2014-02-11 Cyberonics, Inc. Validity test adaptive constraint modification for cardiac data used for detection of state changes
US8679009B2 (en) 2010-06-15 2014-03-25 Flint Hills Scientific, Llc Systems approach to comorbidity assessment
US8684921B2 (en) 2010-10-01 2014-04-01 Flint Hills Scientific Llc Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US8725239B2 (en) 2011-04-25 2014-05-13 Cyberonics, Inc. Identifying seizures using heart rate decrease
US8831732B2 (en) 2010-04-29 2014-09-09 Cyberonics, Inc. Method, apparatus and system for validating and quantifying cardiac beat data quality
US8827912B2 (en) 2009-04-24 2014-09-09 Cyberonics, Inc. Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters
US9050469B1 (en) 2003-11-26 2015-06-09 Flint Hills Scientific, Llc Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
US9314633B2 (en) 2008-01-25 2016-04-19 Cyberonics, Inc. Contingent cardio-protection for epilepsy patients
US9402550B2 (en) 2011-04-29 2016-08-02 Cybertronics, Inc. Dynamic heart rate threshold for neurological event detection
US9504390B2 (en) 2011-03-04 2016-11-29 Globalfoundries Inc. Detecting, assessing and managing a risk of death in epilepsy
US9613184B2 (en) 2008-04-18 2017-04-04 Medtronic, Inc. Analyzing a washout period characteristic for psychiatric disorder therapy delivery
US10206591B2 (en) 2011-10-14 2019-02-19 Flint Hills Scientific, Llc Seizure detection methods, apparatus, and systems using an autoregression algorithm
US10220211B2 (en) 2013-01-22 2019-03-05 Livanova Usa, Inc. Methods and systems to diagnose depression
US10448839B2 (en) 2012-04-23 2019-10-22 Livanova Usa, Inc. Methods, systems and apparatuses for detecting increased risk of sudden death
RU2714296C1 (en) * 2019-04-09 2020-02-13 Федеральное государственное бюджетное образовательное учреждение высшего образования "Алтайский государственный медицинский университет" Министерства здравоохранения Российской Федерации Method of treating patients with chronic insomnia
US11273283B2 (en) 2017-12-31 2022-03-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
US11452839B2 (en) 2018-09-14 2022-09-27 Neuroenhancement Lab, LLC System and method of improving sleep
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11786694B2 (en) 2019-05-24 2023-10-17 NeuroLight, Inc. Device, method, and app for facilitating sleep

Families Citing this family (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7062330B1 (en) * 1998-10-26 2006-06-13 Boveja Birinder R Electrical stimulation adjunct (Add-ON) therapy for urinary incontinence and urological disorders using implanted lead stimulus-receiver and an external pulse generator
US20060217782A1 (en) * 1998-10-26 2006-09-28 Boveja Birinder R Method and system for cortical stimulation to provide adjunct (ADD-ON) therapy for stroke, tinnitus and other medical disorders using implantable and external components
US6959215B2 (en) * 2002-12-09 2005-10-25 Northstar Neuroscience, Inc. Methods for treating essential tremor
AU2003297761A1 (en) * 2002-12-09 2004-06-30 Northstar Neuroscience, Inc. Methods for treating neurological language disorders
US9079030B2 (en) 2004-12-22 2015-07-14 G. Blake Holloway Systems and methods for balancing and maintaining the health of the human autonomic nervous system
US9352145B2 (en) * 2004-12-22 2016-05-31 Boston Scientific Neuromodulation Corporation Methods and systems for treating a psychotic disorder
US20110307030A1 (en) * 2005-03-24 2011-12-15 Michael Sasha John Methods for Evaluating and Selecting Electrode Sites of a Brain Network to Treat Brain Disorders
US8926959B2 (en) 2005-07-22 2015-01-06 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
US9238150B2 (en) * 2005-07-22 2016-01-19 The Board Of Trustees Of The Leland Stanford Junior University Optical tissue interface method and apparatus for stimulating cells
US20070053996A1 (en) 2005-07-22 2007-03-08 Boyden Edward S Light-activated cation channel and uses thereof
US9274099B2 (en) 2005-07-22 2016-03-01 The Board Of Trustees Of The Leland Stanford Junior University Screening test drugs to identify their effects on cell membrane voltage-gated ion channel
US20070027499A1 (en) 2005-07-29 2007-02-01 Cyberonics, Inc. Neurostimulation device for treating mood disorders
US7684867B2 (en) * 2005-11-01 2010-03-23 Boston Scientific Neuromodulation Corporation Treatment of aphasia by electrical stimulation and/or drug infusion
US9352167B2 (en) * 2006-05-05 2016-05-31 Rio Grande Neurosciences, Inc. Enhanced spatial summation for deep-brain transcranial magnetic stimulation
US8280514B2 (en) 2006-10-31 2012-10-02 Advanced Neuromodulation Systems, Inc. Identifying areas of the brain by examining the neuronal signals
DE202007003577U1 (en) * 2006-12-01 2008-04-10 Liebherr-Hausgeräte Ochsenhausen GmbH Fridge and / or freezer
WO2008086470A1 (en) 2007-01-10 2008-07-17 The Board Of Trustees Of The Leland Stanford Junior University System for optical stimulation of target cells
WO2008106694A2 (en) 2007-03-01 2008-09-04 The Board Of Trustees Of The Leland Stanford Junior University Systems, methods and compositions for optical stimulation of target cells
WO2009052454A2 (en) 2007-10-19 2009-04-23 University Of California Compositions and methods for ameliorating cns inflammation, psychosis, delirium, ptsd or ptss
US10434327B2 (en) 2007-10-31 2019-10-08 The Board Of Trustees Of The Leland Stanford Junior University Implantable optical stimulators
US10688303B2 (en) * 2008-04-18 2020-06-23 Medtronic, Inc. Therapy target selection for psychiatric disorder therapy
ES2701349T3 (en) 2008-04-23 2019-02-21 Univ Leland Stanford Junior Systems, methods and compositions for the optical stimulation of target cells
US9282927B2 (en) 2008-04-24 2016-03-15 Invention Science Fund I, Llc Methods and systems for modifying bioactive agent use
US9449150B2 (en) 2008-04-24 2016-09-20 The Invention Science Fund I, Llc Combination treatment selection methods and systems
US9662391B2 (en) 2008-04-24 2017-05-30 The Invention Science Fund I Llc Side effect ameliorating combination therapeutic products and systems
US9649469B2 (en) 2008-04-24 2017-05-16 The Invention Science Fund I Llc Methods and systems for presenting a combination treatment
US9560967B2 (en) 2008-04-24 2017-02-07 The Invention Science Fund I Llc Systems and apparatus for measuring a bioactive agent effect
US20090306750A1 (en) * 2008-06-06 2009-12-10 Neuropace, Inc. Lead Fixation Assembly and Methods of Using Same
BRPI0915583A2 (en) 2008-06-17 2016-01-26 Univ Leland Stanford Junior apparatus and methods for controlling cell development
WO2010006049A1 (en) 2008-07-08 2010-01-14 The Board Of Trustees Of The Leland Stanford Junior University Materials and approaches for optical stimulation of the peripheral nervous system
JP5653918B2 (en) 2008-07-30 2015-01-14 エコーレ ポリテクニーク フェデラーレ デ ローザンヌ (イーピーエフエル) Apparatus and method for optimized stimulation of neural targets
US8788064B2 (en) 2008-11-12 2014-07-22 Ecole Polytechnique Federale De Lausanne Microfabricated neurostimulation device
US20100198281A1 (en) * 2009-01-30 2010-08-05 C.Y. Joseph Chang, MD, PA Methods for treating disorders of perceptual integration by brain modulation
US10232178B2 (en) * 2009-03-20 2019-03-19 Electrocore, Inc. Non-invasive magnetic or electrical nerve stimulation to treat or prevent dementia
US20110040356A1 (en) 2009-08-12 2011-02-17 Fredric Schiffer Methods for Treating Psychiatric Disorders Using Light Energy
JP2013512062A (en) 2009-12-01 2013-04-11 エコーレ ポリテクニーク フェデラーレ デ ローザンヌ Microfabricated surface nerve stimulation device and methods of making and using the same
US20120290058A1 (en) * 2009-12-02 2012-11-15 United States Government Department Of Veterans Affairs Methods and systems for the treatment of anxiety disorders and disorders with psychotic features
EP2552536B1 (en) 2010-04-01 2016-06-08 Ecole Polytechnique Fédérale de Lausanne (EPFL) Device for interacting with neurological tissue
US20110319878A1 (en) * 2010-06-24 2011-12-29 Dimauro Thomas M Red Light Implants for Treating Postpartum Depression
US9522288B2 (en) 2010-11-05 2016-12-20 The Board Of Trustees Of The Leland Stanford Junior University Upconversion of light for use in optogenetic methods
CA2816990A1 (en) 2010-11-05 2012-05-10 The Board Of Trustees Of The Leland Stanford Junior University Stabilized step function opsin proteins and methods of using the same
US10086012B2 (en) 2010-11-05 2018-10-02 The Board Of Trustees Of The Leland Stanford Junior University Control and characterization of memory function
AU2011323226B2 (en) 2010-11-05 2015-03-12 The Board Of Trustees Of The Leland Stanford Junior University Light-activated chimeric opsins and methods of using the same
US8696722B2 (en) 2010-11-22 2014-04-15 The Board Of Trustees Of The Leland Stanford Junior University Optogenetic magnetic resonance imaging
CN103547240B (en) * 2011-06-16 2016-03-30 索雷斯生命科学公司 For the autonomic balance of the mankind and the system and method maintaining health
EP3524676A1 (en) 2011-12-16 2019-08-14 The Board of Trustees of The Leland Stanford Junior University Opsin polypeptides and methods of use thereof
CN104363961B (en) 2012-02-21 2017-10-03 斯坦福大学托管董事会 Composition and method for treating basin bottom neurogenic illness
US9446238B2 (en) 2013-01-25 2016-09-20 Andres M. Lozano Deep brain stimulation of the subcallosal cingulate area for treatment of refractory anorexia nervosa
CN105246550A (en) 2013-03-15 2016-01-13 小利兰·斯坦福大学托管委员会 Optogenetic control of behavioral state
US10220092B2 (en) 2013-04-29 2019-03-05 The Board Of Trustees Of The Leland Stanford Junior University Devices, systems and methods for optogenetic modulation of action potentials in target cells
WO2015017543A2 (en) 2013-07-30 2015-02-05 Massachusetts Institute Of Technology Systems and methods for delivering chemical and electrical stimulation across one or more neural circuits
EP3033427A4 (en) 2013-08-14 2017-05-31 The Board Of Trustees Of The University Of the Leland Stanford Junior University Compositions and methods for controlling pain
EP3476430B1 (en) 2014-05-16 2020-07-01 Aleva Neurotherapeutics SA Device for interacting with neurological tissue
US11311718B2 (en) 2014-05-16 2022-04-26 Aleva Neurotherapeutics Sa Device for interacting with neurological tissue and methods of making and using the same
US9403011B2 (en) 2014-08-27 2016-08-02 Aleva Neurotherapeutics Leadless neurostimulator
US9474894B2 (en) 2014-08-27 2016-10-25 Aleva Neurotherapeutics Deep brain stimulation lead
ES2945599T3 (en) 2014-09-23 2023-07-04 Icahn School Med Mount Sinai Systems and methods for the treatment of a psychiatric disorder
WO2016209654A1 (en) 2015-06-22 2016-12-29 The Board Of Trustees Of The Leland Stanford Junior University Methods and devices for imaging and/or optogenetic control of light-responsive neurons
WO2017021542A1 (en) 2015-08-06 2017-02-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Method and device for modulating fear and/or anxiety
WO2017134587A1 (en) 2016-02-02 2017-08-10 Aleva Neurotherapeutics, Sa Treatment of autoimmune diseases with deep brain stimulation
US11123565B1 (en) 2016-10-31 2021-09-21 Nevro Corp. Treatment of neurodegenerative disease with high frequency stimulation, and associated systems and methods
US11294165B2 (en) 2017-03-30 2022-04-05 The Board Of Trustees Of The Leland Stanford Junior University Modular, electro-optical device for increasing the imaging field of view using time-sequential capture
US11911619B2 (en) 2017-04-07 2024-02-27 The Regents Of The University Of California Method of neural intervention for the treatment of affective neuropsychiatric disorders
US11241575B1 (en) 2017-09-05 2022-02-08 Kelly C.R. Bijanki Anxiolysis without sedation: awake craniotomy facilitated by continuous direct stimulation of cingulum bundle
US11123549B1 (en) 2017-09-08 2021-09-21 Nevro Corp. Electrical therapy applied to the brain with increased efficacy and/or decreased undesirable side effects, and associated systems and methods
US10702692B2 (en) 2018-03-02 2020-07-07 Aleva Neurotherapeutics Neurostimulation device
WO2020068830A1 (en) * 2018-09-24 2020-04-02 Vivek Sharma Auricular nerve stimulation to address patient disorders, and associated systems and methods
WO2022183273A1 (en) * 2021-03-03 2022-09-09 Whitewater West Industries, Ltd. Wave system and method

Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3653385A (en) * 1970-10-20 1972-04-04 Charles Burton Production of focal brain lesions by inductive heating
US5342410A (en) * 1990-10-05 1994-08-30 Eric Braverman Apparatus and method for increasing the amplitude of P300 waves in the human brain
US5752911A (en) * 1995-04-27 1998-05-19 Canedo; Luis E. Electromagnetic method of treatment of epilepsy and apparatus
US6128537A (en) * 1997-05-01 2000-10-03 Medtronic, Inc Techniques for treating anxiety by brain stimulation and drug infusion
US6132361A (en) * 1994-11-28 2000-10-17 Neotonus, Inc. Transcranial brain stimulation
US6567696B2 (en) * 2001-02-06 2003-05-20 Mediseb Ltd. Physiotherapeutic device
US6592509B1 (en) * 2002-02-04 2003-07-15 Thomas W. Hunter, Jr. Electromagnetic stimulator
US6629973B1 (en) * 1999-01-25 2003-10-07 Elekta Ab Method and an apparatus for controlled destruction of tissue
US6782292B2 (en) * 2000-06-20 2004-08-24 Advanced Bionics Corporation System and method for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US20050027284A1 (en) * 2003-06-19 2005-02-03 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US6871098B2 (en) * 2000-10-30 2005-03-22 Medtronic, Inc. Method for treating obsessive-compulsive disorder with electrical stimulation of the brain internal capsule
US20050143800A1 (en) * 2003-12-11 2005-06-30 Lando Peter R. Electrical stimulation system and associated apparatus for securing an electrical stimulation lead in position in a person's brain
US20050143799A1 (en) * 2003-12-11 2005-06-30 Black Damon R. Electrical stimulation system and associated apparatus for securing an electrical stimulation lead in position in a person's brain

Family Cites Families (75)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3731681A (en) 1970-05-18 1973-05-08 Univ Minnesota Implantable indusion pump
US3951147A (en) 1975-04-07 1976-04-20 Metal Bellows Company Implantable infusate pump
US4692147A (en) 1980-04-02 1987-09-08 Medtronic, Inc. Drug administration device
US4883057A (en) 1984-05-09 1989-11-28 Research Foundation, The City University Of New York Cathodic electrochemical current arrangement with telemetric application
US4772263A (en) 1986-02-03 1988-09-20 Regents Of The University Of Minnesota Spring driven infusion pump
US5601835A (en) 1987-04-29 1997-02-11 Massachusetts Institute Of Technology Polymeric device for controlled drug delivery to the CNS
US4892538A (en) 1987-11-17 1990-01-09 Brown University Research Foundation In vivo delivery of neurotransmitters by implanted, encapsulated cells
US5458631A (en) 1989-01-06 1995-10-17 Xavier; Ravi Implantable catheter with electrical pulse nerve stimulators and drug delivery system
US5119832A (en) 1989-07-11 1992-06-09 Ravi Xavier Epidural catheter with nerve stimulators
US5125888A (en) 1990-01-10 1992-06-30 University Of Virginia Alumni Patents Foundation Magnetic stereotactic system for treatment delivery
US5618531A (en) 1990-10-19 1997-04-08 New York University Method for increasing the viability of cells which are administered to the brain or spinal cord
US5263480A (en) 1991-02-01 1993-11-23 Cyberonics, Inc. Treatment of eating disorders by nerve stimulation
US5299569A (en) 1991-05-03 1994-04-05 Cyberonics, Inc. Treatment of neuropsychiatric disorders by nerve stimulation
US5423877A (en) 1992-05-04 1995-06-13 David C. Mackey Method and device for acute pain management by simultaneous spinal cord electrical stimulation and drug infusion
US5470846A (en) 1994-01-14 1995-11-28 Sandyk; Reuven Treatment of neurological and mental disorders
US6129685A (en) 1994-02-09 2000-10-10 The University Of Iowa Research Foundation Stereotactic hypothalamic obesity probe
US5853385A (en) 1994-08-26 1998-12-29 Cytotherapeutics, Inc. Encapsulated PC12 cell transplants for treatment of Parkinson's disease
US5540734A (en) 1994-09-28 1996-07-30 Zabara; Jacob Cranial nerve stimulation treatments using neurocybernetic prosthesis
US6425852B1 (en) 1994-11-28 2002-07-30 Emory University Apparatus and method for transcranial magnetic brain stimulation, including the treatment of depression and the localization and characterization of speech arrest
US5735505A (en) 1995-04-03 1998-04-07 Data Connections, Inc. Cable pulley device and method
US7069634B1 (en) 1995-04-28 2006-07-04 Medtronic, Inc. Method for manufacturing a catheter
AU5545596A (en) 1995-04-28 1996-11-18 Medtronic, Inc. Intraparenchymal infusion catheter system
US5585118A (en) 1995-06-02 1996-12-17 Brigham And Women's Hospital Choline in the treatment of bipolar disorder
US5753505A (en) 1995-07-06 1998-05-19 Emory University Neuronal progenitor cells and uses thereof
US20020169485A1 (en) 1995-10-16 2002-11-14 Neuropace, Inc. Differential neurostimulation therapy driven by physiological context
US6463328B1 (en) 1996-02-02 2002-10-08 Michael Sasha John Adaptive brain stimulation method and system
WO1997029802A2 (en) 1996-02-20 1997-08-21 Advanced Bionics Corporation Improved implantable microstimulator and systems employing the same
US6036459A (en) 1996-04-04 2000-03-14 Medtronic, Inc. Occlusion compensator for implantable peristaltic pump
US5840069A (en) 1996-04-04 1998-11-24 Medtronic, Inc. Implantable peristaltic pump techniques
US6094598A (en) 1996-04-25 2000-07-25 Medtronics, Inc. Method of treating movement disorders by brain stimulation and drug infusion
US5716377A (en) 1996-04-25 1998-02-10 Medtronic, Inc. Method of treating movement disorders by brain stimulation
US5683422A (en) 1996-04-25 1997-11-04 Medtronic, Inc. Method and apparatus for treating neurodegenerative disorders by electrical brain stimulation
US5735814A (en) 1996-04-30 1998-04-07 Medtronic, Inc. Techniques of treating neurodegenerative disorders by brain infusion
US5711316A (en) 1996-04-30 1998-01-27 Medtronic, Inc. Method of treating movement disorders by brain infusion
US5713923A (en) 1996-05-13 1998-02-03 Medtronic, Inc. Techniques for treating epilepsy by brain stimulation and drug infusion
US5921245A (en) 1996-06-03 1999-07-13 O'donnell, Jr.; Francis E. Method for modification of anti-social behavior
US6609031B1 (en) 1996-06-07 2003-08-19 Advanced Neuromodulation Systems, Inc. Multiprogrammable tissue stimulator and method
US6015786A (en) 1997-02-25 2000-01-18 Celtrix Pharmaceuticals, Inc. Method for increasing sex steroid levels using IGF or IGF/IGFBP-3
US6514937B1 (en) 1997-02-25 2003-02-04 Celtrix Pharmaceuticals, Inc. Method of treating psychological and metabolic disorders using IGF or IGF/IGFBP-3
US6025368A (en) * 1997-02-25 2000-02-15 Celtrix Pharmaceuticals, Inc. Method for treating the symptoms of chronic stress-related disorders using IGF
US5873849A (en) 1997-04-24 1999-02-23 Ichor Medical Systems, Inc. Electrodes and electrode arrays for generating electroporation inducing electrical fields
US6042579A (en) 1997-04-30 2000-03-28 Medtronic, Inc. Techniques for treating neurodegenerative disorders by infusion of nerve growth factors into the brain
US5975085A (en) 1997-05-01 1999-11-02 Medtronic, Inc. Method of treating schizophrenia by brain stimulation and drug infusion
US20040092010A1 (en) 2002-04-15 2004-05-13 Ariel Ruiz I Altaba Method of proliferating and inducing brain stem cells to differentiate to neurons
US5938688A (en) 1997-10-22 1999-08-17 Cornell Research Foundation, Inc. Deep brain stimulation method
US6597954B1 (en) 1997-10-27 2003-07-22 Neuropace, Inc. System and method for controlling epileptic seizures with spatially separated detection and stimulation electrodes
US6230049B1 (en) 1999-08-13 2001-05-08 Neuro Pace, Inc. Integrated system for EEG monitoring and electrical stimulation with a multiplicity of electrodes
US6016449A (en) 1997-10-27 2000-01-18 Neuropace, Inc. System for treatment of neurological disorders
ATE280555T1 (en) 1998-01-12 2004-11-15 Ronald P Lesser METHOD FOR TREATING BRAIN DISEASE USING CONTROLLED HEAT SUPPLY
US6227203B1 (en) 1998-02-12 2001-05-08 Medtronic, Inc. Techniques for controlling abnormal involuntary movements by brain stimulation and drug infusion
AUPP398898A0 (en) * 1998-06-09 1998-07-02 University Of Queensland, The Diagnostic method and apparatus
US6735474B1 (en) 1998-07-06 2004-05-11 Advanced Bionics Corporation Implantable stimulator system and method for treatment of incontinence and pain
US6366813B1 (en) 1998-08-05 2002-04-02 Dilorenzo Daniel J. Apparatus and method for closed-loop intracranical stimulation for optimal control of neurological disease
US6214016B1 (en) 1999-04-29 2001-04-10 Medtronic, Inc. Medical instrument positioning device internal to a catheter or lead and method of use
US6176242B1 (en) 1999-04-30 2001-01-23 Medtronic Inc Method of treating manic depression by brain infusion
US6353762B1 (en) 1999-04-30 2002-03-05 Medtronic, Inc. Techniques for selective activation of neurons in the brain, spinal cord parenchyma or peripheral nerve
US6161045A (en) 1999-06-01 2000-12-12 Neuropace, Inc. Method for determining stimulation parameters for the treatment of epileptic seizures
US6539263B1 (en) 1999-06-11 2003-03-25 Cornell Research Foundation, Inc. Feedback mechanism for deep brain stimulation
US6898455B2 (en) 1999-10-29 2005-05-24 The Mclean Hospital Corporation Method for providing optimal drug dosage
AU1943301A (en) 1999-12-02 2001-06-12 General Hospital Corporation, The Method and apparatus for measuring indices of brain activity
US6907280B2 (en) 1999-12-02 2005-06-14 The General Hospital Corporation Method and apparatus for objectively measuring pain, pain treatment and other related techniques
US6609030B1 (en) 2000-02-24 2003-08-19 Electrocore Techniques, Llc Method of treating psychiatric diseases by neuromodulation within the dorsomedial thalamus
US6418344B1 (en) * 2000-02-24 2002-07-09 Electrocore Techniques, Llc Method of treating psychiatric disorders by electrical stimulation within the orbitofrontal cerebral cortex
US6708064B2 (en) 2000-02-24 2004-03-16 Ali R. Rezai Modulation of the brain to affect psychiatric disorders
US6473639B1 (en) 2000-03-02 2002-10-29 Neuropace, Inc. Neurological event detection procedure using processed display channel based algorithms and devices incorporating these procedures
US6399574B1 (en) 2000-03-22 2002-06-04 University Of Utah Research Foundation Use of conantokins
US6353754B1 (en) 2000-04-24 2002-03-05 Neuropace, Inc. System for the creation of patient specific templates for epileptiform activity detection
US7146217B2 (en) 2000-07-13 2006-12-05 Northstar Neuroscience, Inc. Methods and apparatus for effectuating a change in a neural-function of a patient
US6591138B1 (en) 2000-08-31 2003-07-08 Neuropace, Inc. Low frequency neurostimulator for the treatment of neurological disorders
WO2002040080A2 (en) 2000-11-14 2002-05-23 Joseph Manne Electromagnetically induced anesthesia and sensory stimulation
US6666845B2 (en) 2001-01-04 2003-12-23 Advanced Neuromodulation Systems, Inc. Implantable infusion pump
US6735475B1 (en) 2001-01-30 2004-05-11 Advanced Bionics Corporation Fully implantable miniature neurostimulator for stimulation as a therapy for headache and/or facial pain
US6620151B2 (en) 2001-03-01 2003-09-16 Advanced Neuromodulation Systems, Inc. Non-constant pressure infusion pump
WO2002082970A2 (en) 2001-04-06 2002-10-24 The Research Foundation Of The City University Of New York Diagnosis and treatment of neural disease and injury using microvoltammetry
US7110820B2 (en) 2002-02-05 2006-09-19 Tcheng Thomas K Responsive electrical stimulation for movement disorders

Patent Citations (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3653385A (en) * 1970-10-20 1972-04-04 Charles Burton Production of focal brain lesions by inductive heating
US5342410A (en) * 1990-10-05 1994-08-30 Eric Braverman Apparatus and method for increasing the amplitude of P300 waves in the human brain
US6132361A (en) * 1994-11-28 2000-10-17 Neotonus, Inc. Transcranial brain stimulation
US5752911A (en) * 1995-04-27 1998-05-19 Canedo; Luis E. Electromagnetic method of treatment of epilepsy and apparatus
US6128537A (en) * 1997-05-01 2000-10-03 Medtronic, Inc Techniques for treating anxiety by brain stimulation and drug infusion
US6629973B1 (en) * 1999-01-25 2003-10-07 Elekta Ab Method and an apparatus for controlled destruction of tissue
US6782292B2 (en) * 2000-06-20 2004-08-24 Advanced Bionics Corporation System and method for treatment of mood and/or anxiety disorders by electrical brain stimulation and/or drug infusion
US6871098B2 (en) * 2000-10-30 2005-03-22 Medtronic, Inc. Method for treating obsessive-compulsive disorder with electrical stimulation of the brain internal capsule
US6567696B2 (en) * 2001-02-06 2003-05-20 Mediseb Ltd. Physiotherapeutic device
US6592509B1 (en) * 2002-02-04 2003-07-15 Thomas W. Hunter, Jr. Electromagnetic stimulator
US20050027284A1 (en) * 2003-06-19 2005-02-03 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20050143800A1 (en) * 2003-12-11 2005-06-30 Lando Peter R. Electrical stimulation system and associated apparatus for securing an electrical stimulation lead in position in a person's brain
US20050143799A1 (en) * 2003-12-11 2005-06-30 Black Damon R. Electrical stimulation system and associated apparatus for securing an electrical stimulation lead in position in a person's brain

Cited By (136)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070032834A1 (en) * 2000-07-13 2007-02-08 Northstar Neuroscience, Inc. Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US20110208264A1 (en) * 2000-07-13 2011-08-25 Bradford Evan Gliner Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US8195300B2 (en) 2000-07-13 2012-06-05 Advanced Neuromodulation Systems, Inc. Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US8412335B2 (en) 2000-07-13 2013-04-02 Advanced Neuromodulation Systems, Inc. Systems and methods for automatically optimizing stimulus parameters and electrode configurations for neuro-stimulators
US8190264B2 (en) 2003-06-19 2012-05-29 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US8467878B2 (en) 2003-06-19 2013-06-18 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20100114193A1 (en) * 2003-06-19 2010-05-06 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US7653433B2 (en) 2003-06-19 2010-01-26 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20050027284A1 (en) * 2003-06-19 2005-02-03 Advanced Neuromodulation Systems, Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20070005115A1 (en) * 2003-06-19 2007-01-04 Lozano Andres M Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US7684866B2 (en) 2003-08-01 2010-03-23 Advanced Neuromodulation Systems, Inc. Apparatus and methods for applying neural stimulation to a patient
US11185695B1 (en) 2003-11-26 2021-11-30 Flint Hills Scientific, L.L.C. Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
US9050469B1 (en) 2003-11-26 2015-06-09 Flint Hills Scientific, Llc Method and system for logging quantitative seizure information and assessing efficacy of therapy using cardiac signals
US20060052657A9 (en) * 2003-12-30 2006-03-09 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
US20080269542A1 (en) * 2003-12-30 2008-10-30 Jacob Zabara Systems and Methods for Therapeutically Treating Neuro-Psychiatric Disorders and Other Illnesses
US7422555B2 (en) 2003-12-30 2008-09-09 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
US20050182288A1 (en) * 2003-12-30 2005-08-18 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
WO2005065768A1 (en) * 2003-12-30 2005-07-21 Jacob Zabara Systems and methods for therapeutically treating neuro-psychiatric disorders and other illnesses
US20060064138A1 (en) * 2004-04-30 2006-03-23 Francisco Velasco Method of treating mood disorders and/or anxiety disorders by brain stimulation
US7313442B2 (en) 2004-04-30 2007-12-25 Advanced Neuromodulation Systems, Inc. Method of treating mood disorders and/or anxiety disorders by brain stimulation
US20050154425A1 (en) * 2004-08-19 2005-07-14 Boveja Birinder R. Method and system to provide therapy for neuropsychiatric disorders and cognitive impairments using gradient magnetic pulses to the brain and pulsed electrical stimulation to vagus nerve(s)
US7353065B2 (en) 2004-09-14 2008-04-01 Neuropace, Inc. Responsive therapy for psychiatric disorders
US20080125830A1 (en) * 2004-09-14 2008-05-29 Neuropace, Inc. Responsive Therapy for Psychiatric Disorders
US20080125831A1 (en) * 2004-09-14 2008-05-29 Neuropace, Inc. Responsive Therapy for Psychiatric Disorders
US20060058856A1 (en) * 2004-09-14 2006-03-16 Neuropace, Inc. Responsive therapy for psychiatric disorders
US8565867B2 (en) 2005-01-28 2013-10-22 Cyberonics, Inc. Changeable electrode polarity stimulation by an implantable medical device
US9586047B2 (en) 2005-01-28 2017-03-07 Cyberonics, Inc. Contingent cardio-protection for epilepsy patients
US20060212090A1 (en) * 2005-03-01 2006-09-21 Functional Neuroscience Inc. Method of treating cognitive disorders using neuromodulation
US9931500B2 (en) 2005-03-01 2018-04-03 Andres M. Lozano Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20060212091A1 (en) * 2005-03-01 2006-09-21 Functional Neuroscience Inc. Method of treating depression, mood disorders and anxiety disorders using neuromodulation
US20070100398A1 (en) * 2005-10-19 2007-05-03 Northstar Neuroscience, Inc. Neural stimulation system and optical monitoring systems and methods
US20070088403A1 (en) * 2005-10-19 2007-04-19 Allen Wyler Methods and systems for establishing parameters for neural stimulation
US7729773B2 (en) 2005-10-19 2010-06-01 Advanced Neuromodualation Systems, Inc. Neural stimulation and optical monitoring systems and methods
US20070173901A1 (en) * 2006-01-24 2007-07-26 Reeve Helen L Method and device for detecting and treating depression
US7606622B2 (en) 2006-01-24 2009-10-20 Cardiac Pacemakers, Inc. Method and device for detecting and treating depression
US7801601B2 (en) 2006-01-27 2010-09-21 Cyberonics, Inc. Controlling neuromodulation using stimulus modalities
US20070179558A1 (en) * 2006-01-30 2007-08-02 Gliner Bradford E Systems and methods for varying electromagnetic and adjunctive neural therapies
US20070233192A1 (en) * 2006-03-29 2007-10-04 Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) Vagus nerve stimulation method
US20070233194A1 (en) * 2006-03-29 2007-10-04 Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US20090177252A1 (en) * 2006-03-29 2009-07-09 Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US8219188B2 (en) 2006-03-29 2012-07-10 Catholic Healthcare West Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US9533151B2 (en) 2006-03-29 2017-01-03 Dignity Health Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US9289599B2 (en) 2006-03-29 2016-03-22 Dignity Health Vagus nerve stimulation method
US20070233193A1 (en) * 2006-03-29 2007-10-04 Catholic Healthcare West (D/B/A St. Joseph's Hospital And Medical Center) Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US9108041B2 (en) 2006-03-29 2015-08-18 Dignity Health Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US8280505B2 (en) 2006-03-29 2012-10-02 Catholic Healthcare West Vagus nerve stimulation method
US8615309B2 (en) 2006-03-29 2013-12-24 Catholic Healthcare West Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US8150508B2 (en) 2006-03-29 2012-04-03 Catholic Healthcare West Vagus nerve stimulation method
US8738126B2 (en) 2006-03-29 2014-05-27 Catholic Healthcare West Synchronization of vagus nerve stimulation with the cardiac cycle of a patient
US8660666B2 (en) 2006-03-29 2014-02-25 Catholic Healthcare West Microburst electrical stimulation of cranial nerves for the treatment of medical conditions
US20070255351A1 (en) * 2006-04-28 2007-11-01 Cyberonics, Inc. Threshold optimization for tissue stimulation therapy
US7869885B2 (en) 2006-04-28 2011-01-11 Cyberonics, Inc Threshold optimization for tissue stimulation therapy
WO2008003318A1 (en) * 2006-07-05 2008-01-10 Aarhus Universitet A research model system and a method for using electrical stimulation and/ chemical stimulation to induce depressive illness in research animals
US20080103548A1 (en) * 2006-08-02 2008-05-01 Northstar Neuroscience, Inc. Methods for treating neurological disorders, including neuropsychiatric and neuropsychological disorders, and associated systems
US20090320844A1 (en) * 2006-08-04 2009-12-31 Nielsen Joergen Groenlund Method to compensate for the effect of recirculation of inert blood soluble gas on the determination of pulmonary blood flow in repeated inert gas rebreathing tests
US7869867B2 (en) 2006-10-27 2011-01-11 Cyberonics, Inc. Implantable neurostimulator with refractory stimulation
US7987001B2 (en) 2007-01-25 2011-07-26 Warsaw Orthopedic, Inc. Surgical navigational and neuromonitoring instrument
US20080183074A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Method and apparatus for coordinated display of anatomical and neuromonitoring information
US20080183190A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated surgical navigational and neuromonitoring system having automated surgical assistance and control
US20080183068A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated Visualization of Surgical Navigational and Neural Monitoring Information
US20080183188A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Integrated Surgical Navigational and Neuromonitoring System
US20080183189A1 (en) * 2007-01-25 2008-07-31 Warsaw Orthopedic, Inc. Surgical navigational and neuromonitoring instrument
US8374673B2 (en) 2007-01-25 2013-02-12 Warsaw Orthopedic, Inc. Integrated surgical navigational and neuromonitoring system having automated surgical assistance and control
US7974701B2 (en) 2007-04-27 2011-07-05 Cyberonics, Inc. Dosing limitation for an implantable medical device
US20110224758A1 (en) * 2007-04-27 2011-09-15 Cyberonics, Inc. Dosing Limitation For An Implantable Medical Device
US20080269839A1 (en) * 2007-04-27 2008-10-30 Armstrong Randolph K Dosing Limitation for an Implantable Medical Device
US8306627B2 (en) 2007-04-27 2012-11-06 Cyberonics, Inc. Dosing limitation for an implantable medical device
US20090149898A1 (en) * 2007-12-07 2009-06-11 Northstar Neuroscience, Inc. Systems and Methods for Providing Targeted Neural Stimulation Therapy to Address Neurological Disorders, Including Neuropyschiatric and Neuropyschological Disorders
US8538537B2 (en) 2007-12-07 2013-09-17 Advanced Neuromodulations Systems, Inc. Systems and methods for providing targeted neural stimulation therapy to address neurological disorders, including neuropyschiatric and neuropyschological disorders
US9314633B2 (en) 2008-01-25 2016-04-19 Cyberonics, Inc. Contingent cardio-protection for epilepsy patients
US20090210018A1 (en) * 2008-02-15 2009-08-20 Lozano Andres M Method for treating neurological /psychiatric disorders with stimulation to the subcaudate area of the brain
US8195298B2 (en) * 2008-02-15 2012-06-05 Andres M Lozano Method for treating neurological/psychiatric disorders with stimulation to the subcaudate area of the brain
EP2280758A2 (en) * 2008-04-18 2011-02-09 Medtronic, Inc. Psychiatric disorder therapy control
US20090264956A1 (en) * 2008-04-18 2009-10-22 Medtronic, Inc. Psychiatric disorder therapy control
US20090264967A1 (en) * 2008-04-18 2009-10-22 Medtronic, Inc. Timing therapy evaluation trials
US9333350B2 (en) 2008-04-18 2016-05-10 Medtronic, Inc. Psychiatric disorder therapy control
US10493281B2 (en) 2008-04-18 2019-12-03 Medtronic, Inc. Timing therapy evaluation trials
US9613184B2 (en) 2008-04-18 2017-04-04 Medtronic, Inc. Analyzing a washout period characteristic for psychiatric disorder therapy delivery
US8204603B2 (en) 2008-04-25 2012-06-19 Cyberonics, Inc. Blocking exogenous action potentials by an implantable medical device
US8315703B2 (en) 2008-04-30 2012-11-20 Advanced Neuromodulation Systems, Inc. Methods for targeting deep brain sites to treat mood and/or anxiety disorders
US20100057159A1 (en) * 2008-04-30 2010-03-04 Lozano Andres M Methods for targeting deep brain sites to treat mood and/or anxiety disorders
US8262714B2 (en) 2008-08-05 2012-09-11 Advanced Neuromodulation Systems, Inc. Techniques for selecting signal delivery sites and other parameters for treating depression and other neurological disorders, and associated systems and methods
US20100036453A1 (en) * 2008-08-05 2010-02-11 Northstar Neuroscience, Inc. Techniques for selecting signal delivery sites and other parameters for treating depression and other neurological disorders, and associated systems and methods
US20100100151A1 (en) * 2008-10-20 2010-04-22 Terry Jr Reese S Neurostimulation with signal duration determined by a cardiac cycle
US8457747B2 (en) 2008-10-20 2013-06-04 Cyberonics, Inc. Neurostimulation with signal duration determined by a cardiac cycle
US8874218B2 (en) 2008-10-20 2014-10-28 Cyberonics, Inc. Neurostimulation with signal duration determined by a cardiac cycle
US8849409B2 (en) 2008-10-24 2014-09-30 Cyberonics, Inc. Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US8768471B2 (en) 2008-10-24 2014-07-01 Cyberonics, Inc. Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US20100106217A1 (en) * 2008-10-24 2010-04-29 Colborn John C Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US8417344B2 (en) 2008-10-24 2013-04-09 Cyberonics, Inc. Dynamic cranial nerve stimulation based on brain state determination from cardiac data
US20100191304A1 (en) * 2009-01-23 2010-07-29 Scott Timothy L Implantable Medical Device for Providing Chronic Condition Therapy and Acute Condition Therapy Using Vagus Nerve Stimulation
US10653883B2 (en) 2009-01-23 2020-05-19 Livanova Usa, Inc. Implantable medical device for providing chronic condition therapy and acute condition therapy using vagus nerve stimulation
US20100204751A1 (en) * 2009-02-11 2010-08-12 University Of Maryland, Baltimore Methods for Treating Central Pain Syndrome and Other Pain Related Pathologies
US8396558B2 (en) * 2009-02-11 2013-03-12 University Of Maryland, Baltimore Methods for treating central pain syndrome and other pain related pathologies
US8827912B2 (en) 2009-04-24 2014-09-09 Cyberonics, Inc. Methods and systems for detecting epileptic events using NNXX, optionally with nonlinear analysis parameters
US20100274308A1 (en) * 2009-04-24 2010-10-28 Scott Timothy L Use of cardiac parameters in methods and systems for treating a chronic medical condition
US8239028B2 (en) 2009-04-24 2012-08-07 Cyberonics, Inc. Use of cardiac parameters in methods and systems for treating a chronic medical condition
US9700256B2 (en) 2010-04-29 2017-07-11 Cyberonics, Inc. Algorithm for detecting a seizure from cardiac data
US8562536B2 (en) 2010-04-29 2013-10-22 Flint Hills Scientific, Llc Algorithm for detecting a seizure from cardiac data
US8649871B2 (en) 2010-04-29 2014-02-11 Cyberonics, Inc. Validity test adaptive constraint modification for cardiac data used for detection of state changes
US8831732B2 (en) 2010-04-29 2014-09-09 Cyberonics, Inc. Method, apparatus and system for validating and quantifying cardiac beat data quality
US9241647B2 (en) 2010-04-29 2016-01-26 Cyberonics, Inc. Algorithm for detecting a seizure from cardiac data
US8679009B2 (en) 2010-06-15 2014-03-25 Flint Hills Scientific, Llc Systems approach to comorbidity assessment
US9220910B2 (en) 2010-07-30 2015-12-29 Cyberonics, Inc. Seizure detection using coordinate data
US8641646B2 (en) 2010-07-30 2014-02-04 Cyberonics, Inc. Seizure detection using coordinate data
US9020582B2 (en) 2010-09-16 2015-04-28 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8452387B2 (en) 2010-09-16 2013-05-28 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8948855B2 (en) 2010-09-16 2015-02-03 Flint Hills Scientific, Llc Detecting and validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8571643B2 (en) 2010-09-16 2013-10-29 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US8945006B2 (en) 2010-10-01 2015-02-03 Flunt Hills Scientific, LLC Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US8888702B2 (en) 2010-10-01 2014-11-18 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8337404B2 (en) 2010-10-01 2012-12-25 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8852100B2 (en) 2010-10-01 2014-10-07 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US8684921B2 (en) 2010-10-01 2014-04-01 Flint Hills Scientific Llc Detecting, assessing and managing epilepsy using a multi-variate, metric-based classification analysis
US8382667B2 (en) 2010-10-01 2013-02-26 Flint Hills Scientific, Llc Detecting, quantifying, and/or classifying seizures using multimodal data
US9504390B2 (en) 2011-03-04 2016-11-29 Globalfoundries Inc. Detecting, assessing and managing a risk of death in epilepsy
US9498162B2 (en) 2011-04-25 2016-11-22 Cyberonics, Inc. Identifying seizures using heart data from two or more windows
US8725239B2 (en) 2011-04-25 2014-05-13 Cyberonics, Inc. Identifying seizures using heart rate decrease
US9402550B2 (en) 2011-04-29 2016-08-02 Cybertronics, Inc. Dynamic heart rate threshold for neurological event detection
US10206591B2 (en) 2011-10-14 2019-02-19 Flint Hills Scientific, Llc Seizure detection methods, apparatus, and systems using an autoregression algorithm
US10448839B2 (en) 2012-04-23 2019-10-22 Livanova Usa, Inc. Methods, systems and apparatuses for detecting increased risk of sudden death
US11596314B2 (en) 2012-04-23 2023-03-07 Livanova Usa, Inc. Methods, systems and apparatuses for detecting increased risk of sudden death
US20150119689A1 (en) * 2012-05-16 2015-04-30 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
US10137307B2 (en) * 2012-05-16 2018-11-27 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
WO2013172981A1 (en) * 2012-05-16 2013-11-21 Beth Israel Deaconess Medical Center, Inc. Identifying individual target sites for transcranial magnetic stimulation applications
US10220211B2 (en) 2013-01-22 2019-03-05 Livanova Usa, Inc. Methods and systems to diagnose depression
US11103707B2 (en) 2013-01-22 2021-08-31 Livanova Usa, Inc. Methods and systems to diagnose depression
US11723579B2 (en) 2017-09-19 2023-08-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement
US11717686B2 (en) 2017-12-04 2023-08-08 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to facilitate learning and performance
US11273283B2 (en) 2017-12-31 2022-03-15 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11318277B2 (en) 2017-12-31 2022-05-03 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11478603B2 (en) 2017-12-31 2022-10-25 Neuroenhancement Lab, LLC Method and apparatus for neuroenhancement to enhance emotional response
US11364361B2 (en) 2018-04-20 2022-06-21 Neuroenhancement Lab, LLC System and method for inducing sleep by transplanting mental states
US11452839B2 (en) 2018-09-14 2022-09-27 Neuroenhancement Lab, LLC System and method of improving sleep
RU2714296C1 (en) * 2019-04-09 2020-02-13 Федеральное государственное бюджетное образовательное учреждение высшего образования "Алтайский государственный медицинский университет" Министерства здравоохранения Российской Федерации Method of treating patients with chronic insomnia
US11786694B2 (en) 2019-05-24 2023-10-17 NeuroLight, Inc. Device, method, and app for facilitating sleep

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