US20080161882A1 - Methods and apparatus for effectuating a lasting change in a neural-function of a patient - Google Patents

Abstract

Methods and apparatus for treating an impaired neural function in a brain of a patient. In one embodiment, a method for treating a neural function in a brain of a patient includes determining a therapy period during which a plurality of therapy sessions are to be performed to recover functional ability corresponding to the neural function. The method continues by identifying a stimulation site in or on the brain of the patient associated with the neural function, and positioning an electrode at least proximate to the identified stimulation site. The patient is then treated by providing electrical stimulation treatments to the stimulation site. The treatment can comprise delivering electrical stimulation signals to the electrode during the therapy sessions. After expiration of the therapy period, the method includes preventing electrical stimulation signals from being delivered to the stimulation site.

Description

CROSS-REFERENCE TO RELATED APPLICATION(S)
• This application is a Continuation-in-Part of U.S. application Ser. No. 09/802,808, filed Mar. 8, 2001.
TECHNICAL FIELD
• Several embodiments of methods and apparatus in accordance with the invention are related to electrically stimulating a region in the cortex or other area of the brain for a limited treatment period to bring about a lasting change in a physiological function and/or a mental process of a patient.
BACKGROUND
• A wide variety of mental and physical processes are controlled or influenced by neural activity in particular regions of the brain. For example, the neural-functions in some areas of the brain (i.e., the sensory or motor cortices) are organized according to physical or cognitive functions. There are also several other areas of the brain that appear to have distinct functions in most individuals. In the majority of people, for example, the areas of the occipital lobes relate to vision, the regions of the left interior frontal lobes relate to language, and the regions of the cerebral cortex appear to be consistently involved with conscious awareness, memory, and intellect.
• Many problems or abnormalities can be caused by damage, disease and/or disorders in the brain. Effectively treating such abnormalities may be very difficult. For example, a stroke is a common condition that damages the brain. Strokes are generally caused by emboli (e.g., obstruction of a vessel), hemorrhages (e.g., rupture of a vessel), or thrombi (e.g., clotting) in the vascular system of a specific region of the brain. Such events generally result in a loss or impairment of a neural function (e.g., neural functions related to facial muscles, limbs, speech, etc.). Stroke patients are typically treated using various forms of physical therapy to rehabilitate the loss of function of a limb or another affected body part. Stroke patients may also be treated using physical therapy plus an adjunctive therapy such as amphetamine treatment. For most patients, however, such treatments are minimally effective and little can be done to improve the function of an affected body part beyond the recovery that occurs naturally without intervention. As a result, many types of physical and/or cognitive deficits that remain after treating neurological damage or disorders are typically considered permanent conditions that patients must manage for the remainder of their lives.
• Neurological problems or abnormalities are often related to electrical and/or chemical activity in the brain. Neural activity is governed by electrical impulses or “action potentials” generated in neurons and propagated along synoptically connected neurons. When a neuron is in a quiescent state, it is polarized negatively and exhibits a resting membrane potential typically between −70 and −60 mV. Through chemical connections known as synapses, any given neuron receives excitatory and inhibitory input signals or stimuli from other neurons. A neuron integrates the excitatory and inhibitory input signals it receives, and generates or fires a series of action potentials when the integration exceeds a threshold potential. A neural firing threshold, for example, may be approximately −55 mV.
• It follows that neural activity in the brain can be influenced by electrical energy supplied from an external source such as a waveform generator. Various neural functions can be promoted or disrupted by applying an electrical current to the cortex or other region of the brain. As a result, researchers have attempted to treat physical damage, disease and disorders in the brain using electrical or magnetic stimulation signals to control or affect brain functions.
• Transcranial electrical stimulation (TES) is one such approach that involves placing an electrode on the exterior of the scalp and delivering an electrical current to the brain through the scalp and skull. Another treatment approach, transcranial magnetic stimulation (TMS), involves producing a magnetic field adjacent to the exterior of the scalp over an area of the cortex. Yet another treatment approach involves direct electrical stimulation of neural tissue using implanted electrodes.
• The neural stimulation signals used by these approaches may comprise a series of electrical or magnetic pulses that can affect neurons within a target neural population. Stimulation signals may be defined or described in accordance with stimulation signal parameters including pulse amplitude, pulse frequency, duty cycle, stimulation signal duration, and/or other parameters. Electrical or magnetic stimulation signals applied to a population of neurons can depolarize neurons within the population toward their threshold potentials. Depending upon stimulation signal parameters, this depolarization can cause neurons to generate or fire action potentials. Neural stimulation that elicits or induces action potentials in a functionally significant proportion of the neural population to which the stimulation is applied is referred to as supra-threshold stimulation; neural stimulation that fails to elicit action potentials in a functionally significant proportion of the neural population is defined as sub-threshold stimulation. In general, supra-threshold stimulation of a neural population triggers or activates one or more functions associated with the neural population, but sub-threshold stimulation by itself does not trigger or activate such functions. Supra-threshold neural stimulation can induce various types of measurable or monitorable responses in a patient. For example, supra-threshold stimulation applied to a patient's motor cortex can induce muscle fiber contractions in an associated part of the body.
• Although electrical or magnetic stimulation of neural tissue may be directed toward producing an intended type of therapeutic, rehabilitative, or restorative neural activity, such stimulation may result in collateral neural activity. In particular, neural stimulation delivered beyond a certain intensity, period of time, level, or amplitude can give rise to seizure activity and/or other types of collateral activity. It will be appreciated that collateral neural activity may be undesirable and/or inconvenient in a neural stimulation situation.
• Conventional neural stimulation systems and techniques are generally directed toward treating or managing chronic patient symptoms on a perpetual or essentially perpetual basis, i.e., throughout a patient's lifespan. Therefore, conventional neural stimulation systems and methods may not be ideally suited for applications directed toward restoring rather than perpetually treating impaired functions.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1A is a schematic illustration of neurons.
• FIG. 1B is a graph illustrating firing an “action potential” associated with normal neural activity.
• FIG. 1C is a flowchart of a method for effectuating a neural-function of a patient in accordance with one embodiment of the invention.
• FIG. 2 is a top plan image of a portion of a brain illustrating neural activity in a first region of the brain associated with the neural-function of the patient according to the somatotopic organization of the brain.
• FIG. 3 is a top plan image of a portion of the brain illustrating a loss of neural activity associated with the neural-function of the patient used in one stage of a method in accordance with an embodiment of the invention.
• FIG. 4 is a top plan image of the brain ofFIG. 3 showing a change in location of the neural activity associated with the neural-function of the patient at another stage of a method in accordance with an embodiment of the invention.
• FIGS. 5A and 5B are schematic illustrations of an implanting procedure at a stage of a method in accordance with an embodiment of the invention.
• FIGS. 5C and 5D are flowcharts of stimulation procedures for applying electrical stimulation to a region of a patient's brain.
• FIG. 5E is a graph illustrating firing an “action potential” associated with stimulated neural activity in accordance with one embodiment of the invention.
• FIG. 6 is an isometric view of an implantable stimulation apparatus in accordance with one embodiment of the invention.
• FIG. 7 is a cross-sectional view schematically illustrating a part of an implantable stimulation apparatus in accordance with an embodiment of the invention.
• FIG. 8 is a schematic illustration of a pulse system in accordance with one embodiment of the invention.
• FIG. 9 is a schematic illustration of an implanted stimulation apparatus and an external controller in accordance with an embodiment of the invention.
• FIG. 10 is a schematic illustration of an implantable stimulation apparatus having a pulse system and an external controller in accordance with another embodiment of the invention.
• FIG. 11 is a cross-sectional view schematically illustrating a part of an implantable stimulation apparatus in accordance with an embodiment of the invention.
• FIG. 12 is a schematic illustration of an implantable stimulation apparatus having a pulse system and an external controller in accordance with another embodiment of the invention.
• FIG. 13 is a cross-sectional view schematically illustrating a part of an implantable stimulation apparatus having a pulse system and an external controller in accordance with another embodiment of the invention.
• FIG. 14 is a bottom plan view andFIG. 15 is a cross-sectional view illustrating an electrode configuration for an implantable stimulation apparatus in accordance with an embodiment of the invention.
• FIG. 16 is a bottom plan view andFIG. 17 is a cross-sectional view of an electrode configuration for an implantable stimulation apparatus in accordance with another embodiment of the invention.
• FIG. 18 is a bottom plan view andFIG. 19 is a cross-sectional view of an electrode configuration in accordance with yet another embodiment of the invention.
• FIG. 20 is a bottom plan view of an electrode configuration for an implantable stimulation device in accordance with yet another embodiment of the invention.
• FIG. 21 is a bottom plan view of an electrode configuration for an implantable stimulation device in accordance with another embodiment of the invention.
• FIG. 22 is a bottom plan view of yet another embodiment of an electrode configuration for use with an implantable stimulation apparatus in accordance with the invention.
• FIG. 23 is a bottom plan view andFIG. 24 is a cross-sectional view of an electrode configuration for use with a stimulation apparatus in accordance with still another embodiment of the invention.
• FIG. 25 is an isometric view schematically illustrating a part of an implantable stimulation apparatus with a mechanical biasing element in accordance with an embodiment of the invention.
• FIG. 26 is a cross-sectional view of a stimulation apparatus having a mechanical biasing element that has been implanted into a skull of a patient in accordance with an embodiment of the invention.
• FIG. 27 is a cross-sectional view schematically illustrating a part of a stimulation apparatus having a biasing element in accordance with an embodiment of the invention.
• FIG. 28 is a cross-sectional view of a stimulation apparatus having a biasing element in accordance with still another embodiment of the invention.
• FIG. 29 is a cross-sectional view of a stimulation apparatus having a biasing element in accordance with yet another embodiment of the invention.
• FIG. 30 is a cross-sectional view of a stimulation apparatus having a biasing element in accordance with yet another embodiment of the invention.
• FIG. 31 is a cross-sectional view schematically illustrating a portion of an implantable stimulation apparatus having an external power source and pulse generator in accordance with an embodiment of the invention.
• FIG. 32 is a cross-sectional view schematically illustrating a portion of an implantable stimulation apparatus having an external power source and pulse generator in accordance with another embodiment of the invention.
• FIG. 33 is a cross-sectional view illustrating in greater detail a portion of the implantable stimulation apparatus ofFIG. 32.
• FIG. 34 is a cross-sectional view schematically illustrating a portion of an implantable stimulation apparatus and an external controller in accordance with another embodiment of the invention.
• FIG. 35 is a cross-sectional view schematically illustrating a portion of an implantable stimulation apparatus and an external controller in accordance with yet another embodiment of the invention.
• FIG. 36 is a cross-sectional view schematically illustrating a portion of an implantable stimulation apparatus in accordance with yet another embodiment of the invention.
• FIG. 37 is an isometric view andFIG. 38 is a cross-sectional view illustrating an implantable stimulation apparatus in accordance with an embodiment of the invention.
• FIG. 39 is a cross-sectional view illustrating an implantable stimulation apparatus in accordance with yet another embodiment of the invention.
• FIG. 40 is a schematic illustration of an implantable stimulation apparatus in accordance with an embodiment of the invention.
• FIGS. 41A and 41B are schematic illustrations of stimulation units in accordance with other embodiments of the invention.
DETAILED DESCRIPTION
• The following disclosure describes several methods and apparatus for intracranial electrical stimulation to treat or otherwise effectuate a change in neural-functions of a patient. Several embodiments of methods described herein are directed toward enhancing or otherwise inducing neuroplasticity to effectuate a particular neural-function. Neuroplasticity refers to the ability of the brain to change or adapt over time. It was once thought adult brains became relatively “hard wired” such that functionally significant neural networks could not change significantly over time or in response to injury. It has become increasingly more apparent that these neural networks can change and adapt over time so that meaningful function can be restored in response to brain injury. An aspect of several embodiments of methods in accordance with the invention is to provide the appropriate triggers for adaptive neuroplasticity. These appropriate triggers appear to cause or enable increased synchrony of functionally significant populations of neurons in a network.
• Neural stimulation applied or delivered in various manners described herein may excite a portion of a neural network involved in or associated with a functionally significant task such that a selected population of neurons can become more strongly associated with that network. Because such a network will subserve a functionally meaningful task, such as motor relearning, the changes are more likely to be lasting because they are continually being reinforced by natural use mechanisms. The nature of stimulation in accordance with several embodiments of the invention ensures that the stimulated population of neurons links to other neurons in the functional network. It is expected that this occurs because action potentials are not actually caused by the stimulation, but rather the action potentials are caused by interactions with other neurons in the network. Several aspects of the electrical stimulation in accordance with selected embodiments of the invention increase the probability of restoring neural functionality when the network is activated by a combination of electrical stimulation and favorable activities, such as rehabilitation or limb use.
• Various methods in accordance with the invention can be used to treat brain damage (e.g., stroke, trauma, etc.), brain disease (e.g., Alzheimer's, Pick's, Parkinson's, etc.), brain disorders (e.g., epilepsy, depression, etc.), neurological malfunction (e.g., dyslexia, autism, etc. . . . ), and/or other neurological conditions. Various methods in accordance with the invention can also be used to enhance functions of normal, healthy brains (e.g., learning, memory, etc.), or to control sensory functions (e.g., pain).
• Certain embodiments of methods in accordance with the invention electrically stimulate the brain at a stimulation site where neuroplasticity is occurring. The stimulation site may be different than the region in the brain where neural activity is typically present to perform the particular function according to the functional organization of the brain. In one embodiment in which neuroplasticity related to the neural-function occurs in the brain, the method can include identifying the location where such neuroplasticity is present. This particular procedure may accordingly enhance a change in the neural activity to assist the brain in performing the particular neural function. In an alternative embodiment in which neuroplasticity is not occurring in the brain, an aspect, is to induce neuroplasticity at a stimulation site where it is expected to occur. This particular procedure may thus induce a change in the neural activity to instigate performance of the neural function. Several embodiments of these methods are expected to produce a lasting effect on the intended neural activity at the stimulation site.
• The specific details of certain embodiments of the invention are set forth in the following description and inFIGS. 1A-41B to provide a thorough understanding of these embodiments to a person of ordinary skill in the art. More specifically, several embodiments of methods in accordance with the invention are initially described with reference toFIGS. 1-5E, and then several embodiments of devices for stimulating the cortical and/or deep-brain regions of the brain are described with reference toFIGS. 6-41B. A person skilled in the art will understand that the present invention may have additional embodiments, or that the invention can be practiced without several of the details described below.
• A. Methods for Electrically Stimulating Regions of the Brain
• 1. Embodiments of Electrically Enhancing Neural Activity
• FIG. 1A is a schematic representation of several neurons N1-N3 andFIG. 1B is a graph illustrating an “action potential” related to neural activity in a normal neuron. Neural activity is governed by electrical impulses generated in neurons. For example, neuron N1 can send excitatory inputs to neuron N2 (e.g., times t1, t3 and t4 inFIG. 1B), and neuron N3 can send inhibitory inputs to neuron N2 (e.g., time t2 inFIG. 1B). The neurons receive/send excitatory and inhibitory inputs from/to a population of other neurons. The excitatory and inhibitory inputs can produce “action potentials” in the neurons, which are electrical pulses that travel through neurons by changing the flux of sodium (Na) and potassium (K) ions across the cell membrane. An action potential occurs when the resting membrane potential of the neuron surpasses a threshold level. When this threshold level is reached, an “all-or-nothing” action potential is generated. For example, as shown inFIG. 1B, the excitatory input at time t5 causes neuron N2 to “fire” an action potential because the input exceeds the threshold level for generating the action potential. The action potentials propagate down the length of the axon (the long process of the neuron that makes up nerves or neuronal tracts) to cause the release of neurotransmitters from that neuron that will further influence adjacent neurons.
• FIG. 1C is a flowchart illustrating amethod100 for facilitating and/or effectuating a neural-function in a patient in accordance with an embodiment of the invention. The neural-function, for example, can control a specific mental process or physiological function, such as a particular motor function (e.g., movement of a limb) or sensory function that is normally associated with neural activity at a “normal” location in the brain according to the functional organization of the brain. In several embodiments of themethod100, at least some neural activity related to the neural-function can be occurring at a site in the brain. The site of the neural activity may involve one or more portions of a normal location where neural activity typically occurs or is expected to occur to carry out the neural-function according to the functional organization of the brain, and/or the site of the neural activity may be at a different location where the brain has recruited material to perform the neural activity. In either situation, one aspect of several embodiments of themethod100 is to determine or otherwise identify the location in the brain where this neural activity is present.
• Themethod100 includes adiagnostic procedure102 involving identifying a stimulation site at a location of the brain. In one approach, the stimulation site may be a location of the brain where an intended neural activity related to a given type of neural-function is present or is expected to be present. For example, the stimulation site may be particular neurological regions and/or cortical structures that are expected to direct, effectuate, and/or facilitate specific neural functions in most individuals. In another approach, the stimulation site may be a location of the brain that supports or is expected to support the intended neural-function.
• Thediagnostic procedure102 may include identifying one or more exterior anatomical landmarks on the patient that correspond to such neurological regions and/or structures within the brain. The external anatomical landmarks serve as reference points for locating a structure of the brain where an intended neural activity may occur. Thus, one aspect of thediagnostic procedure102 may include referencing the stimulation site on the brain relative to external anatomical landmarks.
• More specifically, identifying an anatomical landmark may include visually determining the location of one or more reference structures (e.g., visible cranial landmarks), and locating underlying brain regions or structures (e.g., the motor strip and/or the Sylvian fissure) relative to the external location of the reference structures. Such reference structures may include, for example, the bregma, the midsagittal suture, and/or other well-known cranial landmarks in a manner understood by those skilled in the art. The methods for locating the underlying brain structure typically involve measuring distances and angles relative to the cerebral topography as known in the art of neurosurgery.
• In another embodiment, thediagnostic procedure102 includes generating an intended neural activity in the brain from a “peripheral” location that is remote from the normal location, and then determining where the intended neural activity is actually present in the brain. In an alternative embodiment, thediagnostic procedure102 can be performed by identifying a stimulation site where neural activity has changed in response to a change in the neural-function.
• Themethod100 continues with an implantingprocedure104 involving positioning at least a first electrode relative to the identified stimulation site; and a stimulatingprocedure106 involving applying an electrical current to the first electrode. Many embodiments of the implantingprocedure104 position two or more electrodes at the stimulation site, but other embodiments of the implanting procedure involve positioning only one electrode at the stimulation site and another electrode remotely from the stimulation site. As such, the implantingprocedure104 of themethod100 can include implanting at least one electrode at the stimulation site. Additional embodiments of thediagnostic procedure102 and theprocedures104 and106 are described in greater detail below.
• FIGS. 2-4 illustrate a specific embodiment of thediagnostic procedure102. Thediagnostic procedure102 can be used to determine the region of the brain where stimulation will likely effectuate the desired function, such as rehabilitating a loss of a neural-function caused by a stroke, trauma, disease or other circumstance.FIG. 2, more specifically, is an image of a normal,healthy brain200 having afirst region210 where the intended neural activity occurs to effectuate a specific neural-function in accordance with the functional organization of the brain. For example, the neural activity in thefirst region210 shown inFIG. 2 is generally associated with the movement of a patient's fingers. Thefirst region210 can have a high-intensity area212 and a low-intensity area214 in which different levels of neural activity occur. It is not necessary to obtain an image of the neural activity in thefirst region210 shown inFIG. 2 to carry out thediagnostic procedure102, but rather it is provided to show an example of neural activity that typically occurs at a “normal location” according to the functional organization of thebrain200 for a large percentage of people with normal brain function. It will be appreciated that the actual location of thefirst region210 will generally vary between individual patients, but those skilled in the art will recognize that thefirst region210 will bear a reasonably predictable spatial relationship with respect to cranial landmarks on the patient.
• The neural activity in thefirst region210, however, can be impaired. In a typical application, thediagnostic procedure102 begins by taking an image of thebrain200 that is capable of detecting neural activity to determine whether the intended neural activity associated with the particular neural function of interest is occurring at the region of thebrain200 where it normally occurs according to the functional organization of the brain.FIG. 3 is an image of thebrain200 after thefirst region210 has been affected (e.g., from a stroke, trauma or other cause). As shown inFIG. 3, the neural activity that controlled the neural-function for moving the fingers no longer occurs in thefirst region210. Thefirst region210 is thus “inactive,” which is expected to result in a corresponding loss of the movement and/or sensation in the fingers. In some instances, the damage to thebrain200 may result in only a partial loss of the neural activity in the damaged region. In either case, the image shown inFIG. 3 establishes that the loss of the neural-function is related to the diminished neural activity in thefirst region210. Thebrain200 may accordingly recruit other neurons to perform neural activity for the affected neural-function (i.e., neuroplasticity), or the neural activity may not be present at any location in the brain.
• FIG. 4 is an image of thebrain200 illustrating a plurality ofpotential stimulation sites220 and230 for effectuating the neural-function that was originally performed in thefirst region210 shown inFIG. 2.FIGS. 3 and 4 show an example of neuroplasticity in which the brain compensates for a loss of neural-function in one region of the brain by recruiting other regions of the brain to perform neural activity for carrying out the affected neural-function. Thediagnostic procedure102 utilizes the neuroplasticity that occurs in the brain to identify the location of a stimulation site that is expected to be more responsive to the results of an electrical, magnetic, sonic, genetic, biologic, and/or pharmaceutical procedure to effectuate the desired neural-function.
• One embodiment of thediagnostic procedure102 involves generating the intended neural activity remotely from thefirst region210 of the brain, and then detecting or sensing the location in the brain where the intended neural activity has been generated. The intended neural activity can be generated by applying an input that causes a signal to be sent to the brain. For example, in the case of a patient that has lost the use of limb, the affected limb is moved and/or stimulated while the brain is scanned using a known imaging technique that can detect neural activity (e.g., functional MRI, positron emission tomography, etc.). In one specific embodiment, the affected limb can be moved by a practitioner or the patient, stimulated by sensory tests (e.g., pricking), or subject to peripheral electrical stimulation. The movement/stimulation of the affected limb produces a peripheral neural signal from the limb that is expected to generate a response neural activity in the brain. The location in the brain where this response neural activity is present can be identified using the imaging technique.FIG. 4, for example, can be created by moving the affected fingers and then noting where neural activity occurs in response to the peripheral stimulus. By peripherally generating the intended neural activity, this embodiment may accurately identify where the brain has recruited matter (i.e.,sites220 and230) to perform the intended neural activity associated with the neural-function.
• An alternative embodiment of thediagnostic procedure102 involves identifying a stimulation site at a second location of the brain where the neural activity has changed in response to a change in the neural-function of the patient. This embodiment of the method does not necessarily require that the intended neural activity be generated by peripherally actuating or stimulating a body part. For example, the brain can be scanned for neural activity associated with the impaired neural-function as a patient regains use of an affected limb or learns a task over a period of time. This embodiment, however, can also include peripherally generating the intended neural activity remotely from the brain explained above.
• In still another embodiment, thediagnostic procedure102 involves identifying a stimulation site at a location of the brain where the intended neural activity is developing to perform the neural-function. This embodiment is similar to the other embodiments of thediagnostic procedure102, but it can be used to identify a stimulation site at (a) the normal region of the brain where the intended neural activity is expected to occur according to the functional organization of the brain and/or (b) a different region where the neural activity occurs because the brain is recruiting additional matter to perform the neural-function. This particular embodiment of the method involves monitoring neural activity at one or more locations where the neural activity occurs in response to the particular neural-function of interest. For example, to enhance the ability to learn a particular task (e.g., playing a musical instrument, memorizing, etc.), the neural activity can be monitored while a person performs the task or thinks about performing the task. The stimulation sites can be defined by the areas of the brain where the neural activity has the highest intensity, the greatest increases, and/or other parameters that indicate areas of the brain that are being used to perform the particular task.
• FIGS. 5A and 5B are schematic illustrations of the implantingprocedure104 described above with reference toFIG. 1C for positioning the first and second electrodes relative to a portion of the brain of apatient500. Referring toFIG. 5A, astimulation site502 is identified in accordance with an embodiment of thediagnostic procedure102. In one embodiment, askull section504 is removed from thepatient500 adjacent to thestimulation site502. Theskull section504 can be removed by boring a hole in the skull in a manner known in the art, or a much smaller hole can be formed in the skull using drilling techniques that are also known in the art. In general, the hole can be 0.2-4.0 cm in diameter. Referring toFIG. 5B, animplantable stimulation apparatus510 having first andsecond electrodes520 can be implanted in thepatient500. Suitable techniques associated with the implantation procedure are known to practitioners skilled in the art. After thestimulation apparatus510 has been implanted in thepatient500, a pulse system generates electrical pulses that are transmitted to thestimulation site502 by the first andsecond electrodes520. Stimulation apparatus suitable for carrying out the foregoing embodiments of methods in accordance with the invention are described in more detail below with reference to theFIGS. 6-40.
• Several embodiments of methods for enhancing neural activity in accordance with the invention are expected to provide lasting results that promote a desired neural-function. Before the present invention, electrical and magnetic stimulation techniques typically stimulated the normal locations of the brain where neural activity related to the neural-functions occurred according to the functional organization of the brain. Such conventional techniques, however, may not by themselves be effective because one or more subpopulations of neurons in the “normal locations” of the brain may not be capable of carrying out the neural activity because of brain damage, disease, disorder, and/or because of variations of the location specific to individual patients. Several embodiments of methods for enhancing neural activity in accordance with the invention overcome this drawback by identifying a stimulation site based on neuroplastic activity that appears to be related to the neural-function. By first identifying a location in the brain that is being recruited to perform the neural activity, it is expected that therapies (e.g., electrical, magnetic, genetic, biologic, and/or pharmaceutical) applied to this location will be more effective than conventional techniques. This is because the location that the brain is recruiting for the neural activity may not be the “normal location” where the neural activity would normally occur according to the functional organization of the brain. Therefore, several embodiments of methods for enhancing neural activity in accordance with the invention are expected to provide lasting results because the therapies are applied to the portion of the brain where neural activity for carrying out the neural-function actually occurs in the particular patient.
• Various embodiments of methods for enhancing neural activity in accordance with the invention may also provide lasting results because electrical stimulation therapies described herein may be applied or delivered to a patient in conjunction or simultaneous with one or more synergistic or adjunctive therapies. Such synertistic or adjunctive therapies may include or involve the patient's performance of one or more behavioral therapies, activities, and/or tasks.
• 2. Electrically Inducing Desired Neural Activity
• Themethod100 for effectuating a neural-function can also be used to induce neural activity in a region of the brain where such neural activity is not present. As opposed to the embodiments of themethod100 described above for enhancing existing neural activity, the embodiments of themethod100 for inducing neural activity initiate the neural activity at a stimulation site where it is estimated that neuroplasticity will occur. In this particular situation, an image of the brain seeking to locate where neuroplasticity is occurring may be similar toFIG. 3. An aspect of inducing neural activity, therefore, is to develop a procedure to determine where neuroplasticity is likely to occur.
• A stimulation site may be identified by estimating where the brain will likely recruit neurons for performing the neural-function. In one embodiment, the location of the stimulation site is estimated by defining a region of the brain that is proximate to the normal location where neural activity related to the neural-function is generally present according to the functional organization of the brain. An alternative embodiment for locating the stimulation site includes determining where neuroplasticity has typically occurred in patients with similar symptoms. For example, if the brain typically recruits a second region of the cortex to compensate for a loss of neural activity in the normal region of the cortex, then the second region of the cortex can be selected as the stimulation site either with or without imaging the neural activity in the brain.
• Several embodiments of methods for inducing neural activity in accordance with the invention are also expected to provide lasting results that initiate and promote a desired neural-function. By first estimating the location of a stimulation site where desired neuroplasticity is expected to occur, therapies applied to this location may be more effective than conventional therapies for reasons that are similar to those explained above regarding enhancing neural activity. Additionally, methods for inducing neural activity may be easier and less expensive to implement because they do not require generating neural activity and/or imaging the brain to determine where the intended neural activity is occurring before applying the therapy.
• 3. Applications of Methods for Electrically Stimulating Regions of the Brain
• The foregoing methods for enhancing existing neural activity or inducing new neural activity are expected to be useful for many applications. As explained above, several embodiments of themethod100 involve determining an efficacious location of the brain to enhance or induce an intended neural activity that causes the desired neural-functions to occur. Additional therapies can also be implemented in combination with the electrical stimulation methods described above. Several specific applications using embodiments of electrical stimulation methods in accordance with the invention either alone or with synergistic or adjunctive therapies will now be described, but it will be appreciated that the methods in accordance with the invention can be used in many additional applications.
• a. General Applications
• The embodiments of the electrical stimulation methods described above are expected to be particularly useful for rehabilitating or restoring a loss of mental functions, motor functions and/or sensory functions caused by damage to the brain. In a typical application, the brain has been damaged by a stroke or trauma (e.g., automobile accident). The extent of the particular brain damage can be assessed using functional MRI or another appropriate imaging technique as explained above with respect toFIG. 3. A stimulation site can be identified in accordance with a variety of techniques, including: (a) identification of one or more anatomical landmarks; (b) peripherally stimulating a body part that was affected by the brain damage to induce the intended neural activity and determining the location where a response neural activity occurs; (c) determining where the neural activity has changed as a patient gains more use of the affected body part; (d) estimating a location that the brain may recruit neurons to carry out a type of neural activity that was previously performed by the damaged portion of the brain; and/or (e) preoperatively (for example, using TMS) and/or intraoperatively stimulating one or more brain locations to identify or map particular neural regions that induce or evoke a given type of patient response (for example, a movement or a sensation). One or more of the aforementioned techniques may be performed in conjunction or association with a neural imaging procedure. An electrical stimulation therapy can be applied to the selected stimulation site by placing or positioning the first and second electrodes relative to the stimulation site to apply an electrical current in or through that portion of the brain. As explained in more detail below, it is expected that applying an electrical current to the portion of the brain that has been recruited to perform the neural activity related to the affected body part will produce a lasting neurological effect for rehabilitating the affected body part. The extent to which electrical stimulation therapy produces a lasting neurological effect may also be related to the performance of behavioral therapy or tasks in conjunction or simultaneous with the electrical stimulation therapy.
• Several specific applications are expected to have a stimulation site in the cortex because neural activity in this part of the brain effectuates motor functions and/or sensory functions that are typically affected by a stroke or trauma. In these applications, the electrical stimulation can be applied directly to the pial surface of the brain or at least proximate to the pial surface (e.g., the dura mater, the fluid surrounding the cortex, or neurons within the cortex). Suitable devices for applying the electrical stimulation to the cortex are described in detail with reference toFIGS. 6-41B.
• FIG. 5C is a flowchart of an embodiment of a stimulatingprocedure106 described above with reference toFIG. 1C for applying electrical stimulation to a region of a patient's brain identified in accordance with an associateddiagnostic procedure102. In one embodiment, the stimulatingprocedure106 includes a limitedduration treatment program110 involving the application of electrical stimulation to the patient in a manner that facilitates or effectuates complete, essentially complete, significant, or partial rehabilitation, restoration, or functional healing of or recovery from a neurological condition such as a neurological malfunction and/or a neurologically based deficit or disorder. One or more portions of thetreatment program110 may involve electrical stimulation by itself, and/or electrical stimulation in conjunction with one or more synergistic or adjunctive therapies, such as behavioral therapies, activities, and/or tasks. Such behavioral therapies, activities, and/or tasks may include physical therapy; physical and/or cognitive skills training or practice, such as training in Activities of Daily Living (ADL); intentional use of an affected body part; speech therapy; vision training or visual tasks; a reading task; a memory task or memory training; comprehension tasks; attention tasks; and/or other therapies or activities. Other synergistic or adjunctive therapies may include, for example, drug therapies, such as treatment with amphetamines. The electrical stimulation and synergistic or adjunctive therapies can be performed simultaneously or serially.
• In accordance with the present invention, a limitedduration treatment program110 may effectuate or facilitate at least some degree of permanent, essentially permanent, or long term rehabilitation or restoration of a patient's ability to perform one or more types of physical and/or cognitive functions that had been lost or degraded due to neurological damage or a neurological disorder. A limitedduration treatment program110 may alternatively or additionally effectuate or facilitate at least some degree of permanent, essentially permanent, or long term development, acquisition, and/or establishment of a patient's ability to perform one or more types of physical and/or cognitive functions that had been at least partially absent or impaired as a result of a neurological malfunction. Therefore, thetreatment program110 need not be directed toward managing a chronic condition that exists over a very long period of time or throughout a patient's life. Rather, thetreatment program110 may be applied over a limited time that corresponds to the extent of the patient's recovery or functional gain(s). For example, thetreatment program110 may occur over a period of six weeks, three months, six months, one year, three years, or another limited timeframe. Alternatively or additionally, thetreatment program110 may be applied over a predetermined number of treatment sessions, for example, twenty, thirty, fifty, or some other number of treatment sessions in total. Another aspect may limit the duration of the treatment program to an accumulated or aggregate time that stimulation has been applied over some number of treatment sessions. Anexemplary treatment program110 may include one to four or more hours of electrical stimulation per stimulation session, three to seven stimulation sessions per week, throughout a therapy period of one to six or more weeks. Alternatively, atreatment program110 may apply continuous or essentially continuous neural stimulation during one or more portions of a therapy period. The overall length or duration of the treatment program110 (i.e., the therapy period), and possibly the type(s) and/or location(s) of applied neural stimulation, may depend upon the nature, number, and/or severity of the patient's functional deficits, as well as a degree of patient recovery or functional development.
• The stimulatingprocedure106 may further include an assessingprocedure112 for determining the extent of the patient's functional rehabilitation, recovery, and/or development at particular intervals or over time. Such intervals may be, for example, every n weeks, or every kth treatment session. The assessingprocedure112 may involve rating or measuring the patient's physical and/or cognitive abilities in accordance with one or more standard functional measures or tests. Such functional measures may include or be based upon, for example, a Fugl-Meyer Assessment of Sensorimotor Impairment; a National Institute of Health (NIH) Stroke Scale; a Stroke Impact Scale (SIS); an ADL scale; a Quality of Life (QoL) scale; physical measures such as grip strength or finger tapping speed; a neuropsychological testing battery; a walking, movement, and/or dexterity test; a behavioral test; a language test; a comprehension test; and/or other measures of patient functional ability. The assessingprocedure112 may additionally or alternatively include one or more neural imaging procedures. The assessingprocedure112 can also be used to determine the severity of the patient's functional deficits or other neurological conditions at the beginning and throughout the therapy period.
• In one embodiment, the stimulatingprocedure106 may include ananalyzing procedure114 for examining results obtained from one or more assessingprocedures112. The analyzingprocedure114 may involve data analysis and/or trend analysis techniques. In the event that the patient's functional development and/or recovery has significantly slowed or plateaued, but further recovery may be likely or possible, the stimulatingprocedure106 may include amodification procedure116 for changing, adjusting, or adapting the limitedduration treatment program110. Thetreatment program110 may be changed, adjusted, or adapted by varying stimulation type(s), stimulation location(s), stimulation parameters, and/or particular synergistic or adjunctive therapies (e.g., behavioral therapies, activities, and/or tasks).
• The stimulatingprocedure106 may further include a determiningprocedure118 for deciding whether to continue atreatment program110. In the event that atreatment program110 is not yet complete or has been modified or adjusted, thetreatment program110 may resume or restart. In the event that the patient has functionally developed and/or recovered to an intended, acceptable, or maximum extent, the stimulatingprocedure106 may include atermination procedure120 for discontinuing thetreatment program110. After thetreatment program110 is completed or discontinued, the patient's functional recovery or gains in functional ability may persist or be retained on a permanent, essentially permanent, or long term basis without further electrical stimulation therapy.
• FIG. 5D is a flow chart of another embodiment of a stimulatingprocedure106 described above with reference toFIG. 1C for applying electrical stimulation to a region of a patient's brain identified in accordance with an associateddiagnostic procedure102. The embodiment of the stimulatingprocedure106 shown inFIG. 5D is similar to the procedure shown inFIG. 5C. The stimulatingprocedure106 show inFIG. 5D, however, further includes amonitoring operation130 in which the status of the recovery and/or functional gains is monitored after a period of time to determine whether they have been retained on a permanent or long-term basis without further electrical stimulation therapy. In many applications it is anticipated that the treatment program of procedures110-120 over a limited therapy period will be sufficient to retain the recovery or gains in functional ability on a permanent, essentially permanent or long-term basis without further electrical stimulation therapy. Theprocedure106 shown inFIG. 5D, however, is applicable in situations that require further treatment. Thestimulation procedure106 inFIG. 5D accordingly further includes a second determiningprocedure132 for deciding whether to restart the treatment program. If the results from themonitoring operation130 indicate that the patient has retained an intended, acceptable or maximum recovery in and/or development of a functional ability, then the determiningprocedure132 may proceed to terminate the treatment program. On the other hand, if themonitoring operation130 establishes that the recovery in and/or development of functional ability has not been retained or can be further improved, then the determiningprocedure132 restarts thetreatment program110. It will be appreciated that this process can include a number of different iterations.
• Various embodiments of the electrical stimulation methods described above may be useful for treating brain diseases, such as Alzheimer's, Parkinson's, and other brain diseases. In this application, a stimulation site can be identified by monitoring the neural activity using functional MRI or other suitable imaging techniques over a period of time to determine where the brain is recruiting material to perform the neural activity that is being affected by the disease. It may also be possible to identify a stimulation site by having the patient try to perform an act that the particular disease has affected, and monitoring the brain to determine whether any response neural activity is present in the brain. After identifying where the brain is recruiting additional matter, the electrical stimulation can be applied to this portion of the brain. It is expected that electrically stimulating the regions of the brain that have been recruited to perform the neural activity which was affected by the disease will assist the brain in offsetting the damage caused by the disease.
• Various embodiments of the electrical stimulation methods described above are also expected to be useful for treating neurological disorders, such as depression, passive-aggressive behavior, weight control, and other disorders. In these applications, the electrical stimulation can be applied to a stimulation site in the cortex or another suitable part of the brain where neural activity related to the particular disorder is present. The embodiments of electrical stimulation methods for carrying out the particular therapy can be adapted to either increase or decrease the particular neural activity in a manner that produces the desired results. For example, an amputee may feel phantom sensations associated with the amputated limb. This phenomenon can be treated by applying an electrical pulse that reduces the phantom sensations. The electrical therapy can be applied so that it will modulate the ability of the neurons in that portion of the brain to execute sensory functions.
• b. Pulse Forms and Potentials
• The electrical stimulation methods in accordance with the invention can use several different pulse forms to effectuate the desired neuroplasticity. The pulses can be a bi-phasic or monophasic stimulus that is applied to achieve a desired potential in a sufficient percentage of a population of neurons at the stimulation site. In one embodiment, the pulse form has a frequency of approximately 2-1000 Hz, but the frequency may be particularly useful in the range of approximately 40-200 Hz. For example, initial clinical trials are expected to use a frequency of approximately 50-100 Hz. The pulses can also have pulse widths of approximately 10 μs-100 ms, or more specifically the pulse width can be approximately 20-200 μs. For example, a pulse width of 50-100 μs may produce beneficial results.
• It is expected that one particularly useful application of the invention involves enhancing or inducing neuroplasticity by raising the resting membrane potential of neurons to bring the neurons closer to the threshold level for firing an action potential. Because the stimulation raises the resting membrane potential of the neurons, it is expected that these neurons are more likely to “fire” an action potential in response to excitatory input at a lower level.
• FIG. 5E is a graph illustrating applying a subthreshold potential to the neurons N1-N3 ofFIG. 1A. At times t1 and t2, the excitory/inhibitory inputs from other neurons do not “bridge-the-gap” from the resting potential at −X mV to the threshold potential. At time t3, the electrical stimulation is applied to the brain to raise the resting potential of neurons in the stimulated population such that the resting potential is at −Y mV. As such, at time t4 when the neurons receive another excitatory input, even a small input exceeds the gap between the raised resting potential −Y mV and the threshold potential to induce action potentials in these neurons. For example, if the resting potential is approximately −70 mV and the threshold potential is approximately −50 mV, then the electrical stimulation can be applied to raise the resting potential of a sufficient number of neurons to approximately −52 to −60 mV.
• The actual electrical potential applied to electrodes implanted in the brain to achieve a subthreshold potential stimulation will vary according to the individual patient, the type of therapy, the type of electrodes, and other factors. In general, the pulse form of the electrical stimulation (e.g., the frequency, pulse width, wave form, and voltage potential) is selected to raise the resting potential in a sufficient number neurons at the stimulation site to a level that is less than a threshold potential for a statistical portion of the neurons in the population. The pulse form, for example, can be selected so that the applied voltage of the stimulus achieves a change in the resting potential of approximately 10%-95%, and more specifically of 60%-80%, of the difference between the unstimulated resting potential and the threshold potential.
• In one specific example of a subthreshold application for treating a patient's hand, electrical stimulation is not initially applied to the stimulation site. Although physical therapy related to the patient's hand may cause some activation of a particular population of neurons that is known to be involved in “hand function,” only a low level of activation might occur because physical therapy only produces a low level of action potential generation in that population of neurons. However, when the subthreshold electrical stimulation is applied, the resting membrane potentials of the neurons in the stimulated population are elevated. These neurons now are much closer to the threshold for action potential formation such that when the same type of physical therapy is given, this population of cells will have a higher level of activation because these cells are more likely to fire action potentials.
• Subthreshold stimulation may produce better results than simply stimulating the neurons with sufficient energy levels to exceed the threshold for action potential formation. One aspect of subthreshold stimulation is to increase the probability that action potentials will occur in response to the ordinary causes of activation—such as physical therapy. This will allow the neurons in this functional network to become entrained together, or “learn” to become associated with these types of activities. If neurons are given so much electricity that they continually fire action potentials without additional excitatory inputs (suprathreshold stimulation), this will create “noise” and disorganization that will not likely cause improvement in function. In fact, neurons that are “overdriven” soon deplete their neurotransmitters and effectively become silent.
• The application of a subthreshold stimulation is very different than suprathreshold stimulation. Subthreshold stimulation in accordance with several embodiments of the invention, for example, does not intend to directly make neurons fire action potentials with the electrical stimulation in a significant population of neurons at the stimulation site. Instead, subthreshold stimulation attempts to decrease the “activation energy” required to activate a large portion of the neurons at the stimulation site As such, subthreshold stimulation in accordance with certain embodiments of the invention is expected to increase the probability that the neurons will fire in response to the usual intrinsic triggers, such as trying to move a limb, physical therapy, or simply thinking about movement of a limb, etc. Moreover, coincident stimulation associated with physical therapy is expected to increase the probability that the action potentials that are occurring with an increased probability due to the subthreshold stimulation will be related to meaningful triggers, and not just “noise.”
• The stimulus parameters set forth above, such as a frequency selection of approximately 50-100 Hz and an amplitude sufficient to achieve an increase of 60% to 80% of the difference between the resting potential and the threshold potential are specifically selected so that they will increase the resting membrane potential of the neurons, thereby increasing the likelihood that they will fire action potentials, without directly causing action potentials in most of the neuron population. In addition, and as explained in more detail below with respect toFIGS. 6-40, several embodiments of stimulation apparatus in accordance with the invention are designed to precisely apply a pulse form that produces subthreshold stimulation by selectively stimulating regions of the cerebral cortex of approximately 1-2 cm (the estimated size of a “functional unit” of cortex), directly contacting the pial surface with the electrodes to consistently create the same alterations in resting membrane potential, and/or biasing the electrodes against the pial surface to provide a positive connection between the electrodes and the cortex.
• B. Devices for Electrically Stimulating Regions of the Brain
• FIGS. 6-40 illustrate stimulation apparatus in accordance with several embodiments of the invention for electrically stimulating regions of the brain in accordance with one or more of the methods described above. The devices illustrated inFIGS. 6-40 are generally used to stimulate a region of the cortex proximate to the pial surface of the brain (e.g., the dura mater, the pia mater, the fluid between the dura mater and the pia mater, and a depth in the cortex outside of the white matter of the brain). The devices can also be adapted for stimulating other portions of the brain in other embodiments.
• 1. Implantable Stimulation Apparatus with Integrated Pulse Systems
• FIG. 6 is an isometric view andFIG. 7 is a cross-sectional view of astimulation apparatus600 in accordance with an embodiment of the invention for stimulating a region of the cortex proximate to the pial surface. In one embodiment, thestimulation apparatus600 includes asupport member610, an integrated pulse-system630 (shown schematically) carried by thesupport member610, and first and second electrodes660 (identified individually byreference numbers660aand660b). The first andsecond electrodes660 are electrically coupled to thepulse system630. Thesupport member610 can be configured to be implanted into the skull or another intracranial region of a patient. In one embodiment, for example, thesupport member610 includes ahousing612 and anattachment element614 connected to thehousing612. Thehousing612 can be a molded casing formed from a biocompatible material that has an interior cavity for carrying thepulse system630. The housing can alternatively be a biocompatible metal or another suitable material. Thehousing612 can have a diameter of approximately 1-4 cm, and in many applications thehousing612 can be 1.5-2.5 cm in diameter. Thehousing612 can also have other shapes (e.g., rectilinear, oval, elliptical) and other surface dimensions. Thestimulation apparatus600 can weigh 35 g or less and/or occupy a volume of 20 cc or less. Theattachment element614 can be a flexible cover, a rigid plate, a contoured cap, or another suitable element for holding thesupport member610 relative to the skull or other body part of the patient. In one embodiment, theattachment element614 is a mesh, such as a biocompatible polymeric mesh, metal mesh, or other suitable woven material. Theattachment element614 can alternatively be a flexible sheet of Mylar, a polyester, or another suitable material.
• FIG. 7, more specifically, is a cross-sectional view of thestimulation apparatus600 after it has been implanted into a patient in accordance with an embodiment of the invention. In this particular embodiment, thestimulation apparatus600 is implanted into the patient by forming an opening in thescalp702 and cutting ahole704 through theskull700 and through thedura mater706. Thehole704 should be sized to receive thehousing612 of thesupport member610, and in most applications, thehole704 should be smaller than theattachment element614. A practitioner inserts thesupport member610 into thehole704 and then secures theattachment element614 to theskull700. Theattachment element614 can be secured to the skull using a plurality of fasteners618 (e.g., screws, spikes, etc.) or an adhesive. In an alternative embodiment, a plurality of downwardly depending spikes can be formed integrally with theattachment element614 to define anchors that can be driven into theskull700.
• The embodiment of thestimulation apparatus600 shown inFIG. 7 is configured to be implanted into a patient so that theelectrodes660 contact a desired portion of the brain at the stimulation site. Thehousing612 and theelectrodes660 can project from theattachment element614 by a distance “D” such that theelectrodes660 are positioned at least proximate to thepia mater708 surrounding thecortex709. Theelectrodes660 can project from ahousing612 as shown inFIG. 7, or theelectrodes660 can be flush with the interior surface of thehousing612. In the particular embodiment shown inFIG. 7, thehousing612 has a thickness “T” and theelectrodes660 project from thehousing612 by a distance “P” so that theelectrodes660 press against the surface of thepia mater708. The thickness of thehousing612 can be approximately 0.5-4 cm, and is more generally about 1-2 cm. The configuration of the stimulation apparatus6Q0 is not limited to the embodiment shown inFIGS. 6 and 7, but rather thehousing612, theattachment element614, and theelectrodes660 can be configured to position the electrodes in several different regions of the brain. For example, in an alternate embodiment, thehousing612 and theelectrodes660 can be configured to position the electrodes deep within thecortex709, and/or adeep brain region710. In general, the electrodes can be flush with the housing or extend 0.1 mm to 5 cm from the housing. More specific embodiments of pulse system and electrode configurations for the stimulation apparatus will be described below.
• Several embodiments of thestimulation apparatus600 are expected to be more effective than existing transcranial electrical stimulation devices and transcranial magnetic stimulation devices. It will be appreciated that much of the power required for transcranial therapies is dissipated in the scalp and skull before it reaches the brain. In contrast to conventional transcranial stimulation devices, thestimulation apparatus600 is implanted so that the electrodes are at least proximate to the pial surface of thebrain708. Several embodiments of methods in accordance with the invention can use thestimulation apparatus600 to apply an electrical therapy directly to thepia mater708, thedura mater706, and/or another portion of thecortex709 at significantly lower power levels than existing transcranial therapies. For example, a potential of approximately 1 mV to 10 V can be applied to theelectrodes660; in many instances a potential of 100 mV to 5 V can be applied to theelectrodes660 for selected applications. It will also be appreciated that other potentials can be applied to theelectrodes660 of thestimulation apparatus600 in accordance with other embodiments of the invention.
• Selected embodiments of thestimulation apparatus600 are also capable of applying stimulation to a precise stimulation site. Again, because thestimulation apparatus600 positions theelectrodes660 at least proximate to thepial surface708, precise levels of stimulation with good pulse shape fidelity will be accurately transmitted to the stimulation site in the brain. It will be appreciated that transcranial therapies may not be able to apply stimulation to a precise stimulation site because the magnetic and electrical properties of the scalp and skull may vary from one patient to another such that an identical stimulation by the transcranial device may produce a different level of stimulation at the neurons in each patient. Moreover, the ability to focus the stimulation to a precise area is hindered by delivering the stimulation transcranially because the scalp, skull and dura all diffuse the energy from a transcranial device. Several embodiments of thestimulation apparatus600 overcome this drawback because theelectrodes660 are positioned under theskull700 such that the pulses generated by thestimulation apparatus600 are not diffused by thescalp702 andskull700.
• 2. Integrated Pulse Systems for Implantable Stimulation Apparatus
• Thepulse system630 shown inFIGS. 6 and 7 generates and/or transmits electrical pulses to theelectrodes660 to create an electrical field at a stimulation site in a region of the brain. The particular embodiment of thepulse system630 shown inFIG. 7 is an “integrated” unit in that is carried by thesupport member610. Thepulse system630, for example, can be housed within thehousing612 so that theelectrodes660 can be connected directly to thepulse system630 without having leads outside of thestimulation apparatus600. The distance between theelectrodes660 and thepulse system630 can be less than 4 cm, and it is generally 0.10 to 2.0 cm. Thestimulation apparatus600 can accordingly provide electrical pulses to the stimulation site without having to surgically create tunnels running through the patient to connect theelectrodes660 to a pulse generator implanted remotely from thestimulation apparatus600. It will be appreciated, however, that alternative embodiments of stimulation apparatus in accordance with the invention can include a pulse system implanted separately from thestimulation apparatus600 in the cranium or an external pulse system. Several particular embodiments of pulse systems that are suitable for use with thestimulation apparatus600 will now be described in more detail.
• FIGS. 8 and 9 schematically illustrate anintegrated pulse system800 in accordance with one embodiment of the invention for being implanted in the cranium within thestimulation apparatus600. Referring toFIG. 8, thepulse system800 can include apower supply810, anintegrated controller820, apulse generator830, and apulse transmitter840. Thepower supply810 can be a primary battery, such as a rechargeable battery or another suitable device for storing electrical energy. In alternative embodiments, thepower supply810 can be an RF transducer or a magnetic transducer that receives broadcast energy emitted from an external power source and converts the broadcast energy into power for the electrical components of thepulse system800. Theintegrated controller820 can be a wireless device that responds to command signals sent by anexternal controller850. Theintegrated controller820, for example, can communicate with theexternal controller850 by RF ormagnetic links860. Theintegrated controller820 provides control signals to thepulse generator830 in response to the command signals sent by theexternal controller850. Thepulse generator830 can have a plurality of channels that send appropriate electrical pulses to thepulse transmitter840, which is coupled to theelectrodes660. Suitable components for thepower supply810, theintegrated controller820, thepulse generator830, and thepulse transmitter840 are known to persons skilled in the art of implantable medical devices.
• Referring toFIG. 9, thepulse system800 can be carried by thesupport member610 of thestimulation apparatus600 in the manner described above with reference toFIGS. 6 and 7. Theexternal controller850 can be located externally to thepatient500 so that theexternal controller850 can be used to control thepulse system800. In one embodiment, several patients that require a common treatment can be simultaneously treated using a singleexternal controller850 by positioning the patients within the operating proximity of thecontroller850. In an alternative embodiment, theexternal controller850 can contain a plurality of operating codes and theintegrated controller820 for a particular patient can have an individual operating code. Asingle controller850 can thus be used to treat a plurality of different patients by entering the appropriate operating code into thecontroller850 corresponding to the particular operating codes of theintegrated controllers820 for the patients.
• FIG. 10 is a schematic view illustrating apulse system1000 and anexternal controller1010 for use with thestimulation apparatus600 in accordance with another embodiment of the invention. In this embodiment, theexternal controller1010 includes apower supply1020, acontroller1022 coupled to thepower supply1020, and auser interface1024 coupled to thecontroller1022. Theexternal controller1010 can also include apulse generator1030 coupled to thepower supply1020, apulse transmitter1040 coupled to thepulse generator1030, and anantenna1042 coupled to thepulse transmitter1040. Theexternal controller1010 generates the power and the pulse signal, and theantenna1042 transmits apulse signal1044 to thepulse system1000 in thestimulation apparatus600. Thepulse system1000 receives thepulse signal1044 and delivers an electrical pulse to the electrodes. Thepulse system1000, therefore, does not necessarily include an integrated power supply, controller and pulse generator within thehousing610 because these components are in theexternal controller1010.
• FIG. 11 is a schematic view illustrating an embodiment of thepulse system1000 in greater detail. In this embodiment, thepulse system1000 is carried by thesupport member610 of thestimulation apparatus600. Thepulse system1000 can include anantenna1060 and apulse delivery system1070 coupled to theantenna1060. Theantenna1060 receives thepulse signal1044 from theexternal controller1010 and sends thepulse signal1044 to thepulse delivery system1070, which transforms thepulse signal1044 into electrical pulses. Accordingly, theelectrodes660 can be coupled to thepulse delivery system1070. Thepulse delivery system1070 can include a filter to remove noise from thepulse signal1044 and a pulse former that creates an electrical pulse from thepulse signal1044. The pulse former can be driven by the energy in thepulse signal1044, or in an alternative embodiment, thepulse system1000 can also include an integrated power supply to drive the pulse former.
• FIG. 12 is a schematic view illustrating an embodiment ofpulse system1200 for use in an embodiment of thestimulation apparatus600, and anexternal controller1210 for controlling thepulse system1200 remotely from the patient using RF energy. In this embodiment, theexternal controller1210 includes apower supply1220, acontroller1222 coupled to thepower supply1220, and apulse generator1230 coupled to thecontroller1222. Theexternal controller1210 can also include amodulator1232 coupled to thepulse generator1230 and anRF generator1234 coupled to themodulator1232. In operation, theexternal controller1210 broadcasts pulses of RF energy via anantenna1242.
• Thepulse system1200 can be housed within the stimulation apparatus600 (not shown). In one embodiment, thepulse system1200 includes anantenna1260 and apulse delivery system1270. Theantenna1260 incorporates a diode (not shown) that rectifies the broadcast RF energy from theantenna1242. Thepulse delivery system1270 can include afilter1272 and a pulse former1274 that forms electrical pulses which correspond to the RF energy broadcast from theantenna1242. Thepulse system1200 is accordingly powered by the RF energy in the pulse signal from theexternal controller1210 such that thepulse system1200 does not need a separate power supply carried by thestimulation apparatus600.
• FIG. 13 is a cross-sectional view of apulse system1300 for use in another embodiment of theimplantable stimulation apparatus600, together with anexternal controller1310 for remotely controlling thepulse system1300 externally from the patient using magnetic energy. In this embodiment, theexternal controller1310 includes apower supply1320, acontroller1322 coupled to thepower supply1320, and auser interface1324 coupled to thecontroller1322. Theexternal controller1310 can also include apulse generator1330 coupled to the controller1332, apulse transmitter1340 coupled to thepulse generator1330, and amagnetic coupler1350 coupled to thepulse transmitter1340. Themagnetic coupler1350 can include aferrite core1352 and acoil1354 wrapped around a portion of theferrite core1352. Thecoil1354 can also be electrically connected to thepulse transmitter1340 so that electrical pulses applied to thecoil1354 generate changes in a corresponding magnetic field. Themagnetic coupler1350 can also include aflexible cap1356 to position themagnetic coupler1350 over the implantedstimulation apparatus600.
• Thepulse system1300 can include aferrite core1360 and acoil1362 wrapped around a portion of theferrite core1360. Thepulse system1310 can also include apulse delivery system1370 including a rectifier and a pulse former. In operation, theferrite core1360 and thecoil1362 convert the changes in the magnetic field generated by themagnetic coupler1350 into electrical pulses that are sent to thepulse delivery system1370. Theelectrodes660 are coupled to thepulse delivery system1370 so that electrical pulses corresponding to the electrical pulses generated by thepulse generator1330 in theexternal controller1310 are delivered to the stimulation site on the patient.
• 3. Electrode Configurations
• FIGS. 14-24 illustrate electrodes in accordance with various embodiments of the invention that can be used with the stimulation apparatus disclosed herein.FIGS. 14-22 illustrate embodiments of electrodes configured to apply an electrical current to a stimulation site at least proximate to the pial surface of the cortex, andFIGS. 23 and 24 illustrate embodiments of electrodes configured to apply an electrical current within the cortex or below the cortex. It will be appreciated that other configurations of electrodes can also be used with other implantable stimulation apparatus.
• FIG. 14 is a bottom plan view andFIG. 15 is a cross-sectional view of astimulation apparatus1400 in accordance with an embodiment of the invention. In this embodiment, thestimulation apparatus1400 includes afirst electrode1410 and asecond electrode1420 concentrically surrounding thefirst electrode1410. Thefirst electrode1410 can be coupled to the positive terminal of apulse generator1430, and thesecond electrode1420 can be coupled to the negative terminal of thepulse generator1430. Referring toFIG. 15, the first andsecond electrodes1410 and1420 generate a toroidalelectric field1440.
• FIG. 16 is a bottom plan view andFIG. 17 is a cross-sectional view of astimulation apparatus1600 in accordance with another embodiment of the invention. In this embodiment, thestimulation apparatus1600 includes afirst electrode1610, asecond electrode1620 surrounding thefirst electrode1610, and athird electrode1630 surrounding thesecond electrode1620. Thefirst electrode1610 can be coupled to the negative terminals of afirst pulse generator1640 and asecond pulse generator1642; thesecond electrode1620 can be coupled to the positive terminal of thefirst pulse generator1640; and thethird electrode1630 can be coupled to the positive terminal of thesecond pulse generator1642. In operation, thefirst electrode1610 and thethird electrode1630 generate a first toroidalelectric field1650, and the first electrode the1610 and thesecond electrode1620 generate a second toroidalelectric field1660. The second toroidalelectric field1660 can be manipulated to vary the depth that the first toroidalelectric field1650 projects away from the base of thestimulation apparatus1600.
• FIG. 18 is a bottom plan view andFIG. 19 is a cross-sectional view of astimulation apparatus1800 in accordance with yet another embodiment of the invention. In this embodiment, thestimulation apparatus1800 includes afirst electrode1810 and asecond electrode1820 spaced apart from thefirst electrode1810. The first andsecond electrodes1810 and1820 are linear electrodes which are coupled to opposite terminals of apulse generator1830. Referring toFIG. 19, the first andsecond electrodes1810 and1820 can generate an approximately linear electric field.
• FIG. 20 is a bottom plan view of astimulation apparatus2000 in accordance with still another embodiment of the invention. In this embodiment, thestimulation apparatus2000 includes afirst electrode2010, asecond electrode2020, athird electrode2030, and afourth electrode2040. The first andsecond electrodes2010 and2020 are coupled to afirst pulse generator2050, and the third andfourth electrodes2030 and2040 are coupled to asecond pulse generator2060. More specifically, thefirst electrode2010 is coupled to the positive terminal and thesecond electrode2020 is coupled to the negative terminal of thefirst pulse generator2050, and thethird electrode2030 is coupled to the positive terminal and thefourth electrode2040 is coupled to the negative terminal of thesecond pulse generator2060. The first andsecond electrodes2010 and2020 are expected to generate a firstelectric field2070, and the third andfourth electrodes2030 and2040 are expected to generate a secondelectric field2072. It will be appreciated that the ions will be relatively free to move through the brain such that a number of ions will cross between the first and secondelectric fields2070 and2072 as shown byarrows2074. This embodiment provides control of electric field gradients at the stimulation sites.
• FIG. 21 is a bottom plan view of another embodiment of thestimulation apparatus2000. In this embodiment, thefirst electrode2010 is coupled to the positive terminal and thesecond electrode2020 is coupled to the negative terminal of thefirst pulse generator2050. In contrast to the embodiment shown inFIG. 20, thethird electrode2030 is coupled to the negative terminal and thefourth electrode2040 is coupled to the positive terminal of thesecond pulse generator2070. It is expected that this electrode arrangement will result in a plurality of electric fields between the electrodes. This allows control of the direction or orientation of the electric field.
• FIG. 22 is a bottom plan view that schematically illustrates astimulation apparatus2200 in accordance with still another embodiment of the invention. In this embodiment, thestimulation apparatus2200 includes afirst electrode2210, asecond electrode2220, athird electrode2230, and afourth electrode2240. The electrodes are coupled to apulse generator2242 by aswitch circuit2250. Theswitch circuit2250 can include afirst switch2252 coupled to thefirst electrode2210, asecond switch2254 coupled to thesecond electrode2220, athird switch2256 coupled to thethird electrode2230, and afourth switch2258 coupled to thefourth electrode2240. In operation, the switches2252-2258 can be opened and closed to establish various electric fields between the electrodes2210-2240. For example, thefirst switch2252 and thefourth switch2258 can be closed in coordination with a pulse from thepulse generator2242 to generate a firstelectric field2260, and/or thesecond switch2254 and thethird switch2256 can be closed in coordination with another pulse from thepulse generator2242 to generate a secondelectric field2270. The first and secondelectric fields2260 and2270 can be generated at the same pulse to produce concurrent fields or alternating pulses to produce alternating or rotating fields.
• FIG. 23 is a bottom plan view andFIG. 24 is a side elevational view of astimulation apparatus2300 in accordance with another embodiment of the invention. In this embodiment, thestimulation apparatus2300 has afirst electrode2310, asecond electrode2320, athird electrode2330, and afourth electrode2340. The electrodes2310-2340 can be configured in any of the arrangements set forth above with reference toFIGS. 14-22. The electrodes2310-2340 also include electricallyconductive pins2350 and/or2360. Thepins2350 and2360 can be configured to extend below the pial surface of the cortex. For example, because the length of thepin2350 is less than the thickness of thecortex709, the tip of thepin2350 will accordingly conduct the electrical pulses to a stimulation site within thecortex709 below the pial surface. The length of thepin2360 is greater than the thickness of thecortex709 to conduct the electrical pulses to a portion of the brain below thecortex709, such as adeep brain region710. The lengths of the pins are selected to conduct the electrical pulses to stimulation sites below thepia mater708. As such, the length of thepins2350 and2360 can be the same for each electrode or different for individual electrodes. Additionally, only a selected portion of the electrodes and the pins can have an exposed conductive area. For example, the electrodes2310-2340 and a portion of thepins2350 and2360 can be covered with a dielectric material so that only exposed conductive material is at the tips of the pins. It will also be appreciated that the configurations of electrodes set forth inFIGS. 14-22 can be adapted to apply an electrical current to stimulation sites below the pia mater by providing pin-like electrodes in a matter similar to the electrodes shown inFIGS. 23 and 24.
• Several embodiments of the stimulation apparatus described above with reference toFIGS. 6-24 are expected to be more effective than existing transcranial or subcranial stimulation devices. In addition to positioning the electrodes under the skull, many embodiments of the stimulation apparatus described above also accurately focus the electrical energy in desired patterns relative to thepia mater708, thedura mater706, and/or thecortex709. It will be appreciated that transcranial devices may not accurately focus the energy because the electrodes or other types of energy emitters are positioned relatively far from the stimulation sites and the skull diffuses some of the energy. Also, existing subcranial devices generally merely place the electrodes proximate to a specific nerve, but they do not provide electrode configurations that generate an electrical field in a pattern designed for the stimulation site. Several of the embodiments of the stimulation apparatus described above with reference toFIGS. 6-24 overcome this drawback because the electrodes can be placed against the neurons at the desired stimulation site. Additionally, the electrode configurations of the stimulation apparatus can be configured to provide a desired electric field that is not diffused by theskull700. Therefore, several embodiments of the stimulation apparatus in accordance with the invention are expected to be more effective because they can accurately focus the energy at the stimulation site.
• 4. Implantable Stimulation Apparatus with Biasing Elements
• FIGS. 25-30 illustrate several embodiments of stimulation apparatus having a biasing element in accordance with a different aspect of the invention. The stimulation apparatus shown inFIGS. 25-30 can be similar to those described above with reference toFIGS. 6-24. Therefore, the embodiments of the stimulation apparatus shown inFIGS. 25-30 can have the same pulse systems, support members and electrode configurations described above with reference toFIGS. 6-24.
• FIG. 25 is an isometric view andFIG. 26 is a cross-sectional view of astimulation apparatus2500 in accordance with an embodiment of the invention. In one embodiment, thestimulation apparatus2500 includes asupport member2510, a pulse-system2530 carried by thesupport member2510, and first andsecond electrodes2560 coupled to thepulse system2530. Thesupport member2510 can be identical or similar to thesupport member610 described above with reference toFIGS. 6 and 7. Thesupport member2510 can accordingly include ahousing2512 configured to be implanted in theskull700 and anattachment element2514 configured to be connected to theskull700 by fasteners2518 (FIG. 2), an adhesive, and/or an anchor. Thepulse system2530 can be identical or similar to any of the pulse systems described above with reference toFIGS. 6-13, and the first andsecond electrodes2560 can have any of the electrode configurations explained above with reference toFIGS. 14-24. Unlike the stimulation apparatus described above, however, thestimulation apparatus2500 includes abiasing element2550 coupled to theelectrodes2560 to mechanically bias theelectrodes2560 away from thesupport member2510. In an alternative embodiment, thebiasing element2550 can be positioned between thehousing2512 and theattachment element2514, and theelectrodes2560 can be attached directly to thehousing2512. As explained in more detail below, thebiasing element2550 can be a compressible member, a fluid filled bladder, a spring, or any other suitable element that resiliently and/or elastically drives theelectrodes2560 away from thesupport member2510.
• FIG. 26 illustrates an embodiment of thestimulation apparatus2500 after it has been implanted into theskull700 of a patient. When thefasteners2518 are attached to theskull700, thebiasing element2550 should be compressed slightly so that theelectrodes2560 contact the stimulation site. In the embodiment shown inFIG. 26, thecompressed biasing element2550 gently presses theelectrodes2560 against the surface of thepia mater708. It is expected that thebiasing element2550 will provide a uniform, consistent contact between theelectrodes2560 and the pial surface of thecortex709. Thestimulation apparatus2500 is expected to be particularly useful when the implantable device is attached to the skull and the stimulation site is on thepia mater708 or thedura mater706. It can be difficult to position the contacts against thepia mater708 because the distance between theskull700, thedura mater706, and thepia mater708 varies within the cranium as the brain moves relative to the skull, and also as the depth varies from one patient to another. Thestimulation apparatus2500 with thebiasing element2550 compensates for the different distances between theskull700 and thepia mater708 so that a single type of device can inherently fit several different patients. Moreover, thestimulation apparatus2500 with thebiasing element2550 adapts to changes as the brain moves within the skull. In contrast to thestimulation apparatus2500 with thebiasing element2550, an implantable device that does not have abiasing element2550 may not fit a particular patient or may not consistently provide electrical contact to the pia mater.
• FIGS. 27 and 28 are cross-sectional views of stimulation apparatus in which the biasing elements are compressible members.FIG. 27, more specifically, illustrates astimulation apparatus2700 having abiasing element2750 in accordance with an embodiment of the invention. Thestimulation apparatus2700 can have an integratedpulse system2530 andelectrodes2560 coupled to thepulse system2530 in a manner similar to thestimulation apparatus2500. Thebiasing element2750 in this embodiment is a compressible foam, such as a biocompatible closed cell foam or open cell foam. As best shown inFIG. 27, thebiasing element2750 compresses when thestimulation apparatus2700 is attached to the skull.FIG. 28 illustrates astimulation apparatus2800 having abiasing element2850 in accordance with another embodiment of the invention. Thebiasing element2850 can be a compressible solid, such as silicon rubber or other suitable compressible materials. Theelectrodes2560 are attached to thebiasing element2850.
• FIG. 29 is a cross-sectional view of astimulation apparatus2900 having abiasing element2950 in accordance with another embodiment of the invention. Thestimulation apparatus2900 can have asupport member2910 including aninternal passageway2912 and adiaphragm2914. Thebiasing element2950 can include aflexible bladder2952 attached to thesupport member2910, and theelectrodes2560 can be attached to theflexible bladder2952. In operation, theflexible bladder2952 is filled with a fluid2954 until theelectrodes2560 press against the stimulation site. In one embodiment, theflexible bladder2952 is filled by inserting a needle of asyringe2956 through thediaphragm2914 and injecting the fluid2954 into theinternal passageway2912 and the flexible bladder.
• FIG. 30 is a cross-sectional view of astimulation apparatus3000 having abiasing element3050 in accordance with another embodiment of the invention. In this embodiment, thebiasing element3050 is a spring and theelectrodes2560 are attached to the spring. Thebiasing element3050 can be a wave spring, a leaf spring, or any other suitable spring that can mechanically bias theelectrodes2560 against the stimulation site.
• Although several embodiments of the stimulation apparatus shown inFIGS. 25-30 can have a biasing element and any of the pulse systems set forth above with respect toFIGS. 6-13, it is not necessary to have a pulse system contained within the support member. Therefore, certain embodiments of implantable stimulation apparatus in accordance with the invention can have a pulse system and/or a biasing member in any combination of the embodiments set forth above with respect toFIGS. 6-30.
• 5. Implantable Stimulation Apparatus with External Pulse Systems
• FIGS. 31-35 are schematic cross-sectional views of various embodiments of implantable stimulation apparatus having external pulse systems.FIG. 31, more specifically, illustrates an embodiment of astimulation apparatus3100 having abiasing element3150 to which a plurality ofelectrodes3160 are attached in a manner similar to the stimulation apparatus described above with reference toFIGS. 25-30. It will be appreciated that thestimulation apparatus3100 may not include thebiasing element3150. Thestimulation apparatus3100 can also include anexternal receptacle3120 having anelectrical socket3122 and an implantedlead line3124 coupling theelectrodes3160 to contacts (not shown) in thesocket3122. Thelead line3124 can be implanted in a subcutaneous tunnel or other passageway in a manner known to a person skilled and art.
• Thestimulation apparatus3100, however, does not have an internal pulse system carried by the portion of the device that is implanted in theskull700 of thepatient500. Thestimulation apparatus3100 receives electrical pulses from anexternal pulse system3130. Theexternal pulse system3130 can have anelectrical connector3132 with a plurality ofcontacts3134 configured to engage the contacts within thereceptacle3120. Theexternal pulse system3130 can also have a power supply, controller, pulse generator, and pulse transmitter to generate the electrical pulses. In operation, theexternal pulse system3130 sends electrical pulses to thestimulation apparatus3100 via theconnector3132, thereceptacle3120, and thelead line3124.
• FIGS. 32 and 33 illustrate an embodiment of astimulation apparatus3200 for use with an external pulse system in accordance with another embodiment of the invention. Referring toFIG. 33, thestimulation apparatus3200 can include asupport structure3210 having asocket3212, a plurality ofcontacts3214 arranged in thesocket3212, and adiaphragm3216 covering thesocket3212. Thestimulation apparatus3200 can also include abiasing element3250 and a plurality ofelectrodes3260 attached to thebiasing element3250. Eachelectrode3260 is directly coupled to one of thecontacts3214 within thesupport structure3210. It will be appreciated that an alternative embodiment of thestimulation apparatus3200 does not include thebiasing element3250.
• Referring toFIGS. 32 and 33 together, thestimulation apparatus3200 receives the electrical pulses from anexternal pulse system3230 that has a power supply, controller, pulse generator, and pulse transmitter. Theexternal pulse system3230 can also include aplug3232 having a needle3233 (FIG. 33) and a plurality of contacts3234 (FIG. 33) arranged on theneedle3233 to contact theinternal contacts3214 in thesocket3212. In operation, theneedle3233 is inserted into thesocket3212 to engage thecontacts3234 with thecontacts3214, and then thepulse system3230 is activated to transmit electrical pulses to theelectrodes3260.
• FIGS. 34 and 35 illustrate additional embodiments of stimulation apparatus for use with external pulse systems.FIG. 34 illustrates an embodiment of astimulation apparatus3400 havingelectrodes3410 coupled to alead line3420 that extends under thescalp702 of thepatient500. Thelead line3420 is coupled to anexternal pulse system3450.FIG. 35 illustrates an embodiment of astimulation apparatus3500 having asupport member3510,electrodes3512 coupled to thesupport member3510, and anexternal receptacle3520 mounted on thescalp702. Theexternal receptacle3520 can also be connected to thesupport member3510. Theexternal receptacle3520 can have asocket3522 with contacts (not shown) electrically coupled to theelectrodes3512. Thestimulation apparatus3500 can be used with theexternal pulse system3130 described above with reference toFIG. 31 by inserting theplug3132 into thesocket3522 until thecontacts3134 on theplug3132 engage the contacts within thesocket3522.
• 6. Alternate Embodiments of Implantable Stimulation Apparatus
• FIG. 36 is a schematic cross-sectional view of animplantable stimulation apparatus3600 in accordance with another embodiment of the invention. In one embodiment, thestimulation apparatus3600 has asupport structure3610 and a plurality ofelectrodes3620 coupled to thesupport structure3610. Thesupport structure3610 can be configured to be implanted under theskull700 between aninterior surface701 of theskull700 and the pial surface of the brain. Thesupport structure3610 can be a flexible or compressible body such that theelectrodes3620 contact thepia mater708 when thestimulation apparatus3600 is implanted under theskull700. In other embodiments, thesupport structure3610 can position theelectrodes3620 so that they are proximate to, but not touching, thepia mater708.
• In one embodiment, thestimulation apparatus3600 can receive electrical pulses from anexternal controller3630. For example, theexternal controller3630 can be electrically coupled to thestimulation apparatus3600 by alead line3632 that passes through ahole711 in theskull700. In an alternative embodiment, thestimulation apparatus3600 can include an integrated pulse system similar to the pulse systems described above with reference toFIGS. 6-13. Such an embodiment of thestimulation apparatus3600 can accordingly use a wireless external control unit. It will be appreciated that theelectrodes3620 of thestimulation apparatus3600 can have several of the electrode configurations described above with reference toFIGS. 14-24.
• FIGS. 37 and 38 illustrate one embodiment of theimplantable stimulation apparatus3600. Referring toFIG. 37, thesupport structure3610 can be a flexible substrate and theelectrodes3620 can be conductive elements that are printed onto the flexible substrate. Thestimulation apparatus3600, for example, can be manufactured in a manner similar to flexible printed circuit assemblies that are used in electrical components. Thestimulation apparatus3600 can be implanted under theskull700 using aninsertion tool3700. In one embodiment, theinsertion tool3700 has ahandle3702 and ashaft3704 projecting from thehandle3702. Theshaft3704 can have aslot3706 configured to receive a flat portion of thesupport member3610. Referring toFIG. 38, thesupport member3610 is wrapped around theshaft3704, and then thestimulation apparatus3600 is passed to atube3720 positioned in thehole711 through thescalp700 and thedura mater706. After thestimulation apparatus3600 has been passed through thetube3720, it is unfurled to place theelectrodes3620 at least proximate to thepia mater708. Theelectrodes3620 can be coupled to an external controller by the lead lines3632.
• FIG. 39 illustrates another embodiment of animplantable stimulation apparatus3900 that is also configured to be positioned between theskull700 and thepia mater708. In one embodiment, thestimulation apparatus3900 can include asupport member3910 and a plurality ofelectrodes3920 coupled to thesupport member3910. Theelectrodes3920 can be coupled toindividual lead lines3922 to connect theelectrodes3920 to an external pulse system. In an alternative embodiment, anintegrated pulse system3930 can be carried by thesupport member3910 so that theelectrodes3920 can be coupled directly to theintegrated pulse system3930 without external lead lines3922. Thesupport member3910 can be a resiliently compressible member, an inflatable balloon-like device, or a substantially solid incompressible body. In the particular embodiment shown inFIG. 39, thesupport member3910 is an inflatable balloon-like device that carries theelectrodes3920. In operation, thestimulation apparatus3900 is implanted by passing the distal end of thesupport member3910 through thehole711 in theskull700 until theelectrodes3920 are positioned at a desired stimulation site.
• FIG. 40 is a schematic illustration of a stimulation apparatus4000 together with an internal pulse system4030 in accordance with another embodiment of the invention. The stimulation apparatus4000 can include a support member4010, a biasing element4015 carried by the support member4010, and a plurality of electrodes4020 carried by the biasing element4015. The internal pulse system4030 can be similar to any of the integrated pulse systems described above with reference toFIGS. 6-13, but the internal pulse system4030 is not an integrated pulse system because it is not carried by the housing4010. The internal pulse system4030 can be coupled to the electrodes4020 by a cable4034. In a typical application, the cable4034 is implanted subcutaneously in a tunnel from a subclavicular region, along the back of the neck, and around the skull. The stimulation apparatus4000 can also include any of the electrode configurations described above with reference toFIGS. 14-24.
• FIG. 41A is a schematic view illustrating astimulation apparatus4100 suitable for performing thestimulation procedures106 described above with reference toFIGS. 5C and 5D. Thestimulation apparatus4100 includes ahousing4102 that is configured to be implanted in or otherwise attached to the patient. Thehousing4102, for example, can be any of the structures described above for being implanted in the patient's cranium or another area located above the patient's neck. In other embodiments, thehousing4102 can be configured to be implanted below the patient's neck, such as a subclavicular or abdominal location.
• Thestimulation apparatus4100 illustrated inFIG. 41A includes acontroller4110, apower supply4120, and a signal orpulse generator4130. Thepower supply4120 and thesignal generator4130 are coupled to thecontroller4110, and thesignal generator4130 is also coupled to thepower supply4120. Thestimulation apparatus4100 further includes a limitingmodule4112 that can be a component of thecontroller4110 or a separate standalone component. The limitingmodule4112 prevents stimulation signals generated by thesignal generator4130 from being provided to an electrode array after expiration of a therapy period. As explained above, the therapy period is the period of one or more therapy sessions that constitute a complete therapy treatment for effectuating recovery of a functional ability corresponding to an impaired neural function.
• The limitingmodule4112 provides a limited duration treatment that terminates operation of the signal general4130 or otherwise disconnects thesignal generator4130 from either thepower supply4120 or the electrode array. The limitingmodule4112 can be a hardware or software switch. In one embodiment, the limiting module causes thecontroller4110 to deactivate thesignal generator4130 so that thesignal generator4130 does not produce signals after expiration of the therapy period. The limitingmodule4112 can also be a hardware or software switch in thecontroller4110 that disconnects thepower supply4120 from thesignal generator4130. In another embodiment, the limitingmodule4112 can be a hardware or software switch that disconnects thesignal generator4130 from the electrode array.
• FIG. 41B is a schematic view illustrating particular examples of several embodiments of thestimulation apparatus4100. In this embodiment, the limiting module comprises one ormore switches4142,4144 and/or4146 that are operated by thecontroller4110. For example, the limiting module can include aswitch4142 between thepower supply4120 and thepulse generator4130. Thecontroller4110 opens theswitch4142 to disconnect thepower supply4120 from thepulse generator4130. In another embodiment, the limiting module can include aswitch4144 and/or aswitch4146 that disconnects thepulse generator4130 from the electrode array. In any of these embodiments, thecontroller4110 can operate these switches, or the switches can be operated by another mechanism that is either a component of thestimulation apparatus4100 or an external devices. For example, theswitches4142,4144, and/or4146 can be operated telemetrically by a magnetic source or an RF source external to the patient for manual operation of the limiting module.
• From the foregoing, it will be appreciated that specific embodiments of the invention have been described herein for purposes of illustration, but that various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.

Claims (40)

1. An apparatus for treating a neural function in a brain of a patient, comprising:

an electrode array having an electrical contact configured to deliver electrical stimulation to the brain; and

an implantable stimulus unit having a pulse generator for outputting electrical stimulation signals to the electrode array and a controller coupled to the pulse generator, wherein the controller includes a limiting module having a preset therapy period during which a plurality of discrete therapy sessions are to be performed for recovering a functional ability corresponding to the neural function, and wherein the limiting module is configured to disable the pulse generator from providing the stimulation signals to the electrode array after expiration of the therapy period.

2. The apparatus ofclaim 1 wherein the pulse generator includes circuitry that biases the electrical contact of the electrode array at a single polarity.

3. The apparatus ofclaim 1 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a therapy period selected from one of the group of not more than (a) one year, (b) three months, (c) one month, and (d) one week.

4. The apparatus ofclaim 1 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a limited number of therapy sessions.

5. The apparatus ofclaim 1 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a limited accumulated time of actual stimulation.

6. The apparatus ofclaim 1 wherein the limiting module comprises a hardware or software switch activated by the controller.

7. The apparatus ofclaim 1 wherein the limiting module is a computer operable medium containing instructions that cause the controller to deactivate the pulse generator at the expiration of the therapy period.

8. The apparatus ofclaim 1 wherein the limiting module comprises a switch between the pulse generator and the electrode array, and the switch is activated by the controller to electrically disconnect the electrode array from the pulse generator.

9. The apparatus ofclaim 1 wherein the limiting module comprises a switch coupled to the pulse generator and a power supply, and the switch is activated by the controller to disconnect the power supply from the pulse generator.

10. An apparatus for treating a neural function in a brain of a patient, comprising:

an electrode array having a support member configured to be implanted under the scalp of the patient and a plurality of electrical contacts carried by the support member; and

an implantable stimulus unit having a signal generator that outputs electrical stimulation signals to the electrode array and a limiting module that prevents the electrical stimulation signals from being provided to the electrode array after expiration of a therapy period for recovering functional ability corresponding to the impaired neural function, and wherein the signal generator includes instructions to output the stimulation signals at a level less than a threshold for the individual patient at which an electrical signal delivered via the implanted electrode directly triggers a reaction in neurons in response to the signal.

11. The apparatus ofclaim 10 wherein the signal generator includes circuitry that biases the plurality of electrical contacts carried by the support member at a single polarity.

12. The apparatus ofclaim 10 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a therapy period of not more than (a) one year, (b) three months, (c) one month, or (d) one week.

13. The apparatus ofclaim 10 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a limited number of therapy sessions.

14. The apparatus ofclaim 10 wherein the limiting module is configured to prevent the electrical stimulation from being provided to the electrode array after a limited accumulated time of actual stimulation.

15. The apparatus ofclaim 10 wherein (a) the stimulus unit further comprises a controller, and (b) the limiting module comprises a switch controlled by the controller.

16. The apparatus ofclaim 10 wherein the limiting module comprises a switch activated by a transponder external with respect to the patient.

17. The apparatus ofclaim 10 wherein (a) the stimulus unit further comprises a controller, and (b) the limiting module is a computer operable medium containing instructions that cause the controller to deactivate the signal generator.

18. The apparatus ofclaim 17 wherein the computer operable medium is hardware and/or software.

19. The apparatus ofclaim 10 wherein (a) the stimulus unit further comprises a controller, (b) the limiting module comprises a switch between the signal generator and the electrode array, and (c) the switch is activated by the controller to electrically disconnect the electrode array from the signal generator.

20. The apparatus ofclaim 10 wherein (a) the stimulus unit further comprises a controller, (b) the limiting module comprises a switch coupled to the signal generator and a power supply, and (c) the switch is activated by the controller to disconnect the power supply from the signal generator.

21. A method for treating a neural function in a brain of a patient, the method comprising:

determining a therapy period during which at least one therapy session is to be performed to recover and/or develop a functional ability corresponding to the neural function;

identifying a stimulation site in and/or on the brain of the patient associated with the neural function;

positioning an electrode at least proximate to the identified stimulation site;

providing at least one electrical stimulation treatment to the stimulation site by delivering electrical stimulation signals to the electrode during the therapy session, wherein the electrical stimulation is applied at a level less than a threshold for the individual patient at which an electrical signal delivered via the implanted electrode directly triggers a reaction in neurons in response to the signal; and

preventing the electrical stimulation signals from being delivered to the stimulation site after expiration of the therapy period.

22. The method ofclaim 21 wherein determining the therapy period comprises setting a limiting module to terminate stimulation after a period from approximately one day to not more than one year.

23. The method ofclaim 21 wherein determining the therapy period comprises setting a limiting module to terminate stimulation after a period from approximately one day to not more than one month.

24. The method ofclaim 21 wherein determining the therapy period comprises setting a limiting module to terminate stimulation after a period from approximately one day to not more than one week.

25. The method ofclaim 21 wherein preventing the electrical stimulation signals from being delivered to the stimulation site comprises setting the limiting module to terminate stimulation after a predetermined number of therapy sessions.

26. A method for stimulating neurons in a brain of a patient using an implanted electrode assembly having a contact positioned at least proximate to the cortex of the patient and an implanted signal generator electrically coupled to the contact, the method comprising:

performing an electrical stimulation session by generating an electrical stimulation waveform with the signal generator to apply an electrical current to the contact at a stimulation site proximate to a surface layer of the cortex, wherein the electrical stimulation is applied at a level less than a threshold for the individual patient at which an electrical signal delivered via the implanted electrode directly triggers a reaction in neurons in response to the signal;

repeating the electrical stimulation session at intervals throughout a therapy period; and

preventing the electrical stimulation from being delivered to the contact upon expiration of the therapy period by disabling the signal generator from generating electrical signals.

27. The method ofclaim 26, further comprising monitoring a characteristic of the patient influenced by the electrical stimulation, and determining whether the characteristic has maintained a desired level after a period of non-stimulation following preventing the electrical stimulation from being delivered to the contact.

28. The method ofclaim 27, further comprising restarting the electrical stimulation sessions when the characteristic has regressed after the period of non-stimulation.

29. The method ofclaim 27, further comprising having the patient engage in a behavioral therapy while applying an electrical current to the contact.

30. The method ofclaim 29 wherein having the patient engage in a behavioral therapy comprises the patient intentionally using a body part in a manner that reinforces the neural function.

31. The method ofclaim 30 wherein intentionally using a body part in a manner that reinforces the neural function comprises the patient intentionally moving a body part associated with the neural function.

32. The method ofclaim 30 wherein the patient has had a stroke affecting a hand, arm or leg of the patient, and wherein intentionally moving a body part associated with the neural function comprises the patient intentionally moving at the affected hand, arm or leg.

33. The method ofclaim 30 wherein the patient has had a stroke affecting speech, and wherein intentionally moving a body part associated with the neural function comprises the patient intentionally speaking.

34. A method for treating a neural function in a brain of a patient, the method comprising:

determining a therapy period during which at least one therapy session is to be performed to recover and/or develop a functional ability corresponding to the neural function;

identifying a stimulation site in and/or on the brain of the patient associated with the neural function by stimulating one or more brain locations to identify particular neural regions that induce or evoke a given type of patient response;

positioning an electrode at least proximate to the identified stimulation site;

providing at least one electrical stimulation treatment to the stimulation site by delivering electrical stimulation signals to the electrode during the therapy session; and

preventing the electrical stimulation signals from being delivered to the stimulation site after expiration of the therapy period.

35. The method ofclaim 34 wherein identifying the stimulation site comprises preoperatively stimulating the one or more brain locations before positioning the electrode at the stimulation site.

36. The method ofclaim 35 wherein preoperatively stimulating the one or more brain locations comprises transcutaneous magnetic stimulation.

37. The method ofclaim 34 wherein identifying the stimulation site comprises intraoperatively stimulating the one or more brain locations.

38. The method ofclaim 34, further comprising having the patient engage in a behavioral therapy while applying an electrical current to the contact.

39. The method ofclaim 38 wherein the electrical stimulation is delivered continuously during the therapy period.

40. The method ofclaim 38 wherein the electrical stimulation is delivered only while the patient engages in behavioral therapy.

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