Patent Publication Number: US-2010131030-A1

Title: Methods and apparatus for effectuating a change in a neural-function of a patient

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application is a continuation of prior application Ser. No. 12/343,427, filed Dec. 23, 2008, which is a continuation of prior application Ser. No. 10/912,815, filed Aug. 6, 2004, now abandoned, which is a continuation of prior application Ser. No. 10/072,700, filed Feb. 7, 2002, now U.S. Pat. No. 7,146,217, which is a continuation-in-part of prior application Ser. No. 09/802,808, filed Mar. 8, 2001, now U.S. Pat. No. 7,010,351, which claims the benefit of U.S. Provisional Application No. 60/217,981, filed Jul. 13, 2000, all of which are incorporated by reference herein in their entirety. 
    
    
     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 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 known to be controlled or are influenced by neural activity in particular regions of the brain. In some areas of the brain, such as in the sensory or motor cortices, the organization of the brain resembles a map of the human body; this is referred to as the “somatotopic organization of the brain.” There are several other areas of the brain that appear to have distinct functions that are located in specific regions of the brain in most individuals. For example, areas of the occipital lobes relate to vision, regions of the left inferior frontal lobes relate to language in the majority of people, and regions of the cerebral cortex appear to be consistently involved with conscious awareness, memory, and intellect. This type of location-specific functional organization of the brain, in which discrete locations of the brain are statistically likely to control particular mental or physical functions in, normal individuals, is herein referred to as the “functional organization of the brain.” 
     Many problems or abnormalities with body functions can be caused by damage, disease and/or disorders of the brain. A stroke, for example, is one very 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 cortex, which in turn generally causes a loss or impairment of a neural function (e.g., neural functions related to face muscles, limbs, speech, etc.). Stroke patients are typically treated using physical therapy to rehabilitate the loss of function of a limb or another affected body part. For most patients, little can be done to improve the function of the affected limb beyond the recovery that occurs naturally without intervention. One existing physical therapy technique for treating stroke patients constrains or restrains the use of a working body part of the patient to force the patient to use the affected body part. For example, the loss of use of a limb is treated by restraining the other limb. Although this type of physical therapy has shown some experimental efficacy, it is expensive, time-consuming and little-used. Stroke patients can also be treated using physical therapy plus adjunctive therapies. For example, some types of drugs, such as amphetamines, that increase the activation of neurons in general, appear to enhance neural networks; these drugs, however, have limited efficacy because they are very non-selective in their mechanisms of action and cannot be delivered in high concentrations directly at the site where they are needed. Therefore, there is a need to develop effective treatments for rehabilitating stroke patients and patients that have other types of brain damage. 
     Other brain disorders and diseases are also difficult to treat. Alzheimer&#39;s disease, for example, is known to affect portions of the cortex, but the cause of Alzheimer&#39;s disease and how it alters the neural activity in the cortex is not fully understood. Similarly, the neural activity of brain disorders (e.g., depression and obsessive-compulsive behavior) is also not fully understood. Therefore, there is also a need to develop more effective treatments for other brain disorders and diseases. 
     The neural activity in the brain can be influenced by electrical energy that is supplied from an external source outside of the body. Various neural functions can thus be promoted or disrupted by applying an electrical current to the cortex or other region of the brain. As a result, the quest for treating damage, disease and disorders in the brain have led to research directed toward using electricity or magnetism to control brain functions. 
     One type of treatment is transcranial electrical stimulation (TES), which involves placing an electrode on the exterior of the scalp and delivering an electrical current to the brain through the scalp and skull. Patents directed to TES include: U.S. Pat. No. 5,540,736 issued to Haimovich et al. (for providing analgesia); U.S. Pat. No. 4,140,133 issued to Katrubin et al. (for providing anesthesia); U.S. Pat. No. 4,646,744 issued to Capel (for treating drug addiction, appetite disorders, stress, insomnia and pain); and U.S. Pat. No. 4,844,075 issued to Liss et al. (for treating pain and motor dysfunction associated with cerebral palsy). TES, however, is not widely used because the patients experience a great amount of pain and the electrical field is difficult to direct or focus accurately. 
     Another type of treatment is transcranial magnetic stimulation (TMS), which involves producing a high-powered magnetic field adjacent to the exterior of the scalp over an area of the cortex. TMS does not cause the painful side effects of TES. Since 1985, TMS has been used primarily for research purposes in brain-mapping endeavors. Recently, however, potential therapeutic applications have been proposed primarily for the treatment of depression. A small number of clinical trials have found TMS to be effective in treating depression when used to stimulate the left prefrontal cortex. 
     The TMS treatment of a few other patient groups have been studied with promising results, such as patients with Parkinson&#39;s disease and hereditary spinocerebellar degeneration. Patents and published patent applications directed to TMS include: published international patent application WO 98/06342 (describing a transcranial magnetic stimulator and its use in brain mapping studies and in treating depression); U.S. Pat. No. 5,885,976 issued to Sandyk (describing the use of transcranial magnetic stimulation to treat a variety of disorders allegedly related to deficient serotonin neurotransmission and impaired pineal melatonin functions); and U.S. Pat. No. 5,092,835 issued to Schurig et al. (describing the treatment of neurological disorders (such as autism), treatment of learning disabilities, and augmentation of mental and physical abilities of “normal” people by a combination of transcranial magnetic stimulation and peripheral electrical stimulation). 
     Independent studies have also demonstrated that TMS is able to produce a lasting change in neural activity within the cortex that occurs for a period of time after terminating the TMS treatment (“neuroplasticity”). For example, Ziemann et al., Modulation of Plasticity in Human Motor Cortex after Forearm Ischemic Nerve Block, 18 J Neuroscience 1115 (February 1998), disclose that TMS at subthreshold levels (e.g., levels at which movement was not induced) in neuro-block models that mimic amputation was able to modify the lasting changes in neural activity that normally accompany amputation. Similarly, Pascual-Leone et al. (submitted for publication) disclose that applying TMS over the contralateral motor cortex in normal subjects who underwent immobilization of a hand in a cast for 5 days can prevent the decreased motor cortex excitability normally associated with immobilization. Other researchers have proposed that the ability of TMS to produce desired changes in the cortex may someday be harnessed to enhance neuro-rehabilitation after a brain injury, such as stroke, but there are no published studies to date. 
     Other publications related to TMS include Cohen et al., Studies of Neuroplasticity With Transcranial Magnetic Stimulation, 15 J. Clin. Neurophysiol. 305 (1998); Pascual-Leone et al., Transcranial Magnetic Stimulation and Neuroplasticity, 37 Neuropsychologia 207 (1999); Stefan et al., Induction of Plasticity in the Human Motor Cortex by Paired Associative Stimulation, 123 Brain 572 (2000); Sievner et al., Lasting Cortical Activation after repetitive TMS of the Motor Cortex, 54 Neurology 956 (February 2000); Pascual-Leone et al., Study and Modulation of Human Cortical Excitability With Transcranial Magnetic Stimulation, 15 J. Clin. Neurophysiol. 333 (1998); and Boylan et al., Magnetoelectric Brain Stimulation in the Assessment Of Brain Physiology And Pathophysiology, 111 Clin. Neurophysiology 504 (2000). 
     Although TMS appears to be able to produce a change in the underlying cortex beyond the time of actual stimulation, TMS is not presently effective for treating many patients because the existing delivery systems are not practical for applying stimulation over an adequate period of time. TMS systems, for example, are relatively complex and require stimulation treatments to be performed by a healthcare professional in a hospital or physician&#39;s office. TMS systems also may not be reliable for longer-term therapies because it is difficult to (a) accurately localize the region of stimulation in a reproducible manner, and (b) hold the device in the correct position over the cranium for a long period, especially when a patient moves or during rehabilitation. Furthermore, current TMS systems generally do not sufficiently focus the electromagnetic energy on the desired region of the cortex for many applications. As such, the potential therapeutic benefit of TMS using existing equipment is relatively limited. 
     Direct and indirect electrical stimulation of the central nervous system has also been proposed to treat a variety of disorders and conditions. For example, U.S. Pat. No. 5,938,688 issued to Schiff notes that the phenomenon of neuroplasticity may be harnessed and enhanced to treat cognitive disorders related to brain injuries caused by trauma or stroke. Schiff&#39;s implant is designed to increase the level of arousal of a comatose patient by stimulating deep brain centers involved in consciousness. To do this, Schiff&#39;s invention involves electrically stimulating at least a portion of the patient&#39;s intralaminar nuclei (i.e., the deep brain) using, e.g., an implantable multipolar electrode and either an implantable pulse generator or an external radiofrequency controlled pulse generator. Schiff&#39;s deep brain implant is highly invasive, however, and could involve serious complications for the patient. 
     Likewise, U.S. Pat. No. 6,066,163 issued to John acknowledges the ability of the brain to overcome some of the results of an injury through neuroplasticity. John also cites a series of articles as evidence that direct electrical stimulation of the brain can reverse the effects of a traumatic injury or stroke on the level of consciousness. The system disclosed in John stimulates the patient and modifies the parameters of stimulation based upon the outcome of comparing the patient&#39;s present state with a reference state in an effort to optimize the results. Like Schiff, however, the invention disclosed in John is directed to a highly invasive deep brain stimulation system. 
     Another device for stimulating a region of the brain is disclosed by King in U.S. Pat. No. 5,713,922. King discloses a device for cortical surface stimulation having electrodes mounted on a paddle implanted under the skull of the patient. The electrodes are implanted on the surface of the brain in a fixed position. The electrodes in King accordingly cannot move to accommodate changes in the shape of the brain. King also discloses that the electrical pulses are generated by a pulse generator that is implanted in the patient remotely from the cranium (e.g., subclavicular implantation). The pulse generator is not directly connected to the electrodes, but rather it is electrically coupled to the electrodes by a cable that extends from the remotely implanted pulse generator to the electrodes implanted in the cranium. The cable disclosed in King extends from the paddle, around the skull, and down the neck to the subclavicular location of the pulse generator. 
     King discloses implanting the electrodes in contact with the surface of the cortex to create paresthesia, which is a sensation of vibration or “buzzing” in a patient. More specifically, King discloses inducing paresthesia in large areas by applying electrical stimulation to a higher element of the central nervous system (e.g., the cortex). As such, King discloses placing the electrodes against particular regions of the brain to induce the desired paresthesia. The purpose of creating paresthesia over a body region is to create a distracting stimulus that effectively reduces perception of pain in the body region. Thus, King appears to require stimulation above activation levels. 
     Although King discloses a device that stimulates a region on the cortical surface, this device is expected to have several drawbacks. First, it is expensive and time-consuming to implant the pulse generator and the cable in the patient. Second, it appears that the electrodes are held at a fixed elevation that does not compensate for anatomical changes in the shape of the brain relative to the skull, which makes it difficult to accurately apply an electrical stimulation to a desired target site of the cortex in a focused, specific manner. Third, King discloses directly activating the neurons to cause paresthesia, which is not expected to cause entrainment of the activity in the stimulated population of neurons with other forms of therapy or adaptive behavior, such as physical or occupational therapy. Thus, King is expected to have several drawbacks. 
     King and the other foregoing references are also expected to, have drawbacks in producing the desired neural activity because these references generally apply the therapy to the region of the brain that is responsible for the physiological function or mental process according to the functional organization of the brain. In the case of a brain injury or disease, however, the region of the brain associated with the affected physiological function or cognitive process may not respond to stimulation therapies. Thus, existing techniques may not produce adequate results that last beyond the stimulation period. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1A  is a schematic view 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 associated with a location in the brain in accordance with one embodiment of the invention. 
         FIG. 2  is a top plan view 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 of  FIG. 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. 
         FIG. 4A  is a flow chart illustrating a method  100   a  for effectuating a neural-function by stimulating a specific anatomic location in accordance with an embodiment of the invention.  FIG. 4B  is a table illustrating a first list containing a plurality of conditions that affect physical and/or cognitive functions, and a second list containing a plurality of anatomic locations where neural-activity is suspected to occur for carrying out the particular functions. 
         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. 
         FIG. 5C  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 and  FIG. 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 and 
         FIG. 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 and 
         FIG. 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 and 
         FIG. 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 of  FIG. 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 and 
         FIG. 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. 
     
    
    
     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 in accordance with the invention 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 regained 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. 
     Electrically enhanced or induced neural stimulation in accordance with several embodiments of the invention excites a portion of a neural network involved in 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 are caused by interactions with other neurons in the network. Several aspects of the electrical stimulation in accordance with selected embodiments of the invention simply allows this to happen with an increased probability when the network is activated by favorable activities, such as rehabilitation or limb use. 
     The methods in accordance with the invention can be used to treat brain damage (e.g., stroke, trauma, etc.), brain disease (e.g., Alzheimer&#39;s, Pick&#39;s, Parkinson&#39;s, etc.), and/or brain disorders (e.g., epilepsy, depression, etc.). The 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 or is not detected using imaging techniques, 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 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 in  FIGS. 1A-40  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 to  FIGS. 1-5C , and then several embodiments of devices for stimulating the cortical and/or deep-brain regions of the brain are described with reference to  FIGS. 6-40 . 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 N 1 -N 3  and  FIG. 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 N 1  can send excitatory inputs to neuron N 2  (e.g., times t 1 , t 3  and t 4  in  FIG. 1B ), and neuron N 3  can send inhibitory inputs to neuron N 2  (e.g., time t 2  in  FIG. 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 in  FIG. 1B , the excitatory input at time t 5  causes neuron N 2  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 a method  100  for 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 or sensory function (e.g., movement of a limb) 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 the method  100 , 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 be at the normal location where neural activity typically occurs to carry out the neural-function according to the functional organization of the brain, 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 the method  100  is to determine the location in the brain where this neural activity is present. 
     The method  100  includes a diagnostic procedure  102  involving identifying a stimulation site at a location of the brain where an intended neural activity related to the neural-function is present. In one embodiment, the diagnostic procedure  102  includes generating the 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, the diagnostic procedure  102  can be performed by identifying a stimulation site where neural activity has changed in response to a change in the neural-function. The method  100  continues with an implanting procedure  104  involving positioning first and second electrodes at the identified stimulation site, and a stimulating procedure  106  involving applying an electrical current between the first and second electrodes. Many embodiments of the implanting procedure  104  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 implanting procedure  104  of the method  100  can include implanting at least one electrode at the stimulation site. The procedures  102 - 106  are described in greater detail below. 
       FIGS. 2-4  illustrate an embodiment of the diagnostic procedure  102 . The diagnostic procedure  102  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 brain  200  having a first region  210  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 the first region  210  shown in  FIG. 2  is generally associated with the movement of a patient&#39;s fingers. The first region  210  can have a high-intensity area  212  and a low-intensity area  214  in which different levels of neural activity occur. It is not necessary to obtain an image of the neural activity in the first region  210  shown in  FIG. 2  to carry out the diagnostic procedure  102 , 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 the brain  200  for a large percentage of people with normal brain function. It will be appreciated that the actual location of the first region  210  will generally vary between individual patients. 
     The neural activity in the first region  210 , however, can be impaired. In a typical application, the diagnostic procedure  102  begins by taking an image of the brain  200  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 the brain  200  where it normally occurs according to the functional organization of the brain.  FIG. 3  is an image of the brain  200  after the first region  210  has been affected (e.g., from a stroke, trauma or other cause). As shown in  FIG. 3 , the neural activity that controlled the neural-function for moving the fingers no longer occurs in the first region  210 . The first region  210  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 the brain  200  may result in only a partial loss of the neural activity in the damaged region. In either case, the image shown in  FIG. 3  establishes that the loss of the neural-function is related to the diminished neural activity in the first region  210 . The brain  200  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 the brain  200  illustrating a plurality of potential stimulation sites  220  and  230  for effectuating the neural-function that was originally performed in the first region  210  shown in  FIG. 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. The diagnostic procedure  102  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 the diagnostic procedure  102  involves generating the intended neural activity remotely from the first region  210  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 a 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., sites  220  and  230 ) to perform the intended neural activity associated with the neural-function. 
     An alternative embodiment of the diagnostic procedure  102  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, the diagnostic procedure  102  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 the diagnostic procedure  102 , 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 implanting procedure  104  described above with reference to  FIG. 1C  for positioning the first and second electrodes relative to a portion of the brain of a patient  500 . Referring to  FIG. 5A , a stimulation site  502  is identified in accordance with an embodiment of the diagnostic procedure  102 . In one embodiment, a skull section  504  is removed from the patient  500  adjacent to the stimulation site  502 . The skull section  504  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 to  FIG. 5B , an implantable stimulation apparatus  510  having first and second electrodes  520  can be implanted in the patient  500 . Suitable techniques associated with the implantation procedure are known to practitioners skilled in the art. After the stimulation apparatus  510  has been implanted in the patient  500 , a pulse system generates electrical pulses that are transmitted to the stimulation site  502  by the first and second electrodes  520 . 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 the  FIGS. 6-40 . 
     Several embodiments of methods for enhancing neural activity in accordance with the invention are expected to provide results that create, promote or prolong the desired neural-function even after terminating the stimulation. 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 be effective because the 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. Several other embodiments of the invention create, promote, or prolong neuroplastic activity by selecting a stimulation site based on a specific anatomic location where neuroplasticity is suspected of occurring or is expected to occur to carry out a particular function. By first identifying or selecting a location in the brain that is being recruited or is suspected of 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 results that last for a period of time after terminating the stimulation 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. 
     2. Electrically Inducing Desired Neural Activity 
     The method  100  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 the method  100  described above for enhancing existing neural activity, the embodiments of the method  100  for inducing neural activity initiate the neural activity at a stimulation site where neuroplasticity is expected to occur. In this particular situation, an image of the brain seeking to locate neuroplasticity may be similar to  FIG. 3 . An aspect of inducing neural activity, therefore, is to develop a procedure to determine where neuroplasticity is likely to occur for carrying out a specific function. 
     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. Inducing or Enhancing Neuroplasticity Based on Specific Anatomic Locations 
     Another aspect of the present invention is to induce or enhance neuroplasticity at specific anatomic locations for carrying out particular functions. Many of the foregoing methods described above determine the stimulation site by imaging the brain to locate regions where neuroplasticity is occurring, but it may also be desirable to select the stimulation site according to a specific anatomic location either with or without imaging. Accordingly, several additional embodiments of methods in accordance with the invention define a specific anatomic region for inducing or enhancing neuroplasticity to carry out a desired function. 
       FIG. 4A  is a flow chart illustrating a method  100   a  for effectuating a neural-function by stimulating a specific anatomic location in accordance with an embodiment of the invention. In this embodiment, the method  100   a  comprises a selecting procedure  112   a,  a positioning procedure  114   a,  and an activating or stimulating procedure  116   a.  The selecting procedure  112   a  includes selecting a site at an anatomical feature of the cortex where a desired neural-activity is suspected of occurring or is expected to begin occurring. The stimulation site, for example, can be an anatomical feature where new neural-activity is expected to carry out a particular physical function and/or cognitive function of the patient. The particular cognitive or physical function may have been altered by damage or disease, or the particular function may be altered in the sense that it has changed to improve an unimpaired function (e.g., learning a skill). The positioning procedure  114   a  can include positioning one or more electrodes at the selected anatomical feature, and the activating procedure  116   a  can include applying an electrical potential to the electrodes. 
     The embodiment of the method  100   a  described above can be used even without directly testing for the presence of neuroplasticity using functional MRI or other imaging techniques. This particular method is premised upon the finding that regions of neuroplasticity associated with carrying out specific functions can be expected to occur at particular anatomic locations in the brain. For example, specific regions of the cortex are likely to be sites where neuroplasticity occurs in response to particular types of brain damage or disorders. A region of neuroplasticity in the brain can be a location that is suspected or proven to be undergoing a sequence of biochemical, electrophysiological, structural, and cellular changes that produce a lasting change in neural-activity for carrying out a mental or physical function. The lasting change may be any period after terminating the activating procedure  116   a,  such as a few seconds or as long as the life of the patient. The selecting procedure  112   a  is unique in that it specifically targets a particular anatomic location as a region of neuroplasticity for carrying out a specific function. 
     The selecting procedure  112   a  can be performed by providing a first listing containing a plurality of physical and/or cognitive conditions, and a second listing containing a plurality of neural-sites in the cortex where neural-activity is suspected to change for carrying out particular functions. In this embodiment, the stimulation site can be selected by identifying a physical and/or cognitive condition in the first listing that correlates to a condition of the patient, and then determining a corresponding neural-site in the cortex of the patient using the second listing. This embodiment of the selecting procedure  112   a  is expected to be particularly useful for treating specific conditions that involve particular types of brain damage or disorders. 
       FIG. 4B  is a table illustrating a first list containing a plurality of conditions that affect physical and/or cognitive functions, and a second list containing a plurality of anatomic locations where neural-activity is suspected to occur for carrying out the particular functions. For example, if a patient has experienced a stroke at the primary motor cortex in the frontal lobe, the stimulation site where neuroplasticity is suspected to be occurring, or expected to occur in the future, is in the pre-motor cortex and/or the supplementary motor cortex anterior to the stroke in the frontal lobe. In another particular embodiment of the method  100   a  for treating expressive language disorders, the stimulation site is located at Broca&#39;s area of the inferior frontal lobe of the cortex. In still another embodiment of the method  100   a  for treating language comprehension disorders, the stimulation site is located at Wernick&#39;s area of the parietal lobe of the cortex. Referring to  FIG. 4B  still, the method  100   a  can also be practiced for treating learning and memory disorders by selecting a stimulation site at the medial temporal lobe of the cortex. Additionally, another embodiment of the method  100   a  includes treating mood disorders by selecting a stimulation site at a limbic system component. 
     It will be appreciated that the foregoing specific embodiments of the method  100   a  provide a few examples of the particular anatomic locations where the electrodes may be positioned. The method  100   a  is not limited to the foregoing embodiments, but rather other anatomical locations can be stimulated for treating other conditions in accordance with this method. For example, the selecting procedure  112   a  can alternatively be performed by choosing a stimulation site adjacent to a damaged region of the cortex where neural-activity for carrying out the altered function was performed before the cortex was damaged. 
     4. 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 the method  100  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 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 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 techniques as explained above with respect to  FIG. 3 . A stimulation site can then be identified by: (a) 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; (b) determining where the neural activity has changed as a patient gains more use of the affected body part; and/or (c) estimating the location that the brain may recruit neurons to carry out the neural activity that was previously performed by the damaged portion of the brain. An electrical stimulation therapy can then be applied to the selected stimulation site by placing the first and second electrodes relative to the stimulation site to apply an electrical current in 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 neurological effect for rehabilitating the affected body part beyond the time period of the stimulation. 
     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 to  FIGS. 6-40 . 
     The electrical stimulation methods can also be used with adjunctive therapies to rehabilitate damaged portions of the brain. In one embodiment, the electrical stimulation methods can be combined with physical therapy and/or drug therapies to rehabilitate an affected neural function. For example, if a stroke patient has lost the use of a limb, the patient can be treated by applying the electrical therapy to a stimulation site where the intended neural activity is present while the affected limb is also subject to physical therapy. An alternative embodiment can involve applying the electrical therapy to the stimulation site and chemically treating the patient using amphetamines or other suitable drugs. 
     The embodiments of the electrical stimulation methods described above are also expected to be useful for treating brain diseases, such as Alzheimer&#39;s, Parkinson&#39;s, and other brain diseases. In this application, the 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 the 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. 
     The 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 .mu.s. 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. 5C  is a graph illustrating applying a subthreshold potential to the neurons N 1 -N 3  of  FIG. 1A . At times t 1  and t 2 , 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 t 3 , 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 t 4  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&#39;s hand, electrical stimulation is not initially applied to the stimulation site. Although physical therapy related to the patient&#39;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 to  FIGS. 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 in  FIGS. 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 and  FIG. 7  is a cross-sectional view of a stimulation apparatus  600  in accordance with an embodiment of the invention for stimulating a region of the cortex proximate to the pial surface. In one embodiment, the stimulation apparatus  600  includes a support member  610 , an integrated pulse-system  630  (shown schematically) carried by the support member  610 , and first and second electrodes  660  (identified individually by reference numbers  660   a  and  660   b ). The first and second electrodes  660  are electrically coupled to the pulse system  630 . The support member  610  can be configured to be implanted into the skull or another intracranial region of a patient. In one embodiment, for example, the support member  610  includes a housing  612  and an attachment element  614  connected to the housing  612 . The housing  612  can be a molded casing formed from a biocompatible material that has an interior cavity for carrying the pulse system  630 . The housing can alternatively be a biocompatible metal or another suitable material. The housing  612  can have a diameter of approximately 1-4 cm, and in many applications the housing  612  can be 1.5-2.5 cm in diameter. The housing  612  can also have other shapes (e.g., rectilinear, oval, elliptical) and other surface dimensions. The stimulation apparatus  600  can weigh 35 g or less and/or occupy a volume of 20 cc or less. The attachment element  614  can be a flexible cover, a rigid plate, a contoured cap, or another suitable element for holding the support member  610  relative to the skull or other body part of the patient. In one embodiment, the attachment element  614  is a mesh, such as a biocompatible polymeric mesh, metal mesh, or other suitable woven material. The attachment element  614  can alternatively be a flexible sheet of Mylar, a polyester, or another suitable material. 
       FIG. 7 , more specifically, is a cross-sectional view of the stimulation apparatus  600  after it has been implanted into a patient in accordance with an embodiment of the invention. In this particular embodiment, the stimulation apparatus  600  is implanted into the patient by forming an opening in the scalp  702  and cutting a hole  704  through the skull  700  and through the dura mater  706 . The hole  704  should be sized to receive the housing  612  of the support member  610 , and in most applications, the hole  704  should be smaller than the attachment element  614 . A practitioner inserts the support member  610  into the hole  704  and then secures the attachment element  614  to the skull  700 . The attachment element  614  can be secured to the skull using a plurality of fasteners  618  (e.g., screws, spikes, etc.) or an adhesive. In an alternative embodiment, a plurality of downwardly depending spikes can be formed integrally with the attachment element  614  to define anchors that can be driven into the skull  700 . 
     The embodiment of the stimulation apparatus  600  shown in  FIG. 7  is configured to be implanted into a patient so that the electrodes  660  contact a desired portion of the brain at the stimulation site. The housing  612  and the electrodes  660  can project from the attachment element  614  by a distance “D” such that the electrodes  660  are positioned at least proximate to the pia mater  708  surrounding the cortex  709 . The electrodes  660  can project from a housing  612  as shown in  FIG. 7 , or the electrodes  660  can be flush with the interior surface of the housing  612 . In the particular embodiment shown in  FIG. 7 , the housing  612  has a thickness “T” and the electrodes  660  project from the housing  612  by a distance “P” so that the electrodes  660  press against the surface of the pia mater  708 . The thickness of the housing  612  can be approximately 0.5-4 cm, and is more generally about 1-2 cm. The configuration of the stimulation apparatus  600  is not limited to the embodiment shown in  FIGS. 6 and 7 , but rather the housing  612 , the attachment element  614 , and the electrodes  660  can be configured to position the electrodes in several different regions of the brain. For example, in an alternate embodiment, the housing  612  and the electrodes  660  can be configured to position the electrodes deep within the cortex  709 , and/or a deep brain region  710 . 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 the stimulation apparatus  600  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, the stimulation apparatus  600  is implanted so that the electrodes are at least proximate to the pial surface of the brain  708 . Several embodiments of methods in accordance with the invention can use the stimulation apparatus  600  to apply an electrical therapy directly to the pia mater  708 , the dura mater  706 , and/or another portion of the cortex  709  at significantly lower power levels than existing transcranial therapies. For example, a potential of approximately 1 mV to 10 V can be applied to the electrodes  660 ; in many instances a potential of 100 mV to 5 V can be applied to the electrodes  660  for selected applications. It will also be appreciated that other potentials can be applied to the electrodes  660  of the stimulation apparatus  600  in accordance with other embodiments of the invention. 
     Selected embodiments of the stimulation apparatus  600  are also capable of applying stimulation to a precise stimulation site. Again, because the stimulation apparatus  600  positions the electrodes  660  at least proximate to the pial surface  708 , 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 the stimulation apparatus  600  overcome this drawback because the electrodes  660  are positioned under the skull  700  such that the pulses generated by the stimulation apparatus  600  are not diffused by the scalp  702  and skull  700 . 
     2. Integrated Pulse Systems for Implantable Stimulation Apparatus 
     The pulse system  630  shown in  FIGS. 6 and 7  generates and/or transmits electrical pulses to the electrodes  660  to create an electrical field at a stimulation site in a region of the brain. The particular embodiment of the pulse system  630  shown in  FIG. 7  is an “integrated” unit in that is carried by the support member  610 . The pulse system  630 , for example, can be housed within the housing  612  so that the electrodes  660  can be connected directly to the pulse system  630  without having leads outside of the stimulation apparatus  600 . The distance between the electrodes  660  and the pulse system  630  can be less than 4 cm, and it is generally 0.10 to 2.0 cm. The stimulation apparatus  600  can accordingly provide electrical pulses to the stimulation site without having to surgically create tunnels running through the patient to connect the electrodes  660  to a pulse generator implanted remotely from the stimulation apparatus  600 . It will be appreciated, however, that alternative embodiments of stimulation apparatus in accordance with the invention can include a pulse system implanted separately from the stimulation apparatus  600  in the cranium or an external pulse system. Several particular embodiments of pulse systems that are suitable for use with the stimulation apparatus  600  will now be described in more detail. 
       FIGS. 8 and 9  schematically illustrate an integrated pulse system  800  in accordance with one embodiment of the invention for being implanted in the cranium within the stimulation apparatus  600 . Referring to  FIG. 8 , the pulse system  800  can include a power supply  810 , an integrated controller  820 , a pulse generator  830 , and a pulse transmitter  840 . The power supply  810  can be a primary battery, such as a rechargeable battery or another suitable device for storing electrical energy. In alternative embodiments, the power supply  810  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 the pulse system  800 . The integrated controller  820  can be a wireless device that responds to command signals sent by an external controller  850 . The integrated controller  820 , for example, can communicate with the external controller  850  by RF or magnetic links  860 . The integrated controller  820  provides control signals to the pulse generator  830  in response to the command signals sent by the external controller  850 . The pulse generator  830  can have a plurality of channels that send appropriate electrical pulses to the pulse transmitter  840 , which is coupled to the electrodes  660 . Suitable components for the power supply  810 , the integrated controller  820 , the pulse generator  830 , and the pulse transmitter  840  are known to persons skilled in the art of implantable medical devices. 
     Referring to  FIG. 9 , the pulse system  800  can be carried by the support member  610  of the stimulation apparatus  600  in the manner described above with reference to  FIGS. 6 and 7 . The external controller  850  can be located externally to the patient  500  so that the external controller  850  can be used to control the pulse system  800 . In one embodiment, several patients that require a common treatment can be simultaneously treated using a single external controller  850  by positioning the patients within the operating proximity of the controller  850 . In an alternative embodiment, the external controller  850  can contain a plurality of operating codes and the integrated controller  820  for a particular patient can have an individual operating code. A single controller  850  can thus be used to treat a plurality of different patients by entering the appropriate operating code into the controller  850  corresponding to the particular operating codes of the integrated controllers  820  for the patients. 
       FIG. 10  is a schematic view illustrating a pulse system  1000  and an external controller  1010  for use with the stimulation apparatus  600  in accordance with another embodiment of the invention. In this embodiment, the external controller  1010  includes a power supply  1020 , a controller  1022  coupled to the power supply  1020 , and a user interface  1024  coupled to the controller  1022 . The external controller  1010  can also include a pulse generator  1030  coupled to the power supply  1020 , a pulse transmitter  1040  coupled to the pulse generator  1030 , and an antenna  1042  coupled to the pulse transmitter  1040 . The external controller  1010  generates the power and the pulse signal, and the antenna  1042  transmits a pulse signal  1044  to the pulse system  1000  in the stimulation apparatus  600 . The pulse system  1000  receives the pulse signal  1044  and delivers an electrical pulse to the electrodes. The pulse system  1000 , therefore, does not necessarily include an integrated power supply, controller and pulse generator within the housing  610  because these components are in the external controller  1010 . 
       FIG. 11  is a schematic view illustrating an embodiment of the pulse system  1000  in greater detail. In this embodiment, the pulse system  1000  is carried by the support member  610  of the stimulation apparatus  600 . The pulse system  1000  can include an antenna  1060  and a pulse delivery system  1070  coupled to the antenna  1060 . The antenna  1060  receives the pulse signal  1044  from the external controller  1010  and sends the pulse signal  1044  to the pulse delivery system  1070 , which transforms the pulse signal  1044  into electrical pulses. Accordingly, the electrodes  660  can be coupled to the pulse delivery system  1070 . The pulse delivery system  1070  can include a filter to remove noise from the pulse signal  1044  and a pulse former that creates an electrical pulse from the pulse signal  1044 . The pulse former can be driven by the energy in the pulse signal  1044 , or in an alternative embodiment, the pulse system  1000  can also include an integrated power supply to drive the pulse former. 
       FIG. 12  is a schematic view illustrating an embodiment of pulse system  1200  for use in an embodiment of the stimulation apparatus  600 , and an external controller  1210  for controlling the pulse system  1200  remotely from the patient using RF energy. In this embodiment, the external controller  1210  includes a power supply  1220 , a controller  1222  coupled to the power supply  1220 , and a pulse generator  1230  coupled to the controller  1222 . The external controller  1210  can also include a modulator  1232  coupled to the pulse generator  1230  and an RF generator  1234  coupled to the modulator  1232 . In operation, the external controller  1210  broadcasts pulses of RF energy via an antenna  1242 . 
     The pulse system  1200  can be housed within the stimulation apparatus  600  (not shown). In one embodiment, the pulse system  1200  includes an antenna  1260  and a pulse delivery system  1270 . The antenna  1260  incorporates a diode (not shown) that rectifies the broadcast RF energy from the antenna  1242 . The pulse delivery system  1270  can include a filter  1272  and a pulse former  1274  that forms electrical pulses which correspond to the RE energy broadcast from the antenna  1242 . The pulse system  1200  is accordingly powered by the RF energy in the pulse signal from the external controller  1210  such that the pulse system  1200  does not need a separate power supply carried by the stimulation apparatus  600 . 
       FIG. 13  is a cross-sectional view of a pulse system  1300  for use in another embodiment of the implantable stimulation apparatus  600 , together with an external controller  1310  for remotely controlling the pulse system  1300  externally from the patient using magnetic energy. In this embodiment, the external controller  1310  includes a power supply  1320 , a controller  1322  coupled to the power supply  1320 , and a user interface  1324  coupled to the controller  1322 . The external controller  1310  can also include a pulse generator  1330  coupled to the controller  1332 , a pulse transmitter  1340  coupled to the pulse generator  1330 , and a magnetic coupler  1350  coupled to the pulse transmitter  1340 . The magnetic coupler  1350  can include a ferrite core  1352  and a coil  1354  wrapped around a portion of the ferrite core  1352 . The coil  1354  can also be electrically connected to the pulse transmitter  1340  so that electrical pulses applied to the coil  1354  generate changes in a corresponding magnetic field. The magnetic coupler  1350  can also include a flexible cap  1356  to position the magnetic coupler  1350  over the implanted stimulation apparatus  600 . 
     The pulse system  1300  can include a ferrite core  1360  and a coil  1362  wrapped around a portion of the ferrite core  1360 . The pulse system  1310  can also include a pulse delivery system  1370  including a rectifier and a pulse former. In operation, the ferrite core  1360  and the coil  1362  convert the changes in the magnetic field generated by the magnetic coupler  1350  into electrical pulses that are sent to the pulse delivery system  1370 . The electrodes  660  are coupled to the pulse delivery system  1370  so that electrical pulses corresponding to the electrical pulses generated by the pulse generator  1330  in the external controller  1310  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, and  FIGS. 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 and  FIG. 15  is a cross-sectional view of a stimulation apparatus  1400  in accordance with an embodiment of the invention. In this embodiment, the stimulation apparatus  1400  includes a first electrode  1410  and a second electrode  1420  concentrically surrounding the first electrode  1410 . The first electrode  1410  can be coupled to the positive terminal of a pulse generator  1430 , and the second electrode  1420  can be coupled to the negative terminal of the pulse generator  1430 . Referring to  FIG. 15 , the first and second electrodes  1410  and  1420  generate a toroidal electric field  1440 . 
       FIG. 16  is a bottom plan view and  FIG. 17  is a cross-sectional view of a stimulation apparatus  1600  in accordance with another embodiment of the invention. In this embodiment, the stimulation apparatus  1600  includes a first electrode  1610 , a second electrode  1620  surrounding the first electrode  1610 , and a third electrode  1630  surrounding the second electrode  1620 . The first electrode  1610  can be coupled to the negative terminals of a first pulse generator  1640  and a second pulse generator  1642 ; the second electrode  1620  can be coupled to the positive terminal of the first pulse generator  1640 ; and the third electrode  1630  can be coupled to the positive terminal of the second pulse generator  1642 . In operation, the first electrode  1610  and the third electrode  1630  generate a first toroidal electric field  1650 , and the first electrode the  1610  and the second electrode  1620  generate a second toroidal electric field  1660 . The second toroidal electric field  1660  can be manipulated to vary the depth that the first toroidal electric field  1650  projects away from the base of the stimulation apparatus  1600 . 
       FIG. 18  is a bottom plan view and  FIG. 19  is a cross-sectional view of a stimulation apparatus  1800  in accordance with yet another embodiment of the invention. In this embodiment, the stimulation apparatus  1800  includes a first electrode  1810  and a second electrode  1820  spaced apart from the first electrode  1810 . The first and second electrodes  1810  and  1820  are linear electrodes which are coupled to opposite terminals of a pulse generator  1830 . Referring to  FIG. 19 , the first and second electrodes  1810  and  1820  can generate an approximately linear electric field. 
       FIG. 20  is a bottom plan view of a stimulation apparatus  2000  in accordance with still another embodiment of the invention. In this embodiment, the stimulation apparatus  2000  includes a first electrode  2010 , a second electrode  2020 , a third electrode  2030 , and a fourth electrode  2040 . The first and second electrodes  2010  and  2020  are coupled to a first pulse generator  2050 , and the third and fourth electrodes  2030  and  2040  are coupled to a second pulse generator  2060 . More specifically, the first electrode  2010  is coupled to the positive terminal and the second electrode  2020  is coupled to the negative terminal of the first pulse generator  2050 , and the third electrode  2030  is coupled to the positive terminal and the fourth electrode  2040  is coupled to the negative terminal of the second pulse generator  2060 . The first and second electrodes  2010  and  2020  are expected to generate a first electric field  2070 , and the third and fourth electrodes  2030  and  2040  are expected to generate a second electric field  2072 . 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 second electric fields  2070  and  2072  as shown by arrows  2074 . This embodiment provides control of electric field gradients at the stimulation sites. 
       FIG. 21  is a bottom plan view of another embodiment of the stimulation apparatus  2000 . In this embodiment, the first electrode  2010  is coupled to the positive terminal and the second electrode  2020  is coupled to the negative terminal of the first pulse generator  2050 . In contrast to the embodiment shown in  FIG. 20 , the third electrode  2030  is coupled to the negative terminal and the fourth electrode  2040  is coupled to the positive terminal of the second pulse generator  2070 . 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 a stimulation apparatus  2200  in accordance with still another embodiment of the invention. In this embodiment, the stimulation apparatus  2200  includes a first electrode  2210 , a second electrode  2220 , a third electrode  2230 , and a fourth electrode  2240 . The electrodes are coupled to a pulse generator  2242  by a switch circuit  2250 . The switch circuit  2250  can include a first switch  2252  coupled to the first electrode  2210 , a second switch  2254  coupled to the second electrode  2220 , a third switch  2256  coupled to the third electrode  2230 , and a fourth switch  2258  coupled to the fourth electrode  2240 . In operation, the switches  2252 - 2258  can be opened and closed to establish various electric fields between the electrodes  2210 - 2240 . For example, the first switch  2252  and the fourth switch  2258  can be closed in coordination with a pulse from the pulse generator  2242  to generate a first electric field  2260 , and/or the second switch  2254  and the third switch  2256  can be closed in coordination with another pulse from the pulse generator  2242  to generate a second electric field  2270 . The first and second electric fields  2260  and  2270  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 and  FIG. 24  is a side elevational view of a stimulation apparatus  2300  in accordance with another embodiment of the invention. In this embodiment, the stimulation apparatus  2300  has a first electrode  2310 , a second electrode  2320 , a third electrode  2330 , and a fourth electrode  2340 . The electrodes  2310 - 2340  can be configured in any of the arrangements set forth above with reference to  FIGS. 14-22 . The electrodes  2310 - 2340  also include electrically conductive pins  2350  and/or  2360 . The pins  2350  and  2360  can be configured to extend below the pial surface of the cortex. For example, because the length of the pin  2350  is less than the thickness of the cortex  709 , the tip of the pin  2350  will accordingly conduct the electrical pulses to a stimulation site within the cortex  709  below the pial surface. The length of the pin  2360  is greater than the thickness of the cortex  709  to conduct the electrical pulses to a portion of the brain below the cortex  709 , such as a deep brain region  710 . The lengths of the pins are selected to conduct the electrical pulses to stimulation sites below the pia mater  708 . As such, the length of the pins  2350  and  2360  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 electrodes  2310 - 2340  and a portion of the pins  2350  and  2360  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 in  FIGS. 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 in  FIGS. 23 and 24 . 
     Several embodiments of the stimulation apparatus described above with reference to  FIGS. 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 the pia mater  708 , the dura mater  706 , and/or the cortex  709 . 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 to  FIGS. 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 the skull  700 . 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 in  FIGS. 25-30  can be similar to those described above with reference to  FIGS. 6-24 . Therefore, the embodiments of the stimulation apparatus shown in  FIGS. 25-30  can have the same pulse systems, support members and electrode configurations described above with reference to  FIGS. 6-24 . 
       FIG. 25  is an isometric view and  FIG. 26  is a cross-sectional view of a stimulation apparatus  2500  in accordance with an embodiment of the invention. In one embodiment, the stimulation apparatus  2500  includes a support member  2510 , a pulse-system  2530  carried by the support member  2510 , and first and second electrodes  2560  coupled to the pulse system  2530 . The support member  2510  can be identical or similar to the support member  610  described above with reference to  FIGS. 6 and 7 . The support member  2510  can accordingly include a housing  2512  configured to be implanted in the skull  700  and an attachment element  2514  configured to be connected to the skull  700  by fasteners  2518  ( FIG. 2 ), an adhesive, and/or an anchor. The pulse system  2530  can be identical or similar to any of the pulse systems described above with reference to  FIGS. 6-13 , and the first and second electrodes  2560  can have any of the electrode configurations explained above with reference to  FIGS. 14-24 . Unlike the stimulation apparatus described above, however, the stimulation apparatus  2500  includes a biasing element  2550  coupled to the electrodes  2560  to mechanically bias the electrodes  2560  away from the support member  2510 . In an alternative embodiment, the biasing element  2550  can be positioned between the housing  2512  and the attachment element  2514 , and the electrodes  2560  can be attached directly to the housing  2512 . As explained in more detail below, the biasing element  2550  can be a compressible member, a fluid filled bladder, a spring, or any other suitable element that resiliently and/or elastically drives the electrodes  2560  away from the support member  2510 . 
       FIG. 26  illustrates an embodiment of the stimulation apparatus  2500  after it has been implanted into the skull  700  of a patient. When the fasteners  2518  are attached to the skull  700 , the biasing element  2550  should be compressed slightly so that the electrodes  2560  contact the stimulation site. In the embodiment shown in  FIG. 26 , the compressed biasing element  2550  gently presses the electrodes  2560  against the surface of the pia mater  708 . It is expected that the biasing element  2550  will provide a uniform, consistent contact between the electrodes  2560  and the pial surface of the cortex  709 . The stimulation apparatus  2500  is expected to be particularly useful when the implantable device is attached to the skull and the stimulation site is on the pia mater  708  or the dura mater  706 . It can be difficult to position the contacts against the pia mater  708  because the distance between the skull  700 , the dura mater  706 , and the pia mater  708  varies within the cranium as the brain moves relative to the skull, and also as the depth varies from one patient to another. The stimulation apparatus  2500  with the biasing element  2550  compensates for the different distances between the skull  700  and the pia mater  708  so that a single type of device can inherently fit several different patients. Moreover, the stimulation apparatus  2500  with the biasing element  2550  adapts to changes as the brain moves within the skull. In contrast to the stimulation apparatus  2500  with the biasing element  2550 , an implantable device that does not have a biasing element  2550  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 a stimulation apparatus  2700  having a biasing element  2750  in accordance with an embodiment of the invention. The stimulation apparatus  2700  can have an integrated pulse system  2530  and electrodes  2560  coupled to the pulse system  2530  in a manner similar to the stimulation apparatus  2500 . The biasing element  2750  in this embodiment is a compressible foam, such as a biocompatible closed cell foam or open cell foam. As best shown in  FIG. 27 , the biasing element  2750  compresses when the stimulation apparatus  2700  is attached to the skull.  FIG. 28  illustrates a stimulation apparatus  2800  having a biasing element  2850  in accordance with another embodiment of the invention. The biasing element  2850  can be a compressible solid, such as silicon rubber or other suitable compressible materials. The electrodes  2560  are attached to the biasing element  2850 . 
       FIG. 29  is a cross-sectional view of a stimulation apparatus  2900  having a biasing element  2950  in accordance with another embodiment of the invention. The stimulation apparatus  2900  can have a support member  2910  including an internal passageway  2912  and a diaphragm  2914 . The biasing element  2950  can include a flexible bladder  2952  attached to the support member  2910 , and the electrodes  2560  can be attached to the flexible bladder  2952 . In operation, the flexible bladder  2952  is filled with a fluid  2954  until the electrodes  2560  press against the stimulation site. In one embodiment, the flexible bladder  2952  is filled by inserting a needle of a syringe  2956  through the diaphragm  2914  and injecting the fluid  2954  into the internal passageway  2912  and the flexible bladder. 
       FIG. 30  is a cross-sectional view of a stimulation apparatus  3000  having a biasing element  3050  in accordance with another embodiment of the invention. In this embodiment, the biasing element  3050  is a spring and the electrodes  2560  are attached to the spring. The biasing element  3050  can be a wave spring, a leaf spring, or any other suitable spring that can mechanically bias the electrodes  2560  against the stimulation site. 
     Although several embodiments of the stimulation apparatus shown in  FIGS. 25-30  can have a biasing element and any of the pulse systems set forth above with respect to  FIGS. 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 to  FIGS. 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 a stimulation apparatus  3100  having a biasing element  3150  to which a plurality of electrodes  3160  are attached in a manner similar to the stimulation apparatus described above with reference to  FIGS. 25-30 . It will be appreciated that the stimulation apparatus  3100  may not include the biasing element  3150 . The stimulation apparatus  3100  can also include an external receptacle  3120  having an electrical socket  3122  and an implanted lead line  3124  coupling the electrodes  3160  to contacts (not shown) in the socket  3122 . The lead line  3124  can be implanted in a subcutaneous tunnel or other passageway in a manner known to a person skilled and art. 
     The stimulation apparatus  3100 , however, does not have an internal pulse system carried by the portion of the device that is implanted in the skull  700  of the patient  500 . The stimulation apparatus  3100  receives electrical pulses from an external pulse system  3130 . The external pulse system  3130  can have an electrical connector  3132  with a plurality of contacts  3134  configured to engage the contacts within the receptacle  3120 . The external pulse system  3130  can also have a power supply, controller, pulse generator, and pulse transmitter to generate the electrical pulses. In operation, the external pulse system  3130  sends electrical pulses to the stimulation apparatus  3100  via the connector  3132 , the receptacle  3120 , and the lead line  3124 . 
       FIGS. 32 and 33  illustrate an embodiment of a stimulation apparatus  3200  for use with an external pulse system in accordance with another embodiment of the invention. Referring to  FIG. 33 , the stimulation apparatus  3200  can include a support structure  3210  having a socket  3212 , a plurality of contacts  3214  arranged in the socket  3212 , and a diaphragm  3216  covering the socket  3212 . The stimulation apparatus  3200  can also include a biasing element  3250  and a plurality of electrodes  3260  attached to the biasing element  3250 . Each electrode  3260  is directly coupled to one of the contacts  3214  within the support structure  3210 . It will be appreciated that an alternative embodiment of the stimulation apparatus  3200  does not include the biasing element  3250 . 
     Referring to  FIGS. 32 and 33  together, the stimulation apparatus  3200  receives the electrical pulses from an external pulse system  3230  that has a power supply, controller, pulse generator, and pulse transmitter. The external pulse system  3230  can also include a plug  3232  having a needle  3233  ( FIG. 33 ) and a plurality of contacts  3234  ( FIG. 33 ) arranged on the needle  3233  to contact the internal contacts  3214  in the socket  3212 . In operation, the needle  3233  is inserted into the socket  3212  to engage the contacts  3234  with the contacts  3214 , and then the pulse system  3230  is activated to transmit electrical pulses to the electrodes  3260 . 
       FIGS. 34 and 35  illustrate additional embodiments of stimulation apparatus for use with external pulse systems.  FIG. 34  illustrates an embodiment of a stimulation apparatus  3400  having electrodes  3410  coupled to a lead line  3420  that extends under the scalp  702  of the patient  500 . The lead line  3420  is coupled to an external pulse system  3450 .  FIG. 35  illustrates an embodiment of a stimulation apparatus  3500  having a support member  3510 , electrodes  3512  coupled to the support member  3510 , and an external receptacle  3520  mounted on the scalp  702 . The external receptacle  3520  can also be connected to the support member  3510 . The external receptacle  3520  can have a socket  3522  with contacts (not shown) electrically coupled to the electrodes  3512 . The stimulation apparatus  3500  can be used with the external pulse system  3130  described above with reference to  FIG. 31  by inserting the plug  3132  into the socket  3522  until the contacts  3134  on the plug  3132  engage the contacts within the socket  3522 . 
     6. Alternate Embodiments of Implantable Stimulation Apparatus 
       FIG. 36  is a schematic cross-sectional view of an implantable stimulation apparatus  3600  in accordance with another embodiment of the invention. In one embodiment, the stimulation apparatus  3600  has a support structure  3610  and a plurality of electrodes  3620  coupled to the support structure  3610 . The support structure  3610  can be configured to be implanted under the skull  700  between an interior surface  701  of the skull  700  and the pial surface of the brain. The support structure  3610  can be a flexible or compressible body such that the electrodes  3620  contact the pia mater  708  when the stimulation apparatus  3600  is implanted under the skull  700 . In other embodiments, the support structure  3610  can position the electrodes  3620  so that they are proximate to, but not touching, the pia mater  708 . 
     In one embodiment, the stimulation apparatus  3600  can receive electrical pulses from an external controller  3630 . For example, the external controller  3630  can be electrically coupled to the stimulation apparatus  3600  by a lead line  3632  that passes through a hole  711  in the skull  700 . In an alternative embodiment, the stimulation apparatus  3600  can include an integrated pulse system similar to the pulse systems described above with reference to  FIGS. 6-13 . Such an embodiment of the stimulation apparatus  3600  can accordingly use a wireless external control unit. It will be appreciated that the electrodes  3620  of the stimulation apparatus  3600  can have several of the electrode configurations described above with reference to  FIGS. 14-24 . 
       FIGS. 37 and 38  illustrate one embodiment of the implantable stimulation apparatus  3600 . Referring to  FIG. 37 , the support structure  3610  can be a flexible substrate and the electrodes  3620  can be conductive elements that are printed onto the flexible substrate. The stimulation apparatus  3600 , for example, can be manufactured in a manner similar to flexible printed circuit assemblies that are used in electrical components. The stimulation apparatus  3600  can be implanted under the skull  700  using an insertion tool  3700 . In one embodiment, the insertion tool  3700  has a handle  3702  and a shaft  3704  projecting from the handle  3702 . The shaft  3704  can have a slot  3706  configured to receive a flat portion of the support member  3610 . Referring to  FIG. 38 , the support member  3610  is wrapped around the shaft  3704 , and then the stimulation apparatus  3600  is passed to a tube  3720  positioned in the hole  711  through the scalp  700  and the dura mater  706 . After the stimulation apparatus  3600  has been passed through the tube  3720 , it is unfurled to place the electrodes  3620  at least proximate to the pia mater  708 . The electrodes  3620  can be coupled to an external controller by the lead lines  3632 . 
       FIG. 39  illustrates another embodiment of an implantable stimulation apparatus  3900  that is also configured to be positioned between the skull  700  and the pia mater  708 . In one embodiment, the stimulation apparatus  3900  can include a support member  3910  and a plurality of electrodes  3920  coupled to the support member  3910 . The electrodes  3920  can be coupled to individual lead lines  3922  to connect the electrodes  3920  to an external pulse system. In an alternative embodiment, an integrated pulse system  3930  can be carried by the support member  3910  so that the electrodes  3920  can be coupled directly to the integrated pulse system  3930  without external lead lines  3922 . The support member  3910  can be a resiliently compressible member, an inflatable balloon-like device, or a substantially solid incompressible body. In the particular embodiment shown in  FIG. 39 , the support member  3910  is an inflatable balloon-like device that carries the electrodes  3920 . In operation, the stimulation apparatus  3900  is implanted by passing the distal end of the support member  3910  through the hole  711  in the skull  700  until the electrodes  3920  are positioned at a desired stimulation site. 
       FIG. 40  is a schematic illustration of a stimulation apparatus  4000  together with an internal pulse system  4030  in accordance with another embodiment of the invention. The stimulation apparatus  4000  can include a support member  4010 , a biasing element  4015  carried by the support member  4010 , and a plurality of electrodes  4020  carried by the biasing element  4015 . The internal pulse system  4030  can be similar to any of the integrated pulse systems described above with reference to  FIGS. 6-13 , but the internal pulse system  4030  is not an integrated pulse system because it is not carried by the housing  4010 . The internal pulse system  4030  can be coupled to the electrodes  4020  by a cable  4034 . In a typical application, the cable  4034  is implanted subcutaneously in a tunnel from a subclavicular region, along the back of the neck, and around the skull. The stimulation apparatus  4000  can also include any of the electrode configurations described above with reference to  FIGS. 14-24 . 
     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.