Patent Publication Number: US-8972013-B2

Title: Using physiological sensor data with an implantable medical device

Description:
CLAIM OF PRIORITY 
     This application is a divisional patent application of, and claims priority from, U.S. patent application Ser. No. 11/261,853, filed on Oct. 28, 2005 and entitled “Using physiological sensor data with an implantable medical device,” which is incorporated hereby by reference in its entirety for all purposes. 
    
    
     FIELD OF THE DISCLOSURE 
     This disclosure relates generally to implantable medical devices, and, more particularly, to methods, apparatus, and systems for using data from a physiological sensor to affect an operation performed by an implantable medical device. 
     BACKGROUND 
     There have been many improvements over the last several decades in medical treatments for disorders of the nervous system, such as epilepsy and other motor disorders, and abnormal neural discharge disorders. One of the more recently available treatments involves the application of an electrical signal to reduce various symptoms or effects caused by such neural disorders. For example, electrical signals have been successfully applied at strategic locations in the human body to provide various benefits, including reducing occurrences of seizures and/or improving or ameliorating other conditions. A particular example of such a treatment regimen involves applying an electrical signal to the vagus nerve of the human body to reduce or eliminate epileptic seizures, as described in U.S. Pat. Nos. 4,702,254, 4,867,164, and 5,025,807 to Dr. Jacob Zabara, which are hereby incorporated in their entirety herein by reference in this specification. 
     Electrical stimulation of the vagus nerve (hereinafter referred to as vagus nerve stimulation therapy) may be provided by implanting an electrical device underneath the skin of a patient and performing a detection and electrical stimulation process. This type of stimulation is generally referred to as “active,” “feedback,” or “triggered” stimulation. Alternatively, the system may operate without a detection system once the patient has been diagnosed with epilepsy, and may periodically apply a series of electrical pulses to the vagus (or other cranial) nerve intermittently throughout the day, or over another predetermined time interval. This type of stimulation is generally referred to as “passive,” “non-feedback,” or “prophylactic,” stimulation. The stimulation may be applied by an implantable medical device that is implanted within the patient&#39;s body. 
     State-of-the-art implantable medical devices generally deliver stimulation signals to one or more regions of a patient&#39;s body in a predetermined periodic cycle. Based upon the diagnosed disorder of the patient, a physician may determine a regimen of therapeutic stimulation signals to treat the disorder. The devices then execute the predetermined stimulation regimen. This regimen may be interrupted by predetermined interruption options, such as an external communication from a physician prompting a change in the regimen, a signal from the patient, etc. 
     The delivery of stimulation may cause physiological variations within a patient&#39;s body. However, state-of-the-art implantable medical devices generally do not allow for affecting the predetermined stimulation regimens in response to the various physiological variations. Barring active initiation of operational changes prompted by an external source, such as a physician, state-of-the-art implantable devices generally continue a predetermined treatment regimen despite physiological variations. This may cause the implantable medical device to become less responsive to changes in a patient&#39;s body. 
     In an attempt to alleviate some of these problems, designers have provided for altering the regimen based on an external input or input from the patient, for example, through a magnetic signal sent to the implantable device. However, this solution may not be sufficiently reactive to adequately address physiological variations resulting from stimulation regimens. Further, these solutions may require an assessment by an external source, such as a physician or the patient. By the time an external source examines the physiological variations, the patient&#39;s body may have gone through further changes, rendering any reaction to the original physiological variation obsolete. 
     Even though delivery of stimulation may cause specific physiological variations in the body, state-of-the-art implantable devices generally behave independently of such variations, at least in the short term. Long term changes may be provided by re-examination by a physician, i.e., re-diagnosis of a disorder, and then making further adjustments to the stimulation treatment. This may result in significant delay between the physiological changes that may occur due to stimulation, and the time period when manual adjustments to the stimulation regimen is made after examination from a physician. Therefore, efficient and effective reaction to physiological changes may not take place utilizing state-of-the-art implantable devices. 
     The present disclosure is directed to overcoming, or at least reducing, the effects of one or more of the problems set forth above. 
     SUMMARY 
     In one aspect, the present disclosure includes a method for providing an electrical neurostimulation therapy to a neural structure of a patient&#39;s body using an implantable medical device (IMD). A first electrical signal is provided using the implantable medical device. The first electrical signal is applied to the neural structure. An implanted sensor is provided. A physiological parameter is sensed using the implanted sensor. The physiological parameter includes at least one of a neurotransmitter parameter, a neurotransmitter breakdown product parameter, a neuropeptide parameter, and a glucocorticoid (GC) parameter. The first electrical signal is modified based upon the sensed physiological parameter to generate a second electrical signal. The second electrical signal is applied to the neural structure. 
     In another aspect, the present disclosure includes a method for providing an electrical neurostimulation therapy to a neural structure of a patient&#39;s body using an IMD. A first electrical signal having a first signal parameter selected from the group consisting of a current magnitude, a pulse width, a pulse period, a frequency, an on-time and an off-time, is provided. The first electrical signal is applied to a target portion of a patient&#39;s body to treat a disorder using an electrode operatively coupled to the implantable medical device. A sensor is provided. A physiological parameter is sensed using the sensor. The physiological parameter includes at least one of a neurotransmitter parameter, a neurotransmitter breakdown product parameter, a metabolite, a nucleotide parameter, a neuromodulator parameter, a neuromodulator breakdown product parameter, a peptide parameter, an enzyme parameter, a ligand parameter, a norepinephrine parameter, a glucocorticoid (GC) parameter, an amino acid parameter, a hormone parameter, a parameter of a bloodborne substance, a medication parameter, and a drug level in a portion of a patient&#39;s body. The first signal parameter is modified based upon the sensed physiological parameter to generate a second electrical signal. The second electrical signal is applied to the target portion of a patient&#39;s body. 
     In one aspect, the present disclosure includes an implantable medical device system for providing an electrical neuro stimulation therapy to a neural structure of a patient&#39;s body using an IMD. The implantable medical device system includes an implantable medical device (IMD) for providing a first electrical signal to a portion of a neural structure to treat a disorder. The IMD includes an electrode operatively coupled to the IMD. The electrode carries the first electrical signal from the IMD to the neural structure. The system includes a sensor operatively coupled to the IMD. The sensor is adapted to sense a physiological parameter. The physiological parameter includes at least one of a neurotransmitter parameter, a neurotransmitter breakdown product parameter, a neuropeptide parameter, a norepinephrine parameter, and a glucocorticoid (GC) parameter. The IMD also includes a control adapted to change a parameter of the first signal. The parameter is selected from the group consisting of a pulse width, a frequency, a polarity, and an amplitude, based upon the physiological parameter to generate a second electrical signal and to apply the second electrical signal to the neural structure. 
     In one aspect, the present disclosure includes a sensor to provide physiological data to an IMD to perform an adaptive stimulation process. The sensor is adapted to acquire data indicative of a neurotransmitter parameter in a patient&#39;s body. The neurotransmitter parameter includes at least one of a neurotransmitter level, a neurotransmitter breakdown product level, a neuropeptide level, a ligand level, an amino acid level, and a change in a glucocorticoid (GC) level in the patient&#39;s body. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The disclosure may be understood by reference to the following description taken in conjunction with the accompanying drawings, in which like reference numerals identify like elements, and in which: 
         FIGS. 1A-1D  provide stylized diagrams of an implantable medical device implanted into a patient&#39;s body for providing stimulation to a portion of the patient&#39;s body, in accordance with one illustrative embodiment; 
         FIG. 2  illustrates a medical device system that includes an implantable medical device, one more sensors operatively coupled to the implantable medical device, and an external device, in accordance with one illustrative embodiment; 
         FIG. 3  illustrates a block diagram depiction of the implantable medical device of  FIGS. 1A-1D , in accordance with one illustrative embodiment; 
         FIG. 4  illustrates a more detailed block diagram depiction of a sensor of  FIGS. 2 and 3 , in accordance with one illustrative embodiment; 
         FIG. 5  illustrates a block diagram depiction of the sensing unit of  FIG. 4 , in accordance with one illustrative embodiment; 
         FIG. 6  illustrates a flowchart depiction of a method of performing an adaptive stimulation process using sensor feedback, in accordance with a first illustrative embodiment; 
         FIG. 7  illustrates a more detailed flowchart depiction of a method of performing the sensor data acquisition and analysis process of  FIG. 6 , in accordance with one illustrative embodiment; and 
         FIG. 8  illustrates a flowchart depiction of a method of performing the adaptive stimulation process using a sensor feedback process, in accordance with a second illustrative embodiment. 
     
    
    
     While the disclosed embodiments are susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are herein described in detail. It should be understood, however, that the description herein of specific embodiments is not intended to limit the disclosure to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the scope of the disclosure as defined by the appended claims. 
     DETAILED DESCRIPTION 
     Illustrative embodiments are described herein. In the interest of clarity, not all features of an actual implementation are described in this specification. In the development of any such actual implementation, numerous implementation-specific decisions must be made to achieve the design-specific goals, which will vary from one implementation to another. It will be appreciated that such a development effort, while possibly complex and time-consuming, would nevertheless be a routine undertaking for persons of ordinary skill in the art having the benefit of this disclosure. 
     Embodiments disclosed herein provide for an adaptive therapeutic stimulation using an implantable medical device. Embodiments disclosed herein provide for using an implantable medical device for delivering a therapeutic stimulation based upon physiological data relating to a patient&#39;s body. The physiological data may be acquired by a sensor that is strategically implanted into the patient&#39;s body. The physiological data may include indications of a neurotransmitter level, a chemical level, an electrical level, a biological substance level, etc. Based upon the physiological data, at least one stimulation parameter may be adaptively modified for subsequent stimulations. 
     Although not so limited, a system capable of implementing embodiments disclosed herein is described below.  FIGS. 1A-1D  depict a stylized implantable medical system  100  for implementing one or more embodiments.  FIGS. 1A-1D  illustrate an electrical signal generator  110  having main body  112  including a case or shell  121  ( FIG. 1A ) with a header  116  ( FIG. 1C ) for connecting to leads  122 . The generator  110  is implanted in the patient&#39;s chest in a pocket or cavity formed by the implanting surgeon just below the skin (indicated by a dotted line  145  in  FIG. 1B ), similar to the implantation procedure for a pacemaker pulse generator. 
     A stimulating nerve electrode assembly  125 , preferably including an electrode pair, is conductively connected to the distal end of an insulated, electrically conductive lead assembly  122 , which preferably includes a pair of lead wires (one wire for each electrode of an electrode pair). Lead assembly  122  is attached at its proximal end to connectors on the header  116  ( FIG. 1C ) on case  121 . The electrode assembly  125  may be surgically coupled to a vagus nerve  127  in the patient&#39;s neck or at another location, e.g., near the patient&#39;s diaphragm. Other cranial nerves may also be used to deliver the electrical neuro stimulation signal. The electrode assembly  125  preferably includes a bipolar stimulating electrode pair  125 - 1 ,  125 - 2  ( FIG. 1D ), such as the electrode pair described in U.S. Pat. No. 4,573,481 issued Mar. 4, 1986 to Bullara. Suitable electrode assemblies are available from Cyberonics, Inc., Houston, Tex., USA, such as the Model 302 electrode assembly. However, persons of skill in the art will appreciate that many electrode designs could be used. The two electrodes are preferably wrapped about the vagus nerve, and the electrode assembly  125  may be secured to the nerve  127  by a spiral anchoring tether or loop  128  ( FIG. 1D ), such as that disclosed in U.S. Pat. No. 4,979,511 issued Dec. 25, 1990 to Reese S. Terry, Jr. and assigned to the same assignee as the instant application. Lead assembly  122  is secured, while retaining the ability to flex with movement of the chest and neck, by a suture connection  130  to nearby tissue ( FIG. 1D ). 
     In one embodiment, the open helical design of the electrode assembly  125  (described in detail in the above-cited Bullara patent), which is self-sizing and flexible, minimizes mechanical trauma to the nerve and allows body fluid interchange with the nerve. The electrode assembly  125  preferably conforms to the shape of the nerve, providing a low stimulation threshold by allowing a large stimulation contact area with the nerve. Structurally, the electrode assembly  125  includes two electrode ribbons (not shown), of a conductive material such as platinum, iridium, platinum-iridium alloys, and/or oxides of the foregoing. The electrode ribbons are individually bonded to an inside surface of an elastomeric body portion of the two spiral electrodes  125 - 1  and  125 - 2  ( FIG. 1D ), which may include two spiral loops of a three-loop helical assembly. The lead assembly  122  may include two distinct lead wires or a coaxial cable whose two conductive elements are respectively coupled to one of the conductive electrode ribbons. One suitable method of coupling the lead wires or cable to the electrodes  125 - 1 ,  125 - 2  includes a spacer assembly such as that disclosed in U.S. Pat. No. 5,531,778, although other known coupling techniques may be used. 
     The elastomeric body portion of each loop is preferably composed of silicone rubber, and the third loop  128  (which typically has no electrode) acts as the anchoring tether for the electrode assembly  125 . 
     In certain embodiments, sensors such as eye movement sensing electrodes  133  ( FIG. 1B ) may be implanted at or near an outer periphery of each eye socket in a suitable location to sense muscle movement or actual eye movement. The electrodes  133  may be electrically connected to leads  134  implanted via a catheter or other suitable means (not shown) and extending along the jaw line through the neck and chest tissue to the header  116  of the electrical signal generator  110 . When included in the system, the sensing electrodes  133  may be utilized for detecting rapid eye movement (REM) in a pattern indicative of a disorder to be treated, as described in greater detail below. The detected indication of the disorder can be used to trigger active stimulation. 
     Other sensor arrangements may alternatively or additionally be employed to trigger active stimulation. Referring again to  FIG. 1B , electroencephalograph (EEG) sensing electrodes  136  may optionally be implanted and placed in spaced-apart relation on the skull, and connected to leads  137  implanted and extending along the scalp and temple, and then connected to the electrical signal generator  110  along the same path and in the same manner as described above for the eye movement electrode leads  134 . 
     In alternative embodiments, temperature sensing elements and/or heart rate sensor elements may be employed to trigger active stimulation. In addition to active stimulation incorporating sensor elements, other embodiments utilize passive stimulation to deliver a continuous, periodic or intermittent electrical signal (each of which constitutes a form of continual application of the signal) to the vagus nerve according to a programmed on/off duty cycle without the use of sensors to trigger therapy delivery. Both passive and active stimulation may be combined or delivered by a single IMD. Either or both modes may be appropriate to treat the particular disorder diagnosed in the case of a specific patient under observation. 
     The electrical pulse generator  110  may be programmed with an external computer  150  using programming software of the type copyrighted by the assignee of the instant application with the Register of Copyrights, Library of Congress, or other suitable software based on the description herein, and a programming wand  155  to facilitate radio frequency (RF) communication between the computer  150  ( FIG. 1A ) and the electrical signal generator  110 . The wand  155  and software permit non-invasive communication with the generator  110  after the latter is implanted. The wand  155  is preferably powered by internal batteries, and provided with a “power on” light to indicate sufficient power for communication. Another indicator light may be provided to show that data transmission is occurring between the wand and the generator. 
     A variety of stimulation therapies may be provided using the implantable medical system  100 . Different types of nerve fibers (e.g., A, B, and C fibers being different fibers targeted for stimulation) respond differently to stimulation from electrical signals. More specifically, the different types of nerve fibers have different conduction velocities and stimulation thresholds and, therefore, differ in their responsiveness to stimulation. Certain pulses of an electrical stimulation signal, for example, may be below the stimulation threshold for a particular fiber and, therefore, may generate no action potential in the fiber. Thus, smaller or narrower pulses may be used to avoid stimulation of certain nerve fibers (such as C fibers) and target other nerve fibers (such as A and/or B fibers, which generally have lower stimulation thresholds and higher conduction velocities than C fibers). Additionally, techniques such as pre-polarization may be employed wherein particular nerve regions may be polarized before a more robust stimulation is delivered, which may better accommodate particular electrode materials. Furthermore, opposing polarity phases separated by a zero current phase may be used to excite particular axons or postpone nerve fatigue during long term stimulation. 
     As used herein, the terms “stimulating” and “stimulator” may generally refer to delivery of a signal, stimulus, or impulse to neural tissue for affecting neuronal activity of a neural tissue (e.g., a volume of neural tissue in the brain or a nerve). The effect of such stimulation on neuronal activity is termed “modulation”; however, for simplicity, the terms “stimulating” and “modulating”, and variants thereof, are sometimes used interchangeably herein. The effect of delivery of the stimulation signal to the neural tissue may be excitatory or inhibitory and may potentiate acute and/or long-term changes in neuronal activity. For example, the effect of “stimulating” or “modulating” a neural tissue may include on one more of the following effects: (a) changes in neural tissue to initiate an action potential (bi-directional or uni-directional); (b) inhibition of conduction of action potentials (endogenous or externally stimulated) or blocking the conduction of action potentials (hyperpolarizing or collision blocking), (c) affecting changes in neurotransmitter/neuromodulator release or uptake, and (d) changes in neuro-plasticity or neurogenesis of brain tissue. Applying an electrical signal to an autonomic nerve may include generating a response that includes an afferent action potential, an efferent action potential, an afferent hyperpolarization, an efferent hyperpolarization, an afferent sub-threshold depolarization, and/or an efferent sub-threshold depolarization. 
     Particular embodiments provide for a method, apparatus, and a system for performing a sensor feedback analysis for providing an adaptive stimulation using an implantable medical device (IMD). A physiological data sensor, such as a neurotransmitter sensor, may be used to detect physiological variations and/or a physiological condition in a patient&#39;s body to affect the therapy stimulation provided by the IMD  200 . Upon delivery of stimulation, various physiological changes (e.g., changes in chemical compounds, neurotransmitter level, a neurotransmitter breakdown product level, a metabolite level, a nucleotide level, a neuromodulator level, a neuromodulator breakdown product level, a peptide level, a ligand level, an amino acid level, a hormone level, a level of a bloodborne substance, a medication level, a drug level, electrical characteristics, etc., in the patient&#39;s body) may be detected and analyzed. This analysis may include comparing various sensed parameters, to corresponding predetermined reference parameters. Using this analysis, the treatment regimen for delivering therapy stimulation by the IMD  200  may be adjusted. 
     Further, in addition or alternative to modifying existing stimulation parameter(s), a second portion of the patient&#39;s body may be stimulated based upon the analysis described above. Adjusting the treatment regimen may include adjusting stimulation parameters to stimulate selective portions of a cranial nerve to activate a neuronal pathway consisting of the type: gustatory, olfactory, pro-inflammatory or anti-inflammatory, respiratory, cardiac, baroreceptor, somatosensory, and/or satiety. Cranial nerve stimulation may also be performed by particular embodiments in order to affect neurotransmitter pathways such as noradrenergic, serotoninergic, dopaminergic, catecholaminergic, GABAergic, opioidergic, and/or cholinergic pathways. 
     When delivering stimulation therapy, variations in the patient&#39;s body may occur. Data relating to these variations may be used to perform a characterization of a particular disorder (e.g., the severity, or lack thereof, of a disorder) to evaluate the effectiveness of the stimulation. Further, based upon the characterization of a disorder, such as depression, the therapy stimulation regimen may be increased or decreased accordingly. Physiological factors, such as serotonin levels, that may be directly or indirectly affected by the stimulation may be used to determine the effectiveness of the therapy stimulation. For example, serotonin re-uptake levels may be altered by the stimulation, affecting the depression state of a patient. Upon detecting the change in the serotonin uptake, therapy stimulation may be continued, increased, and/or decreased. In this manner, feedback associated with a disorder (e.g., depression) may be determined to provide an adaptive stimulation therapy. 
     The sensor provided by the embodiments disclosed herein may be capable of detecting a variety of physiological factors including chemical changes in a patient&#39;s body, biological changes (e.g., hormonal changes), electrical activity variations, neurotransmitter variations, etc., in a patient&#39;s body. Various algorithms may be provided in the IMD  200  to analyze the state of the physiological factors. Based upon this analysis, the stimulation treatment may be adaptively modified. Further, these physiological factors may be stored and/or reported to an external entity such as a physician, who may provide manual adjustments. Based upon the sensor feedback, in conjunction with the IMD, more effective and responsive treatment of a disorder may be performed. 
     Turning now to  FIG. 2 , a stylized system description of an implantable medical device (IMD)  200  being coupled to one or more physiological sensors  250 , in accordance with an illustrative embodiment, is provided.  FIG. 2  illustrates exemplary locations in the patient&#39;s body upon which the sensor  250  may be implanted. For example, the sensor  250  may be implanted in the patient&#39;s brain, in the patient&#39;s neck, proximate a vagus nerve, the upper region of spinal column, the lower region of the spinal column, the gastrointestinal tract of the patient, etc. The sensor  250  may also be implanted into the bloodstream at various locations in the patient&#39;s body. 
     Data from the sensor  250  may be sent to the IMD  200 . The IMD  200  may process the data and perfoilu various analyses relating to the physiological state of the patient. The IMD  200  may also perform various lookup functions and/or other types of calculations to assess the severity of a particular disorder. For example, an indication of serotonin levels in the patient&#39;s body may be used to determine a severity of depression in the patient. This information may be stored and/or sent to an external unit  370 . Further details of the IMD  200 , the sensor  250 , and the external unit  370  are provided in various figures and the accompanying description below. 
     The system described in  FIG. 2  may provide for a feedback adjustment of the stimulation therapy delivered by the IMD  200 . The IMD  200  may also provide data relating to the physiological state of various portions of the patient&#39;s body to an external unit  370 . This data received by the external unit  370  may be monitored and analyzed by a physician. Input from the external unit  370  and/or various sensors  250  positioned in the patient&#39;s body may be received by the IMD  200 . Further, the IMD  200  may perform analyses using the acquired sensor data and provide therapy stimulation adjustments. This feedback may be performed continuously, periodically, or upon manual input from the external unit  370 . Utilizing the feedback system described herein, various disorders such as depression, epilepsy, bulimia, diabetes, heart rhythm disorders, etc., may be treated. 
     Turning now to  FIG. 3  a more detailed block diagram depiction of the IMD  200  of  FIG. 2  in accordance with one illustrative embodiment is provided. The IMD  200  may be used for stimulation to treat various disorders, such as epilepsy, depression, bulimia, heart rhythm disorders, etc. The IMD  200  may be coupled to various leads, e.g.,  122 ,  134 ,  137  ( FIGS. 1A ,  1 B,  1 D). Stimulation signals used for therapy may be transmitted from the IMD  200  to target areas of the patient&#39;s body, specifically to various electrodes associated with the leads  122 . Stimulation signals from the IMD  200  may be transmitted via the leads  122  to stimulation electrodes associated with the electrode assembly  125  ( FIG. 1A ). Further, signals from sensor electrodes, e.g.,  133 ,  136  ( FIG. 1B ) associated with corresponding leads, e.g.,  134 ,  137 , may also traverse the leads back to the IMD  200 . 
     The IMD  200  may include a controller  310  capable of controlling various aspects of the operation of the IMD  200 . The controller  310  is capable of receiving internal data and/or external data and generating and delivering a stimulation signal to target tissues of the patient&#39;s body. For example, the controller  310  may receive manual instructions from an operator externally, or may perform stimulation based on internal calculations and programming. The controller  310  is capable of affecting substantially all functions of the IMD  200 . 
     The controller  310  may include various components, such as a processor  315 , a memory  317 , etc. The processor  315  may include one or more micro controllers, micro processors, etc., that are capable of executing a variety of software components. The memory  317  may include various memory portions, where a number of types of data (e.g., internal data, external data instructions, software codes, status data, diagnostic data, etc.) may be stored. The memory  317  may include random access memory (RAM) dynamic random access memory (DRAM), electrically erasable programmable read-only memory (EEPROM), flash memory, etc. 
     The IMD  200  may also include a stimulation unit  320 . The stimulation unit  320  is capable of generating and delivering a variety of electrical neurostimulation signals to one or more electrodes via leads. The stimulation unit  320  is capable of generating a therapy portion, a ramping-up portion, and a ramping-down portion of the stimulation signal. A number of leads  122 ,  134 ,  137  may be coupled to the MD  200 . Therapy may be delivered to the leads  122  by the stimulation unit  320  based upon instructions from the controller  310 . The stimulation unit  320  may include various types of circuitry, such as stimulation signal generators, impedance control circuitry to control the impedance “seen” by the leads, and other circuitry that receives instructions relating to the type of stimulation to be performed. The stimulation unit  320  is capable of delivering a controlled current stimulation signal to the leads and to the electrodes the leads  122 . 
     The IMD  200  may also include a power supply  330 . The power supply  330  may include a battery, voltage regulators, capacitors, etc., to provide power for the operation of the IMD  200 , including delivering the stimulation signal. The power supply  330  includes a power-source battery that in some embodiments may be rechargeable. In other embodiments, a non-rechargeable battery may be used. The power supply  330  provides power for the operation of the IMD  200 , including electronic operations and the stimulation function. The power supply  330  may include a lithium/thionyl chloride cell or a lithium/carbon monofluoride cell. Other battery types known in the art of implantable medical devices may also be used. 
     The IMD  200  also includes a communication unit  360  capable of facilitating communications between the IMD  200  and various devices. In particular, the communication unit  360  is capable of providing transmission and reception of electronic signals to and from an external unit  370 . The external unit  370  may be a device that is capable of programming various modules and stimulation parameters of the IMD  200 . In one embodiment, the external unit  370  includes a computer system that is capable of executing a data-acquisition program. The external unit  370  may be controlled by a healthcare provider, such as a physician, at a base station in, for example, a doctor&#39;s office. The external unit  370  may be a computer, preferably a handheld computer or PDA, but may alternatively include any other device that is capable of electronic communications and programming. The external unit  370  may download various parameters and program software into the IMD  200  for programming the operation of the implantable device. The external unit  370  may also receive and upload various status conditions and other data from the IMD  200 . The communication unit  360  may be hardware, software, firmware, and/or any combination thereof. Communications between the external unit  370  and the communication unit  360  may occur via a wireless or other type of communication, illustrated generally by line  375  in  FIG. 3 . 
     The IMD  200  may receive various inputs from the sensor  250 . In one embodiment the sensor  250  provides electrical signals indicative of a chemical response, an electrical response, a biological response, a neurotransmitter level, a neurotransmitter breakdown product level, a metabolite, a nucleotide level, a neuromodulator level, a neuromodulator breakdown product level, a peptide level, a ligand level, an amino acid level, a hormone level, a level of a bloodborne substance, a medication level, or a drug level indication associated with a portion of the patient&#39;s body, to the IMD  200 . The sensor  250  illustrated in  FIG. 3  may represent the aggregation of a plurality of sensors implanted in a variety of locations in a patient&#39;s body. The IMD  200  may also include a sensor interface  340 . The sensor interface  340  is capable of receiving and organizing data from the sensor  250 . The sensor interface  340  may include various interface circuitry to receive, perform buffering, and/or register the data received from the sensor  250 . In one embodiment, the sensor  250  may provide digital data that has been converted within the sensor  250  to the IMD  200 . In an alternative embodiment, the sensor  250  may provide analog-type data to the IMD  200 . In one embodiment, the sensor interface  340  may also provide an analog-to-digital converter (A/D converter). The sensor interface  340  is capable of collecting sensor data and providing the sensor data to various modules within the IMD  200 , such as the controller  310  and/or other units described herein. 
     The IMD  200  may also include a sensor data processing unit  350 . The sensor data processing unit  350  is capable of correlating various physiological data to particular stimulation provided by the IMD  200 . Further, the sensor data processing unit  350  may filter and/or perform digital signal processing upon the data from the sensor  250 . The sensor data processing unit  350  may correlate, stack, and organize the sensor data. For example, the sensor data processing unit  350  may collect, organize, and correlate various sets of data relating to neurotransmitter level, a neurotransmitter breakdown product level, a metabolite, a nucleotide level, a neuromodulator level, a neuromodulator breakdown product level, a peptide level, a ligand level, an amino acid level, a hormone level, a level of a bloodborne substance, a medication level, or a drug level. The correlation of this data may include associating the sensor data to particular firings of stimulation signals. 
     The sensor data processing unit  350  may also include a comparator  372 . The comparator  372  may include various comparator circuitry that are capable of comparing sensor data to previously acquired/stored sensor data and/or benchmark sensor data/tables that may be stored in the IMD  200 . The sensor data processing unit  350  may provide compared, stacked, organized, correlated data to the controller  310 , which may then perform further algorithm analysis upon the data. Additionally, data from the sensor data processing unit  350  may be sent to the external unit  370  via the communication unit  360 . The physician examining the data via the external unit  370  may perform further analysis and diagnosis of a particular disorder and make further treatment adjustments. For example, based upon the newly acquired and correlated neurotransmitter levels, a physician and/or an algorithm within the IMD  200 , may make a determination that serotonin re-uptake indicates that the depression level in a patient has changed and further adjustments to the treatment provided by the IMD  200  that should be performed. Other disorders may be diagnosed, analyzed, and/or characterized based upon the sensor data and in response adjustments to the IMD  200  may have been performed. 
     The IMD  200  is capable of delivering stimulation that can be intermittent, periodic, random, sequential, coded, and/or patterned. The stimulation signals may have an electrical stimulation frequency of approximately 0.1 to 2500 Hz. The stimulation signals may have a pulse width of in the range of approximately 1-2000 micro-seconds. The stimulation signals may have current amplitude in the range of approximately 0.1 mA to 10 mA. Stimulation may be delivered through either the cathode (−) electrode or anode (+) electrode. In one embodiment, the various blocks illustrated in  FIG. 3  may include software unit, a firmware unit, a hardware unit, and/or any combination thereof. 
     Turning now to  FIG. 4 , a more detailed block diagram depiction of the sensor  250  in accordance with an illustrative embodiment is provided. The sensor  250  may include a sensor controller  420  that is capable of controlling the various functions performed by the sensor  250 . The sensor controller  420  may be a microcontroller, a processor, etc. that may include integrated memory and program storage space. The sensor controller  420  is capable of receiving commands from the IMD  200  and/or from the external unit  370  and controlling the functions of the sensor  250  accordingly. 
     The sensor may include a sensing unit  410 , which is capable of sensing one or more physiological responses or characteristics of a portion of a patient&#39;s body. A more detailed description of the sensing unit  410  is provided in  FIG. 5  and accompanying descriptions below. Continuing to refer to  FIG. 4 , the sensor  250  may also include an A/D converter  430 . The A/D converter  430  may receive analog signals from the sensing unit  410 . The A/D converter  430  converts the analog data signals from the sensing unit  410  to generate equivalent digital data. 
     The sensor  250  may also include a filter unit  440  that is capable of filtering the sensed physiological data. In one embodiment, the filter unit  440  may be operatively positioned proceeding the A/D converter  430 , wherein the filter unit  440  filters digital data. In an alternative embodiment, the filter unit  440  may be operatively positioned preceding the A/D converter  430 , wherein the filter unit  440  in this embodiment filters analog data. Various filtering techniques known to those skilled in the art having benefited of the present disclosure, may be implemented into the filter unit  440 , including a band-pass filter, a high-pass filter, a low-pass filter, etc. 
     The sensor  250  may also include a sensor interface  450 . The sensor interface  450  is capable of receiving and transmitting data between the sensor  250  and other devices (i.e., the IMD  200 , external unit  370 , etc.). The sensor interface  450  is capable of receiving commands/data from the IMD  200  and/or the external unit  370 . Additionally, the sensor interface  450  may provide physiological sensing data to the IMD  200  and/or to the external unit  370 . 
     The sensor interface  450  may include various registers, transmission circuits, etc., to route data between the sensor  250  and the IMD  200 . The sensor interface  450  may be capable of receiving and processing analog data, digital data, wired data, and/or wireless data. 
     In one embodiment, the sensing unit  410  may include portions developed from materials relating to nanotechnology. The sensing unit  410  may be capable of utilizing an electrochemical measurement based on the oxidation or reduction of a neurotransmitter or other chemical species. The sensing unit  410  may include an electrode held at a particular potential characteristic for a specific, predetermined neurotransmitter (i.e., the redox potential, which is described in further details below) with respect to a reference electrode. In this way, the neurotransmitter molecules may be absorbed upon the electrode surface. This may lead to the exchange of one or more electrons between the electrode and the neurotransmitter molecules. These electrons constitute the redox current. The redox currents are directly proportional to the concentration of the species in a solution. Therefore, the measurements from the electrode surface may be used to determine the concentration of a neurotransmitter. 
     In one embodiment, the sensing unit  410  may include a carbon nanotube/nanofiber array for electrical stimulation and/or acquiring/recording physiological characteristics. In this way, a process of performing an electrochemical acquiring/recording of neurotransmitter levels is possible. The sensing unit  410  may include very large scale integration (VLSI) components. The sensing unit  410  may be adapted to sense, store, and communicate information to the IMD  200  to provide stimulation therapy to increase or decrease neurotransmitter levels, and/or other chemical level(s) in a closed feedback system. 
     Turning now to  FIG. 5 , a block diagram depiction of the sensing unit  410  in accordance with an illustrative embodiment is depicted. The sensing unit  410  may include various types of sensing circuitry. The sensing unit  410  may include a neurotransmitter sensor circuit  510 , an electrical sensor circuit  520 , a chemical sensor circuit  530 , and/or a biological sensor circuit  540 . Each of the sensor circuits  510 - 540  may receive a control signal from sensor controller  420  to control its operations. Further, sensed data from each of the sensor circuits  510 - 540  is provided to other portions of the sensor  250 . 
     The neurotransmitter sensor circuit  510  is capable of receiving and monitoring various neurotransmitter levels in a direct or in an indirect fashion. For example, the neurotransmitter, such as dopamine, may be detected via another indicator such as the Homovanillic Acid (HVA), which may be indicative of the level or concentration of dopamine. Dopamine may modulate the brain&#39;s reward mechanism and movement control. Other factors, such as 5-hydroxyindoleacetic acid (5HIAA) may be indicative of a level of the neurotransmitter serotonin. Neurotransmitters refer to chemicals that are used to delay, amplify, and/or modulate electrical signals between neurons. Neurotransmitters include small-molecule transmitters and neuroactive peptides. There are various small-molecule neurotransmitters that may be detected by the neurotransmitter sensor  510 . For example, acetylcholine, 5 amines, 3 or 4 amino acids, purines, such as adenosine, ATP, GTP and/or their derivatives may be detected by the neurotransmitter sensor  510 . Various neuroactive peptides may also be detected by the neurotransmitter sensor circuit  510 . Neurotransmitters or the, breakdown products or metabolites of neurotransmitters may be detected by the IMD, and through subsequent analysis of the concentration levels, adjustments may be made to therapeutic stimulation. 
     In one embodiment, the neurotransmitter is dopamine, serotonin, acetylcholine, catecholamine, or nicotine. 
     Specific classes of neurotransmitters include, but are not limited to, peptides, enzymes, hormones, amino acids, and nucleotides, in addition to those described herein. 
     In one embodiment, the peptide is substance P, neuropeptide Y, neurokines, cytokines, interleukins, or lymphokines. 
     In one embodiment, the enzyme is adrenoceptor protein kinase, choline acetyltransferase, or acetylcholinesterase. 
     In one embodiment, the hormone is glucocorticoid (GC), serum cortisol, cortisol, prostaglandin, cholecystokinin (CCK), orexias, galinin, corticotrophin releasing hormone (CRH), or adrenocorticotropic hormone (ACTH). 
     In one embodiment, the amino acid is glutamate, gamma-aminobutyric acid (GABA), or glycine. 
     In one embodiment, the nucleotide is adenosine triphosphate (ATP) or guanosine triphosphate (GTP). 
     In neuronal transmission, some action potentials that travel to a neuron cell-body cause a resultant rapid depolarization which causes calcium ion channels to open. Calcium then may stimulate the transport of vesicles to synaptic membranes. The vesicles and cell membranes may fuse, leading to the release of packaged neurotransmitter. This action is called exocytosis. The neurotransmitters may then diffuse across the synaptic cleft to bind to receptors. The receptors may be ionotropic and metabolic receptors. A neurotransmitter&#39;s effect is influenced by its receptors. 
     Neurotransmitters may cause either excitatory or inhibitory post synaptic potentials. Neurotransmitters may help the initiation of a nerve impulse in a receiving neuron. Alternatively, neurotransmitters may discourage such an impulse by modifying the local membrane voltage potential. This modification of the voltage potential may be detected by the electrical sensor circuit  520 . 
     Further, neurotransmitters are removed from the synaptic cleft by the process of re-uptake. Re-uptake provides for the prevention of continuous stimulation or inhibition of the firing of post synaptic neurons. In other words, re-uptake is necessary to control either the excitatory or inhibitory post synaptic potentials. The electrical sensor unit  520  may be capable of detecting voltage levels that are indicative of the excitatory or inhibitory states of post synaptic potentials. This information may lead to a determination of the state of a particular disorder, such as depression. The neurotransmitter sensor circuit  510  is capable of detecting neurotransmitters such as dopamine and/or serotonin Serotonin is generally released by cells in the brainstem region (i.e., raphe nuclei). A sensor  250  may be positioned proximate to the brainstem region such that detection of the neurotransmitter, serotonin, is facilitated. In one embodiment, the sensor may consist of an implantable microdialysis probe coupled to a neurochemical analyzer. 
     Serotonin re-uptake inhibition may be provided by the stimulation delivered by the IMD  200 . This may potentiate serotonin&#39;s effect, thereby changing the depression level in the patient&#39;s body. This process may be detected, monitored, and controlled by using data from the neurotransmitter sensor circuit  510  and/or the electrical sensor  520  to monitor the effects of the treatment provided by the IMD  200 . Serotonin may affect the biochemistry of depression, migraine, bi-polar disorder, and/or anxiety. Further, serotonin may affect sexuality and appetite disorders in a patient&#39;s body. The level of serotonin may be affected by the stimulation delivered by the IMD  200 , wherein the stimulation may be based upon data from the neurotransmitter sensor circuit  510 . 
     The neurotransmitter sensor circuit  510  may also detect dopamine levels in the patient&#39;s body. Dopamine generally activates dopamine receptors and is also a neurohormone released by the hypothalamus. This hormone may also be detected by the biological sensor unit  540 , which is capable of detecting biological substance in the patient&#39;s body. Dopamine may act upon the sympathetic nervous system, the result of which may include increasing heart rate, increasing blood pressure, increasing respiration rate, etc. Other disorders, such as Parkinson&#39;s disease, may be affected by the IMD  200  by varying dopamine levels, which may be detected and controlled in a feedback control manner using data from the neurotransmitter sensor circuit  510  and/or data from the biological sensor unit  540 . Additionally, chemical indications such as HVA, 5-hydroxyindoleacetic acid (5HIAA) acid, etc., may provide an indication of the respective levels of dopamine and serotonin in the body. This chemical detection may be provided by the chemical sensor unit  530 . 
     Various disorders may affect the neurotransmitter passageways inside the patient&#39;s body, which may be detected by the sensing unit  410 . Other components, such as nitric oxide, may also be detected by the sensing unit  410 , which may affect immune system responses. Therefore, data from the sensor may be used by the IMD  200  to treat immune-related disorders. 
     The electrical sensor circuit  520  is capable of detecting electrical factors such as a redox reaction. Redox reaction generally refers to oxidation and reduction associated with transfer of one or more electrons from a donor to an acceptor of chemical species. The oxidation-reduction reaction may accompany a change in energy called free energy. The free energy may cause a flow of electrons that generates a redox potential, which may be measured by the electrical sensor circuit  520 . Other factors like metabolite, etc., may also be detected by the various circuitry of the sensing unit  410 . 
     The neurotransmitter sensor circuit  510  may detect the various neurotransmitter-related physiological conditions such as a neurotransmitter level, a neurotransmitter breakdown product level, a metabolite, change in a neurotransmitter breakdown product level, a peptide level, a change in peptide level, a ligand level, a change in a ligand level, an amino acid level, a change in an amino acid level, a medication level, change in a medication level, a drug level, change in a drug level, change in hormone, change in a hormone level, change in a glucocorticoid (GC), change in a glucocorticoid (GC) level, and/or a change in level of a bloodborne substance. 
     The chemical sensor unit  530  is capable of sensing various chemical factors in the patient&#39;s body, such as a change in the level of serum cortisol, cortisol level, neuropeptide Y, acetylcholine, dopamine, serotonin, prostaglandins, glucocorticoids, catecholamines, adrenoceptor g-protein kinase, glutamate, nicotinic, neuropeptide Y, GABA (A and B), neurokine-a, neurokine-3, choline acteytransferanse, acetylcholinesterase, cytokines, cholecystokinin (CCK), aglutamate, orexins, and/or galinin. Various other chemical physiological factors in the patient&#39;s body may also be detected by the sensing unit  410 . 
     The biological sensor unit  540  is capable of sensing various biological factors in the patient&#39;s body, such as various hormone levels, acetylcholine corticotrophin releasing hormone (CRH), and/or adrenocorticotropic hormone (ACTH). These physiological factors may be analyzed to determine the response as to various physiological states of a patient&#39;s body resulting from a stimulation. 
     Turning now to  FIG. 6 , a flowchart depiction of a method for performing an adaptive stimulation control process using sensor data in accordance with one illustrative embodiment is depicted. In one embodiment, the IMD  200  performs a delivery of stimulation therapy based upon a predetermined set of parameters (block  610 ). Subsequent to the delivery of stimulation, the IMD  200  may perform a sensor data acquisition and analysis process (block  620 ). This process may include acquiring one or more types of physiological data from the sensor  250  and performing an analysis to determine a physiological condition of the patient. For example, the effect of stimulation provided upon a particular disorder such as depression may be analyzed during this process. A more detailed description of the sensor data acquisition and analysis process of block  620 , are provided in  FIG. 7  and the accompanying description below. 
     Continuing referring to  FIG. 6 , upon performing the acquisition of sensor data and analyzing the data, the IMD  200  may determine whether stimulation parameters should be modified (block  630 ). A decision to modify stimulation parameters may be based upon the characteristic(s) relating to various physiological conditions, such as a detected increase in the re-uptake of serotonin levels when treating depression. Based upon this analysis, the IMD  200  may, for example, determine that a reduced amount of stimulation may now be needed since serotonin re-uptake has increased, thereby reducing the possibility of an onset of a severe depression episode. Other factors such as neurotransmitter levels, electrical indications in the patient&#39;s body, chemical indications and/or biological indications may be detected and analyzed to determine whether an increase, a decrease, or no change to the stimulation parameters is desirable. Other modifications may include performing a stimulation in a second portion of the patient in response to a physiological factor. 
     Upon detecting that the stimulation is to be modified, revised stimulation parameter(s) may be implemented by the IMD  200  (block  640 ). Various algorithms and tables may be stored in the IMD  200  to allow for a comparison and analysis of the acquired sensory data with reference data in order to adjust stimulation parameters. Alternatively, sensor signal and analysis may be communicated to an external unit  370 . In this case, a physician may perform an analysis and manually instruct the IMD  200  to modify its stimulation parameters. Upon modification of the stimulation parameters, the IMD  200  may perform a subsequent stimulation based on the modified parameters (block  650 ). This process may then follow another sensor analysis and the entire process indicated in  FIG. 6  may be repeated. 
     In one embodiment, the sensing of the data sensor data may be performed periodically based upon a predetermined interval. In an alternative embodiment, sensing of the data sensor data may be performed reactively based upon an event detected by the IMD  200 . In yet another embodiment, the sensing of the data sensor data may be performed by external prompt (e.g., a prompt from a physician or the patient) from the external unit  370 . Further, the sensing of the data sensor data may be performed based on any combination of the “predetermined interval” approach, the “reactive” approach, and the “external prompt” approach. 
     When the IMD  200  determines that based upon the data and the sensory analysis process that the stimulation should not be monitored or modified, the IMD  200  merely maintains the current stimulation patterns and performs a subsequent stimulation (block  660 ). In this manner, physiological conditions may be monitored and characterization of a disorder may be made to provide an adaptive adjustment of the stimulation provided by the IMD  200 . Therefore, a feedback loop may be established using the sensor data and analysis by the IMD  200  and/or external input to provide an adaptive adjustment of the one or more stimulation parameters. 
     Turning now to  FIG. 7 , a flowchart depiction of performing the sensor data acquisition and analysis process of block  620 , is illustrated. The IMD  200  may identify the type of sensor data to be acquired based upon the specific disorder being treated by the IMD  200  (block  710 ). For example, in the case of treating depression, various neurotransmitters may be analyzed. Accordingly, the neurotransmitter sensor circuit  510  in the sensing unit  410  may be activated (see  FIGS. 4 and 5 ). Continuing referring to  FIG. 7 , if the IMD  200  has been programmed to analyze indication(s) of the neurotransmitter rather than the neurotransmitter itself, the electrical sensor circuit  520 , chemical sensor circuit  530 , and/or biological sensor circuit  540  may be activated by the IMD  200  (block  720 ). 
     Upon activation of the desired type of sensor data to be acquired, one or more specific sensor circuits  510 - 540  in the sensor  250  are activated. 
     Based upon the activation of one or more sensor circuits  510 - 540 , the corresponding sensor data may be acquired (block  730 ). The timing of the acquisition may be determined based on predetermined rules, such as a predetermined protocol for following a stimulation period with an acquisition of physiological data. Therefore, indications of physiological variations in the patient&#39;s body, such as data relating to changes in the neurotransmitter levels, may be acquired and correlated to the preceding stimulation regimen (block  740 ). Based upon this correlation, the IMD  200  may determine whether the stimulation parameters should be changed (block  750 ). In other words, if it is determined that based upon the correlation, the desired affect has been achieved, a parameter relating to the stimulation (e.g., amplitude) may be reduced. Alternatively, if significant physiological changes are detected, the intensity of the stimulation, duration, and/or other parameters associated with the stimulation may be modified to prompt a more appreciable physiological response to the stimulation. 
     Turning now to  FIG. 8 , a flowchart depiction of performing the sensor feedback control of the IMD  200  in accordance with an alternative embodiment is provided. In this embodiment, regardless of whether a stimulation has been recently performed or not, the sensor  250  may be activated to perform a periodic or predetermined sensor data monitoring process (block  810 ). This may include monitoring specific electrical, chemical, biological, and/or neurotransmitter levels. The sensing process may be based upon the specific disorder being treated by the IMD  200 . Based upon the sensing the data, the IMD  200  may process and analyze the data to determine whether unusual responses resulting from the stimulation has occurred (block  820 ). The comparator  372  may use baseline/reference comparison data to compare the current level of physiological characteristics detected by the sensor. This may provide an indication as to whether unusual levels of the sensed materials are found. 
     A determination is made whether unusual level(s) relating to the sensed characteristic(s) have been detected (block  830 ). For example, an unusual amount of serotonin may indicate that sufficient re-uptake has not taken place. If it is determined that no unusual level of physiological characteristic has been detected, the IMD  200  may continue a normal stimulation schedule as predetermined (block  850 ). This block may be looped back to the block  810  where a periodic sensor data acquisition is performed. If normal levels have been detected, the IMD  200  may simply continue performing predetermined, periodic stimulation and continue to periodically monitor the sensor data. Additionally, event-driven and/or manually provoked sensing may also be implemented. 
     If it is determined that the detected sensed characteristic level was unusual (block  830 ), the IMD  200  may determine the type of stimulation adjustment to implement (block  840 ). In other words, if unusual levels of sensed material have been detected, various analyses, comparisons, and algorithms may be performed to determine whether to increase, decrease, or otherwise change the stimulation parameters based on the various factors detected. Based upon a determination of the type of stimulation adjustment to be implemented, a resulting modified stimulation is delivered (block  850 ). For example, increased intensity of a stimulation signal may be now be provided in response to an indication that excessive neurotransmitters have been detected. Therefore, a stimulation may be provided to prompt additional re-uptake of a neurotransmitter (e.g., causing an increase in serotonin re-uptake to decrease the intensity of depression in a patient). 
     Utilizing the concepts provided herein, an adaptive stimulation process may be implemented by modifying stimulation parameters based upon detected sensor data. Various characteristics, such as chemical changes, hormonal changes, electrical activity changes, neurotransmitter level changes, etc., may be detected and analyzed. Based upon this analysis, feedback correction/adjustment of stimulation parameters may be performed by the IMD  200 . In this manner, more efficient response to a patient&#39;s reaction to stimulation may be performed by the IMD  200 . In this way targeted treatment may be adaptively performed, thereby improving treatment of various disorders using an implantable medical device. 
     The particular embodiments disclosed above are illustrative only and may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Furthermore, no limitations are intended to the details of construction or design herein shown other than as described in the claims below. It is, therefore, evident that the particular embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the disclosure. Accordingly, the protection sought herein is as set forth in the claims below.