Patent Publication Number: US-2006009815-A1

Title: Method and system to provide therapy or alleviate symptoms of involuntary movement disorders by providing complex and/or rectangular electrical pulses to vagus nerve(s)

Description:
This application is a continuation of application Ser. No. 10/841,995 filed May 8, 2004, entitled “METHOD AND SYSTEM FOR MODULATING THE VAGUS NERVE (10 TH  CRANIAL NERVE) WITH ELECTRICAL PULSES USING IMPLANTED AND EXTERNAL COMPONANTS, TO PROVIDE THERAPY FOR NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS”, which is a continuation of application Ser. No. 10/196,533 filed Jul. 16, 2002, which is a continuation of application Ser. No. 10/142,298 filed on May 9, 2002. The prior applications being incorporated herein in their entirety by reference, and priority is claimed from the above applications. 
    
    
     FIELD OF INVENTION  
      The present invention relates to neuromodulation, more specifically to provide therapy for involuntary movement disorders (Parkinson&#39;s disease, epilepsy, and the like) by selectively stimulating/neuromodulating vagus nerve(s) by providing complex and/or rectangular electrical pulses to vagus nerve(s).  
     BACKGROUND  
      Parkinson&#39;s disease (PD) belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine producing brain cells. Parkinsonism is the most common movement disorder in adults affecting 1% to 2% of patients &gt;60 years old.  
      The symptoms of PD are tremor, or trembling in hand, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. PD usually affects people over the age of 50. Early symptoms of PD are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of PD patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes; difficulty in swallowing, chewing, and speaking; urinary problems or constipation; skin problems; and sleep disruptions.  
      There is no known treatment that will halt or reverse the neuronal degeneration that presumably underlies Pakinson&#39;s disease. The selective afferent stimulation of vagus nerve(s) provides a pathway to various centers in the brain, including centers that control Parkinsonism tremors, via the projections of the Nucleous of Solitary Tract (NTS). The NTS is the first relay station of vagus nerve afferents in the medulla of the brain. This disclosure is directed to providing complex electrical pulses to vagal nerve(s) for selective stimulation and/or blocking to provide adjunct (add-on) therapy, or to alleviate symptoms for Parkinsonism and epilepsy. Complex electrical pulses comprise at least one of multi-level pulses, biphasic pulses, non-rectangular pulses, or pulses with varying amplitude during the pulse. The method and system to provide electrical pulses may comprise both implantable and external components.  
     Background of Parkinson&#39;s Disease and Movement Disorders  
      Parkinson&#39;s disease (PD) is a progressive neurodegenerative disorder whose pathologic hallmark is loss of dopaminergic neurons in the substantia nigra pars compacta. The cardinal motor signs of PD are tremor, rigidity, bradykinesia, akinesia, and a gait disorder characterized by a flexed posture and short, shuffling steps. Patients may also develop postural instability and freezing, a phenomenon characterized by a sudden inability to continue or initiate movement. Decreased associated movements (masked facies, decreased eye blink, and reduced arm swing) are common early signs of PD. Hyprophonia, micrographia, and difficulty with fine motor control (buttoning buttons, handling utensils, shaving, or applying makeup), and getting out of a chair or rolling over in bed at night are common early complaints of PD patients.  
     Other Concommitent Disorders  
      Sleep disorders are common in Parkinsonian patients and may exacerbate Parkinsonian motor signs as a result of the excessive fatigue and daytime sleepiness.  
      Depression is a common occurrence in patients with PD, but it is often overlooked. It has been clinically observed that successful treatment of their depression is almost always associated with a concurrent improvement in parkinsonian motor signs.  
     Other Movement Disorders  
      Essential tremor (ET), which is the most common movement disorder is an insidiously progressive and often inheritable idsorder usually beginning before the age of 50. The genetic basis is uncertain. It is characterized by involuntary rhythmic oscillations of a body part resulting from either alternating or synchronous contractions of opposing muscles. Tremor is essentially the only symptom present, although subtle gait abnormalities may be noted when the legs are affected. Weakness is not a primary symptom although tremor can produce weakness by reducing the strength of contraction.  
      Huntington&#39;s Disease (HD) is characterized as a triad of symptoms and signs: a movement disorder, a cognitive disorder, and a psychiatric disorder. Each of these: domains may be problematic for the individual at various states of the illness, which on average spans 15 to 20 years.  
      Progressive supranuclear palsy (PSP) is the most common Parkinsonian disorder after Parkinson&#39;s disease (PD). Typically, PSP patients present with early postural instability, supranuclear vertical gaze palsy, and levodopa-nonresponsive parkinsonism (bradykinesia and axial more than limb rigidity).  
     Medical Therapy  
      General Approach to Therapy: Initial medical treatment typically involves the use of drugs to replace striatal dopamine or drugs that have dopaminergic properties, e.g., dopamine agonists.  
      Disease Progression and Development of Motor Complication Wearing Off (End-of-Dose Phenomenon): Over time, patients&#39; symptoms typically become more severe, and they begin to develop wearing-off phenomenon (i.e., symptoms return before the next dose of medication). When this occurs, one can increase the dose of medication, decrease the time interval between doses, add an agonist or begin a COMT inhibitor to minimize the amount of “off” time. There should be a small amount of time before the next dose when the patient notes some loss of effect because this indicates that the patient is not receiving more medication than necessary.  
     Surgical Therapy  
      Patients with PD whose motor symptoms can no longer be controlled adequately be medical therapy are candidates for surgical therapy. Surgical procedures of PD consist of ablative procedures (thalamotomy, pallidotomy) and stimulation procedures (thalamic, pallidal, subthalamic).  
      Thalamotomy: Thalamotomy is effective for the treatment of parkinsonian tremor. Lesions are generally placed in the cerebellar receiving area, ventralis intermedius (VIM). If the lesion is extended more anteriorly into the basal ganglia receiving area, ventralis oralis posterior and ventralis oralis anterior. Thalamotomy may also improve rigidity and drug-induced dyskinesias.  
      Pallidotomy: Pallidotomy is effective for all the cardinal motor signs of PD, including tremor, rigidity, and bradykinesia, as well as motor fluctiations and drug-induced dyskinesias and dystomia. It may also improve axial sympotoms, including gait, balance, and freezing. The improvement in axial symptoms after unilateral pallidotomy, however, is less consistent than that for appenducular symptoms, with many patients losing their benefit anywhere form 6 months to 2 years postpallidotomy.  
      Deep Brain Stimulation (DBS): DBS in the GPi or the STN for PD can be performed either as a staged procedure or simultaneously. Simultaneous procedures may be associated with a higher incidence of postoperative confusion. Based on the patient&#39;s symptoms, unilateral implantaion may benefit the patient enough to preclude or at least delay the necessity for a second implantation on the other side. Most patients, however, will require bilateral implantation to gain optimal control over axial symptoms or to gain bilateral control over appendicular symptoms. Both targets, the GPi and the STN, are effective in treating the cardinal motor signs of PD, including gait, balance, and freezing symptoms.  
      Since surgical therapy and deep brain stimulation are very invasive procedures, applicant&#39;s believe neuromodulation of the vagus nerve(s) will provide therapy or alleviate symptoms of movement disorders by much less invasive procedure. Further, drug therapy may be combined with neuromodulation of vagus nerve(s).  
     Background of Vagus Nerve(s)  
      The 10 th  cranial nerve or the vagus nerve plays a role in mediating afferent information from visceral organs to the brain. The vagus nerve arises directly from the brain, but unlike the other cranial nerves extends well beyond the head. At its farthest extension it reaches the lower parts of the intestines. The vagus nerve provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Observations on the profound effect of electrical stimulation of the vagus nerve on central nervous system (CNS) activity extends back to the 1930&#39;s. The present invention is primarily directed to selective electrical stimulation or neuromodulation of vagus nerve with complex electrical pulses, for providing adjunct (add-on) therapy for involuntary movement disorders (including Parkinson&#39;s disease and epilepsy).  
      In the human body there are two vagal nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagus nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagus nerve does not cause substantial slowing of the heart rate or cause any other significant deleterious side effects.  
     Background of Neuromodulation  
      One of the fundamental features of the nervous system is its ability to generate and conduct electrical impulses. Most nerves in the human body are composed of thousands of fibers of different sizes. This is shown schematically in  FIG. 1 . The different sizes of nerve fibers, which carry signals to and from the brain, are designated by groups A, B, and C. The vagus nerve, for example, may have approximately 100,000 fibers of the three different types, each carrying signals. Each axon or fiber of that nerve conducts only in one direction, in normal circumstances. In the vagus nerve sensory fibers (afferent) outnumber parasympathetic fibers four to one.  
      In a cross section of peripheral nerve it is seen that the diameter of individual fibers vary substantially, as is also shown schematically in  FIG. 2 . The largest nerve fibers are approximately 20 μm in diameter and are heavily myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the smallest nerve fibers are less than 1 μm in diameter and are unmyelinated.  
      The diameters of group A and group B fibers include the thickness of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially in the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter.  
      Nerve cells have membranes that are composed of lipids and proteins (shown schematically in  FIGS. 3A and 3B ), and have unique properties of excitability such that an adequate disturbance of the cell&#39;s resting potential can trigger a sudden change in the membrane conductance. Under resting conditions, the inside of the nerve cell is approximately −90 mV relative to the outside. The electrical signaling capabilities of neurons are based on ionic concentration gradients between the intracellular and extracellular compartments. The cell membrane is a complex of a bilayer of lipid molecules with an assortment of protein molecules embedded in it ( FIG. 3A ), separating these two compartments. Electrical balance is provided by concentration gradients which are maintained by a combination of selective permeability characteristics and active pumping mechanism.  
      The lipid component of the membrane is a double sheet of phospholipids, elongated molecules with polar groups at one end and the fatty acid chains at the other. The ions that carry the currents used for neuronal signaling are among these water-soluble substances, so the lipid bilayer is also an insulator, across which membrane potentials develop. In biophysical terms, the lipid bilayer is not permeable to ions. In electrical terms, it functions as a capacitor, able to store charges of opposite sign that are attracted to each other but unable to cross the membrane. Embedded in the lipid bilayer is a large assortment of proteins. These are proteins that regulate the passage of ions into or out of the cell. Certain membrane-spanning proteins allow selected ions to flow down electrical or concentration gradients or by pumping them across.  
      These membrane-spanning proteins consist of several subunits surrounding a central aqueous pore (shown in  FIG. 3B ). Ions whose size and charge “fit” the pore can diffuse through it, allowing these proteins to serve as ion channels. Hence, unlike the lipid bilayer, ion channels have an appreciable permeability (or conductance) to at least some ions. In electrical terms, they function as resistors, allowing a predicable amount of current flow in response to a voltage across them.  
      A nerve cell can be excited by increasing the electrical charge within the neuron, thus increasing the membrane potential inside the nerve with respect to the surrounding extracellular fluid. As shown in  FIG. 4 , stimuli  4  and  5  are subthreshold, and do not induce a response. Stimulus  6  exceeds a threshold value and induces an action potential (AP)  17  which will be propagated. The threshold stimulus intensity is defined as that value at which the net inward current (which is largely determined by Sodium ions) is just greater than the net outward current (which is largely carried by Potassium ions), and is typically around −55 mV inside the nerve cell relative to the outside (critical firing threshold). If however, the threshold is not reached, the graded depolarization will not generate an action potential and the signal will not be propagated along the axon. This fundamental feature of the nervous system i.e., its ability to generate and conduct electrical impulses, can take the form of action potentials  17 , which are defined as a single electrical impulse passing down an axon. This action potential  17  (nerve impulse or spike) is an “all or nothing” phenomenon, that is to say once the threshold stimulus intensity is reached, an action potential will be generated.  
       FIG. 5A  illustrates a segment of the surface of the membrane of an excitable cell. Metabolic activity maintains ionic gradients across the membrane, resulting in a high concentration of potassium (K + ) ions inside the cell and a high concentration of sodium (Na + ) ions in the extracellular environment. The net result of the ionic gradient is a transmembrane potential that is largely dependent on the K +  gradient. Typically in nerve cells, the resting membrane potential (RMP) is slightly less than 90 mV, with the outside being positive with respect to inside.  
      To stimulate an excitable cell, it is only necessary to reduce the transmembrane potential by a critical amount. When the membrane potential is reduced by an amount ΔV, reaching the critical or threshold potential (TP); Which is shown in  FIG. 5B . When the threshold potential (TP) is reached, a regenerative process takes place: sodium ions enter the cell, potassium ions exit the cell, and the transmembrane potential falls to zero (depolarizes), reverses slightly, and then recovers or repolarizes to the resting membrane potential (RMP).  
      For a stimulus to be effective in producing an excitation, it must have an abrupt onset, be intense enough, and last long enough. These facts can be drawn together by considering the delivery of a suddenly rising cathodal constant-current stimulus of duration d to the cell membrane as shown in  FIG. 5B .  
      Cell membranes can be reasonably well represented by a capacitance C, shunted by a resistance R as shown by a simplified electrical model in diagram  5 C, and shown in a more realistic electrical model in  FIG. 6 , where neuronal process is divided into unit lengths, which is represented in an electrical equivalent circuit. Each unit length of the process is a circuit with its own membrane resistance (r m ), membrane capacitance (c m ), and axonal resistance (r a ).  
      When the stimulation pulse is strong enough, an action potential will be generated and propagated. As shown in  FIG. 7 , the action potential is traveling from right to left. Immediately after the spike of the action potential there is a refractory period when the neuron is either unexcitable (absolute refractory period) or only activated to sub-maximal responses by supra-threshold stimuli (relative refractory period). The absolute refractory period occurs at the time of maximal Sodium channel inactivation while the relative refractory period occurs at a later time when most of the Na +  channels have returned to their resting state by the voltage activated K +  current. The refractory period has two important implications for action potential generation and conduction. First, action potentials can be conducted only in one direction, away from the site of its generation, and secondly, they can be generated only up to certain limiting frequencies.  
      A single electrical impulse passing down an axon is shown schematically in  FIG. 8 . The top portion of the figure (A) shows conduction over mylinated axon (fiber) and the bottom portion (B) shows conduction over nonmylinated axon (fiber). These electrical signals will travel along the nerve fibers.  
      The information in the nervous system is coded by frequency of firing rather than the size of the action potential. This is shown schematically in  FIG. 9 . The bottom portion of the figure shows a train of action potentials  17 .  
      In terms of electrical conduction, myelinated fibers conduct faster, are typically larger, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation, compared to unmyelinated fibers. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (μs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 μs) and a higher amplitude for activation. Because of their very slow conduction, C fibers would not be highly responsive to rapid stimulation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable with traditional rectangular pulses inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.  
      As shown in  FIG. 10A , when the distal part of a nerve is electrically stimulated, a compound action potential is recorded by an electrode located more proximally. A compound action potential contains several peaks or waves of activity that represent the summated response of multiple fibers having similar conduction velocities. The waves in a compound action potential represent different types of nerve fibers that are classified into corresponding functional categories as shown in the Table one below,  
                                   TABLE 1                                       Conduction   Fiber               Fiber   Velocity   Diameter           Type   (m/sec)   (μm)   Myelination                          A Fibers                       Alpha    70-120   12-20    Yes           Beta   40-70   5-12   Yes           Gamma   10-50   3-6    Yes           Delta    6-30   2-5    Yes           B Fibers    5-15   &lt;3   Yes           C Fibers   0.5-2.0   0.4-1.2    No                      
 
       FIG. 10B  further clarifies the differences in action potential conduction velocities between the Aδ-fibers and the C-fibers. For many of the application of current patent application, it is the slow conduction C-fibers that are stimulated by the pulse generator.  
      The modulation of nerve in the periphery, as done by the body, in response to different types of pain is illustrated schematically in  FIGS. 11 and 12 . As shown schematically in  FIG. 11 , the electrical impulses in response to acute pain sensations are transmitted to brain through peripheral nerve and the spinal cord. The first-order peripheral neurons at the point of injury transmit a signal along A-type nerve fibers to the dorsal horns of the spinal cord. Here the second-order neurons take over, transfer the signal to the other side of the spinal cord, and pass it through the spinothalamic tracts to thalamus of the brain. As shown in  FIG. 12 , duller and more persistent pain travel by another-slower route using unmyelinated C-fibers. This route is made up from a chain of interconnected neurons, which run up the spinal cord to connect with the brainstem, the thalamus and finally the cerebral cortex. The autonomic nervous system also senses pain and transmits signals to the brain using a similar route to that for dull pain.  
      Vagus nerve stimulation, as performed by the system and method of the current patent application, is a means of directly affecting central function.  FIG. 13  shows cranial nerves have both afferent pathway  19  (inward conducting nerve fibers which convey impulses toward the brain) and efferent pathway  21  (outward conducting nerve fibers which convey impulses to an effector). Vagus nerve is composed of approximately 80% afferent sensory fibers carrying information to the brain from the head, neck, thorax, and abdomen. The sensory afferent cell bodies of the vagus reside in the nodose ganglion and relay information to the nucleus tractus solitarius (NTS).  
      The vagus nerve is composed of somatic and visceral afferents and efferents. Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally), as described later in this disclosure. The vast majority of vagus nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull.  
      In considering the anatomy, the vagus nerve spans from the brain stem all the way to the splenic flexure of the colon. Not only is the vagus the parasympathetic nerve to the thoracic and abdominal viscera, it also the largest visceral sensory (afferent) nerve. Sensory fibers outnumber parasympathetic fibers four to one. In the medulla, the vagal fibers are connected to the nucleus of the tractus solitarius (viceral sensory), and three other nuclei. The central projections terminate largely in the nucleus of the solitary tract, which sends fibers to various regions of the brain (e.g., the thalamus, hypothalamus and amygdala).  
      As shown in  FIG. 14 , the vagus nerve emerges from the medulla of the brain stem dorsal to the olive as eight to ten rootlets. These rootlets converge into a flat cord that exits the skull through the jugular foramen. Exiting the Jugular foramen, the vagus nerve enlarges into a second swelling, the inferior ganglion.  
      In the neck, the vagus lies in a groove between the internal jugular vein and the internal carotid artery. It descends vertically within the carotid sheath, giving off branches to the pharynx, larynx, and constrictor muscles. From the root of the neck downward, the vagus nerve takes a different path on each side of the body to reach the cardiac, pulmonary, and esophageal plexus (consisting of both sympathetic and parasympathetic axons). From the esophageal plexus, right and left gastric nerves arise to supply the abdominal viscera as far caudal as the splenic flexure.  
      In the body, the vagus nerve regulates viscera, swallowing, speech, and taste. It has sensory, motor, and parasympathetic components. Table two below outlines the innervation and function of these components.  
               TABLE 2                          Vagus Nerve Components                         Component               fibers   Structures innervated   Functions               SENSORY   Pharynx, larynx,   General sensation           esophagus, external ear           Aortic bodies, aortic arch   Chemo- and baroreception           Thoracic and abdominal           viscera       MOTOR   Soft palate, pharynx,   Speech, swallowing           larynx, upper esophagus       PARASYM-   Thoracic and abdominal   Control of cardiovascular       PATHETIC   viscera   system, respiratory and               gastrointestinal tracts                  
 
      On the Afferent side, visceral sensation is carried in the visceral sensory component of the vagus nerve. As shown in  FIGS. 15A and 15B , visceral sensory fibers from plexus around the abdominal viscera converge and join with the right and left gastric nerves of the vagus. These nerves pass upward through the esophageal hiatus (opening) of the diaphragm to merge with the plexus of nerves around the esophagus. Sensory fibers from plexus around the heart and lungs also converge with the esophageal plexus and continue up through the thorax in the right and left vagus nerves. As shown in  FIG. 15B , the central process of the nerve cell bodies in the inferior vagal ganglion enter the medulla and descend in the tractus solitarius to enter the caudal part of the nucleus of the tractus solitarius. From the nucleus, bilateral connections important in the reflex control of cardiovascular, respiratory, and gastrointestinal functions are made with several areas of the reticular formation and the hypothalamus.  
      The afferent fibers project primarily to the nucleus of the solitary tract (shown schematically in  FIGS. 16 and 17 ) which extends throughout the length of the medulla oblongata. A small number of fibers pass directly to the spinal trigeminal nucleus and the reticular formation. As shown in  FIG. 16 , the nucleus of the solitary tract has widespread projections to cerebral cortex, basal forebrain, thalamus, hypothalamus, amygdala, hippocampus, dorsal raphe, and cerebellum. Because of the widespread projections of the Nucleus of the Solitary Tract, neuromodulation of the vagal afferent nerve fibers provide therapy and alleviation of symptoms of involuntary movement disorders including Parkinson&#39;s disease and epilepsy.  
     Prior Art Teachings and Applicant&#39;s Methodology  
      The prior art teachings of Zabara and Wernicke in general relies on the fact, that in anesthetized animals stimulation of vagal nerve afferent fibers evokes detectable changes of the EEG in all of the regions, and that the nature and extent of these EEG changes depends on the stimulation parameters. They postulated (Wernicke et al. U.S. Pat. No. 5,269,303) that synchronization of the EEG may be produced when high frequency (&gt;70 Hz) weak stimuli activate only the myelinated (A and B) nerve fibers, and that desynchronization of the EEG occurs when intensity of the stimulus is increased to a level that activates the unmyelinated (C) nerve fibers.  
      The applicant&#39;s methodology is different, and among other things is based on cumulative effects of vagus nerve afferent stimulation, and does not rely on VNS-induced EEG changes. This is relevant since an intent of Zabara and Wernicke et al. teachings is to have a feedback system, wherein a sensor in the implantable system responds to EEG changes providing vagus nerve stimulation. Applicant&#39;s methodology is based on an open-loop system where the physician determines the parameters for vagus nerve stimulation (and blocking). If the selected parameters are uncomfortable or are not tolerated by the patient, the electrical parameters are re-programmed. Advantageously, according applicant&#39;s disclosure, some re-programming or parameter adjustment may be done from a remote location, over a wide area network. A method of remote communication for neuromodulation therapy system is disclosed in commonly assigned U.S. Pat. No. 6,662,052 B1 and applicant&#39;s co-pending application Ser. No. 10/730,513 (Boveja).  
      It is of interest that clinical investigation (in conscious humans) have not shown VNS-induced changes in the background EEGs of humans. A study, which used awake and freely moving animals, also showed no VNS-induced changes in background EEG activity. Taken together, the findings from animal study and human studies indicate that acute desynchronization of EEG activity is not a prominent feature of VNS when it is administered during physiologic wakefulness and sleep.  
      One of the advantages of applicant&#39;s open-loop methodology is that predetermined/pre-packaged programs may be used. This may be done utilizing an inexpensive implantable pulse generator as disclosed in applicant&#39;s commonly assigned U.S. Pat. No. 6,760,626 B1 referred to as Boveja &#39;626 patent. Predetermined/pre-packaged programs define neuromodulation parameters such as pulse amplitude, pulse width, pulse frequency, on-time and off-time. Examples of predetermined/pre-packaged programs are disclosed in applicant&#39;s &#39;626 patent, and in this disclosure for both implantable and external pulse generator means. If an activated pre-determined program is uncomfortable for the patient, a different pre-determined program may be activated or the program may be selectively modified.  
      Another advantage of applicant&#39;s methodology is that, at any given time a patient will receive the most aggressive therapy that is well tolerated. Since the therapy is cumulative the clinical benefits will be realized quicker.  
      Another advantage of applicant&#39;s method is that complex pulses may be provided. Complex pulses may also be used in conjunction with tripolar electrodes. The use of complex pulses adds another dimension to selective stimulation of vagus nerve, as recruitment of different fibers occurs during the pulse. The Zabara and Wernicke teachings utilize rectangular pulses.  
      In summery, applicant&#39;s invention is based on an open-loop pulse generator means utilizing predetermined (pre-packaged programs), where the effects of the therapy and clinical benefits are cumulative effects, which occur over a period of time with selective stimulation. Prior art teachings (of vagal tuning) point away from using predetermined (pre-packaged programs).  
      In the applicant&#39;s methodology, after the patient has recovered from surgery (approximately 2 weeks), and the stimulation/blocking is turned ON, nothing happens immediately. After a few weeks of intermittent stimulation, the effects start to become noticeable in some patients. Thereafter, the beneficial effects of pulsed electrical therapy accumulate up to a certain point, and are sustained over time, as the therapy is continued.  
     PRIOR ART  
      U.S. Pat. No. 6,708,064 B2 (Rezai) is generally directed to method for treating neurological conditions by stimulating and sensing in the brain especially in the intraminar nuclei (ILN), for affecting psychiatric disorders.  
      U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like. Applicant&#39;s method of neuromodulation is significantly different than that disclosed in Zabara &#39;254, &#39;164’ and &#39;807 patents.  
      U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy needs to be continuously sustained over a prolonged period of time. The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application.  
      U.S. Pat. No. 5,215,086 (Terry et al.) generally discloses vagus nerve modulation based on synchronization and desynchronization of EEGs, among other things. Applicant&#39;s methodology is different in many aspects, some of which were highlighted in the previous section.  
      U.S. Pat. No. 6,205,359 B1 (Boveja) and U.S. Pat. No. 6,356,788 B2 (Boveja) are directed to adjunct therapy for neurological and neuropsychiatric disorders using an implanted lead-receiver and an external stimulator.  
      U.S. Pat. No. 5,193,539 (Schulman, et al) is generally directed to an addressable, implantable microstimulator that is of size and shape which is capable of being implanted by expulsion through a hypodermic needle. In the Schulman patent, up to 256 microstimulators may be implanted within a muscle and they can be used to stimulate in any order as each one is addressable, thereby providing therapy for muscle paralysis.  
      U.S. Pat. No. 5,405,367 (Schulman, et al) is generally directed to the structure and method of manufacture of an implantable microstimulator.  
      U.S. Pat. No. 6,622,041 B2 (Terry, Jr. et al.) is directed to treatment of congestive heart failure and autonomic cardiovascular drive disorders using implantable neurostimulator.  
     SUMMARY OF THE INVENTION  
      The method and system of the current invention provides afferent neuromodulation therapy for involuntary movement disorders (including Parkinson&#39;s disease and epilepsy), by providing rectangular or complex electrical pulses to the vagus nerve(s) for selective stimulation and/or blocking. This may be in addition to any drug therapy. The method and system comprises both implantable and external components. The power source may also be external or implanted in the body.  
      Accordingly, it is one object of the invention to provide predetermined rectangular or complex electrical pulses to vagus nerve(s) for stimulation and/or blocking to provide therapy or to alleviate symptoms of involuntary movement disorders (including Parkinson&#39;s disease and epilepsy).  
      It is another object of the invention to provide predetermined/pre-packaged programs for delivering therapy.  
      In one aspect of the invention, the electrical pulses are provided using an implanted stimulus-receiver adopted to work in conjunction with an external stimulator.  
      In another aspect of the invention, the electrical pulses are provided using an implanted stimulus-receiver which comprises a high value capacitor for storing charge, and is adapted to work in conjunction with an external stimulator.  
      In another aspect of the invention, the electrical pulses are provided using a programmer-less implantable pulse generator (IPG) which can be programmed with a magnet.  
      In another aspect of the invention, the electrical pulses are provided using a microstimulator.  
      In another aspect of the invention, the electrical pulses are provided using a programmable implantable pulse generator (IPG).  
      In another aspect of the invention, the electrical pulses are provided using a combination device which comprises both a stimulus-receiver and a programmable implantable pulse generator.  
      In another aspect of the invention, the electrical pulses are provided using an implantable pulse generator which comprises a re-chargeable battery.  
      In another aspect of the invention, the therapy effects are cummulative.  
      In another aspect of the invention, the selective stimulation to vagus nerve(s) may be anywhere along the length of the nerve, such as at the cervical level or at a level near the diaphram.  
      In another aspect of the invention, stimulation and/or blocking pulses may be provided.  
      In another aspect of the invention, the blocking pulses may be at a single site, or at multiple sites.  
      In another aspect of the invention, the nerve blocking comprises at least one from a group consisting of: DC or anodal block, Wedenski block, and Collision block.  
      In another aspect of the invention, the external components such as the external stimulator or programmer comprise telemetry means adapted to be networked, for remote interrogation or remote programming of the device.  
      In another aspect of the invention, the lead may be bipolar, tripolar, or multipolar to provide stimulation and blocking pulses.  
      In yet another aspect of the invention, the implanted lead comprises at least one electrode selected from the group consisting of spiral electrodes, cuff electrodes, steroid eluting electrodes, wrap-around electrodes, and hydrogel electrodes.  
      Various other features, objects and advantages of the invention will be made apparent from the following description taken together with the drawings. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      For the purpose of illustrating the invention, there are shown in accompanying drawing forms which are presently preferred, it being understood that the invention is not intended to be limited to the precise arrangement and instrumentalities shown.  
       FIG. 1  is a diagram of the structure of a nerve.  
       FIG. 2  is a diagram showing different types of nerve fibers.  
       FIGS. 3A and 3B  are schematic illustrations of the biochemical makeup of nerve cell membrane.  
       FIG. 4  is a figure demonstrating subthreshold and suprathreshold stimuli.  
       FIGS. 5A, 5B ,  5 C are schematic illustrations of the electrical properties of nerve cell membrane.  
       FIG. 6  is a schematic illustration of electrical circuit model of nerve cell membrane.  
       FIG. 7  is an illustration of propagation of action potential in nerve cell membrane.  
       FIG. 8  is an illustration showing propagation of action potential along a myelinated axon and non-myelinated axon.  
       FIG. 9  is an illustration showing a train of action potentials.  
       FIG. 10A  is a diagram showing recordings of compound action potentials.  
       FIG. 10B  is a schematic diagram showing conduction of first pain and second pain.  
       FIG. 11  is a schematic illustration showing mild stimulation being carried over the large diameter A-fibers.  
       FIG. 12  is a schematic illustration showing painful stimulation being carried over small diameter C-fibers  
       FIG. 13  is a schematic diagram of brain showing afferent and efferent pathways.  
       FIG. 14  is a schematic diagram showing the vagus nerve at the level of the nucleus of the solitary tract.  
       FIG. 15A  is a schematic diagram showing the thoracic and visceral innervations of the vagal nerves.  
       FIG. 15B  is a schematic diagram of the medullary section of the brain.  
       FIG. 16  is a simplified block diagram illustrating the connections of solitary tract nucleus to other centers of the brain.  
       FIG. 17  is a schematic diagram of brain showing the relationship of the solitary tract nucleus to other centers of the brain.  
       FIG. 18  is a simplified block diagram depicting supplying amplitude and pulse width modulated electromagnetic pulses to an implanted coil.  
       FIG. 19  depicts a customized garment for placing an external coil to be in close proximity to an implanted coil.  
       FIG. 20  is a diagram showing the implanted lead-receiver in contact with the vagus nerve at the distal end.  
       FIG. 21  is a schematic of the passive circuitry in the implanted lead-receiver.  
       FIG. 22A  is a schematic of an alternative embodiment of the implanted lead-receiver.  
       FIG. 22B  is another alternative embodiment of the implanted lead-receiver.  
       FIG. 23  shows coupling of the external stimulator and the implanted stimulus-receiver.  
       FIG. 24  is a top-level block diagram of the external stimulator and proximity sensing mechanism.  
       FIG. 25  is a diagram showing the proximity sensor circuitry.  
       FIG. 26A  shows the pulse train to be transmitted to the vagus nerve.  
       FIG. 26B  shows the ramp-up and ramp-down characteristic of the pulse train.  
       FIG. 27  is a schematic diagram of the implantable lead.  
       FIG. 28A  is diagram depicting stimulating electrode-tissue interface.  
       FIG. 28B  is diagram depicting an electrical model of the electrode-tissue interface.  
       FIG. 29  is a schematic diagram showing the implantable lead and one form of stimulus-receiver.  
       FIG. 30  is a schematic block diagram showing a system for neuromodulation of the vagus nerve, with an implanted component which is both RF coupled and contains a capacitor power source.  
       FIG. 31  is a simplified block diagram showing control of the implantable neurostimulator with a magnet.  
       FIG. 32  is a schematic diagram showing implementation of a multi-state converter.  
       FIG. 33  is a schematic diagram depicting digital circuitry for state machine.  
      FIGS.  34 A-C depicts various forms of implantable microstimulators.  
       FIG. 35  is a figure depicting an implanted microstimulator for providing pulses to vagus nerve.  
       FIG. 36  is a diagram depicting the components and assembly of a microstimulator.  
       FIG. 37  shows functional block diagram of the circuitry for a microstimulator.  
       FIG. 38  is a simplified block diagram of the implantable pulse generator.  
       FIG. 39  is a functional block diagram of a microprocessor-based implantable pulse generator.  
       FIG. 40  shows details of implanted pulse generator.  
       FIGS. 41A and 41B  shows details of digital components of the implantable circuitry.  
       FIG. 42A  shows a schematic diagram of the register file, timers and ROM/RAM.  
       FIG. 42B  shows datapath and control of custom-designed microprocessor based pulse generator.  
       FIG. 43  is a block diagram for generation of a pre-determined stimulation pulse.  
       FIG. 44  is a simplified schematic for delivering stimulation pulses.  
       FIG. 45  is a circuit diagram of a voltage doubler.  
       FIG. 46A  is a diagram depicting ramping-up of a pulse train.  
       FIG. 46B  depicts rectangular pulses.  
       FIGS. 46C, 46D , and  46 E depict multi-step pulses.  
       FIGS. 46F, 46G , and  46 H depict complex pulse trains.  
       FIG. 46 -I depicts the use of tripolar electrodes.  
       FIGS. 46J and 46K  depict step pulses used in conjunction with tripolar electrodes.  
       FIGS. 46L and 46M  depict biphasic pulses used in conjunction with tripolar pulses.  
      FIGS.  46 N and  46 -O depict modified square pulses to be used in conjunction with tripolar electrodes.  
       FIG. 47A  depicts an implantable system with tripolar lead for selective unidirectional blocking of vagus nerve stimulation  FIG. 47B  depicts selective efferent blocking in the large diameter A and B fibers.  
       FIG. 47C  is a schematic diagram of the implantable lead with three electrodes.  
       FIG. 47D  is a diagram depicting electrical stimulation with conduction in the afferent direction and blocking in the efferent direction.  
       FIG. 47E  is a diagram depicting electrical stimulation with conduction in the afferent direction and selective organ blocking in the efferent direction.  
       FIG. 47F  is a diagram depicting electrical stimulation with conduction in the efferent direction and selective organ blocking in the afferent direction.  
       FIG. 48  depicts unilateral stimulation of vagus nerve at near the diaphram level.  
       FIGS. 49A and 49B  are diagrams showing communication of programmer with the implanted stimulator.  
       FIGS. 50A and 50B  show diagrammatically encoding and decoding of programming pulses.  
       FIG. 51  is a simplified overall block diagram of implanted pulse generator (IPG) programmer.  
       FIG. 52  shows a programmer head positioning circuit.  
       FIG. 53  depicts typical encoding and modulation of programming messages.  
       FIG. 54  shows decoding one bit of the signal from  FIG. 53 .  
       FIG. 55  shows a diagram of receiving and decoding circuitry for programming data.  
       FIG. 56  shows a diagram of receiving and decoding circuitry for telemetry data.  
       FIG. 57  is a block diagram of a battery status test circuit.  
       FIG. 58  is a diagram showing the two modules of the implanted pulse generator (IPG).  
       FIG. 59A  depicts coil around the titanium case with two feedthroughs for a bipolar configuration.  
       FIG. 59B  depicts coil around the titanium case with one feedthrough for a unipolar configuration.  
       FIG. 59C  depicts two feedthroughs for the external coil which are common with the feedthroughs for the lead terminal.  
       FIG. 59D  depicts one feedthrough for the external coil which is common to the feedthrough for the lead terminal.  
       FIG. 60  shows a block diagram of an implantable stimulator which can be used as a stimulus-receiver or an implanted pulse generator with rechargeable battery.  
       FIG. 61  is a block diagram highlighting battery charging circuit of the implantable stimulator of  FIG. 60 .  
       FIG. 62  is a schematic diagram highlighting stimulus-receiver portion of implanted stimulator of one embodiment.  
       FIG. 63A  depicts bipolar version of stimulus-receiver module.  
       FIG. 63B  depicts unipolar version of stimulus-receiver module.  
       FIG. 64  depicts power source select circuit.  
       FIG. 65A  shows energy density of different types of batteries.  
       FIG. 65B  shows discharge curves for different types of batteries.  
       FIG. 66  depicts externalizing recharge and telemetry coil from the titanium case.  
       FIGS. 67A and 67B  depict recharge coil on the titanium case with a magnetic shield in-between.  
       FIG. 68  shows in block diagram form an implantable rechargable pulse generator.  
       FIG. 69  depicts in block diagram form the implanted and external components of an implanted rechargable system.  
       FIG. 70  depicts the alignment function of rechargable implantable pulse generator.  
       FIG. 71  is a block diagram of the external recharger.  
       FIG. 72  depicts remote monitoring of stimulation devices.  
       FIG. 73  is an overall schematic diagram of the external stimulator, showing wireless communication.  
       FIG. 74  is a schematic diagram showing application of Wireless Application Protocol (WAP).  
       FIG. 75  is a simplified block diagram of the networking interface board.  
       FIGS. 76A and 76B  is a simplified diagram showing communication of modified PDA/phone with an external stimulator via a cellular tower/base station.  
    
    
     DETAILED DESCRIPTION OF THE INVENTION  
      The following description is of the best mode presently contemplated for carrying out the invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the invention. The scope of the invention should be determined with reference to the claims.  
      In the method and system of this application, selective pulsed electrical stimulation is applied to a vagus nerve(s) for afferent neuromodulation to provide therapy for involuntary movement disorders (including Parkinson&#39;s disease and epilepsy). An implantable lead is surgically implanted in the patient. The vagus nerve(s) is/are surgically exposed and isolated. The electrodes on the distal end of the lead are wrapped around the vagus nerve(s), and the terminal (proximal) end of the lead is tunneled subcutaneously. A pulse generator means is connected to the terminal (proximal) end of the lead. The power source may be external, implantable, or a combination device.  
      Many of the patients may end up with more than one type of pulse generator in their lifetime. In the methodology of this invention, an implanted lead has a terminal end which is compatible with different embodiments of pulse generators disclosed in this application. Once the lead is implanted in a patient, any embodiment of the pulse generator disclosed in this application, may be implanted in the patient. Furthermore, at replacement the same embodiment or a different embodiment may be implanted in the patient using the same lead. This may be repeated as long as the implanted lead is functional and maintains its integrity.  
      As one example, without limitation, an implanted stimulus-receiver in conjunction with an external stimulator may be used initially to test patient&#39;s response. At a later time, the pulse generator may be exchanged for a more elaborate implanted pulse generator (IPG) model, keeping the same lead. Some examples of stimulation and power sources that may be used for the practice of this invention, and disclosed in this application, include: 
          a) an implanted stimulus-receiver with an external stimulator;     b) an implanted stimulus-receiver comprising a high value capacitor for storing charge, used in conjunction with an external stimulator;     c) a programmer-less implantable pulse generator (IPG) which is operable with a magnet;     d) a microstimulator;     e) a programmable implantable pulse generator;     f) a combination implantable device comprising both a stimulus-receiver and a programmable IPG; and     g) an IPG comprising a rechargeable battery.        

      All of these pulse generator means can generate and emit rectangular and complex electrical pulses. Complex electrical pulses comprise at least one of multi-level pulses, biphasic pulses, non-rectangular pulses, or pulses with varying amplitude during the pulse.  
     Implanted Stimulus-Receiver with an External Stimulator  
      The selective stimulation of various nerve fibers of a cranial nerve such as the vagus nerve (or neuromodulation of the vagus nerve), as performed by one embodiment of the method and system of this invention is shown schematically in  FIG. 18 , as a block diagram. A modulator  246  receives analog (sine wave) high frequency “carrier” signal and modulating signal. The modulating signal can be multilevel digital, binary, or even an analog signal. In this embodiment, mostly multilevel digital type modulating signals are used. The modulated signal is amplified  250 , conditioned  254 , and transmitted via a primary coil  46  which is external to the body. A secondary coil  48  of an implanted stimulus receiver, receives, demodulates, and delivers these pulses to the vagus nerve  54  via electrodes  61  and  62 . The receiver circuitry  256  is described later.  
      The carrier frequency is optimized. One preferred embodiment utilizes electrical signals of around 1 Mega-Hertz, even though other frequencies can be used. Low frequencies are generally not suitable because of energy requirements for longer wavelengths, whereas higher frequencies are absorbed by the tissues and are converted to heat, which again results in power losses.  
      Shown in conjunction with  FIG. 19 , the coil for the external transmitter (primary coil  46 ) may be placed in the pocket  301  of a customized garment  302 , for patient convenience.  
      Shown in conjunction with  FIG. 20 , the primary (external) coil  46  of the external stimulator  42  is inductively coupled to the secondary (implanted) coil  48  of the implanted stimulus-receiver  34 . The implantable stimulus-receiver  34  has circuitry at the proximal end, and has two stimulating electrodes at the distal end  61 , 62 . The negative electrode (cathode)  61  is positioned towards the brain and the positive electrode (anode)  62  is positioned away from the brain.  
      The circuitry contained in the proximal end of the implantable stimulus-receiver  34  is shown schematically in  FIG. 21 , for one embodiment. In this embodiment, the circuit uses all passive components. Approximately 25 turn copper wire of 30 gauge, or comparable thickness, is used for the primary coil  46  and secondary coil  48 . This wire is concentrically wound with the windings all in one plane. The frequency of the pulse-waveform delivered to the implanted coil  48  can vary, and so a variable capacitor  152  provides ability to tune secondary implanted circuit  167  to the signal from the primary coil  46 . The pulse signal from secondary (implanted) coil  48  is rectified by the diode bridge  154  and frequency reduction obtained by capacitor  158  and resistor  164 . The last component in line is capacitor  166 , used for isolating the output signal from the electrode wire. The return path of signal from cathode  61  will be through anode  62  placed in proximity to the cathode  61  for “Bipolar” stimulation. In this embodiment bipolar mode of stimulation is used, however, the return path can be connected to the remote ground connection (case) of implantable circuit  167 , providing for much larger intermediate tissue for “Unipolar” stimulation. The “Bipolar” stimulation offers localized stimulation of tissue compared to “Unipolar” stimulation and is therefore, preferred in this embodiment. Unipolar stimulation is more likely to stimulate skeletal muscle in addition to nerve stimulation. The implanted circuit  167  in this embodiment is passive, so a battery does not have to be implanted.  
      The circuitry shown in  FIGS. 22A and 22B  can be used as an alternative, for the implanted stimulus-receiver. The circuitry of  FIG. 22A  is a slightly simpler version, and circuitry of  FIG. 22B  contains a conventional NPN transistor  168  connected in an emitter-follower configuration.  
      For therapy to commence, the primary (external) coil  46  is placed on the skin  60  on top of the surgically implanted (secondary) coil  48 . An adhesive tape is then placed on the skin  60  and external coil  46  such that the external coil  46 , is taped to the skin  60 . For efficient energy transfer to occur, it is important that the primary (external) and secondary (internal) coils  46 , 48  be positioned along the same axis and be optimally positioned relative to each other. In this embodiment, the external coil  46  may be connected to proximity sensing circuitry  50 . The correct positioning of the external coil  46  with respect to the internal coil  48  is indicated by turning “on” of a light emitting diode (LED) on the external stimulator  42 .  
      Optimal placement of the external (primary) coil  46  is done with the aid of proximity sensing circuitry incorporated in the system, in this embodiment. Proximity sensing occurs utilizing a combination of external and implantable components. The implanted components contains a relatively small magnet composed of materials that exhibit Giant Magneto-Resistor (GMR) characteristics such as Samarium-cobalt, a coil, and passive circuitry. Shown in conjunction with  FIG. 23 , the external coil  46  and proximity sensor circuitry  50  are rigidly connected in a convenient enclosure which is attached externally on the skin. The sensors measure the direction of the field applied from the magnet to sensors within a specific range of field strength magnitude. The dual sensors exhibit accurate sensing under relatively large separation between the sensor and the target magnet. As the external coil  46  placement is “fine tuned”, the condition where the external (primary) coil  46  comes in optimal position, i.e. is located adjacent and parallel to the subcutaneous (secondary) coil  48 , along its axis, is recorded and indicated by a light emitting diode (LED) on the external stimulator  42 .  
       FIG. 24  shows an overall block diagram of the components of the external stimulator and the proximity sensing mechanism. The proximity sensing components are the primary (external) coil  46 , supercutaneous (external) proximity sensors  648 ,  652  ( FIG. 25 ) in the proximity sensor circuit unit  50 , and a subcutaneous secondary coil  48  with a Giant Magneto Resister (GMR) magnet  53  associated with the proximity sensor unit. The proximity sensor circuit  50  provides a measure of the position of the secondary implanted coil  48 . The signal output from proximity sensor circuit  50  is derived from the relative location of the primary and secondary coils  46 ,  48 . The sub-assemblies consist of the coil and the associated electronic components, that are rigidly connected to the coil.  
      The proximity sensors (external) contained in the proximity sensor circuit  50  detect the presence of a GMR magnet  53 , composed of Samarium Cobalt, that is rigidly attached to the implanted secondary coil  48 . The proximity sensors, are mounted externally as a rigid assembly and sense the actual separation between the coils, also known as the proximity distance. In the event that the distance exceeds the system limit, the signal drops off and an alarm sounds to indicate failure of the production of adequate signal in the secondary implanted circuit  167 , as applied in this embodiment of the device. This signal is provided to the location indicator LED  280 .  
       FIG. 25  shows the circuit used to drive the proximity sensors  648 ,  652  of the proximity sensor circuit  50 . The two proximity sensors  648 ,  652  obtain a proximity signal based on their position with respect to the implanted GMR magnet  53 . This circuit also provides temperature compensation. The sensors  648 ,  652  are ‘Giant Magneto Resistor’ (GMR) type sensors packaged as proximity sensor unit  50 . There are two components of the complete proximity sensor circuit. One component is mounted supercutaneously  50 , and the other component, the proximity sensor signal control unit  57  is within the external stimulator  42 . The resistance effect depends on the combination of the soft magnetic layer of magnet  53 , where the change of direction of magnetization from external source can be large, and the hard magnetic layer, where the direction of magnetization remains unchanged. The resistance of this sensor  50  varies along a straight motion through the curvature of the magnetic field. A bridge differential voltage is suitably amplified and used as the proximity signal.  
      The Siemens GMR B6 (Siemens Corp., Special Components Inc., New Jersey) is used for this function in one embodiment. The maximum value of the peak-to-peak signal is observed as the external magnetic field becomes strong enough, at which point the resistance increases, resulting in the increase of the field-angle between the soft magnetic and hard magnetic material. The bridge voltage also increases. In this application, the two sensors  648 ,  652  are oriented orthogonal to each other.  
      The distance between the magnet  53  and sensor  50  is not relevant as long as the magnetic field is between 5 and 15 KA/m, and provides a range of distances between the sensors  648 ,  652  and the magnetic material  53 . The GMR sensor registers the direction of the external magnetic field. A typical magnet to induce permanent magnetic field is approximately 15 by 8 by 5 mm 3 , for this application and these components. The sensors  648 ,  652  are sensitive to temperature, such that the corresponding resistance drops as temperature increases. This effect is quite minimal until about 100° C. A full bridge circuit is used for temperature compensation, as shown in temperature compensation circuit  50  of  FIG. 25 . The sensors  648 ,  652  and a pair of resistors  650 ,  654  are shown as part of the bridge network for temperature compensation. It is also possible to use a full bridge network of two additional sensors in place of the resistors  650 ,  654 .  
      The signal from either proximity sensor  648 ,  652  is rectangular if the surface of the magnetic material is normal to the sensor and is radial to the axis of a circular GMR device. This indicates a shearing motion between the sensor and the magnetic device. When the sensor is parallel to the vertical axis of this device, there is a fall off of the relatively constant signal at about 25 mm. separation. The GMR sensor combination varies its resistance according to the direction of the external magnetic field, thereby providing an absolute angle sensor. The position of the GMR magnet can be registered at any angle from 0 to 360 degrees.  
      In the external stimulator  42  shown in  FIG. 24 , an indicator unit  280  which is provided to indicate proximity distance or coil proximity failure (for situations where the patch containing the external coil  46 , has been removed, or is twisted abnormally etc.). Indication is also provided to assist in the placement of the patch. In case of general failure, a red light with audible signal is provided when the signal is not reaching the subcutaneous circuit. The indicator unit  280  also displays low battery status. The information on the low battery, normal and out of power conditions forewarns the user of the requirements of any corrective actions.  
      Also shown in  FIG. 24 , the programmable parameters are stored in a programmable logic  264 . The predetermined programs stored in the external stimulator are capable of being modified through the use of a separate programming station  77 . The Programmable Array Logic Unit  264  and interface unit  270  are interfaced to the programming station  77 . The programming station  77  can be used to load new programs, change the existing predetermined programs or the program parameters for various stimulation programs. The programming station is connected to the programmable array unit  75  (comprising programmable array logic  304  and interface unit  270 ) with an RS232-C serial connection. The main purpose of the serial line interface is to provide an RS232-C standard interface. Other suitable connectors such as a USB connector or other connectors with standard protocols may also be used.  
      This method enables any portable computer with a serial interface to communicate and program the parameters for storing the various programs. The serial communication interface receives the serial data, buffers this data and converts it to a 16 bit parallel data. The programmable array logic  264  component of programmable array unit receives the parallel data bus and stores or modifies the data into a random access matrix. This array of data also contains special logic and instructions along with the actual data. These special instructions also provide an algorithm for storing, updating and retrieving the parameters from long-term memory. The programmable logic array unit  264 , interfaces with long term memory to store the predetermined programs. All the previously modified programs can be stored here for access at any time, as well as, additional programs can be locked out for the patient. The programs consist of specific parameters and each unique program will be stored sequentially in long-term memory. A battery unit is present to provide power to all the components. The logic for the storage and decoding is stored in a random addressable storage matrix (RASM).  
      Conventional microprocessor and integrated circuits are used for the logic, control and timing circuits. Conventional bipolar transistors are used in radio-frequency oscillator, pulse amplitude ramp control and power amplifier. A standard voltage regulator is used in low-voltage detector. The hardware and software to deliver the pre-determined programs is well known to those skilled in the art.  
      The pulses delivered to the nerve tissue for stimulation therapy are shown graphically in  FIG. 26A . As shown in  FIG. 26B , for patient comfort when the electrical stimulation is turned on, the electrical stimulation is ramped up and ramped down, instead of abrupt delivery of electrical pulses.  
      The selective stimulation to the vagus nerve can be performed in one of two ways. One method is to activate one of several “pre-determined” programs. A second method is to “custom” program the electrical parameters which can be selectively programmed, for specific therapy to the individual patient. The electrical parameters which can be individually programmed, include variables such as pulse amplitude, pulse width, frequency of stimulation, stimulation on-time, and stimulation off-time. Table three below defines the approximate range of parameters,  
               TABLE 3                          Electrical parameter range delivered to the nerve                             PARAMER   RANGE                       Pulse Amplitude   0.1 Volt-15 Volts           Pulse width   20 μS-5 mSec.           Stim. Frequency   5 Hz-200 Hz           Freq. for blocking   DC to 750 Hz           On-time   5 Secs-24 hours           Off-time   5 Secs-24 hours                      
 
      The parameters in Table 3 are the electrical signals delivered to the nerve via the two electrodes  61 , 62  (distal and proximal) around the nerve, as shown in  FIG. 20 . It being understood that the signals generated by the external pulse generator  42  and transmitted via the primary coil  46  are larger, because the attenuation factor between the primary coil and secondary coil is approximately 10-20 times, depending upon the distance, and orientation between the two coils. Accordingly, the range of transmitted signals of the external pulse generator are approximately 10-20 times larger than shown in Table 2.  
      Referring now to  FIG. 27 , the implanted lead  40  component of the system is similar to cardiac pacemaker leads, except for distal portion (or electrode end) of the lead. The lead terminal preferably is linear bipolar, even though it can be bifurcated, and plug(s) into the cavity of the pulse generator means. The lead body  59  insulation may be constructed of medical grade silicone, silicone reinforced with polytetrafluoro-ethylene (PTFE), or polyurethane. The electrodes  61 , 62  for stimulating the vagus nerve  54  may either wrap around the nerve once or may be spiral shaped. These stimulating electrodes may be made of pure platinum, platinum/Iridium alloy or platinum/iridium coated with titanium nitride. The conductor connecting the terminal to the electrodes  61 , 62  is made of an alloy of nickel-cobalt. The implanted lead design variables are also summarized in table four below.  
               TABLE 4                          Lead design variables                                     Proximal End           Conductor       Distal End       Lead   Lead body-       (connecting proximal   Electrode -   Electrode -       Terminal   Insulation Materials   Lead-Coating   and distal ends)   Material   Type               Linear bipolar   Polyurethane   Antimicrobial   Alloy of   Pure Platinum   Spiral electrode               coating   Nickel-Cobalt       Bifurcated   Silicone   Anti-Inflammatory       Platinum-Iridium   Wrap-around               coating       (Pt/Ir) Alloy   electrode           Silicone with   Lubricious       Pt/Ir coated   Steroid eluting           Polytetrafluoroethylene   coating       with Titanium           (PTFE)           Nitride                       Carbon   Hydrogel electrodes               [           [                           Cuff electrodes                  
 
      Examples of electrode designs are also shown in U.S. Pat. No. 5,215,089 (Baker), U.S. Pat. No. 5,351,394 (Weinburg), and U.S. Pat. No. 6,600,956 (Mashino), which are incorporated herein by reference.  
      Once the lead is fabricated, coating such as anti-microbial, anti-inflammatory, or lubricious coating may be applied to the body of the lead.  
       FIG. 28A  summarizes electrode-tissue interface between the nerve tissue and electrodes  61 ,  62 . There is a thin layer of fibrotic tissue between the stimulating electrode  61  and the excitable nerve fibers of the vagus nerve  54 .  FIG. 28B  summarizes the most important properties of the metal/tissue phase boundary in an equivalent circuit diagram. Both the membrane of the nerve fibers and the electrode surface are represented by parallel capacitance and resistance. Application of a constant battery voltage Vbat from the pulse generator, produces voltage changes and current flow, the time course of which is crucially determined by the capacitive components in the equivalent circuit diagram. During the pulse, the capacitors Co, Ch and Cm are charged through the ohmic resistances, and when the voltage Vbat is turned off, the capacitors discharge with current flow on the opposite direction.  
     Implanted Stimulus-Receiver Comprising a High Value Capacitor for Storing Charge, Used in Conjunction with an External Stimulator  
      In one embodiment, the implanted stimulus-receiver may be a system which is RF coupled combined with a power source. In this embodiment, the implanted stimulus-receiver contains high value, small sized capacitor(s) for storing charge and delivering electric stimulation pulses for up to several hours by itself, once the capacitors are charged. The packaging is shown in  FIG. 29 . Using mostly hybrid components and appropriate packaging, the implanted portion of the system described below is conducive to miniaturization. As shown in  FIG. 29 , a solenoid coil  382  wrapped around a ferrite core  380  is used as the secondary of an air-gap transformer for receiving power and data to the implanted device. The primary coil is external to the body. Since the coupling between the external transmitter coil and receiver coil  382  may be weak, a high-efficiency transmitter/amplifier is used in order to supply enough power to the receiver coil  382 . Class-D or Class-E power amplifiers may be used for this purpose. The coil for the external transmitter (primary coil) may be placed in the pocket of a customized garment.  
      As shown in conjunction with  FIG. 30  of the implanted stimulus-receiver  490  and the system, the receiving inductor  48 A and tuning capacitor  403  are tuned to the frequency of the transmitter. The diode  408  rectifies the AC signals, and a small sized capacitor  406  is utilized for smoothing the input voltage V I  fed into the voltage regulator  402 . The output voltage V D  of regulator  402  is applied to capacitive energy power supply and source  400  which establishes source power V DD . Capacitor  400  is a big value, small sized capacative energy source which is classified as low internal impedance, low power loss and high charge rate capacitor, such as Panasonic Model No. 641.  
      The refresh-recharge transmitter unit  460  includes a primary battery  426 , an ON/Off switch  427 , a transmitter electronic module  442 , an RF inductor power coil  46 A, a modulator/demodulator  420  and an antenna  422 .  
      When the ON/OFF switch is on, the primary coil  46 A is placed in close proximity to skin  60  and secondary coil  48 A of the implanted stimulator  490 . The inductor coil  46 A emits RF waves establishing EMF wave fronts which are received by secondary inductor  48 A. Further, transmitter electronic module  442  sends out command signals which are converted by modulator/demodulator decoder  420  and sent via antenna  422  to antenna  418  in the implanted stimulator  490 . These received command signals are demodulated by decoder  416  and replied and responded to, based on a program in memory  414  (matched against a “command table” in the memory). Memory  414  then activates the proper controls and the inductor receiver coil  48 A accepts the RF coupled power from inductor  46 A.  
      The RF coupled power, which is alternating or AC in nature, is converted by the rectifier  408  into a high DC voltage. Small value capacitor  406  operates to filter and level this high DC voltage at a certain level. Voltage regulator  402  converts the high DC voltage to a lower precise DC voltage while capacitive power source  400  refreshes and replenishes.  
      When the voltage in capacative source  400  reaches a predetermined level (that is V DD  reaches a certain predetermined high level), the high threshold comparator  430  fires and stimulating electronic module  412  sends an appropriate command signal to modulator/decoder  416 . Modulator/decoder  416  then sends an appropriate “fully charged” signal indicating that capacitive power source  400  is fully charged, is received by antenna  422  in the refresh-recharge transmitter unit  460 .  
      In one mode of operation, the patient may start or stop stimulation by waving the magnet  442  once near the implant. The magnet emits a magnetic force L m  which pulls reed switch  410  closed. Upon closure of reed switch  410 , stimulating electronic module  412  in conjunction with memory  414  begins the delivery (or cessation as the case may be) of controlled electronic stimulation pulses to the vagus nerve  54  via electrodes  61 ,  62 . In another mode (AUTO), the stimulation is automatically delivered to the implanted lead based upon programmed ON/OFF times.  
      The programmer unit  450  includes keyboard  432 , programming circuit  438 , rechargeable battery  436 , and display  434 . The physician or medical technician programs programming unit  450  via keyboard  432 . This program regarding the frequency, pulse width, modulation program, ON time etc. is stored in programming circuit  438 . The programming unit  450  must be placed relatively close to the implanted stimulator  490  in order to transfer the commands and programming information from antenna  440  to antenna  418 . Upon receipt of this programming data, modulator/demodulator and decoder  416  decodes and conditions these signals, and the digital programming information is captured by memory  414 . This digital programming information is further processed by stimulating electronic module  412 . In the DEMAND operating mode, after programming the implanted stimulator, the patient turns ON and OFF the implanted stimulator via hand held magnet  442  and the reed switch  410 . In the automatic mode (AUTO), the implanted stimulator turns ON and OFF automatically according to the programmed values for the ON and OFF times.  
      Other simplified versions of such a system may also be used. For example, a system such as this, where a separate programmer is eliminated, and simplified programming is performed with a magnet and reed switch, can also be used.  
     Programmer-Less Implantable Pulse Generator (IPG)  
      In one embodiment, a programmer-less implantable pulse generator (IPG) may be used, as disclosed in applicant&#39;s commonly assigned U.S. Pat. No. 6,760,626 B1, which is incorporated herein by reference. In this embodiment, shown in conjunction with  FIG. 31 , the implantable pulse generator  171  is provided with a reed switch  92  and memory circuitry  102 . The reed switch  92  being remotely actuable by means of a magnet  90  brought into proximity of the pulse generator  171 , in accordance with common practice in the art. In this embodiment, the reed switch  92  is coupled to a multi-state converter/timer circuit  96 , such that a single short closure of the reed switch can be used as a means for non-invasive encoding and programming of the pulse generator  171  parameters.  
      In one embodiment, shown in conjunction with  FIG. 32 , the closing of the reed switch  92  triggers a counter. The magnet  90  and timer are ANDed together. The system is configured such that during the time that the magnet  82  is held over the pulse generator  171 , the output level goes from LOW stimulation state to the next higher stimulation state every 5 seconds. Once the magnet  82  is removed, regardless of the state of stimulation, an application of the magnet, without holding it over the pulse generator  171 , triggers the OFF state, which also resets the counter.  
      Once the prepackaged/predetermined logic state is activated by the logic and control circuit  102 , as shown in  FIG. 31 , the pulse generation and amplification circuit  106  deliver the appropriate electrical pulses to the vagus nerve  54  of the patient via an output buffer  108 . The delivery of output pulses is configured such that the distal electrode  61  (electrode closer to the brain) is the cathode and the proximal electrode  62  is the anode. Timing signals for the logic and control circuit  102  of the pulse generator  171  are provided by a crystal oscillator  104 . The battery  86  of the pulse generator  171  has terminals connected to the input of a voltage regulator  94 . The regulator  94  smoothes the battery output and supplies power to the internal components of the pulse generator  171 . A microprocessor  100  controls the program parameters of the device, such as the voltage, pulse width, frequency of pulses, on-time and off-time. The microprocessor may be a commercially available, general purpose microprocessor or microcontroller, or may be a custom integrated circuit device augmented by standard RAM/ROM components.  
      In one embodiment, there are four stimulation states. A larger (or lower) number of states can be achieved using the same methodology, and such is considered within the scope of the invention. These four states are, LOW stimulation state, LOW-MED stimulation state, MED stimulation state, and HIGH stimulation state. Examples of stimulation parameters (delivered to the vagus nerve) for each state are as follows,  
      LOW stimulation state example is, 
      Current output: 0.75 milliAmps.     Pulse width: 0.20 msec.     Pulse frequency: 20 Hz     Cycles: 20 sec. on-time and 2.0 min. off-time in repeating cycles.    

      LOW-MED stimulation state example is, 
      Current output: 1.5 milliAmps,     Pulse width: 0.30 msec.     Pulse frequency: 25 Hz     Cycles: 1.5 min. on-time and 20.0 min. off-time in repeating cycles.    

      MED stimulation state example is, 
      Current output: 2.0 milliAmps.     Pulse width: 0.30 msec.     Pulse frequency: 30 Hz     Cycles: 1.5 min. on-time and 20.0 min. off-time in repeating cycles.    

      HIGH stimulation state example is, 
      Current output: 3.0 milliAmps,     Pulse width: 0.40 msec.     Pulse frequency: 30 Hz     Cycles: 2.0 min. on-time and 20.0 min. off-time in repeating cycles.    

      These prepackaged/predetermined programs are mearly examples, and the actual stimulation parameters will deviate from these depending on the treatment application.  
      It will be readily apparent to one skilled in the art, that other schemes can be used for the same purpose. For example, instead of placing the magnet  90  on the pulse generator  171  for a prolonged period of time, different stimulation states can be encoded by the sequence of magnet applications. Accordingly, in an alternative embodiment there can be three logic states, OFF, LOW stimulation (LS) state, and HIGH stimulation (HS) state. Each logic state again corresponds to a prepackaged/predetermined program such as presented above. In such an embodiment, the system could be configured such that one application of the magnet triggers the generator into LS State. If the generator is already in the LS state then one application triggers the device into OFF State. Two successive magnet applications triggers the generator into MED stimulation state, and three successive magnet applications triggers the pulse generator in the HIGH Stimulation State. Subsequently, one application of the magnet while the device is in any stimulation state, triggers the device OFF.  
       FIG. 33  shows a representative digital circuitry used for the basic state machine circuit. The circuit consists of a PROM  462  that has part of its data fed back as a state address. Other address lines  469  are used as circuit inputs, and the state machine changes its state address on the basis of these inputs. The clock  104  is used to pass the new address to the PROM  462  and then pass the output from the PROM  462  to the outputs and input state circuits. The two latches  464 ,  465  are operated 180° out of phase to prevent glitches from unexpectedly affecting any output circuits when the ROM changes state. Each state responds differently according to the inputs it receives.  
      The advantage of this embodiment is that it is cheaper to manufacture than a fully programmable implantable pulse generator (IPG).  
     Microstimulator  
      In one embodiment, a microstimulator  130  may be used for providing pulses to the vagus nerve(s)  54 . Shown in conjunction with  FIG. 34A , is a microstimulator where the electrical circuitry  132  and power source  134  are encased in a miniature hermetically sealed enclosure, and only the electrodes  63 A,  67 A are exposed.  FIG. 34B  depicts the same microstimulator, except the electrodes are modified and adapted to wrap around the nerve tissue  54 . Because of its small size, the whole microstimulator may be in the proximity of the nerve tissue to be stimulated, or alternatively as shown in conjunction with  FIG. 35 , the microstimulator may be implanted at a different site, and connected to the electrodes via conductors insulated with silicone and polyurethane ( FIG. 34C ).  
      Shown in reference with  FIG. 36  is the overall structure of an implantable microstimulator  130 . It consists of a micromachined silicon substrate that incorporates two stimulating electrodes which are the cathode and anode of a bipolar stimulating electrode pair  63 A,  67 A; a hybrid-connected tantalum chip capacitor  140  for power storage; a receiving coil  142 ; a bipolar-CMOS integrated circuit chip  138  for power regulation and control of the microstimulator; and a custom made glass capsule  146  that is electrostatically bonded to the silicon carrier to provide a hermetic package for the receiver-stimulator circuitry and hybrid elements. The stimulating electrode pair  63 , 64  resides outside of the package and feedthroughs are used to connect the internal electronics to the electrodes.  
       FIG. 37  shows the overall system electronics required for the microstimulator, and the power and data transmission protocol used for radiofrequency telemetry. The circuit receives an amplitude modulated RF carrier from an external transmitter and generates 8-V and 4-V dc supplies, generates a clock from the carrier signal, decodes the modulated control data, interprets the control data, and generates a constant current output pulse when appropriate. The RF carrier used for the telemetry link has a nominal frequency of around 1.8 MHz, and is amplitude modulated to encode control data. Logical “1” and “0” are encoded by varying the width of the amplitude modulated carrier, as shown in the bottom portion of  FIG. 37 . The carrier signal is initially high when the transmitter is turned on and sets up an electromagnetic field inside the transmitter coil. The energy in the field is picked up by receiver coils  142 , and is used to charge the hybrid capacitor  140 . The carrier signal is turned high and then back down again, and is maintained at the low level for a period between 1-200 μsec. The microstimulator  130  will then deliver a constant current pulse into the nerve tissue through the stimulating electrode pair  63 A,  67 A for the period that the carrier is low. Finally, the carrier is turned back high again, which will indicate the end of the stimulation period to the microstimulator  130 , thus allowing it to charge its capacitor  140  back up to the on-chip voltage supply.  
      On-chip circuitry has been designed to generate two regulated power supply voltages (4V and 8V) from the RF carrier, to demodulate the RF carrier in order to recover the control data that is used to program the microstimulator, to generate the clock used by the on-chip control circuitry, to deliver a constant current through a controlled current driver into the nerve tissue, and to control the operation of the overall circuitry using a low-power CMOS logic controller.  
     Programmable Implantable Pulse Generator (IPG)  
      In one embodiment, a fully programmable implantable pulse generator (IPG), capable of generating stimulation and blocking pulses may be used. Shown in conjunction with  FIG. 38 , the implantable pulse generator unit  391  is preferably a microprocessor based device, where the entire circuitry is encased in a hermetically sealed titanium can. As shown in the overall block diagram, the logic &amp; control unit  398  provides the proper timing for the output circuitry  385  to generate electrical pulses that are delivered to electrodes  61 ,  62  via a lead  40 . Programming of the implantable pulse generator (IPG) is done via an external programmer  85 , as described later. Once activated or programmed via an external programmer  85 , the implanted pulse generator  391  provides appropriate electrical stimulation pulses to the vagus nerve(s)  54  via electrodes  61 , 62 .  
      This embodiment also comprises predetermined/pre-packaged programs. Examples of four stimulation states were given in the previous section, under “Programmer-less Implantable Pulse Generator (IPG)”. These predetermined/pre-packaged programs comprise unique combinations of pulse amplitude, pulse width, pulse morphology, pulse frequency, ON-time and OFF-time. Any number of predetermined/pre-packaged programs, even  100 , can be stored in the implantable pulse generator of this invention, and are considered within the scope of the invention.  
     Examples of Additional Predetermined/Pre-Packaged Programs Are:  
     Program One  
     
         
          Current output: 1.0 milliAmps.  
          Pulse width: 0.25 msec.  
          Pulse frequency: 20 Hz  
          Cycles: 20 sec. on-time and 3.0 min. off-time in repeating cycles.  
       
    
     Program Two  
     
         
          Current output: 1.5 milliAmps,  
          Pulse width: 0.40 msec.  
          Pulse frequency: 25 Hz  
          Cycles: 3.0 min. on-time and 20.0 min. off-time in repeating cycles.  
       
    
     Program Three  
     
         
          Current output: 2.0 milliAmps.  
          Pulse width: 0.50 msec.  
          Pulse frequency: 30 Hz  
          Cycles: 4 min. on-time and 20.0 min. off-time in repeating cycles.  
       
    
     Program Four  
     
         
          Current output: 2.5 milliAmps,  
          Pulse width: 0.3 msec.  
          Pulse frequency: 25 Hz  
          Cycles: 4.0 min. on-time and 20.0 min. off-time in repeating cycles.  
       
    
     Program Five  
     
         
          Current output: 3.0 milliAmps,  
          Pulse width: 0.50 msec.  
          Pulse frequency: 30 Hz  
          Cycles: 5.0 min. on-time and 30.0 min. off-time in repeating cycles.  
       
    
     Program Six (Fast Cycle)  
     
         
          Current output: 1.0 milliAmps.  
          Pulse width: 0.25 msec.  
          Pulse frequency: 20 Hz  
          Cycles: 8 sec. on-time and 12 sec. off-time in repeating cycles.  
       
    
     Program Seven (Fast Cycle)  
     
         
          Current output: 1.75 milliAmps.  
          Pulse width: 0.4 msec.  
          Pulse frequency: 30 Hz  
          Cycles: 8 sec. on-time and 12 sec. off-time in repeating cycles.  
       
    
     Program Eight (Complex Pulses)  
     
         
          Current output: 1.5 milliAmps.  
          Pulse width: 0.25 msec.  
          Pulse frequency: 25 Hz  
          Pulse type: step pulses  
          Cycles: 20 sec. on-time and 3.0 min. off-time in repeating cycles.  
       
    
     Program Nine (Complex Pulses)  
     
         
          Current output: 2.0 milliAmps.  
          Pulse width: 0.40 msec.  
          Pulse frequency: 30 Hz  
          Pulse type: step pulses  
          Cycles: 20 sec. on-time and 3.0 min. off-time in repeating cycles.  
       
    
     Program Ten (Complex Pulse Train)  
     
         
          Current output: 1.5 milliAmps.  
          Pulse width: 0.25 msec.  
          Pulse frequency: 25 Hz  
          Pulse type: step pulses with alternating pulse train (as shown in  FIG. 46H )  
          Cycles: 20 sec. on-time and 3.0 min. off-time in repeating cycles.  
       
    
      These prepackaged/predetermined programs are mearly examples, and the actual stimulation parameters will deviate from these depending on the treatment application and physician preference. One advantage of predetermined/pre-packaged program is that it can be readily activated by a program number. A simple version of a programmer, adapted to activate only a limited number of predetermined/pre-packaged programs may also be supplied to the patient.  
      In addition, each parameter may be individually adjusted and stored in the memory  394 . The range of programmable electrical stimulation parameters include both stimulating and blocking frequencies, and are shown in table five below.  
               TABLE 5                          Programmable electrical parameter range                             PARAMER   RANGE                       Pulse Amplitude   0.1 Volt-15 Volts           Pulse width   20 μS-5 mSec.           Stim. Frequency   5 Hz-200 Hz           Freq. for blocking   DC to 750 Hz           On-time   5 Secs-24 hours           Off-time   5 Secs-24 hours           Ramp   ON/OFF                      
 
      Shown in conjunction with  FIGS. 39 and 40 , the electronic stimulation module comprises both digital  350  and analog  352  circuits. A main timing generator  330  (shown in  FIG. 39 ), controls the timing of the analog output circuitry for delivering neuromodulating pulses to the vagus nerve  54 , via output amplifier  334 . Limiter  183  prevents excessive stimulation energy from getting into the vagus nerve  54 . The main timing generator  330  receiving clock pulses from crystal oscillator  393 . Main timing generator  330  also receiving input from programmer  85  via coil  399 .  FIG. 36  highlights other portions of the digital system such as CPU  338 , ROM  337 , RAM  339 , program interface  346 , interrogation interface  348 , timers  340 , and digital O/I  342 .  
      Most of the digital functional circuitry  350  is on a single chip (IC). This monolithic chip along with other IC&#39;s and components such as capacitors and the input protection diodes are assembled together on a hybrid circuit. As well known in the art, hybrid technology is used to establish the connections between the circuit and the other passive components. The integrated circuit is hermetically encapsulated in a chip carrier. A coil  399  situated under the hybrid substrate is used for bidirectional telemetry. The hybrid and battery  397  are encased in a titanium can  65 . This housing is a two-part titanium capsule that is hermetically sealed by laser welding. Alternatively, electron-beam welding can also be used. The header  79  is a cast epoxy-resin with hermetically sealed feed-through, and form the lead  40  connection block.  
      For further details,  FIG. 41A  highlights the general components of an 8-bit microprocessor as an example. It will be obvious to one skilled in the art that higher level microprocessor, such as a 16-bit or 32-bit may be utilized, and is considered within the scope of this invention. It comprises a ROM  337  to store the instructions of the program to be executed and various programmable parameters, a RAM  339  to store the various intermediate parameters, timers  340  to track the elapsed intervals, a register file  321  to hold intermediate values, an ALU  320  to perform the arithmetic calculation, and other auxiliary units that enhance the performance of a microprocessor-based IPG system.  
      The size of ROM  337  and RAM  339  units are selected based on the requirements of the algorithms and the parameters to be stored. The number of registers in the register file  321  are decided based upon the complexity of computation and the required number of intermediate values. Timers  340  of different precision are used to measure the elapsed intervals. Even though this embodiment does not have external sensors to control timing, future embodiments may have sensors  322  to effect the timing as shown in conjunction with  FIG. 41B .  
      In this embodiment, the two main components of microprocessor are the datapath and control. The datapath performs the arithmetic operation and the control directs the datapath, memory, and I/O devices to execute the instruction of the program. The hardware components of the microprocessor are designed to execute a set of simple instructions. In general the complexity of the instruction set determines the complexity of datapth elements and controls of the microprocessor.  
      In this embodiment, the microprocessor is provided with a fixed operating routine. Future embodiments may be provided with the capability of actually introducing program changes in the implanted pulse generator. The instruction set of the microprocessor, the size of the register files, RAM and ROM are selected based on the performance needed and the type of the algorithms used. In this application of pulse generator, in which several algorithms can be loaded and modified, Reduced Instruction Set Computer (RISC) architecture is useful. RISC architecture offers advantages because it can be optimized to reduce the instruction cycle which in turn reduces the run time of the program and hence the current drain. The simple instruction set architecture of RISC and its simple hardware can be used to implement any algorithm without much difficulty. Since size is also a major consideration, an 8-bit microprocessor is used for the purpose. As most of the arithmetic calculation are based on a few parameters and are rather simple, an accumulator architecture is used to save bits from specifying registers. Each instruction is executed in multiple clock cycles, and the clock cycles are broadly classified into five stages: an instruction fetch, instruction decode, execution, memory reference, and write back stages. Depending on the type of the instruction, all or some of these stages are executed for proper completion.  
      Initially, an optimal instruction set architecture is selected based on the algorithm to be implemented and also taking into consideration the special needs of a microprocessor based implanted pulse generator (IPG). The instructions are broadly classified into Load/store instructions, Arithmetic and logic instructions (ALU), control instructions and special purpose instructions.  
      The instruction format is decided based upon the total number of instructions in the instruction set. The instructions fetched from memory are 8 bits long in this example. Each instruction has an opcode field (2 bits), a register specifier field (3-bits), and a 3-bit immediate field. The opcode field indicates the type of the instruction that was fetched. The register specifier indicates the address of the register in the register file on which the operations are performed. The immediate field is shifted and sign extended to obtain the address of the memory location in load/store instruction. Similarly, in branch and jump instruction, the offset field is used to calculate the address of the memory location the control needs to be transferred to.  
      Shown in conjunction with  FIG. 42A , the register file  321 , which is a collection of registers in which any register can be read from or written to specifying the number of the register in the file. Based on the requirements of the design, the size of the register file is decided. For the purposes of implementation of stimulation pulses algorithms, a register file of eight registers is sufficient, with three special purpose register ( 0 - 2 ) and five general purpose registers ( 3 - 7 ), as shown in  FIG. 42A . Register “ 0 ” always holds the value “zero”. Register “ 1 ” is dedicated to the pulse flags. Register “ 2 ” is an accumulator in which all the arithmetic calculations are performed. The read/write address port provides a 3-bit address to identify the register being read or written into. The write data port provides 8-bit data to be written into the registers either from ROM/RAM or timers. Read enable control, when asserted enables the register file to provide data at the read data port. Write enable control enables writing of data being provided at the write data port into a register specified by the read/write address.  
      Generally, two or more timers are required to implement the algorithm for the IPG. The timers are read and written into just as any other memory location. The timers are provided with read and write enable controls.  
      The arithmetic logic unit is an important component of the microprocessor. It performs the arithmetic operation such as addition, subtraction and logical operations such as AND and OR. The instruction format of ALU instructions consists of an opcode field (2 bits), a function field (2 bits) to indicate the function that needs to be performed, and a register specifier (3 bits) or an immediate field (4 bits) to provide an operand.  
      The hardware components discussed above constitute the important components of a datapath. Shown in conjunction with  FIG. 42B , there are some special purpose registers such a program counter (PC) to hold the address of the instruction being fetched from ROM  337  and instruction register (IR)  323 , to hold the instruction that is fetched for further decoding and execution. The program counter is incremented in each instruction fetch stage to fetch sequential instruction from memory. In the case of a branch or jump instruction, the PC multiplexer allows to choose from the incremented PC value or the branch or jump address calculated. The opcode of the instruction fetched (IR) is provided to the control unit to generate the appropriate sequence of control signals, enabling data flow through the datapath. The register specification field of the instruction is given as read/write address to the register file, which provides data from the specified field on the read data port. One port of the ALU is always provided with the contents of the accumulator and the other with the read data port. This design is therefore referred to as accumulator-based architecture. The sign-extended offset is used for address calculation in branch and jump instructions. The timers are used to measure the elapsed interval and are enabled to count down on a low-frequency clock. The timers are read and written into, just as any other memory location ( FIG. 42B ).  
      In a multicycle implementation, each stage of instruction execution takes one clock cycle. Since the datapath takes multiple clock cycles per instruction, the control must specify the signals to be asserted in each stage and also the next step in the sequence. This can be easily implemented as a finite state machine.  
      A finite state machine consists of a set of states and directions on how to change states. The directions are defined by a next-state function, which maps the current state and the inputs to a new state. Each stage also indicates the control signals that need to be asserted. Every state in the finite state machine takes one clock cycle. Since the instruction fetch and decode stages are common to all the instruction, the initial two states are common to all the instruction. After the execution of the last step, the finite state machine returns to the fetch state.  
      A finite state machine can be implemented with a register that holds the current stage and a block of combinational logic such as a PLA. It determines the datapath signals that need to be asserted as well as the next state. A PLA is described as an array of AND gates followed by an array of OR gates. Since any function can be computed in two levels of logic, the two-level logic of PLA is used for generating control signals.  
      The occurrence of a wakeup event initiates a stored operating routine corresponding to the event. In the time interval between a completed operating routine and a next wake up event, the internal logic components of the processor are deactivated and no energy is being expended in performing an operating routine.  
      A further reduction in the average operating current is obtained by providing a plurality of counting rates to minimize the number of state changes during counting cycles. Thus intervals which do not require great precision, may be timed using relatively low counting rates, and intervals requiring relatively high precision, such as stimulating pulse width, may be timed using relatively high counting rates.  
      The logic and control unit  398  of the IPG controls the output amplifiers. The pulses have predetermined energy (pulse amplitude and pulse width) and are delivered at a time determined by the therapy stimulus controller. The circuitry in the output amplifier, shown in conjunction with ( FIG. 43 ) generates an analog voltage or current that represents the pulse amplitude. The stimulation controller module initiates a stimulus pulse by closing a switch  208  that transmits the analog voltage or current pulse to the nerve tissue through the tip electrode  61  of the lead  40 . The output circuit receiving instructions from the stimulus therapy controller  398  that regulates the timing of stimulus pulses and the amplitude and duration (pulse width) of the stimulus. The pulse amplitude generator  206  determines the configuration of charging and output capacitors necessary to generate the programmed stimulus amplitude. The output switch  208  is closed for a period of time that is controlled by the pulse width generator  204 . When the output switch  208  is closed, a stimulus is delivered to the tip electrode  61  of the lead  40 .  
      The constant-voltage output amplifier applies a voltage pulse to the distal electrode (cathode)  61  of the lead  40 . A typical circuit diagram of a voltage output circuit is shown in  FIG. 44 . This configuration contains a stimulus amplitude generator  206  for generating an analog voltage. The analog voltage represents the stimulus amplitude and is stored on a holding capacitor C h    225 . Two switches are used to deliver the stimulus pulses to the lead  40 , a stimulating delivery switch  220 , and a recharge switch  222 , that reestablishes the charge equilibrium after the stimulating pulse has been delivered to the nerve tissue. Since these switches have leakage currents that can cause direct current (DC) to flow into the lead system  40 , a DC blocking capacitor C b    229 , is included. This is to prevent any possible corrosion that may result from the leakage of current in the lead  40 . When the stimulus delivery switch  220  is closed, the pulse amplitude analog voltage stored in the (Ch  225 ) holding capacitor is transferred to the cathode electrode  61  of the lead  40  through the coupling capacitor, C b    229 . At the end of the stimulus pulse, the stimulus delivery switch  220  opens. The pulse duration being the interval from the closing of the switch  220  to its reopening. During the stimulus delivery, some of the charge stored on C h    225  has been transferred to C b    229 , and some has been delivered to the lead system  40  to stimulate the nerve tissue.  
      To re-establish equilibrium, the recharge switch  222  is closed, and a rapid recharge pulse is delivered. This is intended to remove any residual charge remaining on the coupling capacitor C b    229 , and the stimulus electrodes on the lead (polarization). Thus, the stimulus is delivered as the result of closing and opening of the stimulus delivery  220  switch and the closing and opening of the RCHG switch  222 . At this point, the charge on the holding C h    225  must be replenished by the stimulus amplitude generator  206  before another stimulus pulse can be delivered.  
      The pulse generating unit charges up a capacitor and the capacitor is discharged when the control (timing) circuitry requires the delivery of a pulse. This embodiment utilizes a constant voltage pulse generator, even though a constant current pulse generator can also be utilized. Pump-up capacitors are used to deliver pulses of larger magnitude than the potential of the batteries. The pump up capacitors are charged in parallel and discharged into the output capacitor in series. Shown in conjunction with  FIG. 45  is a circuit diagram of a voltage doubler which is shown here as an example. For higher multiples of battery voltage, this doubling circuit can be cascaded with other doubling circuits. As shown in  FIG. 45 , during phase I (top of  FIG. 45 ), the pump capacitor C p  is charged to V bat  and the output capacitor C o  supplies charge to the load. During phase II, the pump capacitor charges the output capacitor, which is still supplying the load current. In this case, the voltage drop across the output capacitor is twice the battery voltage.  
       FIG. 46A  shows one example of the pulse trains that may be delivered with this embodiment or in prior art vagus nerve stimulators. The microcontroller is configured to deliver the pulse train as shown in the figure, i.e. there is “ramping up” of the pulse train. The purpose of the ramping-up is to avoid sudden changes in stimulation, when the pulse train begins. The ramping-up or ramping-down is optional, and may be programmed into the microcontroller.  
      The prior art systems delivering fixed rectangular pulses provide limited capability for selective stimulation or neuromodulation of vagus nerve(s). A fixed rectangular pulse, whether constant voltage or constant current, will recruit either i) A-fibers, or ii) A and B fibers, or iii) A and B and C fibers. Only one of these three discrete states can be achieved. This form of modulation is severely limited for providing therapy for neurological disorders.  
      In the method and system of the current invention, the microcontroller is configured to deliver rectangular and complex pulses. Complex pulses comprise non-rectangular, biphasic, multi-step, and other complex pulses where the amplitude is varying during the pulse. Advantageously, these complex pulses provide a new dimension to selective stimulation or neuromodulation of vagus nerve(s) to provide therapy for neurological disorders, such as involuntary movement disorders.  
      Examples of these pulses and pulse trains are shown in  FIGS. 46B  to  46 H. Selective stimulation with these complex pulses takes into account the threshold properties of different types of nerve fibers, as well as, the different refractory properties of different types of nerve fibers that are contained in the vagus nerve(s).  
      For example in the multi-step pulse shown in  FIG. 46C , the first part of the pulse will tend to recruit large diameter (and myelinated) fibers, such as A and B fibers. The middle portion of the pulse where the amplitude is highest, will tend to recruit c-fibers which are the smallest fibers, and the last portion of the pulse will again tend to recruit the large diameter fibers provided they are not refractory. The multi-step (and multi-amplitude) pulses shown in  FIG. 46E  will tend to recruit large diameter fibers initially, and the later part of the pulse will tend to recruit the smaller diameter C-fibers.  
      Further, as shown in the examples of  FIGS. 46F and 46H , complex and simple pulses, or pulse trains may be alternated. It will be clear to one skilled in the art, that the pulse trains in these two examples take into account both the threshold properties and the refractory properties of different types of nerve fibers which were shown in  FIG. 2 .  
      The pulses and pulse trains of this disclosure gives physicians a lot of flexibility for trying various different neuromodulation algorithms, for providing and optimizing therapy for involuntary movement disorders.  
      Furthermore, as shown in conjunction with  FIG. 46 -I, a combination of tripolar electrodes with different pulse shapes may be used for selective stimulation of vagus nerve(s).  
      The different pulses used in conjunction with tripolar electrodes are shown in conjunction with  FIGS. 46J, 46K ,  47 L,  46 M,  46 N, and  46 -O. This combination is advantageous, because it can be used to provide selective large fiber block as well. As was previously pointed out in Table 2, the vagus nerve also comprises motor components which innervate the soft palate, pharynx, larynx, and upper esophagus. One of the clinical side effects of vagus nerve stimulation is hoarsness of the throat and voice change.  
      The combination of tripolar electrodes and the pulse shapes of FIGS.  46 -J to  46 -O would not only decrease or prevent the unwanted side effects, but the electrical charge of the pulse is also reduced, which will make this technique safer for long-term clinical applications.  
      In the tripolar cuff electrodes ( FIG. 46 -I), the electrode consists of a cathode, flanked by two anodes. When stimulation is applied, the nerve membrane is depolarized near the cathode and hyperpolarized near the anodes. If the membrane is sufficiently hyperpolarized, an action potential (AP) that travels into the depolarized zone cannot pass the hyperpolarized zone and is arrested. As with excitation, a lower external stimulus is needed for blocking large diameter fibers than for blocking smaller ones (C-fibers). Therefore, by applying a current above the blocking threshold for the large fibers but below the blocking threshold for the smaller ones, selective activation of the small fibers can be obtained. This is one of the aims of this invention, where selective stimulation of C-fibers can be achieved, without the unwanted side effects of motor stimulation to the throat region.  
      As shown in  FIGS. 46J and 46K , the microcontroller  398  in the pulse generator  391  is configured to provide stepped pulses. The current of the first step is too low to induce an action potential (AP), but only depolarizes the membrane. The AP is generated during the second step. The pulses in  FIGS. 46J and 46K  are similar, except that the pulses in  FIG. 46J  have a longer first step. In addition to anodel blocking, another advantage of these stepped pulses is that the total charge per pulse can be reduced by almost a third.  
      Other examples of complex pulses, that may be used with tripolar electrodes are shown in FIGS.  46 -L to  46 -O.  FIG. 46L  shows biphasic pulses with a time delay td between the positive and negative pulse.  FIG. 46M  shows biphasic pulses with a time delay td, where the second part of the pulse is a step pulse.  FIG. 46N  shows ramp pulses, and  FIG. 46 -O show pulses with exponential components. Theoretical work, computer modeling, and animal studies have all shown that lower charge is obtained with these modified pulses when compared to square pulses. The charge reduction of these pulses can be approximately 30% less when compared to square pulses, which is fairly significant. The microcontroller  398  of the pulse generator  391  can be configured to deliver these pulses, as is well known to one skilled in the art.  
      Since the number of types of pulses and pulse trains to provide therapy can be complex for many physician&#39;s, in one aspect pre-determined/pre-packaged program comprise a complete program for the pulse trains that deliver therapy. The advantage of the pre-packaged programs is that the physician may program a complicated program simply by selecting a program number.  
      Since a key concept of this invention is to deliver afferent stimulation, in one aspect efferent stimulation of selected types of fibers may be substantially blocked, utilizing the “greenwave” effect. In such a case, as shown in conjunction with  FIGS. 47A and 47B , a tripolar lead is utilized. As depicted on the top right portion of  FIG. 47A , a depolarization peak  10  on the vagus nerve bundle corresponding to electrode  61  (cathode) and the two hyper-polarization peaks  8 ,  12  corresponding to electrodes  62 ,  63  (anodes). With the microcontroller controlling the tripolar device, the size and timing of the hyper-polarizations  8 ,  12  can be controlled. As was shown previously in  FIGS. 2 and 10 A, since the speed of conduction is different between the larger diameter A and B fibers and the smaller diameter c-fibers, by appropriately timing the pulses, collision blocks can be created for conduction via the large diameter A and B fibers in the efferent direction. This is depicted schematically in  FIG. 47B . A lead with tripolar electrodes for stimulation/blocking is shown in conjunction with  FIG. 47C . Alternatively, separate leads may be utilized for stimulation and blocking, and the pulse generator may be adapted for two or three leads, as is well known in the art for dual chamber cardiac pacemakers or implantable defibrillators.  
      Therefore in the method and system of this invention, stimulation without block may be provided. Additionally, stimulation with selective block may be provided. Blocking of nerve impulses, unidirectional blocking, and selective blocking of nerve impulses is well known in the scientific literature. Some of the general literature is listed below and is incorporated herein by reference. (a) “Generation of unidirectionally propagating action potentials using a monopolar electrode cuff”,  Annals of Biomedical Engineering , volume 14, pp. 437-450, By Ira J. Ungar et al. (b) “An asymmetric two electrode cuff for generation of unidirectionally propagated action potentials”,  IEEE Transactions on Biomedical Engineering , volume BME-33, No. 6, June 1986, By James D. Sweeney, et al. (c) A spiral nerve cuff electrode for peripheral nerve stimulation,  IEEE Transactions on Biomedical Engineering , volume 35, No. 11, November 1988, By Gregory G. Naples. et al. (d) “A nerve cuff technique for selective excitation of peripheral nerve trunk regions,  IEEE Transactions on Biomedical Engineering , volume 37, No. 7, July 1990, By James D. Sweeney, et al. (e) “Generation of unidirectionally propagated action potentials in a peripheral nerve by brief stimuli”,  Science , volume 206 pp. 1311-1312, Dec. 14, 1979, By Van Den Honert et al. (f) “A technique for collision block of perpheral nerve: Frequency dependence”  IEEE Transactions on Biomedical Engineering , MP-12, volume 28, pp. 379-382, 1981, By Van Den Honert et al. (g) “A nerve cuff design for the selective activation and blocking of myelinated nerve fibers”  Ann. Conf. of the IEEE Engineering in Medicine and Biology Soc ., volume 13, No. 2, p 906, 1991, By D. M Fitzpatrick et al. (h) “Orderly recruitment of motoneurons in an acute rabbit model”, “ Ann. Conf. of the IEEE Engineering in Medicine and Biology Soc ., volume 20, No. 5, page 2564, 1998, By N. J. M. Rijkhof, et al. (i) “Orderly stimulation of skeletal muscle motor units with tripolar nerve cuff electrode”,  IEEE Transactions on Biomedical Engineering , volume 36, No. 8, pp. 836, 1989, By R. Bratta. (j) M. Devor, “Pain Networks”, Handbook of Brand Theory and Neural Networks, Ed. M. A. Arbib, MIT Press, page 698, 1998.  
      Blocking can be generally divided into 3 categories: (a) DC or anodal block, (b) Wedenski Block, and (c) Collision block. In anodal block there is a steady potential which is applied to the nerve causing a reversible and selective block. In Wedenski Block the nerve is stimulated at a high rate causing the rapid depletion of the neurotransmitter. In collision blocking, unidirectional action potentials are generated anti-dromically. The maximal frequency for complete block is the reciprocal of the refractory period plus the transit time, i.e. typically less than a few hundred hertz. The use of any of these blocking techniques can be applied for the practice of this invention, and all are considered within the scope of this invention.  
      Since one of the objects of this invention is to decease side effects such as hoarsness in the throat, or any cardiac side effects, blocking electrodes may be strategically placed at the relevant branches of vagus nerve.  
      As shown in conjunction with  FIG. 47D , the stimulating electrodes are placed on cervical vagus, and the blocking electrodes are placed on a branch to vocal cords  4 . With the blocking electrodes positioned between the vocal cords and the stimulating electrodes, and the controller supplying blocking pulses to the blocking electrode, the side effects pertaining to vocal response can be eliminated or significantly diminished. Advantageously, more aggressive therapy can be provided, leading to even better efficacy. Similarly, as also depicted in  FIG. 47D , the blocking electrode may be placed on the inferior cardiac nerve  5 , whereby the blocking electrode would be positioned between the heart and stimulating electrode. Again, with the controller delivering blocking pulses to the blocking electrode, the cardiac side effects would be significantly diminished or virtually eliminated.  
      Shown in conjunction with  FIG. 47E  is simplified depiction of efferent block. This time with the blocking electrode placed distal to the stimulating electrode, and the controller supplying blocking pulses to the blocking electrodes, the efferent pulses can be blocked. Advantageously, the side effects related to cardiopulmonary system, gastrointestinal system and pancreobiliary system can be greatly diminished. It will be apparent to one skilled in the art that, as shown in conjunction with  47 F, selective efferent block can also be performed.  
      In one aspect of the invention, the pulsed electrical stimulation to the vagus nerve(s) may be provided anywhere along the length of the vagus nerve(s). As was shown earlier in conjunction with  FIG. 20 , the pulsed electrical stimulation may be at the cervical level. Alternatively, shown in conjunction with  FIG. 48 , the stimulation to the vagus nerve(s) may be around the diaphramatic level. Either above the diaphragm or below the diaphragm.  
      The programming of the implanted pulse generator (IPG)  391  is shown in conjunction with  FIGS. 49A and 49B . With the magnetic Reed Switch  389  ( FIG. 38 ) in the closed position, a coil in the head of the programmer  85 , communicates with a telemetry coil  399  of the implanted pulse generator  391 . Bi-directional inductive telemetry is used to exchange data with the implanted unit  391  by means of the external programming unit  85 .  
      The transmission of programming information involves manipulation of the carrier signal in a manner that is recognizable by the pulse generator  391  as a valid set of instructions. The process of modulation serves as a means of encoding the programming instruction in a language that is interpretable by the implanted pulse generator  391 . Modulation of signal amplitude, pulse width, and time between pulses are all used in the programming system, as will be appreciated by those skilled in the art.  FIG. 50A  shows an example of pulse count modulation, and  FIG. 50B  shows an example of pulse width modulation, that can be used for encoding.  
       FIG. 51  shows a simplified overall block diagram of the implanted pulse generator (IPG)  391  programming and telemetry interface. The left half of  FIG. 51  is programmer  85  which communicates programming and telemetry information with the IPG  391 . The sections of the IPG  391  associated with programming and telemetry are shown on the right half of  FIG. 51 . In this case, the programming sequence is initiated by bringing a permanent magnet in the proximity of the IPG  391  which closes a reed switch  389  in the IPG  391 . Information is then encoded into a special error-correcting pulse sequence and transmitted electromagnetically through a set of coils. The received message is decoded, checked for errors, and passed on to the unit&#39;s logic circuitry. The IPG  391  of this embodiment includes the capability of bi-directional communication.  
      The reed switch  389  is a magnetically-sensitive mechanical switch, which consists of two thin strips of metal (the “reed”) which are ferromagnetic. The reeds normally spring apart when no magnetic field is present. When a field is applied, the reeds come together to form a closed circuit because doing so creates a path of least reluctance. The programming head of the programmer contains a high-field-strength ceramic magnet.  
      When the switch closes, it activates the programming hardware, and initiates an interrupt of the IPG central processor. Closing the reed switch  389  also presents the logic used to encode and decode programming and telemetry signals. A nonmaskable interrupt (NMI) is sent to the IPG processor, which then executes special programming software. Since the NMI is an edge-triggered signal and the reed switch is vulnerable to mechanical bounce, a debouncing circuit is used to avoid multiple interrupts. The overall current consumption of the IPG increases during programming because of the debouncing circuit and other communication circuits.  
      A coil  399  is used as an antenna for both reception and transmission. Another set of coils  383  is placed in the programming head, a relatively small sized unit connected to the programmer  85 . All coils are tuned to the same resonant frequency. The interface is half-duplex with one unit transmitting at a time.  
      Since the relative positions of the programming head  87  and IPG  391  determine the coupling of the coils, this embodiment utilizes a special circuit which has been devised to aid the positioning of the programming head, and is shown in  FIG. 52 . It operates on similar principles to the linear variable differential transformer. An oscillator tuned to the resonant frequency of the pacemaker coil  399  drives the center coil of a three-coil set in the programmer head. The phase difference between the original oscillator signal and the resulting signal from the two outer coils is measured using a phase shift detector. It is proportional to the distance between the implanted pulse generator and the programmer head. The phase shift, as a voltage, is compared to a reference voltage and is then used to control an indicator such as an LED. An enable signal allows switching the circuit on and off.  
      Actual programming is shown in conjunction with  FIGS. 53 and 54 . Programming and telemetry messages comprise many bits; however, the coil interface can only transmit one bit at a time. In addition, the signal is modulated to the resonant frequency of the coils, and must be transmitted in a relatively short period of time, and must provide detection of erroneous data.  
      A programming message is comprised of five parts  FIG. 53 ( a ). The start bit indicates the beginning of the message and is used to synchronize the timing of the rest of the message. The parameter number specifies which parameter (e.g., mode, pulse width, delay) is to be programmed. In the example, in  FIG. 53 ( a ) the number 10010000 specifies the pulse rate to be specified. The parameter value represents the value that the parameter should be set to. This value may be an index into a table of possible values; for example, the value 00101100 represents a pulse stimulus rate of 80 pulses/min. The access code is a fixed number based on the stimulus generator model which must be matched exactly for the message to succeed. It acts as a security mechanism against use of the wrong programmer, errors in the message, or spurious programming from environmental noise. It can also potentially allow more than one programmable implant in the patient. Finally, the parity field is the bitwise exclusive-OR of the parameter number and value fields. It is one of several error-detection mechanisms.  
      All of the bits are then encoded as a sequence of pulses of 0.35-ms duration  FIG. 53 ( b ). The start bit is a single pulse. The remaining bits are delayed from their previous bit according to their bit value. If the bit is a zero, the delay is short (1.0); if it is a one, the delay is long (2.2 ms). This technique of pulse position coding, makes detection of errors easier.  
      The serial pulse sequence is then amplitude modulated for transmission  FIG. 53 ( c ). The carrier frequency is the resonant frequency of the coils. This signal is transmitted from one set of coils to the other and then demodulated back into a pulse sequence  FIG. 53 ( d ).  
       FIG. 54  shows how each bit of the pulse sequence is decoded from the demodulated signal. As soon as each bit is received, a timer begins timing the delay to the next pulse. If the pulse occurs within a specific early interval, it is counted as a zero bit (FIG.  54 ( b )). If it otherwise occurs with a later interval, it is considered to be a one bit ( FIG. 54 ( d )). Pulses that come too early, too late, or between the two intervals are considered to be errors and the entire message is discarded ( FIG. 54  ( a, c, e )). Each bit begins the timing of the bit that follows it. The start bit is used only to time the first bit.  
      Telemetry data may be either analog or digital. Digital signals are first converted into a serial bit stream using an encoding such as shown in  FIG. 54  ( b ). The serial stream or the analog data is then frequency modulated for transmission.  
      An advantage of this and other encodings is that they provide multiple forms of error detection. The coils and receiver circuitry are tuned to the modulation frequency, eliminating noise at other frequencies. Pulse-position coding can detect errors by accepting pulses only within narrowly-intervals. The access code acts as a security key to prevent programming by spurious noise or other equipment. Finally, the parity field and other checksums provides a final verification that the message is valid. At any time, if an error is detected, the entire message is discarded.  
      Another more sophisticated type of pulse position modulation may be used to increase the bit transmission rate. In this, the position of a pulse within a frame is encoded into one of a finite number of values, e.g. 16. A special synchronizing bit is transmitted to signal the start of the frame. Typically, the frame contains a code which specifies the type or data contained in the remainder of the frame.  
       FIG. 55  shows a diagram of receiving and decoding circuitry for programming data. The IPG coil, in parallel with capacitor creates a tuned circuit for receiving data. The signal is band-pass filtered  602  and envelope detected  604  to create the pulsed signal in  FIG. 53  ( d ). After decoding, the parameter value is placed in a RAM at the location specified by the parameter number. The IPG can have two copies of the RAM—a permanent set and a temporary set—which makes it easy for the physician to set the IPG to a temporary configuration and later reprogram it back to the usual settings.  
       FIG. 56  shows the basic circuit used to receive telemetry data. Again, a coil and capacitor create a resonant circuit tuned to the carrier frequency. The signal is further band-pass filtered  614  and then frequency-demodulated using a phase-locked loop  618 .  
      This embodiment also comprises an optional battery status test circuit. Shown in conjunction with  FIG. 57 , the charge delivered by the battery is estimated by keeping track of the number of pulses delivered by the IPG  391 . An internal charge counter is updated during each test mode to read the total charge delivered. This information about battery status is read from the IPG  391  via telemetry.  
     Combination Implantable Device Comprising Both a Stimulus-Receiver and a Programmable Implantable Pulse Generator (IPG)  
      In one embodiment, the implantable device may comprise both a stimulus-receiver and a programmable implantable pulse generator (IPG) in one device. Another embodiment of a similar device is disclosed in applicant&#39;s co-pending application Ser. No. 10/436,017. This embodiment also comprises predetermined/pre-packaged programs. Examples of several stimulation states were given in the previous sections, under “Programmer-less Implantable Pulse Generator (IPG)” and “Programmable Implantable Pulse Generator”. These predetermined/pre-packaged programs comprise unique combinations of pulse amplitude, pulse width, pulse frequency, ON-time and OFF-time.  
       FIG. 58  shows a close up view of the packaging of the implanted stimulator  75  of this embodiment, showing the two subassemblies  120 ,  170 . The two subassemblies are the stimulus-receiver module  120  and the battery operated pulse generator module  170 . The electrical components of the stimulus-receiver module  120  may be substantially in the titanium case along with other circuitry, except for a coil. The coil may be outside the titanium case as shown in  FIG. 58 , or the coil  48 C may be externalized at the header portion  79  of the implanted device, and may be wrapped around the titanium can. In this case, the coil is encased in the same material as the header  79 , as shown in  FIGS. 59A-59D .  FIG. 59A  depicts a bipolar configuration with two separate feed-throughs,  56 ,  58 .  FIG. 59B  depicts a unipolar configuration with one separate feed-through  66 .  FIG. 59C , and  59 D depict the same configuration except the feed-throughs are common with the feed-throughs  66 A for the lead.  
       FIG. 60  is a simplified overall block diagram of the embodiment where the implanted stimulator  75  is a combination device, which may be used as a stimulus-receiver (SR) in conjunction with an external stimulator, or the same implanted device may be used as a traditional programmable implanted pulse generator (IPG). The coil  48 C which is external to the titanium case may be used both as a secondary of a stimulus-receiver, or may also be used as the forward and back telemetry coil.  
      In this embodiment, as disclosed in  FIG. 60 , the IPG circuitry within the titanium case is used for all stimulation pulses whether the energy source is the internal battery  740  or an external power source. The external device serves as a source of energy, and as a programmer that sends telemetry to the IPG. For programming, the energy is sent as high frequency sine waves with superimposed telemetry wave driving the external coil  46 C. Once received by the implanted coil  48 C, the telemetry is passed through coupling capacitor  727  to the IPG&#39;s telemetry circuit  742 . For pulse delivery using external power source, the stimulus-receiver portion will receive the energy coupled to the implanted coil  48 C and, using the power conditioning circuit  726 , rectify it to produce DC, filter and regulate the DC, and couple it to the IPG&#39;s voltage regulator  738  section so that the IPG can run from the externally supplied energy rather than the implanted battery  740 .  
      The system provides a power sense circuit  728  that senses the presence of external power communicated with the power control  730  when adequate and stable power is available from an external source. The power control circuit controls a switch  736  that selects either battery power  740  or conditioned external power from  726 . The logic and control section  732  and memory  744  includes the IPG&#39;s microcontroller, pre-programmed instructions, and stored chagneable parameters. Using input for the telemetry circuit  742  and power control  730 , this section controls the output circuit  734  that generates the output pulses.  
      It will be clear to one skilled in the art that this embodiment of the invention can also be practiced with a rechargeable battery. This version is shown in conjunction with  FIG. 61 . The circuitry in the two versions are similar except for the battery charging circuitry  749 . This circuit is energized when external power is available. It senses the charge state of the battery and provides appropriate charge current to safely recharge the battery without overcharging.  
      The stimulus-receiver portion of the circuitry is shown in conjunction with  FIG. 62 . Capacitor C 1  ( 729 ) makes the combination of C 1  and L 1  sensitive to the resonant frequency and less sensitive to other frequencies, and energy from an external (primary) coil  46 C is inductively transferred to the implanted unit via the secondary coil  48 C. The AC signal is rectified to DC via diode  731 , and filtered via capacitor  733 . A regulator  735  sets the output voltage and limits it to a value just above the maximum IPG cell voltage. The output capacitor C 4  ( 737 ), typically a tantalum capacitor with a value of 100 micro-Farads or greater, stores charge so that the circuit can supply the IPG with high values of current for a short time duration with minimal voltage change during a pulse while the current draw from the external source remains relatively constant. Also shown in conjunction with  FIG. 62 , a capacitor C 3  ( 727 ) couples signals for forward and back telemetry.  
       FIGS. 63A and 63B  show alternate connection of the receiveing coil. In  FIG. 63A , each end of the coil is connected to the circuit through a hermetic feedthrough filter. In this instance, the DC output is floating with respect to the IPG&#39;s case. In  FIG. 63B , one end of the coil is connected to the exterior of the IPG&#39;s case. The circuit is completed by connecting the capacitor  729  and bridge rectifier  739  to the interior of the IPG&#39;s case The advantage of this arrangement is that it requires one less hermetic feedthrough filter, thus reducing the cost and improving the reliabilty of the IPG. Hermetic feedthrough filters are expensive and a possible failure point. However, the case connection may complicit the output circuitry or limit its versatility. When using a bipolar electrode, care must be taken to prevent an unwanted return path for the pulse to the IPG&#39;s case. This is not a concern for unipolar pulses using a single conductor electrode because it relies on the IPG&#39;s case a return for the pulse current.  
      In the unipolar configuration, advantageously a bigger tissue area is stimulated since the difference between the tip (cathode) and case (anode) is larger. Stimulation using both configuration is considered within the scope of this invention.  
      The power source select circuit is highlighted in conjunction with  FIG. 64 . In this embodiment, the IPG provides stimulation pulses according to the stimulation programs stored in the memory  744  of the implanted stimulator, with power being supplied by the implanted battery  740 . When stimulation energy from an external stimulator is inductively received via secondary coil  48 C, the power source select circuit (shown in block  743 ) switches power via transistor Q 1   745  and transistor Q 2   743 . Transistor Q 1  and Q 2  are preferably low loss MOS transistor used as switches, even though other types of transistors may be used.  
     Implantable Pulse Generator (IPG) Comprising a Rechargable Battery  
      In one embodiment, an implantable pulse generator with rechargeable power source can be used. Because of the rapidity of the pulses required for modulating nerve tissue  54  with stimulating and/or blocking pulses, there is a real need for power sources that will provide an acceptable service life under conditions of continuous delivery of high frequency pulses.  FIG. 65A  shows a graph of the energy density of several commonly used battery technologies. Lithium batteries have by far the highest energy density of commonly available batteries. Also, a lithium battery maintains a nearly constant voltage during discharge. This is shown in conjunction with  FIG. 65B , which is normalized to the performance of the lithium battery. Lithium-ion batteries also have a long cycle life, and no memory effect. However, Lithium-ion batteries are not as tolerant to overcharging and overdischarging. One of the most recent development in rechargable battery technology is the Lithium-ion polymer battery. Recently the major battery manufacturers (Sony, Panasonic, Sanyo) have announced plans for Lithium-ion polymer battery production.  
      In another embodiment, existing nerve stimulators and cardiac pacemakers can be modified to incorporate rechargeable batteries. Among the nerve stimulators that can be adopted with rechargeable batteries can for, example, be the vagus nerve stimulator manufactured by Cyberonics Inc. (Houston, Tex.). U.S. Pat. No. 4,702,254 (Zabara), U.S. Pat. No. 5,023,807 (Zabara), and U.S. Pat. No. 4,867,164 (Zabara) on Neurocybernetic Prostheses, which can be practiced with rechargeable power source as disclosed in the next section. These patents are incorporated herein by reference.  
      This embodiment also comprises predetermined/pre-packaged programs. Examples of several stimulation states were given in the previous sections, under “Programmer-less Implantable Pulse Generator (IPG)”, and “Programmable Implantable Pulse Generator”. These pre-packaged/pre-determined programs comprise unique combinations of pulse amplitude, pulse width, pulse frequency, ON-time and OFF-time. Additionally, predetermined programs comprising blocking pulses may also be stored in the memory of the pulse generator.  
      As shown in conjunction with  FIG. 66 , the coil is externalized from the titanium case  57 . The RF pulses transmitted via coil  46  and received via subcutaneous coil  48 A are rectified via a diode bridge. These DC pulses are processed and the resulting current applied to recharge the battery  694 / 740  in the implanted pulse generator. In one embodiment the coil  48 C may be externalized at the header portion  79  of the implanted device, and may be wrapped around the titanium can, as was previously shown in FIGS.  59 A-D.  
      In one embodiment, the coil may also be positioned on the titanium case as shown in conjunction with  FIGS. 67A and 67B .  FIG. 67A  shows a diagram of the finished implantable stimulator  391 R of one embodiment.  FIG. 67B  shows the pulse generator with some of the components used in assembly in an exploded view. These components include a coil cover  15 , the secondary coil  48  and associated components, a magnetic shield  18 , and a coil assembly carrier  19 . The coil assembly carrier  9  has at least one positioning detail  88  located between the coil assembly and the feed through for positioning the electrical connection. The positioning detail  13  secures the electrical connection.  
      A schematic diagram of the implanted pulse generator (IPG  391 R), with re-chargeable battery  694 , is shown in conjunction with  FIG. 68 . The IPG  391 R includes logic and control circuitry  673  connected to memory circuitry  691 . The operating program and stimulation parameters are typically stored within the memory  691  via forward telemetry. Stimulation pulses are provided to the nerve tissue  54  via output circuitry  677  controlled by the microcontroller.  
      The operating power for the IPG  391 R is derived from a rechargeable power source  694 . The rechargeable power source  694  comprises a rechargeable lithium-ion or lithium-ion polymer battery. Recharging occurs inductively from an external charger to an implanted coil  48 B underneath the skin  60 . The rechargeable battery  694  may be recharged repeatedly as needed. Additionally, the IPG  391 R is able to monitor and telemeter the status of its rechargable battery  691  each time a communication link is established with the external programmer  85 .  
      Much of the circuitry included within the IPG  391 R may be realized on a single application specific integrated circuit (ASIC). This allows the overall size of the IPG  391 R to be quite small, and readily housed within a suitable hermetically-sealed case. The IPG case is preferably made from a titanium and is shaped in a rounded case.  
      Shown in conjunction with  FIG. 69  are the recharging elements of this embodiment. The re-charging system uses a portable external charger to couple energy into the power source of the IPG  391 R. The DC-to-AC conversion circuitry  696  of the re-charger receives energy from a battery  672  in the re-charger. A charger base station  680  and conventional AC power line may also be used. The AC signals amplified via power amplifier  674  are inductively coupled between an external coil  46 B and an implanted coil  48 B located subcutaneously with the implanted pulse generator (IPG)  391 R. The AC signal received via implanted coil  48 B is rectified  686  to a DC signal which is used for recharging the rechargeable battery  694  of the IPG, through a charge controller IC  682 . Additional circuitry within the IPG  391 R includes, battery protection IC  688  which controls a FET switch  690  to make sure that the rechargeable battery  694  is charged at the proper rate, and is not overcharged. The battery protection IC  688  can be an off-the-shelf IC available from Motorola (part no. MC 33349N-3R1). This IC monitors the voltage and current of the implanted rechargeable battery  694  to ensure safe operation. If the battery voltage rises above a safe maximum voltage, the battery protection IC  688  opens charge enabling FET switches  690 , and prevents further charging. A fuse  692  acts as an additional safeguard, and disconnects the battery  694  if the battery charging current exceeds a safe level. As also shown in  FIG. 69 , charge completion detection is achieved by a back-telemetry transmitter  684 , which modulates the secondary load by changing the full-wave rectifier into a half-wave rectifier/voltage clamp. This modulation is in turn, sensed by the charger as a change in the coil voltage due to the change in the reflected impedance. When detected through a back telemetry receiver  676 , either an audible alarm is generated or a LED is turned on.  
      A simplified block diagram of charge completion and misalignment detection circuitry is shown in conjunction with  FIG. 70 . As shown, a switch regulator  686  operates as either a full-wave rectifier circuit or a half-wave rectifier circuit as controlled by a control signal (CS) generated by charging and protection circuitry  698 . The energy induced in implanted coil  48 B (from external coil  46 B) passes through the switch rectifier  686  and charging and protection circuitry  698  to the implanted rechargeable battery  694 . As the implanted battery  694  continues to be charged, the charging and protection circuitry  698  continuously monitors the charge current and battery voltage. When the charge current and battery voltage reach a predetermined level, the charging and protection circuitry  698  triggers a control signal. This control signal causes the switch rectifier  686  to switch to half-wave rectifier operation. When this change happens, the voltage sensed by voltage detector  702  causes the alignment indicator  706  to be activated. This indicator  706  may be an audible sound or a flashing LED type of indicator.  
      The indicator  706  may similarly be used as a misalignment indicator. In normal operation, when coils  46 B (external) and  48 B (implanted) are properly aligned, the voltage V s  sensed by voltage detector  704  is at a minimum level because maximum energy transfer is taking place. If and when the coils  46 B and  48 B become misaligned, then less than a maximum energy transfer occurs, and the voltage V s  sensed by detection circuit  704  increases significantly. If the voltage V s  reaches a predetermined level, alignment indicator  706  is activated via an audible speaker and/or LEDs for visual feedback. After adjustment, when an optimum energy transfer condition is established, causing V s  to decrease below the predetermined threshold level, the alignment indicator  706  is turned off.  
      The elements of the external recharger are shown as a block diagram in conjunction with  FIG. 71 . In this disclosure, the words charger and recharger are used interchangeably. The charger base station  680  receives its energy from a standard power outlet  714 , which is then converted to 5 volts DC by a AC-to-DC transformer  712 . When the re-charger is placed in a charger base station  680 , the re-chargeable battery  672  of the re-charger is fully recharged in a few hours and is able to recharge the battery  694  of the IPG  391 R. If the battery  672  of the external re-charger falls below a prescribed limit of 2.5 volt DC, the battery  672  is trickle charged until the voltage is above the prescribed limit, and then at that point resumes a normal charging process.  
      As also shown in  FIG. 71 , a battery protection circuit  718  monitors the voltage condition, and disconnects the battery  672  through one of the FET switches  716 ,  720  if a fault occurs until a normal condition returns. A fuse  724  will disconnect the battery  672  should the charging or discharging current exceed a prescribed amount.  
      In summary, in the method of the current invention for neuromodulation of cranial nerve such as the vagus nerve(s), to provide adjunct therapy for involuntary movement disorders (including Parkinson&#39;s disease and epilepsy) be practiced with any of the several pulse generator systems disclosed including, 
          a) an implanted stimulus-receiver with an external stimulator;     b) an implanted stimulus-receiver comprising a high value capacitor for storing charge, used in conjunction with an external stimulator;     c) a programmer-less implantable pulse generator (IPG) which is operable with a magnet;     d) a microstimulator;     e) a programmable implantable pulse generator;     f) a combination implantable device comprising both a stimulus-receiver and a programmable IPG; and     g) an IPG comprising a rechargeable battery.        

      Neuromodulation of vagus nerve(s) with any of these systems is considered within the scope of this invention.  
      In one embodiment, the external stimulator and/or the programmer has a telecommunications module, as described in a co-pending application, and summarized here for reader convenience. The telecommunications module has two-way communications capabilities.  
       FIGS. 72 and 73  depict communication between an external stimulator  42  and a remote hand-held computer  502 . A desktop or laptop computer can be a server  500  which is situated remotely, perhaps at a physician&#39;s office or a hospital. The stimulation parameter data can be viewed at this facility or reviewed remotely by medical personnel on a hand-held personal data assistant (PDA)  502 , such as a “palm-pilot” from PALM corp. (Santa Clara, Calif.), a “Visor” from Handspring Corp. (Mountain view, Calif.) or on a personal computer (PC). The physician or appropriate medical personnel, is able to interrogate the external stimulator  42  device and know what the device is currently programmed to, as well as, get a graphical display of the pulse train. The wireless communication with the remote server  500  and hand-held PDA  502  would be supported in all geographical locations within and outside the United States (US) that provides cell phone voice and data communication service.  
      In one aspect of the invention, the telecommunications component can use Wireless Application Protocol (WAP). The Wireless Application Protocol (WAP), which is a set of communication protocols standardizing Internet access for wireless devices. While previously, manufacturers used different technologies to get Internet on hand-held devices, with WAP devices and services interoperate. WAP also promotes convergence of wireless data and the Internet. The WAP programming model is heavily based on the existing Internet programming model, and is shown schematically in  FIG. 74 . Introducing a gateway function provides a mechanism for optimizing and extending this model to match the characteristics of the wireless environment. Over-the-air traffic is minimized by binary encoding/decoding of Web pages and readapting the Internet Protocol stack to accommodate the unique characteristics of a wireless medium such as call drops.  
      The key components of the WAP technology, as shown in  FIG. 74 , includes 1) Wireless Mark-up Language (WML)  550  which incorporates the concept of cards and decks, where acard is a single unit of interaction with the user. A service constitutes a number of cards collected in a deck. A card can be displayed on a small screen. WML supported Web pages reside on traditional Web servers. 2) WML Script which is a scripting language, enables application modules or applets to be dynamically transmitted to the client device and allows the user interaction with these applets. 3) Microbrowser, which is a lightweight application resident on the wireless terminal that controls the user interface and interprets the WML/WMLScript content. 4) A lightweight protocol stack  520  which minimizes bandwidth requirements, guaranteeing that a broad range of wireless networks can run WAP applications. The protocol stack of WAP can comprise a set of protocols for the transport (WTP), session (WSP), and security (WTLS) layers. WSP is binary encoded and able to support header caching, thereby economizing on bandwidth requirements. WSP also compensates for high latency by allowing requests and responses to be handled asynchronously, sending before receiving the response to an earlier request. For lost data segments, perhaps due to fading or lack of coverage, WTP only retransmits lost segments using selective retransmission, thereby compensating for a less stable connection in wireless. The above mentioned features are industry standards adopted for wireless applications and greater details have been publicized, and well known to those skilled in the art.  
      In this embodiment, two modes of communication are possible. In the first, the server initiates an upload of the actual parameters being applied to the patient, receives these from the stimulator, and stores these in its memory, accessible to the authorized user as a dedicated content driven web page. The physician or authorized user can make alterations to the actual parameters, as available on the server, and then initiate a communication session with the stimulator device to download these parameters.  
      Shown in conjunction with  FIG. 75 , in one embodiment, the external stimulator  42  and/or the programmer  85  may also be networked to a central collaboration computer  286  as well as other devices such as a remote computer  294 , PDA  502 , phone  141 , physician computer  143 . The interface unit  292  in this embodiment communicates with the central collaborative network  290  via land-lines such as cable modem or wirelessly via the internet. A central computer  286  which has sufficient computing power and storage capability to collect and process large amounts of data, contains information regarding device history and serial number, and is in communication with the network  290 . Communication over collaboration network  290  may be effected by way of a TCP/IP connection, particularly one using the internet, as well as a PSTN, DSL, cable modem, LAN, WAN or a direct dial-up connection.  
      The standard components of interface unit shown in block  292  are processor  305 , storage  310 , memory  308 , transmitter/receiver  306 , and a communication device such as network interface card or modem  312 . In the preferred embodiment these components are embedded in the external stimulator  42  and can also be embedded in the programmer  85 . These can be connected to the network  290  through appropriate security measures (Firewall)  293 .  
      Another type of remote unit that may be accessed via central collaborative network  290  is remote computer  294 . This remote computer  294  may be used by an appropriate attending physician to instruct or interact with interface unit  292 , for example, instructing interface unit  292  to send instruction downloaded from central computer  286  to remote implanted unit.  
      Shown in conjunction with  FIGS. 76A and 76B  the physician&#39;s remote communication&#39;s module is a Modified PDA/Phone  502  in this embodiment. The Modified PDA/Phone  502  is a microprocessor based device as shown in a simplified block diagram in  FIGS. 76A and 76B . The PDA/Phone  502  is configured to accept PCM/CIA cards specially configured to fulfill the role of communication module  292  of the present invention. The Modified PDA/Phone  502  may operate under any of the useful software including Microsoft Window&#39;s based, Linux, Palm OS, Java OS, SYMBIAN, or the like.  
      The telemetry module  362  comprises an RF telemetry antenna  142  coupled to a telemetry transceiver and antenna driver circuit board which includes a telemetry transmitter and telemetry receiver. The telemetry transmitter and receiver are coupled to control circuitry and registers, operated under the control of microprocessor  364 . Similarly, within stimulator a telemetry antenna  142  is coupled to a telemetry transceiver comprising RF telemetry transmitter and receiver circuit. This circuit is coupled to control circuitry and registers operated under the control of microcomputer circuit.  
      With reference to the telecommunications aspects of the invention, the communication and data exchange between Modified PDA/Phone  502  and external stimulator  42  operates on commercially available frequency bands. The 2.4-to-2.4853 GHz bands or 5.15 and 5.825 GHz, are the two unlicensed areas of the spectrum, and set aside for industrial, scientific, and medical (ISM) uses. Most of the technology today including this invention, use either the 2.4 or 5 GHz radio bands and spread-spectrum technology.  
      The telecommunications technology, especially the wireless internet technology, which this invention utilizes in one embodiment, is constantly improving and evolving at a rapid pace, due to advances in RF and chip technology as well as software development. Therefore, one of the intents of this invention is to utilize “state of the art” technology available for data communication between Modified PDA/Phone  502  and external stimulator  42 . The intent of this invention is to use 3G technology for wireless communication and data exchange, even though in some cases 2.5G is being used currently.  
      For the system of the current invention, the use of any of the “3G” technologies for communication for the Modified PDA/Phone  502 , is considered within the scope of the invention. Further, it will be evident to one of ordinary skill in the art that as future 4G systems, which will include new technologies such as improved modulation and smart antennas, can be easily incorporated into the system and method of current invention, and are also considered within the scope of the invention.  
      The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. It is therefore desired that the present embodiment be considered in all aspects as illustrative and not restrictive, reference being made to the appended claims rather than to the foregoing description to indicate the scope of the invention.