Patent Publication Number: US-2007100377-A1

Title: Providing multiple signal modes for a medical device

Description:
BACKGROUND OF THE INVENTION  
      1. Field of the Invention  
      This invention relates generally to medical devices and, more particularly, to methods, apparatus, and systems for providing a background signal using a medical device capable of treating a medical condition of a patient.  
      2. Description of the Related Art  
      The human brain resides in the cranial cavity of the skull and controls the central nervous system (CNS) in a supervisory role. The central nervous system is generally a hub of electrical and/or neural activity requiring appropriate management. For example, properly controlled electrical or neural activity enables the human brain to manage various mental and body functions to maintain homeostasis. Abnormal electrical and/or neural activity is associated with different diseases and disorders in the central and peripheral nervous systems. In addition to a drug regimen or surgical intervention, potential treatments for such diseases and disorders include implantation of a medical device in a patient for electrical stimulation of body tissue. In particular, by selectively applying therapeutic electrical signals to one or more electrodes coupled to the patient&#39;s neural tissue, an implantable medical device (IMD) may electrically stimulate a target neural tissue location. This stimulation may be used to treat a neurological disease, condition or disorder.  
      Therapeutic electrical signals may be used to apply an electrical signal to a neural structure of the body, and more particularly to cranial nerves such as the vagus nerve. The signal may be used to induce afferent action potentials on the nerve and thereby increase the flow of neural signals up the nerve, toward the brain. The signal may also (or alternatively) generate efferent action potentials to modulate a neural response in one or more body structures of the patient, such as any of the numerous organs innervated by efferent signals on the vagus nerve. Finally, therapeutic electrical signals may also or additionally be used to inhibit neural activity and to block neural impulses from moving up or down the nerve the nerve. As used herein, the terms “stimulate” and “modulate” are interchangeable and refer to delivery of a signal (which may comprise an electrical, magnetic, or chemical stimulus) to a target body area, regardless of whether its effects include afferent action potentials, efferent action potentials, and/or the blocking of action potentials. Therapeutic electrical stimulation of the vagus nerve has been used to treat epilepsy and depression. Vagus nerve stimulation (VNS) therapy for treatment of epilepsy is described in many U.S. Patents including U.S. Pat. Nos. 4,702,254, 4,867,164, and 5,025,807, which are incorporated herein by reference.  
      To provide vagus nerve stimulation to a patient, a neurostimulator device may be implanted in a target location in the patient&#39;s body. Such a neurostimulator device system may comprise an electrical signal generator, attached to an electrical lead having one or more electrodes coupled to the vagus nerve.  
      However, depending upon an individual patient or a particular disease being treated, efficacy of the VNS therapy may vary significantly. For instance, VNS efficacy for treatment resistant epilepsy and depression may be generalized as a first percentage of patient population having significant improvement. A second percentage of patient population may be characterized as having some improvement. The remaining percentage of patient population may experience little or no improvement. There is a need to improve the efficacy of VNS therapy for certain treatments. Further concerns include reducing any side effects during stimulation.  
      Neurostimulation has demonstrated the potential to treat a wide variety of neurological disorders; however, there remains a need to increase the breadth of disorders treatable by neurostimulation.  
     SUMMARY OF THE INVENTION  
      In one aspect, the present invention comprises a method for providing multiple stimulation modes for a medical device. The method includes applying a first signal to a nerve of a patient during a primary time period. The method further includes applying a second signal to the nerve of the patient during a secondary time period in which the first signal is not applied. In one embodiment, the first signal is an electrical signal, and the second signal is an electrical signal that is different from the first signal. The nerve may comprise a cranial nerve such as a vagus nerve of the patient.  
      In another aspect, a neurostimulator is provided for treating a patient with a medical condition. The neurostimulator comprises an electrical signal generator to generate a first and a second electrical signal for delivery to a selected nerve of a patient. The neurostimulator may further comprise a controller operatively coupled to the electrical signal generator. The controller may be adapted to apply the first electrical signal to the selected nerve of the patient during a primary time period, and to apply the second electrical signal to the selected nerve of the patient during a secondary time period in which the first electrical signal is off.  
      In a further aspect, a method of providing multiple stimulation modes for a medical device comprises applying a therapeutic stimulus signal to a nerve of a patient during a first time period. The method further comprises entering a non-therapeutic mode during a second time period subsequent to the first time period and applying a background stimulus signal during at least a portion of the second time period during the non-therapeutic mode.  
      In another aspect of the present invention, a method of providing multiple stimulation modes for a medical device comprises applying a first stimulus signal to a nerve of a patient during a first time period. The method further comprises applying a background stimulus signal during at least a portion of the second time period during the non-therapeutic mode.  
      In another aspect of the present invention, a method of providing multiple stimulation modes for a medical device comprises alternatively modulating a nerve of a patient within a stimulation period using a first electrical signal during a primary treatment period and a second electrical signal during a secondary treatment period in which the first electrical signal is not applied. The first and second signals may comprise a signal that generates an afferent action potential, an efferent action potential, or a signal that blocks native action potentials (i.e., action potentials that are not induced by an exogenously applied signal). 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
      The invention may be understood by reference to the following description taken in conjunction with the accompanying drawings, in which like reference numerals identify like elements, and in which:  
       FIGS. 1A-1D  are stylized diagrams of an implantable medical device implanted into a patient&#39;s body for providing stimulation to a portion of the patient&#39;s body, in accordance with one illustrative embodiment of the present invention;  
       FIG. 2  is a block diagram of an implantable medical device and an external user interface that communicates with the implantable medical device, for example, to program the implantable medical device, in accordance with one illustrative embodiment of the present invention;  
       FIG. 3  is a block diagram of the signal generator of  FIG. 2 , in accordance with one illustrative embodiment of the present invention;  
       FIG. 4  schematically illustrates a stylized representation of an electrical signal including a first electrical signal and a second electrical signal that may be applied to a nerve, such as a vagus nerve, by the implantable medical device of  FIG. 2  during a treatment ON and OFF times of a therapy, respectively, in accordance with one illustrative embodiment of the present invention;  
       FIG. 5  is a flowchart depiction of the background stimulation process, in accordance with one illustrative embodiment of the present invention;  
       FIG. 6  is a flowchart of another embodiment of providing overlaid stimulation from the implantable medical device of  FIG. 2 , in accordance with one illustrative embodiment of the present invention; and  
       FIGS. 7A-7C  illustrate stylized diagrams of various randomized electrical stimulus output current signals applied by the implantable medical device of  FIGS. 1 and 2  for providing stimulation, in accordance with one illustrative embodiment of the present invention.  
      While the invention is susceptible of various modifications and alternative forms, specific embodiments thereof have been shown by way of example in the drawings and are herein described in detail. It should be understood, however, that the description herein of specific embodiments is not intended to limit the invention to the particular forms disclosed, but on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention as defined by the appended claims. 
    
    
     DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS  
      Illustrative embodiments of the invention are described herein. In the interest of clarity, not all features of an actual implementation are described in this specification. In the development of any such actual embodiment, numerous implementation-specific decisions must be made to achieve the design-specific goals, which will vary from one implementation to another. It will be appreciated that such a development effort, while possibly complex and time-consuming, would nevertheless be a routine undertaking for persons of ordinary skill in the art having the benefit of this disclosure.  
      Neurostimulation is conventionally delivered as a pulsed electrical signal in discrete stimulation periods known as pulse bursts, which constitute a series of controlled electrical pulses defined by a plurality of parameters. The signal may be generated by an electrical pulse generator and applied to the nerve via a lead/electrode assembly. The parameters defining the signal may include a current magnitude, a pulse width, a pulse frequency, an on-time and an off-time, with optional ramp-up and ramp-down periods immediately before and after the on-time in which the signal is gradually increased (ramp-up) or decreased (ramp-down) in current magnitude before or after the defined magnitude during the on-time. In prior art embodiments, the parameters may be programmed as constant, non-random values.  
      As a non-limiting example, the electrical signal may have a programmed, non-random and constant current, e.g., milliamp, a programmed frequency, e.g., 30 Hz, a programmed pulse width, e.g., 500 microseconds, a programmed current polarity, e.g., current flow from electrode  125 - 1  to electrode  125 - 2  ( FIG. 1A ), for a period of time, e.g., 30 seconds. The period of time in which a stimulation signal is delivered (30 seconds in the example) is referred to herein as on-time. Pulse bursts are typically separated from adjacent bursts by another period of time, e.g. 5 minutes. The period of time between delivery of stimulation signals (5 minutes in the example) is referred to herein as off-time. Ramp-up and ramp-down periods may be employed over predefined periods (typically the first few seconds or pulses of a pulse burst) to avoid discomfort sometimes associated with having the initial pulses of a burst at full amplitude. The ramping signal usually increases or decreases in a predefined, non-random manner, and the on-time portion of the pulse burst is both constant and non-random. The frequency, which is determined by a plurality of similar adjacent pulse-to-pulse intervals, is also generally a constant value, although it is known to employ a swept or randomly set value. A pulse-to-pulse interval is referred to herein as a pulse period, and is distinct from frequency in that a pulse period is independent of adjacent pulse periods, whereas a frequency, by definition, requires a plurality of similar adjacent pulse periods.  
      The combined signal time of a first electrical signal, including the on-time and (if present) the ramp-up and ramp-down times is referred to hereinafter as the primary time period. In embodiments where no ramp-up or ramp-down is provided, the primary period is the same as the on-time. A primary time period is typically followed by an off-time period in which no signal is applied, and the nerve is allowed to recover from the applied first electrical signal. After the off-time period elapses, the first electrical signal is again applied to the nerve for another primary time period, followed by another off-time period with no signal. This process may be repeated until altered by a healthcare provider programming the system. The on-time and the primary time period together comprise the duty cycle of the neurostimulation system.  
      Some embodiments of the present invention provide for applying a first electrical signal from a medical device to a nerve of a patient during a first time period in which the first electrical signal modulates the electrical activity (i.e., afferent and efferent action potentials) on the nerve, followed by a second electrical signal applied to the nerve during a second time period in which the nerve is allowed to rest and/or recover from the first electrical signal. The second electrical signal may be a sub-threshold signal that is insufficient to generate exogenous afferent or efferent action potentials on the nerve or to block native signals on the nerve, or it may comprise a modulating signal capable of generating afferent and/or efferent action potentials, or of blocking native signals. Where the second electrical signal is a sub-threshold signal the second time period is a non-stimulation time period in which the electrical activity on the nerve comprises solely native electrical activity. Regardless of whether a sub-threshold signal or a modulating signal is applied during the second time period, however, the second electrical signal is intended to reinforce and/or supplement a desired therapeutic effect of the first electrical signal, either by facilitating recovery of the nerve fibers from the first electrical signal, generating additional (exogenously induced) electrical activity on the nerve, or both.  
      The medical device may be an implantable medical device that is capable of providing an electrical signal to modulate the electrical activity on the nerve during the second time period to maintain a therapeutic effect of the first signal applied during a first time period. Some embodiments of the present invention provide for methods, apparatus, and systems to provide a first electrical signal to a nerve of a patient during a primary time period and a second electrical signal during a secondary time period in which the first electrical signal is not applied to the nerve of the patient. In certain embodiments the nerve comprises a cranial nerve, and more preferably a vagus nerve. The primary time period may refer to a time period in which a pulse burst (with optional ramp-up and ramp-down periods) is applied to the nerve. The secondary time period may refer to a time period in which the nerve is conventionally allowed to recover from the stimulation of the pulse burst applied during the primary time period. By modulating the electrical activity of the nerve during the secondary time period, the second electrical signal may maintain or enhance a therapeutic effect of the first electrical signal during the secondary time period. In this way, the second electrical signal provides background stimulation to a nerve, such as the vagus nerve (cranial nerve X) from an IMD, such as a neurostimulator for treating a disorder or medical condition.  
      Embodiments of the present invention may be employed to provide a second electrical signal at a low level, e.g., at a level that is substantially imperceptible to a patient, during a secondary period that may include a portion of the off-time of the first signal. A second electrical signal provided during an off-time of the first signal may be referred to hereinafter as “background” stimulation or modulation. For example, an IMD may apply a second electrical signal having a reduced frequency, current, or pulse width relative to the first electrical signal during off-time of the first period, in addition to the first electrical signal applied during a primary period. Without being bound by theory, applying a background electrical signal may allow the first electrical signal to be reduced to level sufficient to reduce one or more side effects without reducing therapeutic efficacy.  
      In some embodiments of the present invention, the first and second time periods at least partially overlap, and a second electrical stimulation signal may be applied during at least a portion of the first time period. In a more particular embodiment, the second time period only partially overlaps the first, and the second electrical stimulation signal is applied during a portion of the first time period, and continues during a period in which the first signal is not applied. This type of stimulation is referred to hereinafter as “overlaid” stimulation or modulation. Overlaid and/or background stimulation embodiments of the invention may increase efficacy of a stimulation therapy, reduce side effects, and/or increase tolerability of the first signal to higher levels of stimulation. An exemplary IMD that may be implanted into a patient&#39;s body for providing a signal to a portion of the patient&#39;s body is described below according to one illustrative embodiment of the present invention.  FIGS. 1A-1D  depict a stylized implantable medical system  100  for implementing one or more embodiments of the present invention.  FIGS. 1A-1D  illustrate an electrical signal generator  110  having a main body  112  comprising a case or shell  121  ( FIG. 1A ) with a header  116  ( FIG. 1C ) for connecting to leads  122 . The electrical signal generator  110  is implanted in the patient&#39;s chest in a pocket or cavity formed by the implanting surgeon just below the skin (indicated by a dotted line  145 ,  FIG. 1B ), similar to the implantation procedure for a pacemaker pulse generator.  
      A stimulating nerve electrode assembly  125 , preferably comprising an electrode pair, is conductively coupled to the distal end of an insulated, electrically conductive lead assembly  122 , which preferably comprises a pair of lead wires (one wire for each electrode of an electrode pair). Lead assembly  122  is conductively coupled at its proximal end to the connectors on the header  116  ( FIG. 1C ) on case  121 . The electrode assembly  125  may be surgically coupled to a vagus nerve  127  in the patient&#39;s neck or at another location, e.g., near the patient&#39;s diaphragm. Other cranial nerves may also be used to deliver the electrical neurostimulation signal. The electrode assembly  125  preferably comprises a bipolar stimulating electrode pair  125 - 1 ,  125 - 2  ( FIG. 1D ), such as the electrode pair described in U.S. Pat. No. 4,573,481 issued Mar. 4, 1986 to Bullara. Suitable electrode assemblies are available from Cyberonics, Inc., Houston, Tex. as the Model 302 electrode assembly. However, persons of skill in the art will appreciate that many electrode designs could be used in the present invention. The two electrodes are preferably wrapped about the vagus nerve, and the electrode assembly  125  may be secured to the nerve  127  by a spiral anchoring tether  128  ( FIG. 1D ) such as that disclosed in U.S. Pat. No. 4,979,511 issued Dec. 25, 1990 to Reese S. Terry, Jr. and assigned to the same assignee as the instant application. Lead assembly  122  is secured, while retaining the ability to flex with movement of the chest and neck, by a suture connection  130  to nearby tissue.  
      In one embodiment, the open helical design of the electrode assembly  125  (described in detail in the above-cited Bullara patent), which is self-sizing and flexible, minimizes mechanical trauma to the nerve and allows body fluid interchange with the nerve. The electrode assembly  125  preferably conforms to the shape of the nerve, providing a low stimulation threshold by allowing a large stimulation contact area with the nerve. Structurally, the electrode assembly  125  comprises two electrode ribbons (not shown), of a conductive material such as platinum, iridium, platinum-iridium alloys, and/or oxides of the foregoing. The electrode ribbons are individually bonded to an inside surface of an elastomeric body portion of the two spiral electrodes  125 - 1  and  125 - 2  ( FIG. 1D ), which may comprise two spiral loops of a three-loop helical assembly. The lead assembly  122  may comprise two distinct lead wires or a coaxial cable whose two conductive elements are respectively coupled to one of the conductive electrode ribbons. One suitable method of coupling the lead wires or cable to the electrodes  125 - 1  and  125 - 2  comprises a spacer assembly such as that disclosed in U.S. Pat. No. 5,531,778, although other known coupling techniques may be used.  
      The elastomeric body portion of each loop is preferably composed of silicone rubber, and the third loop  128  (which typically has no electrode) acts as the anchoring tether  128  for the electrode assembly  125 .  
      In certain embodiments of the invention, sensors such as eye movement sensing electrodes  133  ( FIG. 1B ) may be implanted at or near an outer periphery of each eye socket in a suitable location to sense muscle movement or actual eye movement. The electrodes  133  may be electrically connected to leads  134  implanted via a catheter or other suitable means (not shown) and extending along the jaw line through the neck  10  and chest tissue to the header  116  of the electrical signal generator  110 . When included in systems of the present invention, the sensing electrodes  133  may be utilized for detecting rapid eye movement (REM) in a pattern indicative of a disorder to be treated, as described in greater detail below. The detected indication of the disorder can be used to trigger active stimulation.  
      Other sensor arrangements may alternatively or additionally be employed to trigger active stimulation. Referring again to  FIG. 1B , EEG sensing electrodes  136  may optionally be implanted and placed in spaced-apart relation on the skull, and connected to leads  137  implanted and extending along the scalp and temple, and then connected to the electrical signal generator  110  along the same path and in the same manner as described above for the eye movement electrode leads  134 . In alternative embodiments, temperature-sensing elements and/or heart rate sensor elements may be employed to trigger active stimulation.  
      In contrast to active stimulation embodiments, other embodiments of the present invention utilize passive stimulation to deliver a continuous, periodic or intermittent electrical signal to the vagus nerve according to a programmed on/off duty cycle without the use of sensors to trigger therapy delivery. Both passive and active stimulation may be combined or delivered by a single IMD according to the present invention. Either or both modes may be appropriate to treat the particular disorder diagnosed in the case of a specific patient under observation.  
      The electrical signal generator  110  may be programmed with an external computer  150  using programming software of the type copyrighted by the assignee of the instant application with the Register of Copyrights, Library of Congress, or other suitable software based on the description herein, and a programming wand  155  to facilitate radio frequency (RF) communication between the computer  150  ( FIG. 1A ) and the pulse generator  110 . The wand  155  and software permit non-invasive communication with the generator  110  after the latter is implanted. The wand  155  is preferably powered by internal batteries, and provided with a “power on” light to indicate sufficient power for communication. Another indicator light may be provided to show that data transmission is occurring between the wand and the generator.  
      By providing the stimulation therapy, the electrical signal generator  110  may treat a disorder or a medical condition. A generally suitable form of neurostimulator for use in the method and apparatus of the present invention is disclosed, for example, in U.S. Pat. No. 5,154,172, assigned to the same assignee as the present application. A commercially available example of such a neurostimulator is the NeuroCybernetic Prosthesis (NCP®, Cyberonics, Inc., Houston, Tex., the assignee of the present application). Certain parameters of the electrical signal generated by the electrical signal generator  110  are programmable, such as be means of an external programmer in a manner conventional for implantable electrical medical devices.  
      Turning now to  FIG. 2 , a block diagram is provided depicting an IMD  200  and an external user interface (I/F)  270 , in accordance with one illustrative embodiment of the present invention. The IMD  200  may be used to provide electrical stimulation to body tissue, such as nerve tissue, to treat various disorders, such as epilepsy, depression, bulimia, etc. The IMD  200  may be used to treat neuromuscular, neuropsychiatric, cognitive, autonomic, sensory disorders, and other medical conditions.  
      The IMD  200  may be coupled to various leads, such as lead assembly  122 , shown in  FIG. 1 . Electrical signals from the IMD  200  may be transmitted via the leads  122  to stimulation electrodes associated with the electrode assembly  125 . In addition, where sensors are employed, signals from sensor electrodes may travel by leads, such as leads  122 ,  134  and/or  137 , to the IMD  200 .  
      The IMD  200  may comprise a controller  210  that is capable of controlling various aspects of the operation of the IMD  200 . The controller  210  is capable of receiving therapeutic data  212  including internal data and/or external data to deliver the therapeutic electrical signal to at least one target portion of the human body. For example, the controller  210  may receive manual instructions from an operator externally, or it may perform stimulation based on internal calculations and protocols programmed into or resident in the IMD  200 . The controller  210  is preferably capable of affecting substantially all functions of the IMD  200 .  
      The controller  210  may comprise various components, such as a processor  215 , a memory  217 , and other structures conventional known to those skilled in the art having benefit of the present disclosure. The processor  215  may comprise one or more microcontrollers, microprocessors, etc., that are capable of performing various executions of software components. The memory  217  may comprise various memory portions where the therapeutic data  212  and a number of types of data (e.g., internal data, external data instructions, software codes, status data, diagnostic data, etc.) may be stored and retrieved. The memory  217  may comprise random access memory (RAM), dynamic random access memory (DRAM), electrically erasable programmable read-only memory (EEPROM), flash memory, etc. In one embodiment, the memory  217  may comprise RAM and Flash memory components.  
      The IMD  200  may also comprise an electrical signal generator  220 . The signal generator  220  is capable of generating and delivering a variety of electrical neurostimulation signals to one or more electrodes via leads. A number of lead assemblies  122  may be coupled to the IMD  200 . Therapy may be delivered to the lead(s) by the electrical signal generator  220  based upon instructions from the controller  210 . The electrical signal generator  220  may comprise various circuitry, such as stimulation signal generators, and other circuitry that receives instructions relating to the type of stimulation to be performed. The electrical signal generator  220  is capable of delivering a controlled current neurostimulation signal over the leads. In one embodiment, the controlled current neurostimulation signal may refer to a prescribed or pre-determined current to a neural tissue of a patient.  
      The IMD  200  may also comprise a battery  230 . The battery  230  may comprise one or more cells, voltage regulators, etc., to provide power for the operation of the IMD  200 , including delivering stimulation. The battery  230  may comprise a power supply source that in some embodiments is rechargeable. The battery  230  provides power for the operation of the IMD  200 , including electronic operations and the stimulation function. The battery  230 , in one embodiment, may comprise a lithium/thionyl chloride cell or, more preferably, a lithium/carbon monofluoride (LiCFx) cell. It will be apparent to persons of skill in the art that other types of power supplies, e.g., high charge-density capacitors, may also be used instead of (or in addition to) the battery  230 .  
      The IMD  200  also comprises a communication interface (I/F)  260  capable of facilitating communications between the IMD  200  and various devices. The communication interface  260  is capable of providing transmission and reception of electronic signals to and from the external user interface  270 . The external user interface  270  may be a handheld device, preferably a handheld computer or PDA, but may alternatively comprise any other device that is capable of electronic communications and programming.  
      The external user interface  270  may comprise a programming device  270   a  that is capable of programming various modules and stimulation parameters of the IMD  200 . In one embodiment, the programming device  270   a  is capable of executing a data-acquisition program. The programming device  270   a  may be controlled by a medical professional, such as a physician, at a base station in, for example, a doctor&#39;s office. The programming device  270   a  may download various parameters and program software into the IMD  200  for programming and controlling its operation. The programming device  270   a  may also receive and upload various status conditions and other data from the IMD  200 .  
      The communication user interface  260  may comprise hardware, software, firmware, and/or any combination thereof. Communications between the external user interface  270  and the communication user interface  260  may occur via a non-invasive, wireless or other type of communication, illustrated generally by line  275  in  FIG. 2 . Various software and/or firmware applications may be loaded into the programming device  270   a  for programming the external user interface  270  for communications with the IMD  200 . In one embodiment, the external user interface  270  may be controlled by Windows® CE operating system offered by Microsoft Corporation of Redmond, Wash.  
      In one aspect of the present invention, a neurostimulation system generates a first electrical signal having a plurality of parameters including a primary time period and an off-time, and applies the first electrical signal to a nerve. During the off-time of the first electrical signal, the system generates a second electrical signal and delivers the second signal to the nerve. In some embodiments, both the first and second electrical signals are pulsed electrical signals further defined by a current magnitude, a pulse width, and a frequency. Preferably, at least one of the current magnitude, the pulse width, and the frequency of the second electrical signal is less than that of the first electrical signal. In some embodiments the frequency of the second electrical signal is less than 10 percent of the frequency of the first electrical signal. In some embodiments, the current of the second electrical signal is less than 75% of the magnitude of the current of the first electrical signal. In some embodiments, the pulse width of the second electrical signal is less than 75% of the magnitude of the pulse width of the second electrical signal.  
      In another aspect of the present invention, a neurostimulation system generates a first electrical signal defined by a primary time period and an off-time. The system also provide a second electrical signal having a secondary time period (which comprises an on-time and optional ramp-up and ramp-down signals for the second signal), and a secondary off-time. At least a portion of the secondary time period of the second electrical signal occurs during the off-time of the first electrical signal. In a more particular embodiment, the second electrical signal comprises an on-time that occurs entirely during the off-time of the first electrical signal. In a still more particular embodiment, the on-time of the second electrical signal is the same as the off-time of the first electrical signal. In an even more particular embodiment, the off-time of the second electrical signal is the same as the primary time period of the first electrical signal.  
      Referring to  FIG. 3 , a particular embodiment of the electrical signal generator  220  of  FIG. 2  is shown, with a first stimulation unit  305   a  to generate a first electrical signal  310   a , and a second stimulation unit  305   b  to generate a second electrical signal  310   b . In another embodiment (not shown), electrical signal generator  220  may be capable of generating both the first and second electrical signals  310   a ,  310   b  from a single stimulation unit. Various types of stimulus signals may be generated by the first and second stimulation units  305   a ,  305   b  with different signal characteristics based on separate sets of parameters that define the first and second electrical signals  310   a ,  310   b , respectively. Preferably, both parameter sets may be programmed into IMD  200  by external user interface  270 . An example of a composite stimulation signal for treatment of a medical disorder, including first and second electrical signals  310   a ,  310   b , is illustrated in  FIG. 4  and described hereinafter.  
       FIG. 4  depicts a stylized representation of a composite electrical stimulation signal  400 , which comprises first and second electrical signals  310   a ,  310   b , in accordance with one illustrative embodiment of the present invention. The IMD  200  shown in  FIG. 2  may use the electrical signal generator  220  to generate the composite stimulation signal  400  to stimulate a nerve of a patient. For example, the implantable medical device  100  may generate and apply to the nerve the first electrical signal  310   a  during a primary time period  405   a  comprising a ramp-up time  415   a , a treatment on-time  410   a  and a ramp-down time  415   b . The second electrical signal  310   b  is applied to the nerve during a secondary time period  405   b  corresponding to at least a portion of the off-time  410   b  of the first signal  310   a . In one embodiment, the nerve or the portion of the nerve may comprise a selected cranial nerve such as the vagus nerve. By applying a stimulation signal  400  comprising both first and second electrical signals  310   a ,  310   b , the implantable medical device  100  may provide a desired therapy to the patient for treating a disorder or a medical condition.  
      To condition a nerve or the brain of the patient, the primary time period  405   a  of the first electrical signal  310   a  may comprise one or more sub-periods such as a ramp-up period  415   a , during which a pulsed signal that increases in current magnitude is provided; the on-time period  410   a  comprising a pulsed, constant current; and a ramp-down period  415   b , in which the current decreases in magnitude. As shown in  FIG. 4 , the second electrical signal  310   b  may comprise a constant current signal having a reduced current magnitude and frequency relative to the first electrical signal  301   a . Although both the first electrical signal  310   a  and the second electrical signal  310   b  are shown in  FIG. 4  as being defined by a plurality of non-random parameters, one or more parameters of either or both of the first and second electrical signals may be randomized, as described more fully in co-pending U.S. patent application Ser. No. 11/193,520 (Enhancing Intrinsic Neural Activity Using a Medical Device to Treat a Patient), and Ser. No. 11/193,842 (Medical Devices For Enhancing Intrinsic Neural Activity), each filed in the name of Randolph K. Armstrong and assigned to the assignee of the present application. The entirety of each of the &#39;520 and &#39;842 applications is hereby incorporated herein by reference.  
      Referring again to  FIG. 4 , the IMD  200  may apply the second electrical signal  310   b  for a secondary time period that is a predefined portion of the off-time  410   b  of the first electrical signal  310   a . In one embodiment, the predefined portion may end before the primary time period  405   a  begins, i.e., the second electrical signal  310   b  may be applied for only a portion of the off-time  410   b  of the first electrical signal  310   a . In another embodiment, the predefined portion may be substantially the entire off-time  410   b  of first electrical signal  310   a . In alternative embodiments not shown in  FIG. 4 , the secondary time period  405   b  may partially overlap primary time period  405   a , and the first electrical signal  310   a  may overlap the second electrical signal  310   b , as set forth below.  
      The electrical signal generator  220  may provide a second electrical signal  310   b  having a low frequency relative to the first electrical signal  310   a . Alternatively, the second electrical signal  310   b  may comprise a low current magnitude relative to the first electrical signal  310   a . Without being bound by theory, providing a second electrical signal  310   b  during an off-time  410   b  for the first electrical signal  310   a  may reduce discomfort experienced during the first signal by conditioning the nerve prior to the start of the first signal  310   a.    
      In some embodiments, one or more parameters defining the second signal (e.g., current magnitude, frequency, pulse width, and the length of the secondary time period itself) may be determined as part of a feedback system in which the IMD  200  detects a body parameter of interest. The body parameter sensor may provide an indication to substantially turn off a primary therapeutic stimulation function of the IMD  200 , and the IMD  200  may in response set one or more parameters defining the second electrical signal as a fraction or multiple of the corresponding parameter of the first electrical signal  310   a , such that second electrical signal  310   b  is provided at a level  425  that is below a predetermined threshold  430 . The given threshold  430  may be a sub side-effect level. Thus, the IMD  200  may provide an option to bring the output level  420  down to the sub-side-effect level instead of completely turning off the therapeutic stimulation function of the IMD  200  during the secondary time period  405   b . In other embodiments, the parameters defining the second electrical signal  310   b  may not be determined by a feedback signal.  
      By separately generating the second electrical signal  310   b  and the first electrical signal  310   a , in one embodiment, the IMD  200  may provide for overlaying the second electrical signal  310   b  during at least a part of the primary time period  405   a . The IMD  200  may programmably adjust one or more parameters of the first electrical signal  310   a  and/or the second electrical signal  310   b  during their respective time periods based on a sensed body parameter.  
      Referring simultaneously to  FIGS. 3 and 4 , the second unit  305   b  may provide the second electrical signal  310   b  to apply a low-level signal relative to the first electrical signal  310   a  during the secondary time period  405   b  for at least a portion of the off-time  410   b  of first signal  310   a . To provide the second electrical signal  310   b  during the secondary time period  405   b , the second stimulation unit  305   b  may use the therapeutic data  212  that includes programmable parameter data. In an alternative embodiment (not shown) the secondary time period  405   b  may exceed the off-time  410   b  of the first electrical signal. In another embodiment, the secondary time period  405   b  may be the same as the off-time for the first electrical signal  310   a . In a still further embodiment, the secondary time period  405   b  may be substantially smaller than the off-time  410   b  or the on-time  410   a.    
      The IMD  200  may programmably change the primary time period  405   a  (including ramp-up, on-time and/or ramp-down time) and the off-time  410   b  of the first electrical signal  310   a , as well as the secondary time period and off-time of the second electrical signal  310   b , to provide a wide variety of composite electrical signals  400 . The IMD  200  may modulate one or more parameters (e.g., a current magnitude, a pulse period, a polarity, and a pulse width, etc.) of first and/or second electrical signals  310   a ,  310   b  by selectively varying at least one parameter of the parameters associated with the first or the second electrical signals.  
      The IMD  200  may stimulate the nerve with the second stimulus signal  310   b  at a frequency that modulates a nerve receptor. For example, the nerve, such as a cranial nerve of the patient, may be stimulated to maintain a therapeutic effect of the first electrical signal  310   a  during the secondary time period  405   b . The IMD  200  may stimulate the nerve at a sub-threshold level that causes the second electrical signal  310   b  to remain below a perception level  470  of the patient during the secondary time period  405   b . At the same time, the second electrical signal  310   b  may provide benefits, such as an increase in the efficacy of a stimulation therapy, a reduction in side effects, and/or an increase in tolerability to higher levels of stimulation.  
      Turning now to  FIG. 5 , a flowchart depiction of a method of providing first and second electrical signals from the IMD  200 , in accordance with one illustrative embodiment of the present invention, is provided. At block  500 , the IMD  200  may enter a background stimulation mode in which a background electrical signal is provided in addition to a primary electrical signal. Initially, the IMD  200  may receive the therapeutic data  212  input, indicating whether to perform a background stimulation therapy that affects a disease state of the patient, as shown in block  505 . For example, the IMD  200  may receive the therapeutic data  212  to provide a stimulation therapy that affects a disease state of the patient, wherein the therapy includes stimulation during a primary period and a secondary period. Using the therapeutic data  212 , the IMD  200  may define the first and second electrical signals  310   a ,  310   b , as shown in block  510 . Defining the first and second electrical signals  310   a ,  310   b  may include defining the primary and secondary time periods  405   a ,  405   b , in addition to other parameters (e.g., a current magnitude, a pulse period, a polarity, and a pulse width, etc.) relating to the signals.  
      To apply a therapeutic stimulus signal to a nerve of a patient during a first time period, i.e., the primary time period  405   a , at block  515 , the IMD  200  may provide the first electrical signal  310   a . A check at a decision block  520  determines whether the primary time period  405   a  for stimulation or treatment has lapsed. If the primary time period  405   a  has lapsed, the IMD  200  provides the second electrical signal  310   b , at block  525 . If the primary period has not lapsed, the IMD  200  continues to provide the first electrical signal  310   a  until the primary time period  405   a  ends. That is, the IMD  200  may enter in a non-therapeutic or a secondary therapeutic mode during a second time period subsequent to a first time period. In the secondary therapeutic mode, the IMD  200  may apply a background stimulus signal comprising the second electrical signal during at least a portion of the second time period.  
      A check at a decision block  530  determines whether the secondary time period  405   b  has lapsed. If the secondary time period  405   b  has lapsed, the IMD  200  may repeat the first and second electrical signals, at block  535 . If the secondary time period  405   b  has not ended, the IMD  200  continues to provide the second electrical signal  310   b  until the secondary time period  405   b  ends.  
      Based on the therapeutic data  212 , in another embodiment, the IMD  200  may alternatively stimulate a patient&#39;s nerve with the first electrical signal  310   a  during the primary time period  405   a  and with the second electrical signal  310   b  during the secondary time period  405   b  for a given overall treatment period of a stimulation therapy. In a particular embodiment, the IMD  200  may provide electrical neurostimulation therapy to the patient such that the second electrical signal  310   b  comprises a pulsed electrical signal defined by a plurality of parameters, such as a current magnitude, a pulse period, a polarity, and/or pulse width, with at least one of the parameters comprising a random value. In this embodiment, the IMD  200  may randomly vary the current magnitude, pulse period, polarity, and/or the pulse width of adjacent pulses during the secondary time period within defined limits. In a more specific embodiment, both the current magnitude and the pulse width of electrical pulses in the second electrical signal  310   b  may vary randomly during the secondary time period  405   b . As one example, the current magnitude for each pulse may randomly vary from 0.25 to 1.50 milliamps, and the pulse width for each pulse may randomly vary from 50 microseconds to 750 microseconds.  
      The electrical signal generator  220  may generate the first and the second electrical signals  310   a ,  310   b  for delivery to a selected portion of a selected nerve of a patient. The controller  215  operatively coupled to the electrical signal generator  220  may be adapted to apply the first electrical signal  310   a  to the selected nerve of the patient during the primary time period  405   a . The controller  215  may apply the second electrical stimulus signal  310   b  to the selected nerve of the patient during the secondary time period  405   b  in which the first electrical stimulus signal  310   a  is off.  
      In this manner, the IMD  200  may stimulate the selected portion of the selected nerve of the patient with a predetermined sequence of electrical pulses from the electrical signal generator  220  applied to the selected nerve. To affect a disease state, the IMD  200  may provide a reduced therapeutic stimulation relative to the first electrical signal  310   a  during the secondary time period  405   b . The IMD  200  may stimulate the nerve of the patient with the second electrical signal  310   b  based on the therapeutic data  212  at a frequency that aids in maintaining a therapeutic effect and/or eliminating or reducing side effects associated with the first electrical signal  310   a  during the secondary time period  405   b.    
      The first and second electrical signals  310   a ,  310   b  may be defined based on a plurality of parameters, e.g., a current magnitude, a pulse period, a polarity, and/or a pulse width. The second electrical signal  31   b  may stimulate a portion of a nerve at a sub-threshold level that is below the perception level  470  of the patient during the secondary time period  405   b.    
      Referring to  FIG. 6 , a flowchart depiction of an embodiment of a method for providing overlaid stimulation using the implantable medical device of  FIG. 2  is provided. In this embodiment, the IMD  200  may employ the first and second electrical signals  310   a ,  310   b  in an overlapping fashion. A background stimulation mode may be initiated (block  500 ). A check at a decision block  600  determines whether an overlap of the primary and secondary time periods  405   a ,  405   b  is indicated for a stimulation or a treatment therapy. If the therapeutic data  212  indicates an overlaid stimulation mode with the primary and secondary time periods  405   a ,  405   b  at least partially overlaid, the first stimulation unit  305   a  may proceed to provide the first electrical signal  310   a , as shown at block  610 . If overlaid stimulation is not indicated, the IMD  200  may exit from the overlaid stimulation mode, as depicted in block  605 . In one embodiment, upon exiting the overlaid stimulation mode, the IMD  200  may implement the background stimulation mode described in  FIG. 5 .  
      Referring again to  FIG. 6 , a check at a decision block  615  may determine whether to start the overlapping of the second electrical signal  310   b  with the first electrical signal  310   a . Upon reaching an overlaid stimulation start point at which the primary and secondary time periods  405   a ,  405   b  overlap, the second stimulation unit  305   b  begins applying the second electrical signal  310   b , as shown at block  620 . If the time to begin overlapping the electrical signals/time periods has not arrived, the IMD  200  may continue to provide only the first electrical signal  310   a , as depicted in block  610 .  
      A check at decision block  625  may ascertain whether an end of an overlapping period of the first and second electrical signals  310   a ,  310   b  has been reached. Upon reaching the end of an overlapping period, the first electrical signal  310   a  is stopped, as shown in block  635 . Conversely, if the overlapping period is not over, the IMD  200  continues to overlay the second electrical signal  310   b  over the first electrical signal  310   a , as shown at block  630 . This process may continue until the overlapping period has lapsed.  
      Subsequent to determining that the overlapping period has ended and the first electrical signal  310   a  has been stopped, at a decision block  640 , the IMD  200  determines whether to start overlapping the first electrical signal  310   a  with the second electrical signal  310   b . Upon reaching an overlap stimulation start point at which the primary and secondary time periods  405   b ,  405   b  overlap, the first stimulation unit  305   a  begins apply the first electrical signal  310   a , as shown at block  645 . Otherwise, at the decision block  640 , the IMD  200  may continue to provide only the second electrical signal  310   b , as depicted in block  620 .  
      A check at a decision block  650  ascertains whether an end of an overlapping period of the first and second electrical signals  310   a ,  310   b  has been reached. Upon reaching the end of an overlapping period, the second electrical signal  310   b  is stopped, as shown in block  655 . If the end of the overlapping period has not been reached, the IMD  200  continues to overlay the first electrical signal  310   a  over the second electrical signal  310   b , as shown at block  652 .  
      Referring to  FIGS. 7A-7C , one embodiment of waveforms illustrates a pulsed first electrical signal  310   a  suitable for use in the present invention. The illustrations are presented principally for the sake of clarifying terminology for a plurality of parameters that may be used to define a pulsed electrical signal including a current amplitude, a pulse width, a pulse period (i.e., time interval between the start of adjacent pulses), and a pulse polarity, that may be used by the electrical signal generator  220  to generate a pulsed electrical signal. Other parameters (not shown) include signal on-time and signal off-time for non-continuous signals. In embodiments of the present invention, at least one of the voltage amplitude, current amplitude, pulse width, pulse period, pulse polarity, and (for non-continuous signals), signal on-time and signal off-time comprises a random value within a defined range. Examples of the defined range(s) for generating a desired stimulation based treatment therapy from the electrical signal generator  220  is described with reference to  FIGS. 7A-7C , which illustrate the general nature, in idealized representation, of pulsed output signal waveforms delivered by the output section of the IMD  200  to electrode assembly  125 . One or more biasing parameters may be randomly generated by the electrical signal generator  220  to generate a pulsed electrical signal that varies within a defined range.  
      A continuous signal, as used herein, refers to an electrical signal without a distinct on-time and off-time. A continuous signal may be delivered without a distinct on-time and off-time as either a pulsed signal having a constant or random pulse period or frequency, or as a purely continuous signal with no break in current flow (although other parameters, such as current magnitude and polarity, may vary within the signal). A non-pulsed signal, as used herein, refers to a signal in which a current is always being delivered during the on-time period, as distinct from a pulsed signal in which flow of current during an on-time period is separated by short periods (typically milliseconds or seconds) of no current flow. It should be noted that non-pulsed signals may be delivered according to a programmed or random on-time and off-time (for example, to allow a recovery/refractory period for the neural tissue stimulated). However, unless the on-time periods have breaks in current flow within each on-time period, the signal remains a non-pulsed signal as used herein.  
       FIG. 7A  illustrates an exemplary pulsed electrical stimulus signal provided by embodiments of the present invention. The electrical stimulus signal may be a non-continuous signal defined by an on-time and an on-time, or may comprise a continuous signal (i.e., a signal that does not comprise a distinct on-time and off-time) without discrete pulse bursts. The electrical stimulus signal may alternatively comprise a non-pulsed signal (which may be continuous or non-continuous) with no current breaks during a stimulation period. Whether continuous or non-continuous, in one embodiment the invention comprises signals in which one or more stimulus signal parameters are randomly changed for particular pulses in a pulse train (pulse-to-pulse randomization), or alternatively for pulses in adjacent pulse trains (burst-to-burst randomization). Burst-to-burst randomization may comprise changing only the on-time and/or off-time, in which case each of the pulses may be non-random as defined by any of voltage, current, pulse width, pulse period, or frequency, but the duration of adjacent pulse bursts or the interval separating them may comprise a random time interval.  
      In particular, as  FIG. 7A  illustrates, the electrical signal pulses in the a pulsed electrical stimulus current signal provided by the IMD  200  may randomly vary in current amplitude, as shown by pulses having first, second and third random amplitudes, respectively, and/or in pulse widths as illustrated by the pulses having first, second and third random pulse widths, respectively. For example, current magnitude of the pulses may be random and vary within any arbitrarily defined range within the range of from −8.0 milliamps (mA) to 8.0 milliamps, such as from −3.0 to 3.0 milliamps or from 0.25 to 1.5 milliamps, with optional charge-balancing. Similarly, pulse widths may be random and vary within any arbitrarily defined range within the range of 1 microsecond to 1 second, such as from 50 to 750 microseconds, or from 200 to 500 microseconds.  
      In addition to current magnitude and pulse width,  FIG. 7A  further shows that in some embodiments pulse polarity may vary randomly between a first polarity, indicated by the pulses having a peak above the horizontal zero current line, and a second, opposite polarity, indicated by a peak below the zero current line.  FIG. 7A  omits, for convenience, any charge-balancing component for a particular pulse. However, it will be understood that each pulse may include a passive or active charge-balancing component.  FIG. 7A  further illustrates that pulse periods of the electrical pulses also may vary randomly, as illustrated by adjacent pulse pairs having first, second and third random pulse periods. For example, pulse periods of the pulses may be random and vary randomly within any arbitrarily defined range within the range of 1 microsecond to 1 second, for example from 50 microseconds to 200 milliseconds.  
      While not shown in  FIG. 7A , for non-continuous electrical stimulus signals defined by an off-time and an on-time, one or both of the on-time and off-time may vary randomly within defined ranges. For example, the on-time defining a pulse burst (or a non-pulsed signal) may be random and vary randomly within any arbitrarily defined range within the range of 1 second to 24 hours and the off-time defining a pulse burst or non-pulsed signal may also be random and vary randomly within any arbitrarily defined range within the range of 1 second to 24 hours.  
      While  FIG. 7A  describes parameter randomization for a pulsed electrical stimulus signal, similar randomization of parameters may be provided for a non-pulsed electrical biasing signal. In particular, while not defined by a pulse width or a pulse interval, a non-pulsed signal may nevertheless be defined by one or more of a current amplitude and a current polarity, and a non-continuous non-pulsed signal may further be defined by an ON-time and an OFF-time. One or more of the foregoing parameters may be randomized for a non-pulsed signal, in similar manner to that described for a pulsed signal, supra.  
       FIG. 7B  and illustrates that first and second electrical signals  310   a ,  310   b  may comprise a randomized signal for a first period of time and non-randomized signals for a second period of time. A stimulus parameter for one or both of the first and second electrical signals  310   a ,  310   b  may comprise a random value on a pulse-to-pulse basis and vary within a defined range across a random and/or periodic time interval, but otherwise is non-random. For example, pulse period, amplitude, pulse width, polarity, and/or a combination thereof may randomly vary within a defined range for a first time interval ranging from 1 second to 24 hours. One or more stimulus parameters may be randomly varied in first and second periodic ranges during the first time period. For example, the pulse period may be varied randomly for a 30 second period at a value from 50 microseconds to 750 microseconds. In a second time period, the pulse period may comprise a non-random value, for example 500 microseconds for a period of 1 minute. In other embodiments, the ranges of the randomization parameters may comprise a split range. For example, the current magnitude may be allowed to vary on a pulse-to-pulse basis within the ranges of 0.25 to 0.75 milliamps and also in the range of 1.25 to 1.50 milliamps. Accordingly, the current may comprise any value between 0.25 milliamps and 1.50 milliamps except for values comprising 0.76 milliamps to 1.24 milliamps. Such split range randomization may be beneficial for some patients, and is considered to be within the scope of the present invention.  
      The randomized electrical stimulus current signal provided by the IMD  200  may be directed to performing selective activation of various electrodes (described below) to target particular tissue for excitation. An exemplary randomized electrical stimulus current pulse signal provided by the IMD  200  is illustrated in  FIG. 7A , where randomly varying polarity of a pulse signal is illustrated. In one embodiment, the randomly varying polarity may be employed in conjunction with alternating electrodes for targeting specific tissues.  
       FIG. 7C  illustrates an exemplary randomized electrical signal pulse that provides various random phases that correspond to a change in amplitude and a change in polarity. As described above, a phase of a pulse may randomly take on various shapes and current levels, including a current level of zero amps. In one embodiment, a phase with zero current may be used as a time delay between two current delivery phases of a pulse.  
      More specifically,  FIG. 7C  illustrates a randomized electrical signal pulse and having a first phase with a first random amplitude relating to a first charge, Q 1 , and a second phase that corresponds to a second random amplitude relating to a second charge, Q 2 . In the signal illustrated in  FIG. 7C , the second charge Q 2  is substantially equal to the negative value of the first charge Q 1 . Therefore, the charges, Q 1  and Q 2 , balance each other, reducing the need for active and/or passive balancing of the charges. Hence, the signal pulse illustrated in  FIG. 7C  is a charge-balanced, randomized electrical signal pulse. Reducing the need for performing active and/or passive charge balancing may provide various advantages, such as power savings from the reduction of charge discharge, fewer circuit requirements, and the like. For example, applying the first and/or second electrical signals  310   a ,  310   b  may comprise applying a series of charge-balanced pulses (i.e., pulse bursts) for balancing an electrical charge resulting from the electrical signals. The current magnitude of the pulses may be random and vary within any arbitrarily defined range within the range of −8.0 milliamps to 8.0 milliamps, or may be non-random and programmably defined.  
      Various other pulse shapes may be employed in the randomized electrical biasing signal concepts provided by embodiments of the present invention and remain within the scope and spirit of the present invention. Use of the IMD  200  may improve efficacy of the vagus nerve stimulation (VNS) therapy in many neurological or neuropsychiatric conditions. In one embodiment, the second electrical signal  310   b  may comprise providing, during the off-time  410   b  of the first electrical signal  310   a , a pulse burst in which the pulses have the same constant current magnitude and constant pulse width as the first electrical signal  310   a , but at a frequency of 5 Hz or less. In another embodiment, the current magnitude of the second electrical signal pulses is below a perception threshold of the patient. By providing such a second electrical signal  310   b , the current magnitude of the first electrical signal  310   a  may be able to be reduced without loss of efficacy and with reduced discomfort. Many prior art neurostimulators allow a patient to manually turn off the electrical signal (which may be done using, e.g., a magnet), typically to avoid an undesired side effect. In embodiments of the present invention, instead of causing the IMD  200  to completely turn off the electrical signal, a programmable or user option may provide a second electrical signal  310   b  having a reduced level of stimulation, e.g., below a perception threshold.  
      In one embodiment, providing a second electrical signal  310   b  at a reduced level during the off-time  410   b  of the first electrical signal  310   a  allows the duration of the off-time  410   b  to be increased without significantly decreasing efficacy of a therapy or a treatment. Increasing the duration of the off-time  410   b  period may provide reduced energy consumption of the battery in IMD  200 . Providing a second electrical signal  310   b  may, in another embodiment, increase the patient&#39;s tolerance for higher current magnitudes for the first electrical signal  310   a . In another embodiment, the second electrical signal  310   b  may reduce or eliminate a need for ramp-up and ramp-down periods. As a result, the IMD  200  according to embodiments of the present invention may improve efficacy of the therapy, increase longevity of a medical device, and/or reduce side effects of stimulation in the patient&#39;s body.  
      The particular embodiments disclosed above are illustrative only, as the invention may be modified and practiced in different but equivalent manners apparent to those skilled in the art having the benefit of the teachings herein. Furthermore, no limitations are intended to the details of construction or design herein shown, other than as described in the claims below. It is therefore evident that the particular embodiments disclosed above may be altered or modified and all such variations are considered within the scope and spirit of the invention. Accordingly, the protection sought herein is as set forth in the claims below.