Patent Publication Number: US-2023158302-A1

Title: Systems, Devices, Components and Methods for the Delivery of Electrical Stimulation to Cranial Nerves to Treat Mood or Mood Affective Disorders

Description:
RELATED APPLICATION 
     This application is related to, and claims priority and other benefits from, U.S. Provisional Patent Application Ser. No. 62/896,867 entitled “Cranial Nerve Stimulation for the Treatment of Mood Disorders and Other Disease States” to Swayer et at filed Sep. 6, 2020 (hereafter “the &#39;867 patent application”). The entirety of the &#39;867 patent application is hereby incorporated by reference herein. 
    
    
     FIELD OF THE INVENTION 
     Various embodiments described and disclosed herein relate to the field of neurostimulation, and more particularly to delivering electrical stimulation therapy to cranial nerves of a patient, including, but not limited to, for the purpose of treating mood disorder and/or mood affective disorders. 
     BACKGROUND 
     A variety of therapies are known and have been employed to treat mood disorders and mood affective disorders such as depression, insomnia, and bipolar disorder, most notably the many different types of pharmaceutical drugs that have been developed for such purposes. Pharmaceutical drugs are commonly prescribed for such disorders, but also generally become quite expensive over time, and not uncommonly have significant side effects. 
     Besides pharmaceutical drugs, other methods have been developed to treat mood and mood affective disorders, such as out-patient or office-based transcranial magnetic, stimulation methods to treat depression. Transcutaneous electrical nerve stimulation (TENS) methods to treat depression may also be administered in a patient&#39;s home by the patient, where surface electrodes are placed on the exterior of the head and held in place with a temporary adhesive or a device such as a head band. External transcutaneous electrical stimulation of nerves, whether peripheral or cranial, has met with limited and highly uneven and murky degrees of success over the years. 
     In the field of implantable nerve stimulation devices that have been developed to treat mood disorders such as depression and insomnia, implantable pulse generators employed to effect such treatments have frequently been found to be too large to implant in the head or neck of a patient, and therefore require the use of relatively long medical electrical leads that must be routed from the patient&#39;s shoulder or back to a nerve stimulation location in the patient&#39;s head or neck. 
     What is needed are improved and alternative, means and methods of treating mood disorder and mood affective disorder patients. The present disclosure is directed to devices systems, and methods that address one or more deficiencies in the prior art. 
     SUMMARY 
     In some embodiments, there is provided an implantable neurostimulator configured to electrically stimulate one or more cranial nerves in a head or neck of a patient to treat a mood disorder or mood affective disorder of the patient, the neurostimulator comprising a housing, at least one medical electrical lead comprising at least one stimulation electrode, pulse generation circuitry operably connected to the lead, and power, energy or electrical charge receiving circuitry operably connected to the pulse generation circuitry and configured to receive power, energy or electrical charge signals transcutaneously from an external power source and external power transmitting circuitry associated therewith, wherein one or more of the pulse generation circuitry, the at least one lead and at least one electrode, and the power receiving circuitry are mounted on or in, or formed as a portion of, one or more flex circuits, and further wherein the pulse generation circuitry, the power receiving circuitry, and at least portions of the one or more flex circuits are disposed within a sealed housing, the implantable neurostimulator is sized, shaped and configured to be implanted in the head neck of the patient beneath the patient&#39;s skin, and the lead and one or more electrodes are sized, shaped and configured to be implanted beneath the patient&#39;s skin and positioned adjacent to, in contact with, or in operative positional relationship to, the one or more target cranial nerves. 
     Such an implantable neurostimulator may further comprise one or more of: (a) the mood or mood affective disorder being one or more of depression, a depressive disorder, insomnia, sadness, mania, bipolar disorder, manic depression, bipolar affective disorder, postpartum depression, seasonal affective disorder (SAD), cyclothymic disorder, premenstrual dysphoric disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, depression related to medical illness, and depression induced by substance use or medication; (b) the implantable neurostimulator being configured to electrically stimulate one or more of a facial nerve or portion thereof, a trigeminal nerve or portion thereof, an occipital nerve or portion thereof, a hypoglossal nerve or portion thereof, a cranial portion of a vagus nerve, a glossopharyngeal nerve or portion thereof, an auricular branch of the vagus nerve or portion thereof, a tympanic branch of the vagus nerve or portion thereof, a superior ganglion branch of the vagus nerve or portion thereof, an inferior ganglion branch of the vagus nerve or portion thereof, an olfactory nerve or portion thereof, an optic nerve or portion thereof, an oculomotor nerve or portion thereof, a trochlear nerve or portion thereof, an abducens nerve or portion thereof, a vestibulocochlear nerve or portion thereof, and a spinal accessory nerve or portion thereof; (c) the one or more flex circuits comprising a polyimide substrate; (d) the lead further comprising proximal and distal portions, the proximal portion of the lead being operably connected to the pulse generation circuitry, the at least one electrode being disposed distally from the proximal portion of the lead, the lead comprising one or more electrical conductors operably connecting the at least one electrode to the pulse generation circuitry, the electrical conductors being formed on or in one or more of the lead flex circuits; (e) the sealed housing having a thickness ranging between about 0.1 inches and about 0.4 inches; (f) the sealed housing having a diameter ranging between about 0.05 inches and about 0.8 inches; (g) the sealed housing comprising a flexible polymer configured to conform to at least one of a shape of the patient&#39;s skull or overlying skin; (h) the flexible polymer being a thermosettable or shapeable material that can be formed into and will retain a desired shape or curvature; (i) the lead having a length extending beyond the housing ranging between about 0.1 inches and about 4 inches; (j) the lead having a width beyond the housing that ranges between about 0.01 inches an about 0.05 inches; (k) the pulse generation circuitry and the power receiving and storage circuitry being potted within the housing using a medical grade polymer; (l) the at least one lead, the pulse generation circuitry, and the power receiving and storage circuitry being mounted on or in, or formed as a portion of, a single flex circuit or flex circuit substrate; (m) the lead having a length extending beyond the housing ranging between about 0.1 inches and about 4 inches; (n) the power receiving circuitry further comprising electrical charge storage circuitry; (a) the power receiving circuitry further comprising one or more internal induction coils configured to receive electrical power transcutaneously from one or more corresponding external induction coils; (p) the power receiving circuitry further comprising one or more wireless, RF, acoustic, piezoelectric, Thin film bulk wave acoustic resonators (FBAR), microwave energy receiving circuits, and (q) the pulse generation circuitry being configured to deliver stimulation signals comprising one or more of: (1) frequencies ranging between about 2 Hz and about 100 Hz; (2)frequencies ranging between about 2 Hz and about 75 Hz; (3) frequencies ranging between about 4 Hz and about 50 Hz; (4) frequencies ranging between about 5 Hz and about 25 Hz; (5) frequencies ranging between about 7 Hz and about 100 Hz; (6) frequencies ranging between about 100 Hz and about 10,000 Hz; (7) frequencies ranging between about 100 Hz and about 5,000 Hz; (h) frequencies ranging between about 100 Hz and about 2,000 Hz; (8) frequencies ranging between about 100 Hz and about 1,000 Hz; (9) frequencies ranging between about 200 Hz and about 750 Hz; (10) voltages ranging between about 0.1 mV and about 30 V; (11) currents ranging between about 0.1 mA and about 30 mA; (12) pulse widths so ranging between about 20 μsec and about 1000 μsec, and (13) durations or periods of time ranging between about 30 seconds and about 2 hours, 5 minutes and about 1 hour, and about 10 minutes and about 45 minutes. 
     In another embodiment, there is provided a system configured to electrically stimulate one or more cranial nerves in a head or neck of a patient to treat a mood disorder or mood affective disorder of the patient, the system comprising an implantable neurostimulator comprising a housing, at least one medical electrical lead comprising at least one stimulation electrode, pulse generation circuitry operably connected to the lead, and power, energy or electrical charge receiving circuitry operably connected to the pulse generation circuitry and configured to receive power, energy or electrical charge signals transcutaneously from an external power source and external power transmitting circuitry associated therewith, pulse generation circuitry operably connected to the lead, and power or electrical charge receiving circuitry operably connected to the pulse generation circuitry and further configured to receive power signals or electrical charge transcutaneously from an external power source and external power transmitting circuitry associated therewith, wherein one or more of the pulse generation circuitry, the at least one lead and at least one electrode, and the power receiving circuitry are mounted on or in, or formed as a portion of, one or more flex circuits, and further wherein the pulse generation circuitry, the power or charge receiving circuitry, and at least portions of the one or more flex circuits are disposed within a sealed housing, the implantable neurostimulator is sized, shaped and configured to be implanted in the head or neck of the patient beneath the patient&#39;s skin, and the lead and one or more electrodes are sized, shaped and configured to be implanted beneath the patient&#39;s skin and positioned adjacent to, in contact with, or in operative positional relationship to, the one or more target cranial nerves, an external energy supply device configured to transmit energy transcutaneously through the skin of the patient to the implantable neurostimulator, and a controller or programmer configured to permit a health care provider or the patient to set, adjust, or change at least one of operational and stimulation parameters of the implantable neurostimulator. 
     Such a system may further comprise one or more of (a) the external energy supply device comprising one or more batteries and one or more transmitting coils operably connected to the one or more batteries and configured to provide electromagnetic energy transcutaneously to one or more receiving coils included in or operably connected to the power or charge receiving circuitry of the neurostimulator; (b) the external energy supply device comprising wireless, RF, acoustic, piezoelectric, thin film bulk wave acoustic resonator (FBAR), or microwave transmitter circuitry configured to transmit energy transcutaneously through the skin of the patient to the power or electrical charge receiving circuitry of the implantable neurostimulator; (c) the mood disorder or mood affective disorder being treated one or more of depression, a depressive disorder, insomnia, sadness, mania, bipolar disorder, manic depression, bipolar affective disorder, postpartum depression, seasonal affective disorder (SAD), cyclothymic disorder, premenstrual dysphoric disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, depression related to med al illness, and depression induced by substance use or medication; (d) the system being configured to electrically stimulate one or more of a facial nerve or portion thereof, a trigeminal nerve or portion thereof, an occipital nerve or portion thereof, a hypoglossal nerve or portion thereof, a cranial portion of a vagus nerve, a glossopharyngeal nerve or portion thereof, an auricular branch of the vagus nerve or portion thereof, a tympanic branch of the vagus nerve or portion thereof, a superior ganglion branch of the vagus nerve or portion thereof, an inferior ganglion branch of the vagus nerve or portion thereof, an olfactory nerve or portion thereof, an optic nerve or portion thereof, an oculomotor nerve or portion thereof, a trochlear nerve or portion thereof, an abducens nerve or portion thereof, a vestibulocochlear nerve or portion thereof, and a spinal accessory nerve or portion thereof: (e) the one or more flex circuits comprising a polyimide substrate; (f) the lead further comprising proximal and distal portions, the proximal portion of the lead being operably connected to the pulse generation circuitry, the at least one electrode being disposed distally from the proximal portion of the lead, the lead comprising one or more electrical conductors operably connecting the at least one electrode to the pulse generation circuitry, the electrical conductors being formed on or in one or more of the lead flex circuits; (g) the sealed housing having a thickness ranging between about 0.1 inches and about 0.4 inches; (h) the sealed housing having a diameter ranging between about 0.05 inches and about 0.8 inches; (h) the sealed housing comprising a flexible polymer configured to conform to at least one of a shape of the patient&#39;s skull or overlying skin; (i) the flexible polymer being a thermosettable or shapeable material that can be formed into and will retain a desired shape or curvature; (j) the lead having a length extending beyond the housing ranging between about 0.1 inches and about 4 inches; (k) the lead having a width beyond the housing that ranges between about 0.01 inches and about 0.05 inches; (l) the pulse generation circuitry and the power receiving and storage circuitry being potted within the housing using a medical grade polymer; (m) the at least one lead, the pulse generation circuitry, and the power receiving and storage circuitry being mounted on or in, or formed as a portion of, a single flex circuit or flex circuit substrate; (n) the lead having a length extending beyond the housing ranging between about 0.1 inches and about 4 inches; (o) the power receiving circuitry further comprising electrical charge storage circuitry; (p) the power receiving circuitry further comprising one or more internal induction coils configured to receive electrical power transcutaneously from one or more corresponding external induction coils, and (q) the power receiving circuitry further comprising one or more wireless, RF, acoustic, piezoelectric, thin film bulk wave acoustic resonators (FGAR), or microwave energy receiving circuits. 
     In yet another embodiment, there is provided a method of electrically stimulating one or more cranial nerves in a head or neck of a patient to treat a mood disorder or mood affective disorder of the patient, the method comprising providing or implanting beneath the skin of the patient&#39;s head or neck an implantable neurostimulator comprising a housing, at least one medical electrical lead comprising at least one stimulation electrode, pulse generation circuitry operably connected to the lead, and power, energy or electrical charge receiving circuitry operably connected to the pulse generation circuitry and configured to receive power, energy or electrical charge signals transcutaneously from an external power source and external power transmitting circuitry associated therewith, wherein one or more of the pulse generation circuitry, the at least one lead and at least one electrode, and the power receiving circuitry are mounted on or in, or formed as a portion of, one or more flex circuits, and further wherein the pulse generation circuitry, the power or charge receiving circuitry, and at least portions of the one or more flex circuits are disposed within a sealed housing, the implantable neurostimulator is sized, shaped and configured to be implanted in the head or neck of the patient beneath the patient&#39;s skin, and the lead and one or more electrodes are sized, shaped and configured to be implanted beneath the patient&#39;s skin and positioned adjacent to, in contact with, or in operative positional relationship to, the one or more target cranial nerves, and electrically stimulating the one or more cranial nerves of the patient with the implantable neurostimulator to treat the mood disorder or mood affective disorder. 
     Such a method may further comprise one or more of: (a) setting, adjusting, or changing at least one of operational and stimulation parameters of the implantable neurostimulator using a controller or programmer; (b) transmitting energy transcutaneously from an external energy supply device through the skin of the patient to the implantable neurostimulator; (c) tunneling beneath the patient&#39;s skin to form a pocket to receive the implantable neurostimulator and lead therein; (d) the mood disorder or mood affective disorder being treated being one or more of depression, a depressive disorder, insomnia, sadness, mania, bipolar disorder, manic depression, bipolar affective disorder, postpartum depression, seasonal affective disorder (SAD), cyclothymic disorder, premenstrual dysphoric disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, depression related to medical illness, and depression induced by substance use or medication; (e) the cranial nerve being electrically stimulated being one or more of a facial nerve or portion thereof, a trigeminal nerve or portion thereof, an occipital nerve or portion thereof, a hypoglossal nerve or portion thereof, a cranial portion of a vagus nerve, a glossopharyngeal nerve or portion thereof, an auricular branch of the vagus nerve or portion thereof, a tympanic branch of the vagus nerve or portion thereof, a superior ganglion branch of the vagus nerve or portion thereof, an inferior ganglion branch of the vagus nerve or portion thereof, an olfactory nerve or portion thereof, an optic nerve or portion thereof, an oculomotor nerve or portion thereof, a trochlear nerve or portion thereof, an abducens nerve or portion thereof, a vestibulocochlear nerve or portion thereof, and a spinal accessory nerve or portion thereof; (f) the pulse generation circuitry delivering stimulation signals comprising one or more of: (1) frequencies ranging between about 2 Hz and about 100 Hz: (2) frequencies ranging between about 2 Hz and about 75 Hz; (3) frequencies ranging between about 4 Hz and about 50 Hz; (4) frequencies ranging between about 5 Hz and about 25 Hz; (5) frequencies ranging between about 7 Hz and about 100 Hz; (6) frequencies ranging between about 100 Hz and about 10,000 Hz; (7) frequencies ranging between about 100 Hz and about 5,000 Hz; (h) frequencies ranging between about 100 Hz and about 2,000 Hz; (8) frequencies ranging between about 100 Hz and about 1,000 Hz; (9) frequencies ranging between about 200 Hz and about 750 Hz; (10) voltages ranging between about 0.1 mV and about 30 V; (11) currents ranging between about 0.1 mA and about 30 mA; (12) pulse widths ranging between about 20 μsec and about 1000 used, and (13) durations or periods of time ranging between about 30 seconds and about 2 hours, 5 minutes and about 1 hour, and about 10 minutes and about 45 minutes. 
     Further embodiments are disclosed herein or will become apparent to those skilled in the art after having read and understood the claims specification and drawings hereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Different aspects of the various embodiments will become apparent from the following specification, drawings and claims in which: 
         FIG.  1    shows a block diagram of one embodiment of a cranial stimulation system  10 ; 
         FIG.  2    shows a block diagram of another embodiment of cranial nerve stimulation system  10 ; 
         FIG.  3    shows a top view of one embodiment of implantable stimulator ( 15 )  12 ; 
         FIG.  4    shows a side view of IS  12  from  FIG.  3   ; 
         FIG.  5    shows a top view of another embodiment of IS  12 ; 
         FIG.  6    shows a top right perspective view of IS  12  from  FIGS.  3  and  4   ; 
         FIG.  7    shows a functional block diagram of IS  12  implanted within a patient and external device  33  located outside the patient and in communication therewith transcutaneously; 
         FIG.  8    shows one embodiment of block diagrams for CP  1 , PP  16 , and IS  12 ; 
         FIG.  9    shows various embodiments of medical electrical leads  8  that may be utilized in at least some embodiments of system  10 ; 
         FIG.  10    shows one embodiment of a method  200  for implanting IS  12  in a patient; 
         FIG.  11    shows one embodiment of a method  220  for delivering and adjusting stimulation signals delivered to one or more target cranial nerves pf a patient; 
         FIG.  12    shows a cross-sectional view of one embodiment of IS  12  implanted beneath a patient&#39;s skin  153  adjacent a patient&#39;s skull  155 ; 
         FIG.  13    shows an inferior view of the human brain  95  and the locations of various cranial nerves associated therewith; 
         FIG.  14    shows human brain  95  and the external locations of various cranial nerves  80  emerging therefrom or entering therein; 
         FIG.  16    shows patient  22 , and patient&#39;s head  51  and neck  53 , along with zones of sensation or effect corresponding to facial nerves V 1  V 2 , and V 3  shown in  FIG.  15   ; 
         FIG.  16    shows the posterior of patient  22 &#39;s head  51  and neck  53 , and occipital nerves  122  (greater occipital nerves and their branches) and  124  (lesser occipital nerves and their branches); 
         FIG.  17    shows a lateral view of patient  22 &#39;s head  51  and neck  55  and the locations of various cranial nerve zones therein; 
         FIG.  18    shows patient  22  and patient&#39;s head  51  and neck  53  as well as hypoglossal nerve  150  and its branches and portions, and 
         FIG.  19    shows portions of vagus nerve  86  and branches thereof connected to various cranial nerves  80  in patient&#39;s head  51  and neck  53 . 
     
    
    
     The drawings are not necessarily to scale. Like numbers refer to like parts or steps throughout the drawings. 
     DETAILED DESCRIPTIONS OF SOME EMBODIMENTS 
     Described herein are various embodiments of systems, devices, components and methods for treating mood disorders and mood affective disorders in a patient using cranial nerve neurostimulation techniques. 
     Examples of mood disorders and mood affective disorders that may be treated with the cranial nerve electrical stimulation systems, devices, components and methods disclosed and described herein include, but are not limited to, one or more of depression, a depressive disorder, insomnia, sadness, mania, bipolar disorder, manic depression, bipolar affective disorder, postpartum depression, seasonal affective disorder (SAD), cyclothymic disorder, premenstrual dysphoric disorder, persistent depressive disorder (dysthymia), disruptive mood dysregulation disorder, depression related to medical illness, and depression induced by substance use or medication. 
     Examples of cranial nerves that may be electrically stimulated using the systems, devices, components and methods disclosed and described herein include, but are not necessarily limited to, one or more of a facial nerve or portion thereof, a trigeminal nerve or portion thereof, an occipital nerve or portion thereof, a hypoglossal nerve or portion thereof, a cranial portion of a vagus nerve, a glossopharyngeal nerve or portion thereof, an auricular branch of the vagus nerve or portion thereof, a tympanic branch of the vagus nerve or portion thereof, a superior ganglion branch of the vagus nerve or portion thereof, an inferior ganglion branch of the vagus nerve or portion thereof, an olfactory nerve or portion thereof, an optic nerve or portion thereof, an oculomotor nerve or portion thereof, a trochlear nerve or portion thereof, an abducens nerve or portion thereof, a vestibulocochlear nerve or portion thereof, and a spinal accessory nerve or portion thereof. 
     In one embodiment, and with general reference to  FIGS.  1  through  7   , implantable neurostimulator  12  is configured to electrically stimulate one or more cranial nerves  80  in a head or neck of a patient to treat a mood disorder or mood affective disorder of the patient. Implantable neurostimulator  12  comprises housing  31 , at least one medical electrical lead  18  comprising at least one stimulation electrode  39 , pulse generation circuitry  34  operably connected to lead  18 , power, energy or electrical charge receiving circuitry  40  operably connected to pulse generation circuitry  34 , and control circuitry  36 . In one embodiment, power, energy or electrical charge receiving circuitry  40  is configured to receive power, energy or electrical charge signals transcutaneously from an external power source and external power transmitting circuitry associated therewith. One or more of pulse generation circuitry  34 , at least one lead  18  and at least one electrode  39 , and power receiving circuitry  40  are mounted on or in, or formed as a portion of, one or more flex circuits  37 . 
     Pulse generation circuitry  34 , power receiving circuitry  40 , and at least portions of one or more flex circuits  37  are disposed within sealed housing  31 , which may or may not be hermetically sealed, Hermetic sealing of housing  31 , if desired, may be accomplished in a number of ways, such as by disposing a hermetic coating or layer over the interior or exterior surfaces of housing  31 , or forming housing  31  out of a suitable malleable, bendable, or shapeable metal or metal alloy. The components and circuitry disposed inside housing  31  may also be sealed and potted therein using epoxy, silicone, a polymer, or other suitable materials. Implantable neurostimulator  12  is sized, shaped and configured to be implanted in the head  51  or neck  53  of the patient beneath the patient&#39;s skin  153 , and lead  18  and one or more electrodes  39  are sized, shaped and configured to be implanted beneath the patient&#39;s skin  153  and positioned adjacent to, in contact with, or in operative positional relationship to, one or more target cranial nerves  80 . 
       FIG.  1    shows a block diagram of one embodiment of a cranial nerve stimulation system  10 , which as shown comprises implantable stimulator (IS)  12  including one or more medical electrical leads  18 , clinician programmer (CP)  14 , patient programmer (PP)  16 , and central server, remote computer, and/or local computer  30 . Other components of system  10  are also contemplated, more about which is said below. IS  12  includes one or more leads  18  to which the circuitry internal of IS  12  is operably connected. In the Figures, only one such lead  18  is shown, although 2, 3 or more medical electrical leads can also be included in IS  12  or operably connected thereto. Thus, IS  12  contains or is operably connected to the proximal ends  57  of one or more medical electrical leads  18 , which according to one embodiment are implantable leads configured for chronic placement beneath a patient&#39;s skin  153 , near or in proximity to a desired cranial nerve  80  or bundle of cranial nerves that are then to be electrically stimulated under the control of IS  12 . In some embodiments, IS  12  features operational and/or stimulation parameters that can be programmed, and in other embodiments such parameters are predetermined or predetermined but selectable form a memory of control circuitry  36 , as further described below. In the embodiment shown in  FIG.  1   , distal end  47  of lead  18  is situated near a branch of facial nerve  100  and provides electrical stimulation signals originating from IS  12  to or near, by way of non-limiting example, such cranial nerve. Other cranial nerves may also be stimulated by system  10 , as further described below. 
     In some embodiments, the electrical stimulation parameters, therapy delivery, and/or operational parameters of IS  12  may be programmed by CP  14  under the control of a physician or other health care provider and/or may be stored and preprogrammed in a memory of IS  12  (included, for example, in control circuitry  36 —see  FIG.  7   ). Optional PP  16  operates under the control of patient  22 , and may be configured to permit patient  22  to turn IS  12  on or off, to change electrical stimulation parameters (in some embodiments within certain limits), or to effect other changes in the operation of IS  12 . In one embodiment, CP  14  is configured to permit a physician or other health care provider to program PP  16  via wireless or other communication and connection means (e.g., Bluetooth, RF, telemetry, inductive or magnetic coupling, cable, etc.)  26 . Remote or local server or computer  30  may be configured to receive and/or transmit data, programming instructions, and the like from and to CP  14  and/or PP  16 , as well as to process, analyze, and facilitate interpretation of such data. 
       FIG.  2    shows a block diagram of another embodiment of a peripheral nerve stimulation system  10 , which as shown comprises implantable neurostimulator (IS)  12  comprising housing  31 , and transition component or protective covering  32 , which can be configured to cover and protect the transition between circuitry contained within IS  12  such as pulse generation circuitry  34  and proximal end  57  of lead  18 , thereby to permit lead  18  to be more both more flexible and more robust at its proximal end  57 . Lead  18  comprises proximal end  57 , distal end  47 , and one or more electrodes  39 . 
     In the embodiments of IS  12  shown in  FIGS.  3  and  4   , bipolar electrodes (or a set of two electrodes)  39  are shown, although other configurations of electrodes for lead(s)  18  are also contemplated, such as unipolar electrodes, tri-polar electrodes, and more. See  FIG.  10    and the discussion corresponding thereto below. 
     In some embodiments, IS  12  includes a conventional connector block to which the proximal ends of one or more lead(s)  18  and/or lead extensions are connected. In other embodiments, as shown in  FIGS.  17   , a single lead  18  forms a portion of IS  12  and no connector block is required. In still other embodiments, multiple leads  18  form a portion of IS  12  and no connector block is also required. 
     In embodiments of IS  12  where no connector block is required, flex circuits  37  can be employed to form a single flexible substrate upon which lead conductor traces are disposed between the output stages of pulse generation circuitry  34  and electrodes  39 , and further upon which pulse generation circuitry  34 , power receiving circuitry  40 /communication interface  61 , and coil and/or antenna are also formed or to which such circuitry is operably connected. Such a configuration of flex circuit  37  imparts increased mechanical robustness, reliability, and flexibility to the substrate of flex circuit  37 , and further aids in the miniaturization of IS  12 . 
     Continuing to refer to  FIG.  2   , CP  14  is shown as a tablet device configured to communicate wirelessly (e.g., via Bluetooth) with IS  12  and/or patient  22 &#39;s PP  16  (which as shown in  FIG.  2    is a smart phone). In some embodiments, PP  16  is configured to permit patient  22  to activate, deactivate, program and/or adjust the electrical stimulation parameters and operation of IS  12 . As further shown in  FIG.  2   , bipolar lead  18  may be employed in system  10 ; other numbers and types of medical electrical leads are contemplated for use in system  10  (as discussed briefly above and in further detail below).  FIGS.  3 ,  4  and  5    show side, top, and top see-through or semi-transparent views, respectively, of various portions of one embodiment of IS  12   FIG.  6    shows a top perspective view of one embodiment of IS  12 . 
       FIG.  7    shows a block diagram of one embodiment of IS  14  it implanted beneath the skin  153  of a patient, with lead  18  and electrodes  39  thereof positioned near a cranial nerve  80  to provide electrical stimulation thereto. External power transmitting device  33  is configured to provide power, energy or charge transcutaneously to IS  12 , and may also be configured to communicate with IS  12  in a manner similar to that of PP  16 . In some embodiments, PP  16  includes the functionality of external power transmitting device  33 . In other embodiments, external device  33  is configured to transfer power, energy or charge to IS  12  so that it may operate and stimulate a given cranial nerve  80 , or so that it may charge a capacitor or battery in IS  12 , or both. In still further embodiments, power receiving circuitry  40 / 61  can comprise one or more of electrical charge storage circuitry, one or more internal induction coils configured to receive electrical power transcutaneously from one or more corresponding external induction coils, or one or more wireless, RF, acoustic, piezoelectric, thin film bulk wave acoustic resonators (FBAR), microwave energy receiving circuits. 
     Referring now to  FIG.  3   , there is shown a side view of IS  12  comprising housing  31 , antenna or coil  38 , flex circuit  37 , lead protective cover  32 , lead  18 , distal end of lead  47 , proximal end of lead  57 , and bi-polar electrodes  39 .  FIG.  4    shows a top view of IS  12  with the same components shown in  FIG.  3   , and also showing coil or antenna  38 , which terminates in power receiving circuitry  40  and communications interface  61 . Per  FIG.  7   , power receiving circuitry  40  and communications interface  61  are operably connected to pulse generation circuitry  34  and control circuitry  36 . Circuitry  34 ,  40 ,  61  and  36  and antenna or coil  38  are shown disposed atop and operably connected to flex circuit  37 , but in alternative embodiments may be formed directly into or upon flex circuit  37  and its corresponding substrate, or some such components may be disposed atop, beside, or underneath flex circuit  37  while others of such components may be formed directly into or upon flex circuit  37 . 
     As shown in  FIGS.  4  and  5   , lead conductors  18   a  and  18   b  are routed from the output stages, of pulse generation circuitry  34  to flex circuit  37  and its corresponding substrate along lead  18  for electrical connection to electrodes  39 . In one embodiment, flex circuit  37  forms a substrate that includes and/or has disposed in or on it the circuitry shown in IS  12  of  FIG.  7   . In some embodiments, the same substrate or single piece of flex, circuit  37  is used to form a substrate for lead  18 . Flex circuit  37  may also be divided into different pieces or portions of flex circuit material that are electrically and operably connected to one another using appropriate electrical connection means and methods known in the art. 
     In some embodiments, flex circuit  37  comprises polyimide or KAPTON® and has electrical circuitry disposed thereon by, for example, vapor deposition or other thin film electrical circuitry forming and manufacturing techniques, and can include traces or electrical conductors, transistors, capacitors, inductors, logic circuitry, and so on. For further information regarding biocompatible polyimides and KAPTON, see, for example: (a) “Biocompatibility of Polyimides: A Mini-Review” to Constantin et al., in Materials, 2019, 12, 3166; doi:10.3390/mia12193166 (“the Constantin reference”), and (b) “Assessment of the biocompatibility of photosensitive polyimide for implantable medical device use” to Sun et al., J. Biomed. Mater. Res. A., 2009, Sep. 1; 90(3):6418-55. 10.1002/jbm.a.32125 (“the Sun reference”), The Constantin and Sun references are hereby incorporated by reference herein, each in its respective entirety pursuant to copies of both publications being submitted in an Information Disclosure Statement to the LISPTO on even date herewith. 
     In some embodiments, ASICs or other integrated circuits are employed to provide the functionalities and operations of circuitry  34 ,  36 ,  38 ,  40 , and/or  61  shown in  FIGS.  3 ,  4 ,  5  and  7   , and may be mounted on or operably connected to flex circuit  37  using, for example, flip chip techniques.  FIG.  5    shows one such embodiment, where circuitry  34 , circuitry  36 , circuitry  38 , circuitry  40 , and/or circuitry  61  (which in most embodiments are integrated circuits) are mounted on flex circuit  37 . 
     Antenna or coil  38  can assume various different configurations as shown in  FIGS.  4  and  5   . In one embodiment, a first purpose of antenna or coil  38  may be to receive power, charge, or energy from an external device  33  and employ such power, charge, or energy to operate the various electrical and electronic components of IS  12 . A second purpose of antenna or coil  38  can be to provide communication functionality between IS  12  and an external device such as device  33  (see  FIG.  7   ), CP  14 , and/or PP  16 . In some embodiments, antenna or coil  38  is configured to receive and/or transmit data, information, and/or instructions from and/or to external devices such as CP  14 , PP  16 , and/or external device  33 . In other embodiments, antenna or coil  38  is configured to receive electrical or other power from an external device and has limited or no communication abilities, Thus, the communication capabilities and functionality of IS  12  may be “primitive” or limited, or may be sophisticated, depending on how small or large IS  12  is to be, and also on the operational complexity of the specifications or objectives of IS  12  that are to be achieved. 
     For example, in one embodiment IS  12  is configured to deliver to electrical stimulation pulses through lead  18  and electrodes  39  only when an external power source is positioned directly over or very close to IS  12 , and energy is transferred transcutaneously to coil or antenna  38 , thereby triggering and maintaining the operation of pulse generation circuitry  34  only so long as the external power source is held in sufficiently close proximity to coil or antenna  38  of IS  12 . In such an embodiment, no battery or only a very small battery, capacitor or charge buffer may be required in IS  12 . In other embodiments which will necessarily be larger and less compact, IS  12  contains a rechargeable battery that can provide the electrical power necessary to operate IS  12  after an overlying recharging coil or other device has been withdrawn from a charging position over coil or antenna  38 . In still another embodiment, IS  12  contains a primary battery that provides the electrical power necessary to operate IS  12  for a limited duration of time that may extend over days, weeks, months or years, depending on the charge capacity of the primary battery and other factors. 
     Referring now to  FIGS.  2  through  5   , in some embodiments sealed housing  31  may have a thickness ranging between about 0.1 inches and about 0.4 inches, a diameter ranging between about 0.05 inches and about 0.8 inches, and lead(s)  18  may have a length extending beyond housing  31  ranging between about 0.1 inches and about 4 inches, ad/or a width beyond the housing that ranges between about 0.01 inches and about 0.05 inches. 
     Referring to  FIGS.  3 - 5  and  7   , pulse generation circuitry  34 , control circuitry  36 , and power receiving and storage circuitry  36  may be potted within housing  31  using, for example, a medical grade polymer. 
     Referring  FIGS.  3 - 6   , at least one lead  18 , pulse generation circuitry  34 , control circuitry  36 , and power receiving and storage circuitry  40 / 61  may be mounted on or in, or formed as a portion of, a single flex circuit or flex circuit substrate  37 . Power receiving circuitry  40 / 61  may further comprise electrical charge storage circuitry, one or more internal induction coils configured to receive electrical power transcutaneously from one or more corresponding external induction coils, and/or one or more wireless, RF, acoustic, piezoelectric, Thin film bulk wave acoustic resonators (FBAR), microwave energy receiving circuits. 
     With reference to  FIG.  7   , in some embodiments pulse generation circuitry  34  may be configured to deliver stimulation signals comprising one or more of: (1) frequencies ranging between about 2 Hz and about 100 Hz; (2) frequencies ranging between about 2 Hz and about 75 Hz; (3) frequencies ranging between about 4 Hz and about 50 Hz; (4) frequencies ranging between about 5 Hz and about 25 Hz; (5) frequencies ranging between about 7 Hz and about 100 Hz; (6) frequencies ranging between about 100 Hz and about 10,000 Hz; (7) frequencies ranging between about 100 Hz and about 5,000 Hz; (h) frequencies ranging between about 100 Hz and about 2,000 Hz; (8) frequencies ranging between about 100 Hz and about 1,800 Hz; (9) frequencies ranging between about 200 Hz and about 750 Hz; (10) voltages ranging between about 0.1 mV and about 30 V; (11) currents ranging between about 0.1 mA and about 30 mA; and (12) pulse widths ranging between about 20 μsec and about 1000 μsec. Pulse generation circuitry  34  may further be configured to deliver stimulation signals over periods of time ranging between about 30 seconds and about 2 hours, 5 minutes and about 1 hour, and about 10 minutes and about 45 minutes. Other frequencies, amplitudes, and durations for electrical nerve stimulation are also contemplated. 
     In some embodiments, and with reference to  FIG.  7   , external device may be fitted to an adhesive substrate or bandage that patient  22  may wear on or attach to the surface of skin  153  while IS  12  is being powered transcutaneously and/or while IS  12  is electrically simulating a target cranial nerve  80 , or while IS  12  is being recharged. Alternatively, external device  33  may be affixed or attached to a headband or head strap that is configured to hold external device  33  on patient&#39;s skin  153  in a location and position that permits appropriate or suitable power of signal coupling between IS  12  and external device  33  to occur. 
       FIG.  8    shows one embodiment of block diagrams for CP  14 , PP  16 , and IS  12 , with a focus on communications that can occur in some embodiments between such components of system  10 , As shown in  FIG.  8   , Bluetooth or other communication means  26  may be employed for communication between system components  14 ,  16 , and  12 . CP  14  includes processor or CPU  11 , memory  15 , which among other things stores programming instructions and control instructions to operate and control IS  12 , and user interface  17 , which can include a screen  19  and an input mechanism  21  (e.g., keypad, microphone, buttons, etc.). Communication interface  69  is configured to permit wireless or wired communications with IS  12  and/or PP  16 . Communication interface  61  is configured to communicate wirelessly or in a wired manner with CP  14  and/or PP  16  PP  16  comprises display screen  25 , communication interface  27 , and input mechanism  63 . 
       FIG.  9    shows various embodiments of medical electrical leads  18  that can be utilized in at least some embodiments of system  10 . The various embodiments of medical electrical leads  18  and/or  20  shown in  FIG.  10    include the following:
         Lead A—a unipolar lead with a lead body  41  and a single electrode  39  disposed near its distal end  47 ;   Lead B—a bipolar lead with a lead body  41  and two electrodes  39  disposed near its distal end  47 ;   Lead C—a quadripolar lead with a lead body  41  and four electrodes  39  disposed near its distal end  47 ;   Lead D—an octopolar lead with a lead body  41  and eight electrodes  39  disposed near its distal end  47 ;   Lead E—a paddle lead with a lead body  41  and a plurality of paddle electrodes  39  disposed in two columns;   Lead F—a paddle lead with a plurality of electrodes  39  disposed in a single column:   Lead G an active fixation lead with a helically wound wire coil  49  disposed at its distal end  47 , where coil  49  serves both as a fixation device  49  and an electrode  39 ;   Lead H—a tined lead with one or more flexible or deformable tines  57  disposed near its distal end  47 ; and   Lead I—a bipolar lead with a lead body  41  and two electrodes  39  disposed near its distal end  47 . In some embodiments, cuff electrode leads may also be employed, as is known in the neurostimulation arts.       

     Other non-limiting examples of medical electrical leads  18  suitable for use in some embodiments of IS 12 include leads used in conjunction with one or more ground electrodes, leads having arrays of cathodes employed in various configurations respecting corresponding anodes (all serving as electrodes  39 ), wire electrodes  39 , hook-shaped electrodes  39 , and barb-shaped electrodes  39 . In a case where a lead  18  comprises three or more electrodes  39 , IS  12  can be configured to controllably switch and control one or more specific pairs or other groupings of electrodes  39  to which, electrical stimulation is delivered in various combinations as anodes and/or cathodes. Likewise, pairs or other groups of electrodes  39  in different leads  18  (by way of non-limiting example) can be controllably switched or controlled so that the electrical fields emitted by electrodes  39  extend at least some distance between the different leads  18  and  20 . In such a manner, optimum electrode pairings or groupings tailored to the specific patient  22 , lead(s) placement, nerve location, etc., can be achieved to deliver the best therapy to patient  22 . 
     In some embodiments, each of leads  18  comprises at least one cathode (electrode  39 ) that can be placed near a portion of the target cranial nerve  80 . Alternatively, more than one cathode (electrode  39 ) can be utilized. As one of the electrodes is being used as a cathode for stimulation, the other electrode can be used as an anode for a return path to complete the electrical circuit. Alternatively, both stimulation electrodes could utilize a(n) additional electrode(s) as the anode. This anode could be on the one or more leads  18  described above, a separate lead  18 , or an external ground pad or other grounding device. 
     The lead examples and embodiments shown in  FIG.  6    are not mended to be limiting or exhaustive, but are merely illustrative of different types of leads that can be employed in system  10 . Other types and configurations of medical electrical leads other than those shown in  FIG.  6    are contemplated, including various permutations and combinations of the different lead elements and components shown in  FIG.  9   . 
       FIG.  10    shows one embodiment of method  200  of implanting IS  12  and corresponding/included lead  18 (s) in a patient for the purpose of delivering mood or mood affective disorder therapy to a patient by means of cranial nerve electrical stimulation. In step  202 , ultrasound, fluoroscopic, MRI, PET scan, and/or CT scan techniques, or any other suitable imaging techniques, are employed to guide a test stimulation needle(s) to appropriate locations near one or more cranial target nerves (see, e.g.,  FIGS.  14 - 20   ). By way of non-limiting example, in one embodiment, needle(s) is/are guided to appropriate target nerve locations, which as described below are in suitably close proximity to the one or more target cranial nerves  80 . 
     Once one or both needle(s) have been guided to a desired location near the one or more target cranial nerves  80  of interest, at step  204  target nerve(s)  80  are electrically stimulated by operably attaching the proximal ends of the needles to an external pulse generator and activating a desired output stimulation pattern or regime for delivery to the needles. Different stimulation parameters can be tested at this time by varying any one or more of the voltage, current, frequency, pulse width, amplitude, overlap, interleaving, and delivery of the stimulation signals, as well as other electrical stimulation parameters. 
     In addition to experimenting with different stimulation parameters, the needles can be repositioned or their locations changed as required or desired at step  206  so that optimum stimulation results are obtained (e.g., maximum, sufficient, or acceptable mood or mood affective disorder therapy in response to test stimulation signals). Once step  206  has been completed, at step  208  an introducer may be inserted over each needle, and at step  210  the needle(s) are withdrawn from the patient. Distal ends  47  of lead(s)  18  are then inserted through the introducers to their respective target nerve locations at step  212 . Alternatively, the needles are hollow needles having inner diameters sufficiently large (e.g., 2 mm or more) to accept therein leads)  18  having diameters less than the inner diameters of the needles. Other techniques for implanting lead(s)  18  are also contemplated. 
     At step  214 , further refinement and adjustment of electrical stimulation and programming instructions may then be carried out at step  116 . 
     As an example, patient  22  with a mood or mood affective disorder is implanted with a lead(s)  18  near one or more appropriate target cranial nerves  80 , The one or more appropriate nerve targets are identified using percutaneous needle sticks, and demonstrating activation of the target nerve as viewed using an ultrasound apparatus. Once the target nerve and location have been established, lead(s)  18  are inserted using standard techniques. System  10  and IS  12  are then programmed using a clinician programmer app in CP  14  to determine appropriate stimulation parameters (e.g., amplitude, frequency, pulse width, duration of electrical stimulation, etc.) for patient  22 . 
     In addition, an MRI can be used to image one or more cranial nerves in the patient to assess the precise and optimal locations for lead placement before lead(s)  18  are implanted in patient  22 . An MRI may also be used to image one or more cranial nerves  80  in patient  22  after therapy has been delivered to patient  22  by nerve stimulation signals, and after the lead(s) have been implanted in patient  22 . 
     Referring now to  FIG.  11   , there is shown one embodiment of a method  220  of electrically stimulating a patient using an implantable cranial nerve stimulation system  10  as described herein. At step  222 , stimulation signals are delivered to one or more target cranial nerves  80 . At step  224 , nerve stimulation signal parameters are adjusted to optimize the therapy that is being delivered to patient  22  for the mood or mood affective disorder. 
     Methods other than  200  and  220  are contemplated for testing stimulation and implanting stimulator  12 . 
       FIG.  12    shows a cross-section view of one embodiment of IS  12  implanted beneath a patient&#39;s skin  153  adjacent a patient&#39;s skull  155 . As shown, bottom surface  29  of housing  31  is curved and conforms generally to the curvature and shape of skull  151 . Such a curved configuration of IS  12  so that it conformably engages and fits along the shape and outline of skull  151  helps prevent erosion of or damage to patient&#39;s skin  153 , and also increases the degree of comfort patient  12  experiences while having IS  12  implanted in his or her head or neck. Sealed housing  21  can comprise a flexible polymer that is configured to conform to at least one of a shape of the patient&#39;s skull  151  or overlying skin  153 . The flexible polymer of housing  31  may be a thermosettable or shapeable material that can be formed into and will retain a desired shape or curvature. Such forming or shaping can be carried out by a health care provider during the implantation of IS  12  using, for example, a form that has been preconfigured to the appropriate shape or curvature of the patient&#39;s skull;  151  or skin  153 . 
       FIG.  13    shows human brain  95  and the external locations of various cranial nerves  80  emerging therefrom or entering therein; namely: olfactory nerves  81 , vestibulocochlear nerves  82 , optic nerves  83 , glossopharyngeal nerves  84 , oculomotor nerves  85 , vagus nerves  86 , trochlear nerves  87 , spinal accessory nerves  88 , abducens nerves  89 , trigeminal nerves  90 , facial nerves  100 , and hypoglossal nerves  150 . One aspect of the various embodiments described and disclosed herein, is that lead  18  and electrodes  39  can be placed much closer to a target cranial nerve than is possible using an external TENS system simply because lead  18  is located beneath the skin and can be placed much more closely to the target nerve than is possible with a TENS electrode. Consequently, electrical stimulation can be provided to a much smaller nerve target region, which as a result provides superior therapeutic results owing to the more focused electrical filed being provided to the target cranial nerve. 
       FIG.  14    shows a head  51  and neck  53  of a patient  22 , and the locations of various facial nerves  100  and trigeminal nerves  90  thereon. Facial nerve branches V 1 , V 2  and V 3  are shown, as well as other portions and branches of the facial nerves  100 . Posterior auricle nerve  103  located beneath patient  22 &#39;s ear is also shown in  FIG.  14   . Trigeminal nerve root  91  (which is connected to the trigeminal nerve nucleus) and trigeminal gasserian ganglion  93  are also shown in  FIG.  14   , One nerve target, and depending on the precise electrical stimulation therapy to be delivered, along with all the other facial nerves and trigeminal nerves shown in  FIG.  14   , for treating a mood disorder or mood affective disorder, is posterior auricle nerve  103 . For illustrative purposes, IS  12  and lead  18  are shown situated in proximity to nerve  103  so as to deliver electrical stimulation therapy thereto. As described above, CP  14 , PP  16  and/or device  33  may be is employed to set up and control the electrical stimulation parameters of IS  12 . Note that the relative sizes of IS  12  and patient&#39;s head  51  shown in  FIG.  15    are merely illustrative and not necessarily to scale. IS  12  can be configured to be very small, and far smaller than conventional implantable pulse generators and their corresponding leads, more about which is said below. 
       FIG.  15    shows patient  22 , and patient&#39;s head  51  and neck  53 , along with zones of sensation or effect corresponding to facial nerves V 1 , V 2 , and V 3  shown in  FIG.  15   . The therapy delivered by IS  12 , and the location of implantation of IS  12  within head  51  or neck  53  of patient  22 , may be selected in accordance with the illustrated ophthalmic (V 1 ), maxillary (V 2 ), and mandibular (V 3 ) zones. 
       FIG.  16    shows the rear of patient  22 &#39;s head  51  and neck  53 , and occipital nerves  122  (greater occipital nerves and their branches) and  124  (lesser occipital nerves and their branches). Nerves  122  and  124  may also be target nerves for IS  12  and lead  18  to electrically stimulate and thereby provide therapy for mood disorders and mood affective disorders. 
       FIG.  17    shows a side view of patient  22 &#39;s head  51  and neck  53 , and the locations of various cranial nerve zones therein, including zones corresponding to: (a) a zone containing occipital nerves  122 ,  124  and  125 , and C4 nerve  127 ; (b) a zone containing great auricular nerve  140 ; (c) a zone containing auriculotemporal nerve  130 ; (d) a zone containing supratrochlear nerve  121  and supraorbital nerve  123 . IS  12  and corresponding lead  18  may be implanted beneath patient&#39;s skin  153  in operative relationship and location to electrically stimulate any of such cranial nerves  80  in any of such zones, depending on the specific therapy that is to be delivered, to treat the patient&#39;s mood disorder or mood affective disorder. 
       FIG.  13    shows patient  22  and patient&#39;s head  51  and neck  53 , as well as hypoglossal nerve  150  and its branches and portions, including hypoglossal canal  152  and medulla oblongata  154 . IS  12  and corresponding lead  18  may be implanted beneath patient&#39;s skin  153  in operative relationship and location to electrically stimulate any of such cranial nerves  80  in any of such zones, depending on the specific therapy that is to be delivered, to treat the patient&#39;s mood disorder or mood affective disorder. 
       FIG.  19    shows portions of vagus nerve  86  and branches thereof that are connected to various cranial nerves  80  in patient&#39;s head  51  and neck  53 , These nerves and nerve branches of the vagus nerve include Arnold&#39;s Nerve  107  (which is connected to nerve  103 ), Jacobson&#39;s Nerve (or tympanic nerve)  105 , vagus nerve CN X, glossopharyngeal nerve CN X, and others. IS  12  and corresponding lead  18  may be implanted beneath patient&#39;s skin  153  in operative relationship and location to electrically stimulate any of such cranial nerves  80  or vagus nerves  86 , depending on the specific therapy that is to be delivered, to treat the patient&#39;s mood disorder or mood affective disorder, The auricular branch of vagus nerve  86  is Arnold&#39;s nerve  107 , the eponymous name of the auricular branch, also known as the mastoid branch, of the vagus nerve (CN X). This nerve may be stimulated as a diagnostic or therapeutic technique to treat mood or mood affective disorders. 
     In some embodiments, one or more stimulation parameters of nerve stimulation signals comprise one or more of: (a) frequencies ranging between about 2 Hz and about 100 Hz; (b) frequencies ranging between about 2 Hz and about 75 Hz; (c) frequencies ranging between about 4 Hz and about 50 Hz, (d) frequencies ranging between about 5 Hz and about 25 Hz; (e) frequencies ranging between about 7 Hz and about 100 Hz; (f) voltage ranging between about 0.1 mV and about 30 V; (g) current ranging between about 0.1 mA and about 30 mA, pulse width ranging between about 20 μsec and about 1000 μsec The first stimulation signal may also be provided as a constant voltage signal or a constant current signal. 
     In various embodiments, one or more stimulation parameters of the nerve stimulation signals may also be provided as constant voltage signals, constant current signals, triangular signals, biphasic signals, triphasic signals, chirp or swept signals, standard rectangular pulse signals, burst signals, and so on. Tapering of signals using, for example, Hanning, Hamming, and/or Blackman windowing techniques, may also be employed. 
     In further embodiments, the nerve stimulation signals are delivered to the one or more target nerves for periods of time ranging between about 60 seconds and about 180 minutes. In various embodiments, nerve stimulation signals are delivered to the one or more target nerves in bursts ranging between about 20 seconds and about 2 hours in duration. Such bursts can be delivered sequentially. 
     Therapy sessions can be adjusted or modified as required over the multi-day or multi-month time period over which the nerve stimulation signals are delivered to the patient. For example, the stimulation parameters of the nerve stimulation therapy sessions can be changed or modified as a day, or the multi-day or multi-month time period, progresses. Nerve stimulation therapy sessions can be shortened as the patient&#39;s mood or mood affective disorder symptoms are reduced. 
     In still further embodiments, electrodes  39  on lead(s)  18  may also be employed not only to stimulate targeted nerve bundles or nerves, but also to sense depolarization and repolarization signals originating from the targeted nerve bundles or tissue in proximity thereto. These sensed signals may in turn be employed by programming instructions loaded and circuitry disposed in IS  12  to process the sensed signals, and then determine whether or not the stimulation parameters of the nerve stimulation signals should be adjusted, thereby forming a feedback control loop for peripheral nerve stimulation. 
     It will now be seen that the various systems, devices, components and methods disclosed and described herein are capable of providing effective therapies to patients having different types of mood or mood affective disorders. Note, however, that the systems, devices, components, and methods disclosed and described herein are not limited to treating mood or mood affective disorders by stimulating one or more cranial nerves, and instead may be employed to treat, by way of non-limiting example, post-traumatic stress disorder (PTSD), epilepsy, drug or opioid addiction, tinnitus, Parkinson&#39;s disease, Alzheimer&#39;s disease, dementia, chronic balance deficit due to mild-to-moderate traumatic brain injury, movement disorders, attention or memory dysfunction associated with traumatic brain injury, sleep apnea (by, for example stimulating the hypoglossal or other cranial nerve(s) disclosed and described herein), and/or to modulate the activity of one or more targeted brain regions (by, for example, stimulating one or more the trigeminal nerves), 
     What have been described above are examples and embodiments of the devices and methods described and disclosed herein. It is, of course, not possible to describe every conceivable combination of components or methodologies for purposes of describing the invention, but one of ordinary skill in the art well recognize that many further combinations and permutations of the devices and methods described and disclosed herein are possible. Accordingly, the devices and methods described and disclosed herein are intended to embrace all such alterations, modifications and variations that fall within the scope of the appended claims. In the deans, unless otherwise indicated, the article “a” is to refer to“lone or more than one.” 
     The foregoing description and disclosure outline features of several embodiments so that those skilled in the art may better understand the detailed description set forth herein. Those skilled in the art will now understand that many different permutations, combinations and variations of hearing aid  10  fall within the scope of the various embodiments. Those skilled in the art should appreciate that they may readily use the present disclosure as a basis for designing or modifying other processes and structures for carrying out the same purposes and/or achieving the same advantages of the embodiments introduced herein. Those skilled in the art should also realize that such equivalent constructions do not depart from the spirit and scope of the present disclosure, and that they may make various changes, substitutions and alterations herein without departing from the spirit and scope of the present disclosure. 
     After having read and understood the present specification, those skilled in the art will now understand and appreciate that the various embodiments described herein provide solutions to long-standing problems in delivering cost-effective therapies to patients suffering from mood and mood affective disorders.