Patent Document

FIELD OF THE INVENTION 
       [0001]    In general, the invention relates to devices and methods for non-invasive neurostimulation of a subject&#39;s brain. More specifically, the invention relates to devices and methods for non-invasive neurostimulation of a subject&#39;s brain to effect treatment of various maladies. 
       BACKGROUND OF THE INVENTION 
       [0002]    Traumatic brain injury (TBI) is a leading cause of disability around the world. Each year in the United States, about two million people suffer a TBI, with many suffering long term symptoms. Long term symptoms can include impaired attention, impaired judgment, reduced processing speed, and defects in abstract reasoning, planning, problem-solving and multitasking. 
         [0003]    A stroke is a loss of brain function due to a disturbance in the blood supply to the brain. Every year, about 800,000 people in the United States will have a stroke. Stroke is a leading cause of long-term disability in the United States, with nearly half of older stroke survivors experiencing moderate to severe disability. Long term effects can include seizures, incontinence, vision disturbance or loss of vision, dysphagia, pain, fatigue, loss of cognitive function, aphasia, loss of short-term and/or long-term memory, and depression. 
         [0004]    Multiple sclerosis (MS) is a disease that causes damage to the nerve cells in the brain and spinal cord. Globally, there are about 2.5 million people who suffer from MS. Symptoms can vary greatly depending on the specific location of the damaged portion of the brain or spinal cord. Symptoms include hypoesthesia, difficulties with coordination and balance, dysarthria, dysphagia, nystagmus, bladder and bowel difficulties, cognitive impairment and major depression to name a few. 
         [0005]    Alzheimer&#39;s disease (AD) is a neurodegenerative disorder affecting over 25 million people worldwide. Symptoms of AD include confusion, irritability, aggression, mood swings, trouble with language, and both short and long term memory loss. In developed countries, AD is one of the most costly diseases to society. 
         [0006]    Parkinson&#39;s disease (PD) is a degenerative disorder of the central nervous system, affecting more than 7 million people globally. Symptoms of PD include tremor, bradykinesia, rigidity, postural instability, cognitive disturbances, and behavior and mood alterations. 
         [0007]    One approach to treating the long term symptoms associated with TBI, stroke, MS, AD, and PD is neurorehabilitation. Neurorehabilitation involves processes designed to help patients recover from nervous system injuries. Traditionally, neurorehabilitation involves physical therapy (e.g., balance retraining), occupational therapy (e.g., safety training, cognitive retraining for memory), psychological therapy, speech and language therapy, and therapies focused on daily function and community re-integration. 
         [0008]    Another approach to treating the long term symptoms associated with TBI, stroke, MS, AD, and PD is neurostimulation. Neurostimulation is a therapeutic activation of part of the nervous system. For example, activation of the nervous system can be achieved through electrical stimulation, magnetic stimulation, or mechanical stimulation. Typical approaches focused mainly on invasive techniques, such as deep brain stimulation (DBS), spinal cord stimulation (SCS), cochlear implants, visual prosthesis, and cardiac electrostimulation devices. Only recently have non-invasive approaches to neurostimulation become more mainstream. 
         [0009]    Despite many advances in the areas of neurorehabilitation and neurostimulation, there exists an urgent need for treatments that employ a combined approach, including both neurorehabilitation and neurostimulation to improve the recovery of patients having TBI, stroke, multiple sclerosis, Alzheimer&#39;s, Parkinson&#39;s or any other neurological impairment. 
       SUMMARY OF THE INVENTION 
       [0010]    The invention, in various embodiments, features methods and devices for combining non-invasive neuromodulation with traditional neurorehabilitation therapies. Clinical studies have shown that methods combining neurostimulation with neurorehabilitation are effective in treating the long term neurological impairments due to a range of maladies such as TBI, stroke, MS, AD, and PD. 
         [0011]    In one aspect, the invention features a system for providing non-invasive neuromodulation to a patient. The system includes a mouthpiece and a controller. The mouthpiece includes an elongated housing having an anterior region and a posterior region, the elongated housing having a non-planar exterior top surface. The mouthpiece also includes a printed circuit board mounted to a bottom portion of the elongated housing, the printed circuit board having a plurality of electrodes for delivering subcutaneous local electrical stimulation to the patient&#39;s tongue. The mouthpiece also includes control circuitry mounted within a top portion of the elongated housing for controlling electrical signals delivered to the electrodes. The mouthpiece also includes a cable with a first end attached to the anterior portion of the elongated housing and having a connector at a second end for connecting to a controller, the cable delivering electrical current to the electrodes via the control circuitry. The controller includes an elongated u-shaped element configured to rest upon a patient&#39;s shoulders. The controller also includes an electronic receptacle located at a terminus of the u-shaped element connecting to the cable. The controller also includes a microcontroller located within the three-dimensional u-shaped element, the microcontroller configured to send electrical control signals to the mouthpiece, the electrical control signals determining an amplitude and duration of electrical signals delivered to the patient&#39;s tongue. 
         [0012]    In some embodiments, the system also includes an accelerometer for measuring an activity level of the patient. In some embodiments, the system also includes a data logger for logging information related to the activity level of the patient. In some embodiments, the system also includes tongue sense circuitry for determining if a patient&#39;s tongue is in contact with the plurality of electrodes located on the bottom portion of the mouthpiece. In some embodiments, the system also includes a real time clock for determining a total time of usage of the mouthpiece. In some embodiments, the system also includes a battery for providing a current to the mouthpiece. In some embodiments, the system also includes an optical indicator that indicates a power level of the battery. In some embodiments, the system also includes an audio indicator that can warn the patient when the remaining battery charge is inadequate to complete a therapy session. In some embodiments, the exterior top surface of the elongated housing is planar. In some embodiments, the printed circuit board is mounted to a middle or top portion of the elongated housing. In some embodiments, the control circuitry is mounted within a middle or top portion of the elongated housing. In some embodiments, the cable is permanently attached to the controller and is removably attached to the mouthpiece. 
         [0013]    In another aspect, the invention features a system for providing non-invasive neuromodulation to a patient. The system includes a mouthpiece and a controller. The mouthpiece includes an elongated housing having an anterior region and a posterior region, the elongated housing having a non-planar exterior top surface. The mouthpiece also includes a printed circuit board mounted to the elongated housing, the printed circuit board having a plurality of electrodes for delivering subcutaneous local electrical stimulation to the patient&#39;s tongue. The mouthpiece also includes control circuitry mounted within the elongated housing for controlling electrical signals delivered to the electrodes. The mouthpiece also includes a first communication module delivering electrical current to the electrodes via the control circuitry. The controller includes an elongated u-shaped housing configured to rest upon a patient&#39;s shoulders. The controller also includes a second communication module within the housing coupled to and in communication with the first communication module. The controller also includes a microcontroller located within the housing and configured to exchange electrical signals with the mouthpiece, the electrical signals determining an amplitude and duration of electrostimulation energy pulses delivered to the patient&#39;s tongue. 
         [0014]    In some embodiments, the system also includes an accelerometer for measuring an activity level of the patient. In some embodiments, the system also includes a data logger for logging information related to the activity level of the patient. In some embodiments, the system also includes tongue sense circuitry for determining if a patient&#39;s tongue is in contact with the plurality of electrodes located on the bottom portion of the mouthpiece. In some embodiments, the system also includes a real time clock for determining a total time of usage of the mouthpiece. In some embodiments, the system also includes a battery for providing a current to the mouthpiece. In some embodiments, the system also includes an optical indicator that indicates a power level of the battery. In some embodiments, the system also includes an audio indicator that can warn the patient when the remaining battery charge is inadequate to complete a therapy session. 
         [0015]    In yet another aspect, the invention features a system for providing non-invasive neuromodulation to a patient. The system includes a mouthpiece. The mouthpiece includes an elongated housing having an anterior region and a posterior region, the elongated housing having a non-planar exterior top surface. The mouthpiece also includes a printed circuit board mounted to a bottom portion of the elongated housing, the printed circuit board having a plurality of electrodes for delivering subcutaneous local electrical stimulation to the patient&#39;s tongue. The mouthpiece also includes control circuitry mounted within a top portion of the elongated housing for controlling electrical signals delivered to the electrodes. The system also includes a mobile device configured to send electrical control signals to the mouthpiece, the electrical control signals determining an amplitude and duration of electrical signals delivered to the patient&#39;s tongue. 
         [0016]    In some embodiments, the system also includes an accelerometer for measuring an activity level of the patient. In some embodiments, the system also includes a data logger for logging information related to the activity level of the patient. In some embodiments, the system also includes tongue sense circuitry for determining if a patient&#39;s tongue is in contact with the plurality of electrodes located on the bottom portion of the mouthpiece. In some embodiments, the system also includes a real time clock for determining a total time of usage of the mouthpiece. In some embodiments, the system also includes an audio indicator that can warn the patient when the remaining battery charge is inadequate to complete a therapy session. 
         [0017]    In yet another aspect, the invention features a controller for delivering electrical control signals to a mouthpiece during a non-invasive neuromodulation therapy session. The controller includes an elongated u-shaped element configured to rest upon a patient&#39;s shoulders. The controller also includes an electronic receptacle located at a terminus of the three-dimensional u-shaped element for connecting to a cable. The controller also includes a microcontroller located within the three-dimensional u-shaped element, the microprocessor configured to send electrical control signals to the mouthpiece, the electrical control signals determining an amplitude and duration of electrical signals delivered to the patient&#39;s tongue. 
         [0018]    In some embodiments, the controller also includes an accelerometer for measuring an activity level of the patient and a data logger for logging information related to the activity level of the patient. In some embodiments, the controller also includes an audio alarm for indicating at least one of the end of a therapy session, a low electrical signal delivered to the patient&#39;s tongue, activation/deactivation of the controller, or pausing of the electrical signals delivered to the patient&#39;s tongue. In some embodiments, the controller also includes a power switch for activating and deactivating the controller and one or more intensity buttons for controlling the intensity of electrical signals delivered to the mouthpiece by the controller. In some embodiments, the controller also includes a display for presenting information and receiving input from the patient. In some embodiments, the controller also includes a battery for providing a current to the mouthpiece. In some embodiments, the controller also includes a motor for causing the u-shaped element to vibrate. In some embodiments, the controller also includes at least one printed circuit board for mounting electrical isolation circuitry, battery management circuitry, and a microcontroller, at least one printed circuit board for mounting a play button, a pause button, and the electronic receptacle, and at least one circuit board for mounting one or more intensity buttons. In some embodiments, the controller also includes circuitry for sensing a current delivered to a patient&#39;s tongue via the mouthpiece. In some embodiments, the controller also includes a cable forming an integral portion of the mouthpiece. 
         [0019]    In yet another aspect, the invention features a controller for delivering electrical control signals to a mouthpiece during a non-invasive neuromodulation therapy session. The controller includes a coextensively dimensioned element configured to rest in proximity to a patient&#39;s face. The controller also includes a receptacle located at a central portion of a first surface of the coextensively dimensioned element, the receptacle providing an electrical and mechanical connection to the mouthpiece. The controller also includes a display located on a second surface of the coextensively dimensioned element, the display providing visual indications to the patient. The controller also includes a microcontroller located within the coextensively dimensioned element, the microcontroller configured to send electrical control signals to the mouthpiece, the electrical control signals determining an amplitude and duration of electrical signals delivered to the patient&#39;s tongue. 
         [0020]    In some embodiments, the controller also includes an accelerometer for measuring an activity level of the patient and a data logger for logging the activity level of the patient, transmissions to or from the controller, the intensity of electrical signals delivered to the mouthpiece, and information received circuitry configured to determine if the patient&#39;s tongue is in contact with the mouthpiece. In some embodiments, the controller also includes an audio alarm for indicating at least one of the end of a therapy session, a low electrical signal delivered to the patient&#39;s tongue, activation/deactivation of the controller, or pausing of the electrical signals delivered to the patient&#39;s tongue. In some embodiments, the controller also includes a power switch for activating and deactivating the controller and one or more intensity buttons located on a third surface of the coextensively dimensioned element, the intensity buttons controlling the intensity of electrical signals delivered to the mouthpiece by the controller. In some embodiments, the controller also includes a display for presenting information and receiving input from the patient. In some embodiments, the controller also includes a battery for providing a current to the mouthpiece. In some embodiments, the controller also includes a motor for causing the coextensively dimensioned element to vibrate. In some embodiments, the controller also includes at least one printed circuit board for mounting electrical isolation circuitry, battery management circuitry, and a microcontroller, at least one printed circuit board for mounting a play button and a pause button, at least one printed circuit board for mounting the circuitry associated with the receptacle, and at least one circuit board for mounting one or more intensity buttons. In some embodiments, the controller also includes circuitry for sensing a current delivered to a patient&#39;s tongue via the mouthpiece. 
         [0021]    In yet another aspect, the invention features a method for providing non-invasive neurorehabilitation of a patient. The method includes connecting a mouthpiece to a controller. The method also includes transmitting a numeric sequence generated by a first processor within the controller to the mouthpiece. The method also includes generating a first hash code by a second processor within the mouthpiece, the first hash code based on the received numeric sequence and a shared secret key stored in memory within the mouthpiece. The method also includes transmitting the first hash code from the mouthpiece to the controller. The method also includes generating a second hash code by the first processor within the controller, the second hash code based on the random number and the shared secret key. The method also includes comparing, by the first processor, the first hash code with the second hash code. The method also includes enabling electrical communication between the mouthpiece and the controller only if the first hash code matches the second hash code. The method also includes contacting the mouthpiece with the patient&#39;s intraoral cavity. The method also includes delivering neurostimulation to the patient&#39;s intraoral cavity, the neurostimulation being delivered by the controller via the mouthpiece. 
         [0022]    In some embodiments, the method also includes connecting the mouthpiece to the controller via a cable. In some embodiments, the method also includes providing power to the controller. In some embodiments, the method also includes delivering electrical neurostimulation via an electrode array to the patient&#39;s intraoral cavity. 
         [0023]    In yet another aspect, the invention features a method for providing non-invasive neurorehabilitation of a patient via a controller and a mouthpiece. The method includes connecting the mouthpiece to the controller. The method also includes generating a first hash code based on a unique serial number and a shared secret key. The method also includes storing the unique serial number and the first hash code in memory located in the mouthpiece. The method also includes transmitting the first hash code and the unique serial number from the mouthpiece to the controller. The method also includes generating a second hash code in a first processor in the controller, the second hash code based on the unique serial number and the shared secret key. The method also includes permitting electrical communication between the mouthpiece and the controller only if the first hash code matches the second hash code. The method also includes contacting the mouthpiece with the patient&#39;s intraoral cavity. The method also includes delivering neurostimulation to the patient&#39;s intraoral cavity, the neurostimulation being delivered by the controller via the mouthpiece. 
         [0024]    In some embodiments, the method also includes connecting the mouthpiece to the controller via a cable. In some embodiments, the method also includes providing power to the controller. In some embodiments, the method also includes delivering electrical neurostimulation via an electrode array to the patient&#39;s intraoral cavity. In some embodiments, the first hash code is an SHA-256 hash code. 
         [0025]    In yet another aspect, the invention features a mouthpiece for providing neurorehabilitation to a patient, the mouthpiece receiving electrical neurostimulation signals from a controller and selectively delivering the received electrical neurostimulation signals to the patient. The mouthpiece includes an elongated housing having an anterior region and a posterior region, the elongated housing having a non-planar exterior top surface. The mouthpiece also includes a printed circuit board mounted to a bottom portion of the elongated housing, the printed circuit board having a plurality of electrodes for delivering subcutaneous local electrical stimulation to the patient&#39;s tongue. The mouthpiece also includes control circuitry mounted within a top portion of the elongated housing for controlling electrical signals delivered to the electrodes. The mouthpiece also includes a memory mounted within a top portion of the elongated housing. The mouthpiece also includes a processor mounted within the top portion of the elongated housing, the processor configured to (i) receive a numeric sequence from the controller, (ii) generate a first hash code based on the received numeric sequence and a shared secret key stored in the memory, (iii) transmit the first hash code to the controller, (iv) receive communications from the controller only if a second hash code based on the numeric sequence and the shared secret key generated at the controller matches the first hash code. 
         [0026]    In yet another aspect, the invention features a mouthpiece for providing neurorehabilitation to a patient, the mouthpiece receiving electrical neurostimulation signals from a controller and selectively delivering the received electrical neurostimulation signals to the patient. The mouthpiece includes an elongated housing having an anterior region and a posterior region, the elongated housing having a non-planar exterior top surface. The mouthpiece also includes a printed circuit board mounted to a bottom portion of the elongated housing, the printed circuit board having a plurality of electrodes for delivering subcutaneous local electrical stimulation to the patient&#39;s tongue. The mouthpiece also includes control circuitry mounted within a top portion of the elongated housing for controlling electrical signals delivered to the electrodes. The mouthpiece also includes a memory mounted within the top portion of the elongated housing. The mouthpiece also includes a processor mounted within the top portion of the elongated housing, the processor configured to (i) store a first hash code and a unique serial number, the first hash code based on the unique serial number and a shared secret key (ii) transmit the first hash code and the unique serial number to the controller, (iv) receive communications from the controller only if a second hash code based on the unique serial number and the shared secret key generated at the controller matches the first hash code. In some embodiments, the first hash code is an SHA-256 hash code. 
         [0027]    As used herein, the terms “approximately,” “roughly,” and “substantially” mean±10%, and in some embodiments, ±5%. Reference throughout this specification to “one example,” “an example,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example of the present technology. Thus, the occurrences of the phrases “in one example,” “in an example,” “one embodiment,” or “an embodiment” in various places throughout this specification are not necessarily all referring to the same example. Furthermore, the particular features, structures, routines, steps, or characteristics may be combined in any suitable manner in one or more examples of the technology. The headings provided herein are for convenience only and are not intended to limit or interpret the scope or meaning of the claimed technology. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0028]    The advantages of the invention described above, together with further advantages, may be better understood by referring to the following description taken in conjunction with the accompanying drawings. The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. 
           [0029]      FIG. 1  is a drawing of a patient engaged in a non-invasive neurostimulation therapy session according to an illustrative embodiment of the invention. 
           [0030]      FIGS. 2A and 2B  are diagrams showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0031]      FIG. 2C  is a diagram showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0032]      FIG. 3A  is a diagram showing a more detailed view of the neurostimulation system depicted in  FIGS. 2A and 2B . 
           [0033]      FIG. 3B  is a diagram showing a more detailed view of the neurostimulation system depicted in  FIG. 2C . 
           [0034]      FIG. 3C  is a diagram showing a more detailed view of an electrode array. 
           [0035]      FIG. 3D  is a graph showing an exemplary sequence of pulses for effecting neurostimulation of a patient. 
           [0036]      FIG. 4A  is a flow chart illustrating a method in accordance with one embodiment for operating a neurostimulation system. 
           [0037]      FIG. 4B  is a flow chart illustrating a method in accordance with one embodiment for operating a neurostimulation system. 
           [0038]      FIG. 5A  is a diagram showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0039]      FIG. 5B  is a diagram showing a controller according to an illustrative embodiment of the invention. 
           [0040]      FIG. 5C  is a flow chart illustrating a method in accordance with one embodiment for operating a neurostimulation system. 
           [0041]      FIGS. 6A and 6B  are diagrams showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0042]      FIGS. 7A and 7B  are diagrams showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0043]      FIGS. 8A and 8B  are diagrams showing a neurostimulation system according to an illustrative embodiment of the invention. 
           [0044]      FIG. 9A  is a flow chart illustrating a method in accordance with one embodiment for operating a neurostimulation system. 
           [0045]      FIG. 9B  is a flow chart illustrating a method in accordance with one embodiment for operating a neurostimulation system. 
       
    
    
     DETAILED DESCRIPTION 
       [0046]      FIG. 1  shows a patient  101  undergoing non-invasive neuromodulation therapy (NINM) using a neurostimulation system  100 . During a therapy session, the neurostimulation system  100  non-invasively stimulates various nerves located within the patient&#39;s oral cavity, including at least one of the trigeminal and facial nerves. In combination with the NINM, the patient engages in an exercise or other activity specifically designed to assist in the neurorehabilitation of the patient. For example, the patient can perform a physical therapy routine (e.g., moving an affected limb, or walking on a treadmill) engage in a mental therapy (e.g., meditation or breathing exercises), or a cognitive exercise (e.g., computer assisted memory exercises) during the application of NINM. The combination of NINM with an appropriately chosen exercise or activity has been shown to be useful in treating a range of maladies including, for example, traumatic brain injury, stroke (TBI), multiple sclerosis (MS), balance, gait, vestibular disorders, visual deficiencies, tremor, headache, migraines, neuropathic pain, hearing loss, speech recognition, auditory problems, speech therapy, cerebral palsy, blood pressure, relaxation, and heart rate. For example, a useful non-invasive neuromodulation (NINM) therapy routine has been recently developed as described in U.S. Pat. No. 8,849,407, the entirety of which is incorporated herein by reference. 
         [0047]      FIGS. 2A and 2B  show a non-invasive neurostimulation system  100 . The non-invasive neurostimulation system  100  includes a controller  120  and a mouthpiece  140 . The controller  120  includes a receptacle  126  and pushbuttons  122 . The mouthpiece  140  includes an electrode array  142  and a cable  144 . The cable  144  connects to the receptacle  126 , providing an electrical connection between the mouthpiece  140  and the controller  120 . In some embodiments, the controller  120  includes a cable. In some embodiments, the mouthpiece  140  and the controller  120  are connected wirelessly (e.g., without the use of a cable). During operation, a patient activates the neurostimulation system  100  by actuating one of the pushbuttons  122 . In some embodiments, the neurostimulation system  100  periodically transmits electrical pulses to determine if the electrode array  142  is in contact with the patient&#39;s tongue and automatically activates based on the determination. After activation, the patient can start an NINM treatment session, stop the NINM treatment session, or pause the NINM treatment session by pressing one of the pushbuttons  122 . In some embodiments, the neurostimulation system  100  periodically transmits electrical pulses to determine if the electrode array  142  is in contact with the patient&#39;s tongue and automatically pauses the NINM treatment session based on the determination. During an NINM treatment session, the patient engages in an exercise or other activity designed to facilitate neurorehabilitation. For example, during an NINM treatment session, the patient can engage in a physical exercise, a mental exercise, or a cognitive exercise. In some embodiments, the controller  120  has pushbuttons on both arms. In some embodiments, a mobile device can be used in conjunction with the controller  120  and the mouthpiece  140 . The mobile device can include a software application that allows a user to activate the neurostimulation system  100  and start or stop an NINM treatment session by for example, pressing a button on the mobile device, or speaking a command into the mobile device. The mobile device can obtain patient information and treatment session information before, during, or after an NINM treatment session. In some embodiments, the controller  120  includes a secure cryptoprocessor that holds a secret key, to be described in more detail below in connection with  FIGS. 9A and 9B . The secure cryptoprocessor is in communication with a microcontroller. The secure cryptoprocessor can be tamper proof. For example, if outer portions of the cryptoprocessor are removed in an attempt to access the secret key, the cryptoprocessor erases all memory, preventing unauthorized access of the secret key. 
         [0048]      FIG. 2C  shows a non-invasive neurostimulation system  100 . As shown, a mobile device  121  is in communication with a mouthpiece  140 . More specifically, the mobile device  121  includes a processor running a software application that facilitates communications with the mouthpiece  140 . The mobile device  121  can be, for example, a mobile phone, a portable digital assistant (PDA), or a laptop. The mobile device  121  can communicate with the mouthpiece  140  by a wireless or wired connection. During operation, a patient activates the neurostimulation system  100  via the mobile device  121 . After activation, the patient can start an NINM treatment session, stop the NINM treatment session, or pause the NINM treatment session by manipulating the mobile device  121 . During an NINM treatment session, the patient engages in an exercise or activity designed to provide neurorehabilitation. For example, during an NINM treatment session, the patient can engage in a physical exercise, a mental exercise, or a cognitive exercise. 
         [0049]      FIG. 3A  shows the internal circuitry housed within the controller  120 . The circuitry includes a microcontroller  360 , isolation circuitry  379 , a universal serial bus (USB) connection  380 , a battery management controller  382 , a battery  362 , a push-button interface  364 , a display  366 , a real time clock  368 , an accelerometer  370 , drive circuitry  372 , tongue sense circuitry  374 , audio feedback circuitry  376 , vibratory feedback circuitry  377 , and a non-volatile memory  378 . The drive circuitry  372  includes a multiplexor, and an array of resistors to control voltages delivered to the electrode array  142 . The microcontroller  360  is in electrical communication with each of the components shown in  FIG. 3A . The isolation circuitry  379  provides electrical isolation between the USB connection  380  and all other components included in the controller  120 . Additionally, the circuitry shown in  FIG. 3A  is in communication with the mouthpiece  140  via the external cable  144 . During operation, the microcontroller  360  receives electrical power from battery  362  and can store and retrieve information from the non-volatile memory  378 . The battery can be charged via the USB connection  380 . The battery management circuitry controls the charging of the battery  362 . A patient can interact with the controller  120  via the push-button interface  122  that converts the patient&#39;s pressing of a button (e.g. an info button, a power button, an intensity-up button, an intensity-down button, and a start/stop button) into an electrical signal that is transmitted to the microcontroller  360 . For example, a therapy session can be started when the patient presses a start/stop button after powering on the controller  120 . During the therapy session, the drive circuitry  372  provides an electrical signal to the mouthpiece  140  via the cable  144 . The electrical signal is communicated to the patient&#39;s intraoral cavity via the electrode array  142 . The accelerometer  370  can be used to provide information about the patient&#39;s motion during the therapy session. Information provided by the accelerometer  370  can be stored in the non-volatile memory  378  at a coarse or detailed level. For example, a therapy session aggregate motion index can be stored based on the number of instances where acceleration rises above a predefined threshold, with or without low pass filtering. Alternatively, acceleration readings could be stored at a predefined sampling interval. The information provided by the accelerometer  370  can be used to determine if the patient is engaged in a physical activity. Based on the information received from the accelerometer  370 , the microcontroller  360  can determine an activity level of the patient during a therapy session. For example, if the patient engages in a physical activity for 30 minutes during a therapy session, the accelerometer  370  can periodically communicate (e.g. once every second) to the microcontroller  360  that the sensed motion is larger than a predetermined threshold (e.g. greater than 1 m/s 2 ). In some embodiments, the accelerometer data is stored in the non-volatile memory  378  during the therapy session and transmitted to the mobile device  121  after the therapy session has ended. After the therapy session has ended, the microcontroller  360  can record the amount of time during the therapy session in which the patient was active. In some embodiments, the recorded information can include other data about the therapy session (e.g., the date and time of the session start, the average intensity of electrical neurostimulation delivered to the patient during the session, the average activity level of the patient during the session, the total session time the mouthpiece has been in the patient&#39;s mouth, the total session pause time, the number of session shorting events, and/or the length of the session or the type of exercise or activity performed during the therapy session) and can be transmitted to a mobile device. A session shorting event can occur if the current transmitted from the drive circuitry to the electrode array  142  exceeds a predetermined threshold or if the charge transmitted from the drive circuitry to the electrode array exceeds a predetermined threshold over a predetermined time interval. After a session shorting event has occurred, the patient must manually press a pushbutton to resume the therapy session. The real time clock (RTC)  368  provides time and date information to the microcontroller  360 . In some embodiments, the controller  120  is authorized by a physician for a predetermined period of time (e.g., two weeks). The RTC  368  periodically communicates date and time information to the microcontroller  360 . In some embodiments, the RTC  368  is integrated with the microcontroller. In some embodiments, the RTC  368  is powered by the battery  362 , and upon failure of the battery  362 , the RTC  368  is powered by a backup battery. After the predetermined period of time has elapsed, the controller  120  can no longer initiate the delivery of electrical signals to the mouthpiece  140  and the patient must visit the physician to reauthorize use of the controller  120 . The display  366  displays information received by the microcontroller  360  to the patient. For example, the display  366  can display the time of day, therapy information, battery information, time remaining in a therapy session, error information, and the status of the controller  120 . The audio feedback circuitry  376  and vibratory feedback circuitry  377  can give feedback to a user when the device changes state. For example, when a therapy session begins, the audio feedback circuitry  376  and the vibratory feedback circuitry  377  can provide auditory and/or vibratory cues to the patient, notifying the patient that the therapy session has been initiated. Other possible state changes that may trigger audio and/or vibratory cues include pausing a therapy session, resuming a therapy session, the end of a timed session, canceling a timed session, or error messaging. In some embodiments, a clinician can turn off one or more of the auditory or vibratory cues to tailor the feedback to an individual patient&#39;s needs. The tongue sense circuitry  374  measures the current passing from the drive circuitry to the electrode array  142 . Upon sensing a current above a predetermined threshold, the tongue sense circuitry  374  presents a high digital signal to the microcontroller  360 , indicating that the tongue is in contact with the electrode array  142 . If the current is below the predetermined threshold, the tongue sense circuitry  374  presents a low digital signal to the microcontroller  360 , indicating that the tongue is not in contact or is in partial contact with the electrode array  142 . The indications received from the tongue sense circuitry  374  can be stored in the non-volatile memory  378 . In some embodiments, the display  366  can be an organic light emitting diode (OLED) display. In some embodiments, the display  366  can be a liquid crystal display (LCD). In some embodiments, a display  366  is not included with the controller  120 . In some embodiments, neither the controller  120  nor the mouthpiece  140  includes a cable, and the controller  120  communicates wirelessly with the mouthpiece  140 . In some embodiments, neither the controller  120  nor the mouthpiece  140  includes an accelerometer. In some embodiments, the drive circuitry  372  is located within the mouthpiece. In some embodiments, a portion of the drive circuitry  372  is located within the mouthpiece  140  and a portion of the drive circuitry  372  is located within the controller  120 . In some embodiments, neither the controller  120  nor the mouthpiece  140  includes tongue sense circuitry  374 . In some embodiments, the mouthpiece  140  includes a microcontroller and a multiplexer. 
         [0050]      FIG. 3B  shows a more detailed view of  FIG. 2C . The mouthpiece  140  includes a battery  362 , tongue sense circuitry  374 , an accelerometer  370 , a microcontroller  360 , drive circuitry  372 , a non-volatile memory  378 , a universal serial bus controller (USB)  380 , and battery management circuitry  382 . During operation, the microcontroller receives electrical power from battery  362  and can store and retrieve information from the non-volatile memory  378 . The battery can be charged via the USB connection  380 . The battery management circuitry  382  controls the charging of the battery  362 . A patient can interact with the mouthpiece  140  via the mobile device  121 . The mobile device  121  includes an application (e.g. software running on a processor) that allows the patient to control the mouthpiece  140 . For example, the application can include an info button, a power button an intensity-up button, an intensity-down button, and a start/stop button that are presented to the user visually via the mobile device  121 . When the patient presses a button presented by the application running on the mobile device  121 , a signal is transmitted to the microcontroller  360  housed within the mouthpiece  140 . For example, a therapy session can be started when the patient presses a start/stop button on the mobile device  121 . During the therapy session, the drive circuitry  372  provides an electrical signal to an electrode array  142  located on the mouthpiece  140 . The accelerometer  370  can be used to provide information about the patient&#39;s motion during the therapy session. The information provided by the accelerometer  370  can be used to determine if the patient is engaged in a physical activity. Based on the information received from the accelerometer  370 , the microcontroller  360  can determine an activity level of the patient during a therapy session. For example, if the patient engages in a physical activity for 30 minutes during a therapy session, the accelerometer  370  can periodically communicate (e.g. once every second) to the microcontroller  360  that the sensed motion is larger than a predetermined threshold (e.g. greater than 1 m/s 2 ). After the therapy session has ended, the microcontroller  360  can record the amount of time during the therapy session in which the patient was active. In some embodiments, the accelerometer  370  is located within the mobile device  121  and the mobile device  121  determines an activity level of a patient during the therapy session based on information received from the accelerometer  370 . The mobile device can then record the amount of time during the therapy session in which the patient was active. The mobile device  121  includes a real time clock (RTC)  368  that provides time and date information to the microcontroller  360 . In some embodiments, the mouthpiece  140  is authorized by a physician for a predetermined period of time (e.g., two weeks). After the predetermined period of time has elapsed, the mouthpiece  140  can no longer deliver electrical signals to the patient via the electrode array  142  and the patient must visit the physician to reauthorize use of the mouthpiece  140 . In some embodiments, the mouthpiece  140  includes pushbuttons (e.g., an on/off button) and a patient can manually operate the mouthpiece  140  via the pushbuttons. After a therapy session, the mouthpiece  140  can transmit information about the therapy session to a mobile device. In some embodiments, the mouthpiece  140  does not include a USB controller  380  and instead communicates only via wireless communications with the controller. 
         [0051]      FIG. 3C  shows a more detailed view of the electrode array  142 . The electrode array  142  can be separated into 9 groups of electrodes, labelled a-i, with each group having 16 electrodes, except group b which has 15 electrodes. Each electrode within the group corresponds to one of 16 electrical channels. During operation, the drive circuitry can deliver a sequence of electrical pulses to the electrode array  142  to provide neurostimulation of at least one of the patient&#39;s trigeminal or facial nerve. The electrical pulse amplitude delivered to each group of electrodes can be larger near a posterior portion of the tongue and smaller at an anterior portion of the tongue. For example, the pulse amplitude of electrical signals delivered to groups a-c can be 19 volts or 100% of a maximum value, the pulse amplitude of electrical signals delivered to groups d-f can be 14.25 volts or 75% of the maximum value, the pulse amplitude of electrical signals delivered to groups g-h can be 11.4 volts or 60% of the maximum value, and the pulse amplitude of electrical signals delivered to group i can be 9.025 volts or 47.5% of the maximum value. In some embodiments, the maximum voltage is in the range of 0 to 40 volts. The pulses delivered to the patient by the electrode array  142  can be random or repeating. The location of pulses can be varied across the electrode array  142  such that different electrodes are active at different times, and the duration and/or intensity of pulses may vary from electrode. For oral tissue stimulation, currents of 0.5-50 mA and voltages of 1-40 volts can be used. In some embodiments, transient currents can be larger than 50 mA. The stimulus waveform may have a variety of time-dependent forms, and for cutaneous electrical stimulation, pulse trains and bursts of pulses can be used. Where continuously supplied, pulses may be 1-500 microseconds long and repeat at rates from 1-1000 pulses/second. Where supplied in bursts, pulses may be grouped into bursts of 1-100 pulses/burst, with a burst rate of 1-100 bursts/second. 
         [0052]    In some embodiments, pulsed waveforms are delivered to the electrode array  142 .  FIG. 3D  shows an exemplary sequence of pulses that can be delivered to the electrode array  142  by the drive circuitry  372 . A burst of three pulses, each spaced apart by 5 ms is delivered to each of the 16 channels. The pulses in neighboring channels are offset from one another by 312.5 μs. The burst of pulses repeats every 20 ms. The width of each pulse can be varied from 0.3-60 μs to control an intensity of neurostimulation (e.g., a pulse having a width of 0.3 μs will cause a smaller amount of neurostimulation than a pulse having a width of 60 μs). 
         [0053]      FIG. 4A  shows a method of operation  400  of a controller  120  as described in  FIGS. 2A, 2B and 3A . A patient attaches a mouthpiece  140  to a controller  120  (step  404 ). The patient turns on the controller  120  (step  408 ) using, for example, a power button. The patient places the controller  120  around his/her neck (step  412 ) as shown in  FIG. 1B . The patient places a mouthpiece  140  in his/her mouth (step  416 ). The patient initiates a therapy session by pressing a start/stop button (step  420 ). During the therapy session, the controller  120  delivers electrical signals to the mouthpiece  140 . The patient calibrates the intensity of the electrical signals (step  424 ). The patient raises the intensity of the electrical signals delivered to the mouthpiece by pressing an intensity-up button until the neurostimulation is above the patient&#39;s sensitivity level. The patient presses an intensity-down button until the neurostimulation is comfortable and non-painful. After the calibration step, the patient performs a prescribed exercise (step  428 ). The exercise can be cognitive, mental, or physical. In some embodiments, physical exercise includes the patient attempting to maintain a normal posture or gait, the patient moving his/her limbs, or the patient undergoing speech exercises. Cognitive exercises can include “brain training” exercises, typically computerized, that are designed to require the use of attention span, memory, or reading comprehension. Mental exercises can include visualization exercises, meditation, relaxation techniques, and progressive exposure to “triggers” for compulsive behaviors. 
         [0054]    In some embodiments, the patient can rest for a period of time during the therapy session (e.g. the patient can rest for 2 minutes during a 30 minute therapy session). After a predetermined period of time (for example, thirty minutes) has elapsed, the therapy session ends (step  432 ) and the controller  120  stops delivering electrical signals to the mouthpiece  140 . In some embodiments, the intensity of electrical signals increases from zero to the last use level selected by the patient over a time duration in the range of 1-5 seconds after the patient starts a therapy session by pressing the start/stop button. In some embodiments, the intensity of electrical signals is set to a fraction of the last use level selected by the patient (e.g. 3/4 of the last level selected) after the patient starts a therapy session by pressing the start/stop button. In some embodiments, the intensity of electrical signals increases from zero to a fraction of the last use level selected by the patient (e.g. 3/4 of the last level selected) over a time duration in the range of 1-5 seconds after the patient starts a therapy session by pressing the start/stop button. In some embodiments, the intensity of electrical signals increases instantaneously from zero to the last use level selected by the patient after the patient starts a therapy session by pressing the start/stop button. 
         [0055]    In some embodiments, the mouthpiece  140  is connected to the controller  120  after the controller  120  is turned on. In some embodiments, the mouthpiece  140  is connected to the controller  120  after the controller  120  is donned by the patient. In some embodiments, the patient calibrates the intensity of the electrical signals before initiating a therapy session. In some embodiments, a patient performs an initial calibration of the intensity of electrical signals in the presence of a clinician and does not calibrate the intensity of the electrical signals during subsequent treatments performed in the absence of a clinician. 
         [0056]      FIG. 4B  shows a method of operation  449  of the non-invasive neurostimulation system  100  described in  FIGS. 2C and 3B . A patient activates a mobile device  121  (step  450 ). The patient places a mouthpiece  140  in his/her mouth (step  454 ). The patient initiates a therapy session by pressing a start/stop button within an application running on the mobile device  121  (step  458 ). During the therapy session, circuitry within the mouthpiece  140  delivers electrical signals to an electrode array  142  located on the mouthpiece  140 . The patient calibrates the intensity of the electrical signals (step  462 ). The patient first raises the intensity of the electrical signals delivered to the mouthpiece  140  by pressing an intensity-up button located within an application running on the mobile device  121  until the neurostimulation is above the patient&#39;s sensitivity level. The patient presses an intensity-down button running within an application on the mobile device  121  until the neurostimulation is comfortable and non-painful. After the calibration step, the patient performs a prescribed exercise (step  464 ). The exercise can be cognitive, mental, or physical. In some embodiments, the patient can rest for a period of time during the therapy session (e.g. the patient can rest for 5 minutes during a 30 minute therapy session). After a predetermined period of time (for example, thirty minutes) has elapsed, the therapy session ends (step  468 ) and the circuitry located within the mouthpiece  140  stops delivering electrical signals to the electrode array  142 . In some embodiments, the calibration of the intensity of the electrical signals takes place before the patient initiates a therapy session. 
         [0057]      FIG. 5A  shows a neurostimulation system  500  and  FIG. 5B  shows a back view of a controller  520 . The neurostimulation system  500  includes a controller  520  and a mouthpiece  540  connected via a cable  544 . The mouthpiece  540  includes an electrode array on a bottom portion thereof. The controller  520  includes an anterior portion  560  and a posterior portion  564 . The controller  520  also includes a mouthpiece port  516 , an intensity-up button  508 , an intensity-down button  512 , a power button  521 , an info button  524 , a start/stop button  504  and a display  528 . The mouthpiece  540  is in electrical communication with the controller  520  via the cable  544 . In some embodiments, the power button  521  includes a light emitting diode (LED) indicator. In some embodiments, the port  516  is located on the mouthpiece  540  instead of the controller  520  and the cable  544  is permanently attached to the controller  520 . In some embodiments the port is a universal serial bus (USB) port and/or a charging port. 
         [0058]      FIG. 5C  describes a method  200  of operating the neurostimulation system  500  shown in  FIGS. 5A and 5B . A patient activates the neurostimulation system  500  by pressing a power button  521  (step  208 ). After activation, the neurostimulation system  500  enters an idle state (step  212 ). While in the idle state, non-invasive neurostimulation is not delivered to the patient. If the neurostimulation system  500  remains in the idle state for a predetermined time period, the neurostimulation system  500  can shut down or enter a power-saving state (e.g., after idling for 10 minutes). Additionally, if the power button  521  is pressed while in the idle state, the neurostimulation system  500  shuts down. If the patient presses a start button (step  224 ), an NINM therapy session begins and non-invasive neurostimulation generated by the controller  520  is delivered to the patient&#39;s oral cavity via the mouthpiece  540  for a predetermined period of time. In some embodiments, the neurostimulation system  500  enters an intensity adjustment state when the patient presses a start button (step  224 ). The patient then raises the intensity of the electrical signals delivered to the mouthpiece by pressing the intensity-up button  508  until the neurostimulation is above the patient&#39;s sensitivity level. The patient presses the intensity-down button  512  until the neurostimulation is comfortable and non-painful. After the intensity adjustment is completed, the patient presses the start button again to begin an NINM therapy session. In one embodiment, the predetermined period of time can be in the user-selectable range of 20-30 minutes. Additionally, the patient performs a physical, cognitive, or mental exercise during the NINM therapy session. The physical, cognitive, or mental exercise is performed simultaneously with the delivery of electrical signals from the controller  520  to the mouthpiece  540 . If the patient presses a pause button (step  232 ) while neurostimulation is being delivered, the therapy session is paused (step  233 ) and the neurostimulation system  500  ceases to deliver non-invasive neurostimulation to the patient&#39;s oral cavity. In some embodiments, if the neurostimulation system  500  loses contact with the patient&#39;s oral cavity (e.g. determined by tongue sensing circuitry), the therapy session is paused. If the patient presses unpause (step  234 ), the treatment is resumed and non-invasive neurostimulation is again delivered to the patient&#39;s intraoral cavity. If the patient presses the stop button while the neurostimulation system  500  is paused, or if there is no patient input for more than a predetermined time, for example, two minutes (step  235 ) after the patient has pressed the pause button, the neurostimulation system  500  enters an idle state (step  212 ) and a “treatment ended due to pause timeout” message is presented by the display  528 . If the patient presses the stop button (step  240 ) while neurostimulation is being delivered, the neurostimulation system  500  enters an idle state (step  212 ) and a “treatment ended due to session stop” message is presented by the display  528 . Alternatively, if the neurostimulation system  500  delivers neurostimulation to the patient for the full predetermined period of time at step  240 , the system enters an idle state at step  212  and a “full session completed” message is presented by the display  528 . 
         [0059]    While the system is in the idle state at step  212 , a number of conditions can prevent the patient from initiating a therapy session. For example, if there is not enough charge remaining in the battery to complete at least one NINM therapy session, the controller  520  can block the patient from initiating the therapy session and a “low battery” message will be presented on the display  528 . In some embodiments, the controller can emit an audible sound to alert the patient that there is not enough charge remaining in the battery to complete at least one NINM therapy session. Additionally, if the mouthpiece  540  is not attached to the controller  520 , the controller  520  can block the patient from initiating a therapy session and a “no mouthpiece” message is presented on the display  528 . 
         [0060]    In some embodiments, the neurostimulation system  500  delivers neurostimulation for a limited number of hours per day. For example, the neurostimulation system  500  can be configured to stop delivering neurostimulation after 200 minutes of use in a single day. In the idle state at step  212 , if the daily limit has been exceeded, the controller  520  can block the patient from initiating a therapy session and a “daily limit reached” message is presented by the display  528 . The patient can begin treatment the next day (i.e., after midnight), when the daily limit is reset. 
         [0061]    In some embodiments, the neurostimulation system  500  delivers neurostimulation for a limited number of weeks. In the idle state at step  212 , if the calendar limit has been exceeded, the controller  520  can block the patient from initiating a therapy session and a “calendar limit reached” message is presented by the display  528 . For example, the neurostimulation system  500  can be configured to stop delivering neurostimulation 1-14 weeks after the patient receives the neurostimulation system  500  from a physician. To re-enable the neurostimulation system  500  after the calendar limit has been exceeded, the patient is required to visit a physician or a clinician. In some embodiments, a “calendar limit approaching” message is presented by the display  528 , warning the patient that the calendar limit will be reached soon (e.g. in two weeks). The “calendar limit approaching” message can be beneficial to patients by allowing them to schedule appointments with their clinicians prior to the calendar limit being reached. 
         [0062]    In some embodiments, the mouthpiece  540  can become damaged over time and require replacement. For example, the patient&#39;s bites down on the mouthpiece  540  during each therapy session, slowly causing the surface of the mouthpiece to be damaged. This damage can cause the mouthpiece  540  to malfunction. The average time to failure can be statistically determined by testing a number of mouthpieces  540  over a number of therapy sessions and examining the mouthpieces for damage at the end of each therapy session. The average time to failure, once determined, can be programmed into the controller  520 . During the idle state at step  212 , if the average time to failure has been reached, the controller  520  can block the patient from initiating a therapy session and a “mouthpiece expired” message is presented by the display  528 . In some embodiments, a message is presented by the display  528 , warning the patient that the mouthpiece is set to expire soon. For example, the message presented by the display  528  can be “mouthpiece expires in 14 days.” 
         [0063]    In some embodiments, the display  528  can present an “authentication error” message if a mouthpiece  540  cannot be authenticated, for example as described in  FIGS. 9A and 9B . In some embodiments, the neurostimulation system  500  tracks an activity level of a patient. For example, the neurostimulation system  500  can include an accelerometer that detects an activity level of the patient (e.g., at rest, walking, or running) In some embodiments, the activity level can be recorded and stored on an external computer for analysis. For example, the recorded activity level data can be analyzed by a physician to determine an effectiveness of a prescribed treatment plan. In some embodiments, the neurostimulation system  500  sets an intensity level to 75% of the last used intensity level when the treatment begins at step  228 . In some embodiments, data including time stamps, intensity levels, data received from the accelerometer, and data received from the tongue sense circuitry can be recorded and stored on an external computer or mobile device for analysis. 
         [0064]    In some embodiments, the port  516  can facilitate charging of the neurostimulation system  500 . For example, when the port  516  is connected to a charging source, the neurostimulation system  500  enters a charging state. In the charging state, a “Charging” message is presented by the display  528 . Additionally, in the charging state, an LED can indicate a remaining battery charge. For example, the LED can emit flashing red light if there is not sufficient battery charge for at least one NINM therapy session. If there is sufficient battery charge remaining to complete at least one NINM therapy session, the LED can emit flashing green. When the battery charging is complete, the LED can emit a solid green light (e.g. a non-flashing green light). While the neurostimulation system  500  is in the charging state, the patient cannot begin an NINM therapy session. When the port is disconnected in the charging state, the neurostimulation system  500  enters an idle state (step  212 ). 
         [0065]    In some embodiments, an LED included with the power button  521  can indicate a remaining battery charge. For example, the LED can emit green light if there is sufficient battery charge remaining to complete two or more NINM therapy sessions. If there is sufficient battery charge remaining to complete one NINM therapy session, the LED can emit yellow light. If there is not enough charge remaining for one NINM therapy session, the LED can emit red light. In some embodiments, the controller  520  includes LEDs for providing visual indication, an audio indicator, or a vibratory indicator that can provide indications to the patient. For example, the LEDs, the audio indicator, and the vibratory indicator can provide an indication to the patient if electrical neurostimulation is being delivered to the mouthpiece  540 , if electrical neurostimulation delivery to the mouthpiece  540  has been disabled or cancelled, or if the NINM therapy session has ended. The indications can include a solid or flashing light emitted by the LEDs or a predetermined sound such as a ring, buzz, or chirp emitted by the audio indicator. The vibratory indicator can provide tactile feedback or other vibratory feedback to the patient. In some embodiments, the audio and/or vibratory indicator includes a piezoelectric element or a magnetic buzzer that vibrates and provides a mechanical indication to the patient. In some embodiments, the LEDs and/or the audio indicator provide an indication when an NINM therapy session is 50% complete. In some embodiments, the LEDs and/or the audio indicator provide an indication when any button on the controller  520  is pressed by the patient. In some embodiments, the LEDs and/or the audio indicator provide an indication of the intensity level of the electrical neurostimulation. In some embodiments, the LEDs and/or the audio indicator provide an indication of the remaining NINM therapy session time. In some embodiments, the LEDs and/or the audio indicator provide an indication of the remaining stimulation minutes for the current day (e.g., before a daily limit is reached). In some embodiments, the LEDs and/or the audio indicator provide an indication of the remaining stimulation minutes for the current calendar period (e.g., before a calendar limit is reached). In some embodiments, pressing a start/stop/pause button while neurostimulation is being delivered pauses the therapy session (step  233 ) and the neurostimulation system  500  ceases to deliver non-invasive neurostimulation to the patient&#39;s oral cavity. 
         [0066]      FIGS. 6A and 6B  show a non-invasive neurostimulation system  600 . The non-invasive neurostimulation system  600  includes headband  618 , a controller  620 , pushbuttons  622 , a display  628 , a mouthpiece  640 , an electrode array  642 , and a cable  624 . The controller  620  is in electrical communication with the mouthpiece  640  and the electrode array  642  via the cable  624 . During operation, a patient rests the headband  618  along his/her ears and inserts the mouthpiece  640  into his/her mouth. Operation of the non-invasive neurostimulation system  600  is similar to that described above in reference to  FIGS. 5A and 5B  where similarly referenced elements have the same functionality (e.g. controller  620  has the same functionality as controller  520  etc.). In some embodiments, the headband  618  maintains an orientation of the mouthpiece  640  within the patient&#39;s mouth during an NINM therapy session. In some embodiments, the headband  618  maintains the position of the mouthpiece  640  within the patient&#39;s mouth, even if the patient is in a horizontal orientation or is upside-down. 
         [0067]      FIGS. 7A and 7B  show a non-invasive neurostimulation system  700 . The non-invasive neurostimulation system  700  includes headband  718 , a controller  720 , an intensity setting wheel  722 , a mouthpiece  740 , an electrode array  742 , and a cable  724 . The controller  720  is in electrical communication with the mouthpiece  740  and the electrode array  742  via the cable  724 . During operation, a patient rests the headband  718  along an upper circumference of his/her head and inserts the mouthpiece  740  into his/her mouth. The patient can increase the intensity of the electrical signals delivered to the mouthpiece  740  by rotating the intensity setting wheel in a clockwise direction. The patient can decrease the intensity of the electrical signals delivered to the mouthpiece  740  by rotating the intensity setting wheel in a counterclockwise direction. Operation of the non-invasive neurostimulation system  700  is otherwise similar to that described above in reference to  FIGS. 5A and 5B  where similarly referenced elements have the same functionality (e.g. controller  720  has the same functionality as controller  520  etc.). In some embodiments, the headband  718  is configured to allow the patient to wear his/her glasses during an NINM therapy session. 
         [0068]      FIGS. 8A and 8B  show a non-invasive neurostimulation system  800 . The non-invasive neurostimulation system  800  includes a controller  820 , a mouthpiece  840 , pushbuttons  822 , display screen  828 , and indicator light  832 . The controller  820  and the mouthpiece  840  are integrated into a monolithic package. The controller  820  is in electrical communication with the mouthpiece  840  and the electrode array  842 . During operation, a patient inserts the mouthpiece  840  into his/her mouth and the rigidly attached controller  820  rests just outside of the patient&#39;s mouth. Operation of the non-invasive neurostimulation system  800  is otherwise similar to that described above in reference to  FIGS. 5A and 5B  where similarly referenced elements have the same functionality (e.g. controller  820  has the same functionality as controller  520  etc.). In some embodiments, the controller  820  is in mechanical contact with the patient&#39;s chin and is configured to mechanically secure the mouthpiece  840  during an NINM therapy session. In some embodiments, a display screen  828  is not included with non-invasive neurostimulation system  800 . In some embodiments, a display screen  828  is replaced with an auditory indicator that provides auditory messages to the patient. In some embodiments, the controller  820  and the mouthpiece  840  are each monolithic and connected at a connection point between the mouthpiece  840  and the controller  820 . In some embodiments, the mouthpiece  840  is removably attached to the controller  820  and can be replaced at predetermined usage intervals or upon wearing out. 
         [0069]      FIG. 9A  shows a method of operation  900  of the non-invasive neurostimulation device illustrated in  FIGS. 5-8 . Initially a patient connects a mouthpiece to a controller or mobile device (step  904 ). The connection can be a wired or wireless connection. A processor within the controller or mobile device generates a numeric sequence and transmits the generated sequence to the mouthpiece (step  908 ). The numeric sequence generated at step  908  can be a sequence of random values, produced by a software pseudorandom number generator, or by a hardware random number generator. Based on the received numeric sequence and a secret key shared between the mouthpiece and the controller, a processor located within the mouthpiece generates a first hash code (step  912 ). The first hash code can be generated using an HMAC (keyed-hash message authentication code) algorithm. In some embodiments, the first hash code is generated in accordance with an SHA-256 algorithm. The mouthpiece then transmits the first hashcode to the controller (step  916 ). A processor located within the controller generates a second hash code based on the shared secret key and the numeric sequence (step  920 ) and then compares the first hash code with the second hash code (step  924 ). The numeric sequence generated at step  920  can be a sequence of random values, produced by a software pseudorandom number generator, or by a hardware random number generator. In some embodiments, the second hash code is generated in accordance with an SHA-256 algorithm. If the first hash code matches the second hash code, then electrical communications are enabled between the controller and the mouthpiece (step  928 ). The patient then inserts the mouthpiece into his/her mouth bringing the mouthpiece into contact with the patient&#39;s intraoral cavity (step  932 ). Electrical neurostimulation signals can then be delivered by the controller via the mouthpiece to the patient&#39;s intraoral cavity (step  936 ). 
         [0070]      FIG. 9B  shows another method of operation  939  of the non-invasive neurostimulation device as shown in  FIGS. 5-8  in accordance with an embodiment of the invention. Initially, a patient connects a mouthpiece to a controller or mobile device (step  940 ). The connection can be a wired or wireless connection. At the time of manufacture, a first hash code is generated based on a unique serial number and a secret key shared between the mouthpiece and the controller (step  944 ). The first hash code can be generated by an HMAC (keyed-hash message authentication code) algorithm. In some embodiments, the first hash code is generated in accordance with an SHA-256 algorithm. The first hash code and the unique serial number are stored in memory within the mouthpiece. The mouthpiece then transmits the first hash code and the unique serial number to the controller (step  948 ). The controller generates a second hash code based on the received unique serial number and the shared secret key (step  952 ). The second hash code can be generated by an HMAC (keyed-hash message authentication code) algorithm. In some embodiments, the second hash code is generated in accordance with an SHA-256 algorithm. The controller then compares the second hash code and the first hash code. The controller only permits continued electrical communications with the mouthpiece if the second hash code and the first hash code match (step  956 ). The patient then inserts the mouthpiece into his/her mouth bringing the mouthpiece into contact with the patient&#39;s intraoral cavity (step  960 ). Electrical neurostimulation signals can then be delivered by the controller via the mouthpiece to the patient&#39;s intraoral cavity (step  964 ). 
         [0071]    The terminology used herein is for the purpose of describing particular embodiments and is not intended to be limiting of the inventive concepts. It will be understood that, although the terms first, second, third etc. are used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another element, component, region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present application. 
         [0072]    While the present inventive concepts have been particularly shown and described above with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art, that various changes in form and detail can be made without departing from the spirit and scope of the present inventive concepts described and defined by the following claims.

Technology Category: a