Systems and methods for bimodal neuromodulation for tinnitus treatment

Abstract

In some aspects, a system for suppressing tinnitus perception of a subject is presented. The system includes an electrical stimulation module including one or more electrical stimulators that are configured to provide electrical stimulation to the subject by producing a series of electrical pulses with a pulse repetition frequency. Each electrical pulse has a pulse duration and current amplitude. The system further includes an acoustic stimulation module that is configured to provide an acoustic stimulation to the subject by producing a soundwave having a frequency range, an acoustic stimulation duration, and frequency-specific amplitudes.

Description

SYSTEMS AND METHODS FOR BIMODAL NEUROMODULATION FOR TINNITUS TREATMENTCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is based on, claims priority to, and incorporates herein by reference for all purposes, U.S. Provisional Patent Application No. 63 / 549,300 filed on February 2, 2024.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

[0002] N / ABACKGROUND

[0003] Tinnitus is a common health condition that bothers 10-25% of adults with and without hearing loss. It is characterized by the perception of phantom sound without external sound sources and is often described as ringing, buzzing, hissing, humming, roaring, etc. Individuals who experience chronic tinnitus are often distressed and suffer from a range of tinnitus-related psychological or physical concerns, such as degraded sleep quality and cognition, depression, anxiety, and hyper-vigilance. Treatments for suppressing tinnitus are still lacking and require further development to provide patients with relief.SUMMARY OF THE DISCLOSURE

[0004] The present disclosure addresses the aforementioned drawbacks by providing a system and method for tinnitus suppression. Bimodal stimulation, including electrical and acoustic stimulation, can be presented to cause neuromodulation that drives suppression of tinnitus. The bimodal stimulation can optionally be presented with additional auditory stimuli, such as calming music. The stimulation parameters can be tuned to specific patients for individualized care.

[0005] In some aspects, a system for suppressing tinnitus perception of a subject is presented. The system includes an electrical stimulation module including one or more electrical stimulators that are configured to provide electrical stimulation to the subject by producing a series of electrical pulses with a pulse repetition frequency. Each electrical pulse has a pulse duration and current amplitude. The system further includes an acoustic stimulation module that is configured to provide an acoustic stimulation to the subject by producing a soundwave having a frequency range, an acoustic stimulation duration, and frequency-specific amplitudes.

[0006] In some aspects, a method of suppressing tinnitus in a subject is presented.The method includes determining a first set of parameters for electrical stimulation. The first set of parameters includes an electrical pulse repetition frequency, a number of pulses, a pulse duration, and a current amplitude. The method further includes determining a second set of parameters for acoustic stimulation. The second set of parameters includes a frequency range, an acoustic wave duration, and frequencyspecific amplitudes. The method further includes using an electrical stimulation module to present electrical stimulation to the subject, which is characterized by the first set of parameters. The method also includes using an acoustic stimulation module to present acoustic stimulation to the subject, which is characterized by the second set of parameters.

[0007] These are but a few, non-limiting examples of aspects of the present disclosures. Other features, aspects and implementation details will be described hereinafter.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Various objects, features, and advantages of the disclosed subject mattercan be more fully appreciated with reference to the following detailed description of the disclosed subject matter when considered in connection with the following drawings, in which like reference numerals identify like elements.

[0009] FIG. 1 shows a schematic of an example system that can be used to provide bimodal stimulation to a patient.

[0010] FIG. 2 shows a flowchart setting for an example process that can be used to provide bimodal stimulation to a patient.

[0011] FIG. 3 shows a block diagram showing example parameters that may be tuned to provide bimodal stimulation to a patient.

[0012] FIG.4A shows a flowchart setting forth an example process that can be used to characterize an acoustic sensation level function for a patient.

[0013] FIG.4B shows a flowchart setting forth an example process that can be used to characterize a peak tinnitus frequency percept for a patient.

[0014] FIG.4C shows a flowchart setting forth an example process that can be used to characterize electrical stimulation perception for a patient.

[0015] FIG. 5 is a block diagram of an example stimulation system that can implement the methods of the present disclosure.

[0016] FIG. 6 is a block diagram of example components that can implement the system of FIG. 5.

[0017] FIG. 7A shows an example of paired stimulation that may be used in accordance with the present disclosure.

[0018] FIG. 7B shows an example notch that can be applied to the acoustic stimulation signal in accordance with the present disclosure.

[0019] FIG. 7C shows an example of an experimental stimulation session inaccordance with the present disclosure.

[0020] FIG. 7D shows an example of disked electrodes used experimentally in accordance with the present disclosure.

[0021] FIG. 8A shows example experimental audiograms measured without background noise for the left ear.

[0022] FIG. 8B shows example experimental audiograms measured without background noise for the right ear.

[0023] FIG. 8C shows example experimental audiograms measured with background noise for the left ear.

[0024] FIG. 8D shows example experimental audiograms measured with background noise for the right ear.

[0025] FIG. 9 shows an example experimental characterization of tinnitus for 8 participants measured with and without paired stimulation in accordance with the present disclosure.

[0026] FIG. 10 shows examples of reaction times measured for participants with and without paired stimulation in accordance with the present disclosure.

[0027] FIG. 11 shows example experimental results plotting late latency responses (LLR) and mismatch negativity (MMN) measured with and without paired stimulation in accordance with the present disclosure.

[0028] FIG. 12 shows an example of a paired stimulation pattern.

[0029] FIG. 13 shows examples of noise spectra used for paired stimulation in accordance with the present disclosure.

[0030] FIG. 14 shows example background noise patterns that can be used with paired stimulation in accordance with the present disclosure.

[0031] FIG. 15 shows example experimental results showing tinnitus perception after stimulation provided in accordance with the present disclosure.DETAILED DESCRIPTION

[0032] Before any aspects of the present disclosure are explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the following drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of “including,” “comprising,” or “having” and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. Unless specified or limited otherwise, the terms “mounted,” “connected,” “supported,” and “coupled” and variations thereof are used broadly and encompass both direct and indirect mountings, connections, supports, and couplings. Further, “connected” and “coupled” are not restricted to physical or mechanical connections or couplings.

[0033] The present disclosure provides systems and methods for presenting sound and electrical stimulation with tuned parameters of bimodal neuromodulation that drive suppression of tinnitus. In some implementations, suppression of tinnitus can include reducing the perceived volume or amplitude of tinnitus for a patient. In some implementations, suppression of tinnitus can include reducing the perception of tinnitus. In some implementations, suppression of tinnitus can include reducing the attention that a patient pays to their tinnitus (e.g., score of how often a patient notices their tinnitus) or the level of annoyance that tinnitus causes a subject (e.g., a score of how tinnitus impactsa patient’s daily life, a score of how bothersome a patient considers their tinnitus). In some implementations, suppression of tinnitus can include improved hearing function in a patient.

[0034] Electrical stimulation (e.g., of the cymba concha region of both ears) can be paired with customized sound stimulation. Advantageously, the acoustic stimuli can be tailored to each individual’s primary tinnitus for a precise range of spectral regions to desensitize the patient to tinnitus perception through paired stimulation. Optionally, a secondary acoustic element can be used to provide a soothing and relaxing sound environment during treatment sessions.

[0035] The stimulation can be presented using in-lab or clinical equipment. In some embodiments, the paired stimuli can be presented to the subject or patient using a so-called “take-home” device outside of the clinic. Such device may be portable and able to be brought to the subject’s home, work, or elsewhere. In some embodiments, the stimuli can be presented using a convenient wearable or portable device. For example, the stimulation parameters can be tuned in a lab or clinic and transferred to or communicated to the take-home or wearable device such that the subject can perform treatment sessions on their own.

[0036] The present disclosure also describes parameter sets that provide improved tinnitus relief. For example, a 25 Hz electrical pulse repetition frequency may be preferable for reducing the perception of tinnitus. The stimuli can be further paired with noise and music that excludes approximate frequencies based on the individual tinnitus percept of the patient.

[0037] In some implementations, the methods provided herein include tuning of the paired stimuli parameters for the specific user or a group of users. The presentedsystems can have preset stimulation parameters or a variety of preset parameter sets that can be selected by a user. In some implementations, the user can adjust the parameters to improve tinnitus relief or comfort during treatment. The methods can also include presenting the paired stimuli to the subject or patient for one or more treatment sessions.

[0038] In the examples provided below, 30-minute treatment sessions provided temporary alleviation or elimination of chronic tonal tinnitus after one or up to five stimulation sessions. Sessions can be repeated (e.g., at home in or a clinic), which may include adjusting the parameters between treatment sessions.

[0039] In some aspects, a system is presented for presenting paired stimulation, including a combination of acoustic and electrical stimulation. Such system can be non- invasive. The system may also be portable, allowing for convenient therapeutic tinnitus management.

[0040] FIG. 1 provides a schematic of an example system that can be used to present bimodal stimulation to a patient or subject. Such system may be used in a clinic, or healthcare setting. The system can also be portable such that it can be used outside of a clinic (e.g., in the home of a patient) or can be wearable. The system includes an electrical stimulation module 102 that can be used to present electrical stimulation to a patient. The electrical stimulation module 102 can include one or more electrical stimulators that produce electrical pulses. For example, the electrical stimulation module may include one or more electrodes that can be placed on the skin or body of the patient. In some embodiments, the electrical stimulators may be constant current stimulators.

[0041] The system can further include an acoustic stimulation module 104 that can be used to present acoustic stimulation to the patient 110. In some implementations, the acoustic stimulation module 104 can additionally be used to present backgroundnoise (e.g., music) to the patient 110. The acoustic stimulation module 104 may include headphones (e.g., in-ear headphones or earbuds, circumaural or over-the-ear headphones, supra-aural or on-ear headphones, in-ear monitors, wireless headphones, Bluetooth headphones, noise-cancelling headphones, bone conduction headphones, and so forth) or one or more external speakers, which may be placed near or in contact with the patient 110. In some implementations, the acoustic stimulation module 104 may include ear inserts. In this way, the acoustic stimulation module 104 can be used to produce one or more soundwaves that are presented to the subject.

[0042] The electrical stimulation module 102 and acoustic stimulation module 104 can be controlled by a processor 106. For example, the processor 106 can control or determine stimulation parameters and timing of the bimodal stimulation. The processor 106 may also record stimulation details or feedback from the electrical stimulation module 102, acoustic stimulation module 104, or user interface. In some implementations, the processor 106 can determine stimulation parameters based on input, feedback, or other information received from the user interface.

[0043] The system may also include a user interface 108. A patient or health care provider can use the user interface to control the system or otherwise input parameters or feedback to the system or processor 106. For example, the user interface 108 can be used to initiate a training session, input patient information (e.g., age, sex, tinnitus characterization, hearing level, presence of other medical conditions, and so forth). The user interface 108 may also be used to select stimulation parameters (e.g., durations, intensities, repetition rates, and so forth). The user interface 108 may also be used to provide feedback to the system. For example, a subject or user can indicate whether they can perceive the current stimulus (e.g., auditory or electrical), as will be described furtherbelow.

[0044] Referring to FIG. 2, a flowchart is provided, which sets forth the steps of an example process 200 that may be used to present bimodal stimulation to a subject or patient. The process includes selecting stimulation parameters as in process block 202. The stimulation parameters will be described in further detail below. The parameters may be pre-selected for all patients or selected on a group- or individual-level. For example, the stimulation parameters can be selected from a predetermined range of parameters. Such parameter selection may be determined based on the individual subject, based on some characteristic of the subject (e.g., hearing condition, tinnitus percept frequency, age, sex, hearing level, and so forth). Parameter selection can be determined based on effectiveness of prior treatments, patient comfort, or a combination thereof. In some aspects, selecting the stimuli parameters may include characterizing an acoustic sensation level, characterizing a peak tinnitus percept frequency, characterizing electrical stimulation perception, or a combination thereof. Such characterizations will be described in further detail below (e.g., with respect to FIGS. 4A-4C).

[0045] The treatment session is started, as indicated in process block 204. Upon starting treatment, background noise may optionally be presented to the patient.

[0046] During the treatment session, the bimodal stimulation can be applied for a stimulation duration as in process block 206. Bimodal stimulation includes a combination of electrical stimulation and acoustic stimulation. In some implementations, the electrical stimulation can be applied to a patient by placing electrodes onto the skin or body of the patient. For example, the electrodes may be placed on one or both ears of the subject (e.g., various locations on the ear, left ear, right ear, both ears, ear region, cymba or cavum concha region of ear, tragus, antitragus, triangular fossa, helix, lobe, superior crus ofantihelix, and so forth).

[0047] The electrical stimulation may be presented as a series of repeated electrical pulses. The electrical pulses maybe monophasic (positive or negative polarity) or biphasic pulses that is cathodic- or anodic-leading. The stimulation can include monopolar, bipolar, or multipolar electrical pulses. The pulses can be repeated with a constant or variable pulse repetition frequency for a given number of pulses or repetitions. In this way, the electrical stimulation can be presented over the course of an electrical stimulation duration.

[0048] The acoustic stimulation can be presented to the subject using one or more external speakers or headphones (e.g., in-ear headphones or earbuds, circumaural or over-the-ear headphones, supra-aural or on-ear headphones, in-ear monitors, wireless headphones, Bluetooth headphones, noise-noise cancelling headphones, bone conduction headphones, and so forth).

[0049] The acoustic stimulation may be presented by playing noise or a soundwave from the speakers or headphones. For example, the acoustic stimulation may include white noise, broadband noise, or Gaussian noise with a range of frequencies. The frequency range may be notched or have some other pattern. For example, the acoustic stimulation may use a notched frequency band in order to suppress sound frequencies near the patient’s tinnitus percept. The noise may be presented with a desired amplitude or intensity, which may have a temporal dependence (gradual increase or decrease in volume). The noise may have constant amplitude or have a frequency-specific amplitude (e.g., louder at lower frequencies, louder at higher frequencies). The acoustic stimulation may be presented for a given acoustic stimulation duration. The acoustic stimulation can be presented as a step function (e.g., instantaneously turned on and off) or may bepresented by gradually increasing / decreasing the intensity. In this way, the acoustic stimulation may also be characterized by a ramp pattern and duration that describes the increase or decrease in volume of the sound. However, other patterns may be used as well.

[0050] In some implementations, both the electrical and acoustic stimulation may be applied or presented for the whole stimulation duration. In other implementations, the electrical stimulation can be applied for the whole stimulation duration while the acoustic stimulation can be applied during a portion of the stimulation duration. In some implementations, the acoustic stimulation can be applied (e.g., as a continuous stimulus or as repeated bursts) for the whole stimulation duration, while the electrical stimulation can be applied for a portion of the stimulation duration.

[0051] Bimodal stimulation can be followed by a pause period, as in process block 208. Such pause period can provide a stimulation break for the subject. Such break periods can help to increase patient comfort and allow for repeated bimodal stimulation. The pause period can be characterized in part by a pause duration. In some implementations, background noise can be played during the pause period.

[0052] In some implementations, background noise can be presented to the subject for at least a portion of the treatment session, as indicated in process block 204. For example, background music can be presented over the whole treatment period, including during the pause periods. As another example, background music can be played continuously for a portion of the treatment session. The background noise may improve patient comfort and tolerance of the treatment. For example, the use of background noise can slightly or fully mask the participant’s perception of the repeated acoustic stimulus(e.g., reduce potentially annoying clicking sounds). Such background noise can includesoothing music (e.g., harp, piano, electric piano, string instruments, vocals, or others) or other soothing sounds (e.g., running water, birds chirping or singing, white noise, soothing tones, filtered noise, evening wind chimes, and so forth). The background music may be configured to include a range of frequencies that is determined based on the subject’s tinnitus percept. In this way, the background music may include sounds that are particularly soothing to the patient and avoid exacerbating their tinnitus. For example, the background music can have a notch range that aligns with the peak tinnitus percept frequency (e.g., one or half an octave below and above that peak tinnitus frequency) so as to cause that tinnitus percept to be suppressed from the treatment. A range around the peak tinnitus percept frequency can also be suppressed, with or without a ramp or other filter (e.g., step function, ramped function, Gaussian filter, and so forth). In other implementations, the music or other sounds can be designed to avoid the peak tinnitus percept frequency and surrounding frequencies. Such background noise can be played or presented using one or more external speakers, headphones, or instruments.

[0053] The background noise may be characterized by a frequency range, which may optionally be further described by a range of notched frequencies. It may also have a frequency pattern (e.g., melody). The background noise can also be presented with a temporally-constant amplitude or temporally-varying amplitude or volume. The amplitude of the background noise can also be constant over all frequencies or vary in a frequency-specific manner.

[0054] The bimodal stimulation is repeated with intermittent pause or break periods for the treatment duration, as indicated in process block 210. For example, a treatment session may last about 30 minutes long until it is ended, as in process block 212. Treatment sessions can be repeated as needed based on a recommendation by aclinician or as desired by the patient (e.g., several times a day, daily, weekly, monthly, when tinnitus perception returns, and so forth).

[0055] FIG. 3 summarizes exemplary parameters that can be used to characterize the bimodal stimulation. In general, such parameters can characterize the timing, patterns, frequencies, intensities, repetitions, and so forth of electrical stimulation, acoustic stimulation, background noise, pause periods, and treatment sessions. The list of parameters provided in FIG. 3 serves as an example and may not be exhaustive of all the parameters that may be used characterize the stimulation or treatment.

[0056] The electrical stimulation can be characterized by a current amplitude 312 that may be constant or vary over time (e.g., for each pulse). The current amplitude 312 can be determined based on a combination of considerations, such as safety levels, patient comfort levels, efficacy levels, and so forth. As a non-limiting example, the current amplitude 312 can be set between 500 microamps and 10 mA. In some implementations, the current amplitude 312 is determined as the minimum current that a patient perceives. In some implementations, the current amplitude 312 is determined as 110% minimum current that a patient perceives. In some implementations, the current amplitude 312 is determined as the maximum current that a patient considers comfortable or tolerable. In some implementations, the current amplitude 312 is determined as an amplitude between (e.g., midway) the lowest perceivable current level and highest tolerable current level. In some implementations, the current amplitude 312 may decrease, increase, or alternatingly increase and decrease over the course of the stimulation period or over the course of the treatment duration 330. For example, a patient may be able to turn down the current level if they find it uncomfortable partway through treatment.

[0057] The electrical stimulation can be further characterized by a pulse duration 316, pulse repetition frequency 314, and number of pulses 318. The pulse duration 316 can be described by the duration of a single pulse, which can be repeated with the pulse repetition frequency for a number of pulses 318 over the stimulation duration 320.

[0058] As a non-limiting example, the pulse duration can be defined in the range between 1 ps and 1 s pulses. In some implementations, the pulse duration can be defined between 1 ps - 500 ps , 1 ps - 25 ps, 5 ps - 200 ps, 25 ps - 50 ps, 50 ps - 75 ps, 50 ps - 150 ps, 75 ps - 125 ps, 95 ps - 105 ps, 99 ps - 101 ps, 100 ps - 150 ps, 150 ps - 200 ps, 200 ps - 300 ps, 300 ps - 500 ps, 500 ps - 1 ms, 1 ms - 10 ms, 1 ms - 100 ms, 1 ms - 500 ms, or 1 ms - 1 s. In a non-limiting example, the pulse duration may be set to 100 ps.

[0059] As a non-limiting example, the pulse repetition frequency may be set between 0.1 and 1000 Hz. For example, the pulse repetition frequency may be set within the range 0.1 Hz - 1 Hz, 1 Hz - 5 Hz, 1 Hz - 10 Hz, 1 Hz - 50 Hz, 1 Hz - 100 Hz, 1 Hz - 200 Hz, 1 Hz - 500 Hz, 10 Hz - 50 Hz, 20 Hz - 30 Hz, 50 Hz - 150 Hz, or 100 Hz - 500 Hz. As a non-limiting example, the pulse repetition frequency can be chosen from 5 Hz, 25 Hz, or 100 Hz.

[0060] The electrical pulses can be repeated between 1 - 500 times (e.g., 1 - 500 pulses. In some implementations, the number of pulses per stimulation period may be chosen as 1 - 10 pulses, 1 - 50 pulses, 1 - 100 pulses, 4 - 80 pulses, 75 - 125 pulses, 100 - 200 pulses, or 100 - 500 pulses. In some implementations, the number of pulses may be set and used to define an overall electrical stimulation duration 320. In some implementations, the stimulation duration may be set and used to determine a number of pulses that can be presented within the stimulation duration.

[0061] The electrical stimulation can have a stimulation duration 320 between 1ms and 10 s. Electrical stimulation duration 320 can refer to the duration that a series of electrical pulses is presented in a repeated way before a stimulation break or pause. In this way, a treatment session can include several stimulation periods, each having an electrical stimulation duration 320. In some implementations, the electrical stimulation duration 320 can be in a range of 1-100 ms, 1-500 ms, 50-500 ms, 80-810 ms, or 1 ms - 1 s.

[0062] As a non-limiting example, the electrical stimulation may have a pulse duration 316 of 100 ps with a repetition rate 314 of 5 Hz, 25 Hz, or 100 Hz and may be repeated for 4 - 80 pulses over the course of an electrical stimulation duration 320 of 80 - 810 ms.

[0063] The acoustic stimulation can be characterized by a frequency range 350 or frequency function. For example, the acoustic stimulation may include broadband noise within a defined frequency range 350. As non-limiting examples, the frequency range 350 may be defined generally as the standard audible frequency spectrum (e.g., 0 kHz - 20 kHz, or 20 Hz - 20 kHz) or as an audible frequency spectrum for a given individual (e.g., 20 Hz - 17 kHz). The frequency range 350 may further be defined by a so-called “notch range,” 354 which may refer to a range of frequencies that is suppressed or eliminated. As one non-limiting example, the notch range 354 may be determined for an individual subject. For example, the notch range 354 may be defined as a range of frequencies (e.g., 50% of the peak frequency to 150% of the peak frequency on a linear or octave scale) around the individual’s peak tinnitus percept frequency. In other implementations, the notch range 354 may be determined as a range of frequencies in which the average individual’s tinnitus percept falls (e.g., 3-8 kHz).

[0064] The acoustic stimulation can be further described by an amplitude pattern.In some implementations, the amplitude may be constant over the frequency range 350. In other implementations, the amplitude pattern may be described by frequency-specific amplitudes 352. For example, the amplitude of the signal maybe frequency-specific based on a patient’s frequency-specific hearing sensitivity. As a non-limiting example, the amplitude of each frequency may be determined as 20 dB sensation level (SL) compared to the minimum amplitude detectable by the patient. As another non-limiting example, the amplitude for the whole frequency range can be determined as 20 dB SL or 40 dB SL over the average minimum amplitude detectable by the patient over the audible range. For an individual patient or subject, dB SL refers to the number of decibels over the threshold hearing level for a given frequency. In this way, the acoustic stimulus can be individually tuned to each subject. The amplitude may also be described in dB sound pressure level (SPL) or dB hearing level (HL), which is measured in reference to an individual with normal hearing. For example, the amplitude at each frequency can be chosen as 20 dB HL at each frequency. In this way, the acoustic stimuli may not require tuning on a patient-specific level.

[0065] The amplitude pattern may also have temporal dependence. For example, the amplitude function may be a step function in which the acoustic stimulus is instantaneously turned on and off. In other implementations, the acoustic stimulus can be gradually presented and removed by using a ramped or other amplitude function over time. In this way, the acoustic stimulus may be further described by a ramp pattern 356 and ramp duration 358 or other characterization of the temporal dependence of the amplitude pattern.

[0066] The acoustic stimulus can be further described by an acoustic stimulation duration 360. The acoustic stimulation duration 360 can describe the total duration ofeach presented acoustic stimulus, which may include ramping and plateau periods. The acoustic stimulation duration 360 may be chosen between 1 ms - 10 seconds. As nonlimiting examples, the acoustic stimulation duration may be chosen in the range of 1-100 ms, 1-500 ms, 50-500 ms, 80-810 ms, or 1 ms - 1 s.

[0067] In some implementations, the acoustic stimulation duration 360 may be equal to the electrical stimulation duration 320. In some implementations, the acoustic stimulation duration 360 may be longer or shorter than the electrical stimulation duration 320. As a non-limiting example, electrical stimulation can be paired with the plateau region of the acoustic stimulation.

[0068] The stimulation duration can refer to the duration during which either electrical stimulation or acoustic stimulation or both are presented to the subject. Each treatment session can include a series of stimulation periods defined by stimulation durations and interleaved with pauses or breaks. Background noise can optionally be presented during the breaks or throughout the entire paired stimulation period. In some implementations the stimulation duration may refer to the longer of the electrical stimulation duration or the acoustic stimulation duration. In some implementations, the stimulation duration may be equal to both the electrical stimulation duration and the acoustic stimulation duration.

[0069] The pause period can be characterized in part by a pause duration 370. Such pause duration 370 may be referred to as an inter-burst interval. In some implementations, the inter-burst interval can refer to the whole burst duration (e.g., length of bimodal stimulation + pause period), which describes the frequency of stimulation periods.

[0070] The pause duration 370 may be defined between 0.5 s and 100 s. In someimplementations, the pause duration 370 may be 1-2 s, 1-5 s, 1-10 s, 1-100 s, 3 or 6 s, or 10-100 s. In some implementations the pause duration 370 may be variable over the course of treatment. For example, the pause duration may be randomly modified for each stimulation period by weighted random jitter. This jitter can be characterized by a jitter level 372. In some implementations, the pause duration 370 may be modified by randomly increasing or decreasing the pause duration by a fixed interval. In some implementations, the pause duration may be modified by a random amount within a minimum and maximum (e.g., pause duration ± 5%, pause duration ± 25%, and so forth). In this way, the acoustic stimulus may have a more randomized perception instead of having a constant on / off frequency throughout the course of treatment. As a non-limiting example, the pause duration may be set as 3 or 6 seconds with a 5% jitter.

[0071] The pause period can also be characterized by use of background noise. For example, soothing background music (e.g., harp music) can be presented to the patient during the pause period. The background noise can be characterized by a frequency range 380 and frequency pattern 384. For example, the frequency pattern may include soothing or calming melodies. Several examples of frequency spectra of various types of background noise (e.g., generative harps and string, generative electric piano, environmental birds, filtered noise and evening wind chimes) are presented in Example 3 below.

[0072] The frequency pattern may be further characterized by a notch range 382. In some implementations, the notch range 382 of the background music corresponds with the notch range 354 of the acoustic stimulus. For example, the frequency of the peak tinnitus percept may be eliminated or suppressed from the background noise. The frequency notch may also include a range of frequencies around the peak tinnitusfrequency. The background noise can also be described by an amplitude 386, which may be temporally or frequency dependent. For example, the background music can be presented gradually up to a peak amplitude. As a non-limiting example, the background sound may have frequency-specific peak amplitudes of 20 dB SL. As another non-limiting example, the background music may have an amplitude 10 dB below the frequencyspecific amplitudes of the acoustic stimulus. In some implementations, the background sound amplitude may be further adjusted based on the comfort of the patient. As another non-limiting example, the background noise may have an amplitude between 10 dB SL and 30 dB SL.

[0073] In some implementations, the background noise can be composed to avoid listening expectations while increasing relaxation responses. For example, the melody may be determined by setting a maximum probability of repeating notes to a desired threshold (e.g., 50%). Silences can be used to disrupt the regularity of the sounds. Various keys (e.g., B minor pentatonic) may be used, especially those that avoid dissonance. As one non-limiting example, the background noise can include whole notes for a 4 / 4 bar followed by silence for 3 bars, 1 bar, or % bar, which provides variation. Voices can be added to or used instead of instrumental sounds. The music pace can also be chosen to encourage a calm heart rate (e.g., 56 beats per minute). In some implementations, the background noise can be composed to mimic natural patterns of nature (e.g., wind, water).

[0074] The treatment can be further described by a treatment duration 330 and number of stimulation periods or repetitions 340. The treatment duration 330 may be 1 minute - 2 hours. In some implementations, the treatment duration 330 can be set in the range 1-10 minutes, 1-30 minutes, 1-45 minutes, 1-60 minutes, 10-20 minutes, 15-45minutes, 10 minutes - 1.5 hours, or 1 minute - 2 hours. The number of stimulation repetitions 340 can be determined as the number of stimulation repetitions 340 that can fit within the treatment duration 330. The number of stimulation repetitions 340 can be between 1 and 10000. In some implementations, the number of stimulation repetitions 340 can be defined in the range 1-500, 1-1000, 1-10000, 500-1000, or 1000-10000.

[0075] As a non-limiting example, the acoustic stimulus can be set to have a 250 ms duration. The acoustic stimulus can have a 240 ms plateau (e.g., peak amplitude of each frequency) with a 5 ms cosine increasing ramp and a 5 ms cosine decreasing ramp. The peak amplitude of each frequency can be chosen as 20 dB SL at each frequency for the given patient. Electrical stimulation can be presented with a duration of 240 ms during the plateau region of acoustic stimulation. Such electrical stimulation may include 6 repeated pulses of 100 ps pulse duration. This paired stimulation may be repeated every 3 seconds for a total of a 30-minute treatment session. Such treatment session may include 600 stimulation periods, which includes 3600 individual electrical pulses.

[0076] Referring now to FIGS. 4A-4C, example processes are presented that can be used to characterize a patient’s or subject’s perception of sound, tinnitus, or electrical stimulation. In this way, FIGS. 4A-4C provide example methods that can be used to generate a patient-specific audiogram. However, other methods for characterizing an audiogram for a patient or group of patients may also be used. Such characterization can be used to individually tune the stimulation system in a patient-specific manner. The feedback received in such processes can be input into the system using the user interface to tune various parameters of the bimodal stimulation, background noise, or treatment session.

[0077] FIG. 4A provides an example process 400 that can be used to characterizean acoustic sensation level function for a patient. In process block 402, an acoustic stimulus can be presented to a patient at a given frequency or range of frequencies and amplitudes. The subject or patient can provide feedback based on the presented acoustic stimulus, as in process block 404. For example, the feedback may include a binary indication of whether the subject could hear or perceive the stimulus. The feedback may also include a discrete response that indicates the level at which the subject perceives the stimulus (e.g., very quiet, quiet, moderate, loud, very loud). As shown in process block 406, the stimulus can be repeatedly presented to the subject while varying the amplitude or intensity. This repeated process can be performed to characterize a sensation level at the given frequency, as in process block 408. This process can be repeated for varying frequencies or ranges of frequencies, as in process block 410. Repeating the process for varying frequencies can allow the subject’s sensation level to be fully characterized as a function of frequency, which may be referred to as a sensation level function, as in process block 412. Such sensation level function can be used to determine the optimal sound intensity level as a function of frequency for a given subject.

[0078] FIG. 4B shows an example process 420 that can be used to characterize a peak tinnitus frequency, which may be referred to as a peak tinnitus percept or tinnitus percept. An acoustic stimulus can be presented to a subject at a given frequency or range of frequencies, as in process block 422. The subject can provide feedback to characterize the acoustic tone or frequency (or range of frequencies) with respect to their perception of tinnitus, as in process block 424. For example, the feedback may include a discrete characterization of the pitch with respect to their tinnitus perception (e.g., much higher than, slightly higher than, similar to, slightly lower than, or much lower than my typical tinnitus perception.) The feedback may also include a binary characterization of the pitch(e.g., matches or does not match my typical tinnitus perception). This process can be repeated for varying frequencies, as in process block 426, which may be informed by previous feedback from the patient (e.g., present a lower frequency if the previous frequency was characterized as much higher than the patient’s tinnitus perception). This process can be used to characterize a peak tinnitus perception or frequency of the individual subject in process block 428. Such peak tinnitus frequency may be characterized by a range of frequencies. The peak tinnitus frequency can be used to inform the notch frequency range of stimulation or background noise, as previously described.

[0079] FIG. 4C provides an example process 440 that can be used to characterize electrical stimulation perception of a subject or group of subjects. An electrical stimulus can be presented to a subject at a given current amplitude. For example, the current amplitude may be initially set very low where a typical person would not perceive the stimulus. The subject can provide feedback to characterize their perception of the stimulation in process block 444. For example, they can provide a binary indication of whether they can perceive the electrical stimulation or a discrete characterization of their perception (e.g., barely perceivable, slightly perceivable, moderately perceivable, annoying, uncomfortable, painful, intolerable). The stimulation level or current amplitude can be repeatedly adjusted, as in process block 446, in order to characterize the subject’s electrical stimulation perception, as in process block 448. Such characterization can be used to determine a proper electrical stimulation level for a subject that can be comfortably applied over the course of a treatment session (e.g., midway between barely perceivable and painful).

[0080] Referring now to FIG. 5, an example of a stimulation system 500 is shown,which may be used in accordance with some aspects of the systems and methods described in the present disclosure. As shown in FIG. 5, a computing device 550 can receive one or more types of data (e.g., user input, stimulation feedback data, stimulation records, stimulation parameter data) from data source 502. In some configurations, computing device 550 can execute at least a portion of a stimulation system 504 to determine and control stimulation parameters and timing. In some configurations, the stimulation system 504 can implement an automated pipeline to provide stimulation for tinnitus relief, treatment reports, treatment plans, etc.

[0081] Additionally or alternatively, in some configurations, the computing device 550 can communicate information about data received from the data source 502 to a server 552 over a communication network 554, which can execute at least a portion of the stimulation system 504. In such configurations, the server 552 can return information to the computing device 550 (and / or any other suitable computing device) indicative of an output of the stimulation system 504.

[0082] In some configurations, computing device 550 and / or server 552 can be any suitable computing device or combination of devices, such as a desktop computer, a laptop computer, a smartphone, a tablet computer, a wearable computer, a server computer, a virtual machine being executed by a physical computing device, and so on.

[0083] In some configurations, data source 502 can be any suitable source of data (e.g., stimulation feedback, treatment reports, treatment plans, stimulation parameter data, patient feedback data), such as a system, another computing device (e.g., a server storing patient data or stimulation parameter sets), and so on. In some configurations, data source 502 can be local to computing device 550. For example, data source 502 can be incorporated with computing device 550 (e.g., computing device 550 can beconfigured as part of a device for controlling stimulation or measuring, recording, estimating, acquiring, or otherwise collecting or storing data). As another example, data source 502 can be connected to computing device 550 by a cable, a direct wireless link, and so on. Additionally or alternatively, in some configurations, data source 502 can be located locally and / or remotely from computing device 550, and can communicate data to computing device 550 (and / or server 552) via a communication network (e.g., communication network 554).

[0084] In some configurations, communication network 554 can be any suitable communication network or combination of communication networks. For example, communication network 554 can include a Wi-Fi network (which can include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, WiMAX, etc.), other types of wireless network, a wired network, and so on. In some configurations, communication network 554 can be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of network, or any suitable combination of networks. Communications links shown in FIG. 5 can each be any suitable communications link or combination of communications links, such as wired links, fiber optic links, Wi-Fi links, Bluetooth links, cellular links, and so on.

[0085] Referring now to FIG. 6, an example of hardware 600 that can be used to implement data source 502, computing device 550, and server 552 in accordance with some configurations of the systems and methods described in the present disclosure is shown.

[0086] As shown in FIG. 6, in some configurations, computing device 550 can include a processor 602, a display 604, one or more inputs 606, one or more communication systems 608, and / or memory 610. In some configurations, processor 602 can be any suitable hardware processor or combination of processors, such as a central processing unit (“CPU”), a graphics processing unit (“GPU”), and so on. In some configurations, display 604 can include any suitable display devices, such as a liquid crystal display (“LCD”) screen, a light- emitting diode (“LED”) display, an organic LED (“OLED”) display, an electrophoretic display (e.g., an “e-ink” display), a computer monitor, a touchscreen, a television, and so on. In some configurations, inputs 606 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

[0087] In some configurations, communications systems 608 can include any suitable hardware, firmware, and / or software for communicating information over communication network 554 and / or any other suitable communication networks. For example, communications systems 608 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 608 can include hardware, firmware, and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0088] In some configurations, memory 610 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 602 to present content using display 604, to communicate with server 552 via communications system(s) 608, and so on. Memory610 can include any suitable volatile memory, non-volatile memory, storage, or anysuitable combination thereof. For example, memory 610 can include random-access memory (“RAM”), read-only memory (“ROM”), electrically programmable ROM (“EPROM”), electrically erasable ROM (“EEPROM”), other forms of volatile memory, other forms of non-volatile memory, one or more forms of semi-volatile memory, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some configurations, memory 610 can have encoded thereon, or otherwise stored therein, a computer program for controlling operation of computing device 550. In such configurations, processor 602 can execute at least a portion of the computer program to present content (e.g., user feedback, stimulation parameters, user interfaces, graphics, tables), receive content from server 552, transmit information to server 552, and so on. For example, the processor 602 and the memory 610 can be configured to perform the methods described herein.

[0089] In some configurations, server 552 can include a processor 612, a display 614, one or more inputs 616, one or more communications systems 618, and / or memory 620. In some configurations, processor 612 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some configurations, display 614 can include any suitable display devices, such as an LCD screen, LED display, OLED display, electrophoretic display, a computer monitor, a touchscreen, a television, and so on. In some configurations, inputs 616 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

[0090] In some configurations, communications systems 618 can include any suitable hardware, firmware, and / or software for communicating information over communication network 554 and / or any other suitable communication networks. Forexample, communications systems 618 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 618 can include hardware, firmware, and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0091] In some configurations, memory 620 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 612 to present content using display 614, to communicate with one or more computing devices 550, and so on. Memory 620 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 620 can include RAM, ROM, EPROM, EEPROM, other types of volatile memory, other types of non-volatile memory, one or more types of semi-volatile memory, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some configurations, memory 620 can have encoded thereon a server program for controlling operation of server 552. In such configurations, processor 612 can execute at least a portion of the server program to transmit information and / or content (e.g., data, images, a user interface) to one or more computing devices 550, receive information and / or content from one or more computing devices 550, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone), and so on.

[0092] In some configurations, the server 552 is configured to perform the methods described in the present disclosure. For example, the processor 612 and memory 620 can be configured to perform the methods described herein.

[0093] In some configurations, data source 502 can include a processor 622, one or more data acquisition systems 624, one or more communications systems 626, and / or memory 628. In some configurations, processor 622 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some configurations, the one or more data acquisition systems 624 are generally configured to acquire data, user feedback, treatment history data, or a combination thereof, and can include a stimulation system. Additionally or alternatively, in some configurations, the one or more data acquisition systems 624 can include any suitable hardware, firmware, and / or software for coupling to and / or controlling operations of a stimulation system. In some configurations, one or more portions of the data acquisition system(s) 624 can be removable and / or replaceable.

[0094] Note that, although not shown, data source 502 can include any suitable inputs and / or outputs. For example, data source 502 can include input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, a trackpad, a trackball, and so on. As another example, data source 502 can include any suitable display devices, such as an LCD screen, an LED display, an OLED display, an electrophoretic display, a computer monitor, a touchscreen, a television, etc., one or more speakers, and so on.

[0095] In some configurations, communications systems 626 can include any suitable hardware, firmware, and / or software for communicating information to computing device 550 (and, in some configurations, over communication network 554 and / or any other suitable communication networks). For example, communications systems 626 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 626can include hardware, firmware, and / or software that can be used to establish a wired connection using any suitable port and / or communication standard (e.g., VGA, DV1 video, USB, RS-232, etc.), Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0096] In some configurations, memory 628 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 622 to control the one or more data acquisition systems 624, and / or receive data from the one or more data acquisition systems 624; to generate a treatment plan from data; present content (e.g., data, images, a user interface) using a display; communicate with one or more computing devices 550; and so on. Memory 628 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 628 can include RAM, ROM, EPROM, EEPROM, other types of volatile memory, other types of non-volatile memory, one or more types of semi-volatile memory, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some configurations, memory 628 can have encoded thereon, or otherwise stored therein, a program for controlling operation of a stimulation data source 502. In such configurations, processor 622 can execute at least a portion of the program to control stimulation, generate a treatment plan, determine stimulation parameters, transmit information and / or content (e.g., data, stimulation history, images, a user interface) to one or more computing devices 550, receive information and / or content from one or more computing devices 550, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone, etc.), and so on.

[0097] In some configurations, any suitable computer-readable media can be usedfor storing instructions for performing the functions and / or processes described herein. For example, in some configurations, computer-readable media can be transitory or non- transitory. For example, non-transitory computer-readable media can include media such as magnetic media (e.g., hard disks, floppy disks), optical media (e.g., compact discs, digital video discs, Blu-ray discs), semiconductor media (e.g., RAM, flash memory, EPROM, EEPROM), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and / or any suitable tangible media. As another example, transitory computer-readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and / or any suitable intangible media.

[0098] Examples

[0099] The following examples provide several parameter sets that can be used for the paired stimuli. The parameters listed throughout the present disclosure provide example parameter sets. Other parameters may be used depending on the patient, type or frequency of tinnitus, and so forth. The location of electrical stimulation can also be adjusted (e.g., various locations on the ear, one ear, both ears, cymba or cavum concha region of ear, tragus, antitragus, triangular fossa, helix, lobe, superior crus of antihelix, and so forth).

[0100] Example 1

[0101] Background

[0102] Bimodal stimulation drives plasticity in the auditory pathway, such as the auditory brainstem, midbrain, or cortex that can be adapted for rehabilitative purposes. One example is the application of paired auditory and somatosensory or autonomic stimulation in alleviating tinnitus. The core of such rehabilitative effects is the alteredneural encoding of sounds, resulting from repeated presentation with paired electrical stimulation of the somatosensory or autonomic nervous system. A great challenge in the field is to translate the observed neural effects in animals to behavioral benefits in humans. Therefore, systematic investigations of stimulation paradigms in humans are needed. A bimodal stimulation paradigm is presented herein, which delivers paired auditory and electrical stimulation on the external ear to affect hearing sensitivity and tinnitus perception.

[0103] Methods

[0104] Participants with various hearing statuses were recruited into the study, with and without tinnitus. Sixteen tinnitus participants have completed the study. All participants were given approximately 30 minutes of paired stimulation (PS) on five or seven separate visits. Each PS trial consisted of a 25-Hz burst of 6 electrical pulses delivered to the left cymba concha (using a return electrode on the ear lobe) and a target 250-ms or 420-ms bilateral auditory stimulus (notched Gaussian noise that is symmetric and centered around the most dominant tinnitus pitch of each participant, about 1 / 3- to 1-octave wide, approximately at 40 dB SL relative to their pure tone audiogram at 0.25 to 2 kHz. Four of the 16 participants were also presented with a soothing background music at 20 dB SL relative to their pure tone audiogram at 0.25 to 2 kHz. The background music contained an identical spectral notch as in the noise. A total of 600 PS trials ( s burst / s) were delivered during a PS session (lasting about 30 minutes). A calming background sound of string instruments was consistently presented during the PS sessions for half of the participants. Individual perceptual thresholds of electrical stimulation were obtained before every PS session. The electrical pulses were delivered at a level rated as medium intense on a scale of 0 (not detectable) to 10 (extremely intense). To assess possiblebehavioral and electrophysiological changes, a test battery of audiograms, questionnaires, auditory brainstem responses, and the cortical auditory evoked potentials was used before and after all the PS sessions. For tinnitus participants, tinnitus loudness and frequency were evaluated with custom tests to help determine the location of the tinnitus notch in the white noise stimulus.

[0105] Results

[0106] The current paired stimulation paradigm has shown tinnitus suppression or alteration in 62.5% of study participants (10 of 16 participants) after 1-3 visits or by the last visit. Results are promising, considering such short-term stimulation. Repeating stimulation for weeks to months can lead to even greater success. The duration of the suppressive effects varied drastically from minutes to hours or even days. Further data collection and analysis can be used to reveal changes in the electrophysiological responses.

[0107] Conclusions

[0108] Results show that the paired auditory and electrical stimulation on the ears can reduce tinnitus. Treatment can be varied or tuned to induce greater plasticity that can be reflected in fundamental hearing capabilities. The effective stimulation paradigm described herein can lead to new techniques for improving hearing health, including tinnitus and hearing restoration or enhancement.

[0109] Example 2

[0110] Introduction

[0111] Bimodal stimulation can drive neural plasticity across the auditory pathway that can be leveraged for rehabilitative purposes. One example is the application of paired sound and somatosensory or autonomic stimulation in alleviating tinnitus.Some studies in animals and humans have demonstrated that electrical stimulation of certain body regions or nerves (e.g., the surface of the tongue or neck, or trigeminal or vagus nerve) paired with sound stimulation can reduce tinnitus symptoms. Yet, there is still a need for more human data on the ability to alter hearing sensitivity or tinnitus perception through paired stimulation (PS) involving electrical stimulation of the ear. Here, we developed a bimodal stimulation paradigm that delivered paired sound and electrical stimulation on the cymba concha and investigated the effects of this paradigm on hearing sensitivity and tinnitus perception using psychoacoustical and EEG measures.

[0112] Methods

[0113] Participants included eights tinnitus patients (age = 61.6 ± 3.5 yrs, 4F, 4M) with various degrees of hearing loss. Participants provided initial self-reported hearing and tinnitus status (M ± ISE): HH1A-S = 10 ± 2.5, SSQ-12 = 89 ± 9.3, TH1 = 19 ± 5.8, TF1 = 31 ± 6.0.

[0114] The paired stimulation stimuli include bursts of notched Gaussian noise paired with six 100 s electrical pulses (rate = 25 Hz, positive polarity), as shown in FIG. 7A. The notch was symmetric and centered around the most dominant tinnitus pitch of each participant, about 1-oct wide, as shown in FIG. 7B. Participants received a 30-min PS session every other day, for a total of 5 sessions (600 bursts of PS per session), as shown in FIG. 7C. Disked electrodes were placed on the cymba concha and ear lobe, as shown in FIG. 7D.

[0115] Notched noise was presented binaurally at 40 dB SL re: PTA@0.25-2k. Half of the participants were also presented with a soothing background music at 20 dB SL re: PTA@o.25-2k. The background music contained an identical spectral notch as in the noise. Intensity of electrical stimulation was determined at each session for each individual.Participants rated the intensity and comfort level of a range of levels (from sub- to suprathreshold) in ascending order for two rounds. The final level used was rated medium intense (mean rating = 4.5, with 0-cannot feel, 10-too intense) and comfortable (mean rating = 3.5, with 0-very comfortable, 10-very uncomfortable) on an adapted rating scale.

[0116] Outcome measures included psychoacoustical measures including Bekesy audiometry, as shown in FIGS. 8A-8D; tinnitus loudness and pitch matching, as shown in FIG.9; and choice response time to tones with paired or non-paired frequencies, as shown in FIG. 10. Outcome measures also included EEG measures including click ABR, tone- evoked late latency responses (LLR), and mismatch negativity (MMN) with an oddball task. Questionnaires including HH1A-S, SSQ-12, TH1, and TF1. All outcome measures were performed before the first PS session and after the last PS session. VAS-tinnitus annoyance and VAS-tinnitus loudness were measured for every session.

[0117] Results

[0118] FIGS. 8A-8D provide audiograms measured using automated Bekesy audiometry procedure. FIGS. 8A-8B show results without background music (noBG) for the left (FIG. 8A) and right (FIG. 8B) ear, while FIGS. 8C-8D show results with background music (BG) for the left (FIG. 8C) and right (FIG. 8D) ear. Hearing sensitivity does not seem to change before and after 5 PS sessions in both groups.

[0119] FIG. 9 shows tinnitus characterization, including loudness and pitch matching for individual participants. Each panel shows rated tinnitus spectra before (solid line) and after (dashed line) PS sessions. The filled circles represent the matched tinnitus levels. Frequency regions used in PS stimuli are marked. Participants BG01-03 and NoBG02-04 reported noticeably reduced tinnitus loudness after 1-3 PS sessions (75% of all participants), three of which were captured by the loudness matching test,including NoBG03 and BG02-03.

[0120] FIG. 10 provides choice reaction time for 4 participants. The left side of each pair provides reaction times on day 1, while the right side shows reaction times on day 5. The response speed to the paired frequency improves after PS (bottom panel) compared to without PS (top panel). The task was to respond to two odd-ball tones at nonpaired and paired frequencies (both odd rates = 0.2). Standard stimulus was a narrowband noise centered at 1kHz. LLR was simultaneously measured during this task. All stimuli were loudness matched to the 10 dB SL with 1 kHz standard noise.

[0121] LLR and MMN are reported in FIG. 11. Tone-evoked N1-P2 components were assessed when participants passively listening to non-paired and paired frequencies. No noticeable difference was found between test frequencies or in before- after comparisons (n=3). In a different condition, MMN was measured while participants performing the RT odd-ball task, as shown in FIG. 6 for n=5. Although loudness levels were matched, a relatively larger P3 component was seen in the LLR to the paired frequency (FIG. 11, middle left) than to the non-paired frequency. MMN to deviants at non-paired and paired frequencies didn’t seem to differ based on visual inspection.

[0122] Discussion

[0123] The current paired stimulation paradigm has shown encouraging results in terms of tinnitus suppression or alteration. 75% of study participants reported a temporary reduction or even elimination of their tinnitus sensation after 1-3 visits. The duration of the suppressive effects varied drastically from minutes to hours. The tool may be refined by determining parameters and parameter ranges essential to somatosensory sensation (e.g., electrical stimulation on any body location). A few factors that did not seem to influence the therapeutic effect are notched background music, degree of hearingloss, and type of tinnitus (tonal or pitched hissing)

[0124] Example 3

[0125] Methods

[0126] Electrical stimulus was provided using DS7A High Voltage ConstantCurrent Stimulators available from Digitimer Ltd., Welwyn Garden City, UK, paired EMG disk electrodes available from MFI Medical, CA, US, and RME FireFace UCX as the master triggering device.

[0127] The paired stimulation included electrical and acoustic stimuli. The electrical stimulus included 100 ps positive monopolar electrical pulses, delivered at a range of stimulation rates (e.g., 5, 25, 100 Hz). Each paired stimulation burst contains 4- 80 pulses for a total duration of 80-810 ms. The inter-burst interval was set to either 3 or 6 s with and without a 5% jitter. Current amplitude was determined by individual perceptual ratings of the electrical stimulation that is measured separately. Ratings of intensity and comfortability were used to determine a level that the participant can feel for the duration of the paired stimulation. The level was set between the individual’s just noticeable and maximal acceptable levels. An example of the electrical stimulus is shown with an example acoustic stimulus in FIG. 12.

[0128] The acoustic stimulus was provided using Sennheiser HD 650 circumaural headphones. The major acoustic component is made of a notched broadband noise. The notch is placed where a participant’s tinnitus frequency is, as shown in FIG. 13 on the left. The low frequency cutoff was set as Peak Tinnitus Freq x 0.5. The high frequency cutoff was set as Peak Tinnitus Freq x 1.5. Soothing background music (notched in the same frequency region) is added as an optional and secondary acoustic component, as shown in FIG. 13 on the right.

[0129] Acoustic stimulus lasts the entire duration of the paired stimuli burst with onset and offset ramps. Intensity level is determined by a participant’s audibility in that frequency range. The level is 20 dB SL at the relevant frequencies present in the stimulus, which is measured separately. The background music is played at 20 dB SL, 10 dB below the paired stimulus, or adjusted based on comfortability of the sound.

[0130] For the 25 Hz stimulation condition, the paired stimulus included a 250 ms paired stimulus with 5 ms cosine ramps (240 ms plateau). Background sound is 2750 ms with 25 ms cosine ramps played between the paired stimuli. Electrical Stimulation occurs when the paired stimulus reaches its plateau and is on for 240 ms, where 6 pulses (100 ps pulse width) are delivered per paired stimulus. Paired stimulation occurs once every 3 seconds for a total of 30 minutes, including 600 paired stimuli and 3600 individual electrical pulses delivered.

[0131] Each participant competes at least 5 study visits in which a 30-minute paired stimulation session is conducted, including electrical pulses and sounds delivered to the participant.

[0132] To produce background noise, we set to avoid listening expectations while maintaining a spacious minimal approach in order not to add more sonic inputthan what felt necessary. In terms of melody we set up a system so the highest probability of repeating notes was 50 percent. This approach ideally offsets expectation and enhances relaxation responses. With silences as well we wanted to disrupt the regularity of the material. We chose melodic source material of B minor pentatonic which makes it easy to layer and avoids what most people consider or experience as dissonance. Underlying tempo is set to 56 BPM to encourage calm heart rate. Additionally we attempted to mimic natural patterns of nature (wind and water) where possible or relevant.

[0133] Example background noise tracks are shown in FIG. 14. In the Generative Electric Piano track (FIG. 14 top left) each note is set to be a whole note (4 / 4 bar) and silences are set to be 3 bars, 1 bar or % bar to provide variation and offset grid between the two generated voices. The peak frequency is 247 Hz, and most energy falls below 1 kHz. In the Strings and Harp track (FIG. 14 top right) there are two pairs of voices. The peak frequency is 370 Hz, and most energy falls below 3 kHz. In the Environmental Birds track (FIG. 14 bottom left) the peak frequency is 4.2 kHz, and most energy falls below 8 kHz. In the filtered noise and evening wind chimes track (FIG. 14 bottom right) the peak frequency is 120 Hz, and most energy falls below 2 kHz.

[0134] FIG. 15 shows results reported for three participants (A, B, and C) that received stimulation with a 25 Hz electrical pulse rate and two participants (D and E) that received stimulation with a 100 Hz electrical pulse rate. In each case, the bar on the left represents the response recorded on day 1, and the bar on the right represents the response recorded on day 5. Participant A noted, “My tinnitus was relieved, and I can hear more layers of sounds now!” Participant B reported, “My tinnitus stopped right after the last session! I wish I could be in the study longer!” Participant C said, “My tinnitus was much softer and almost disappeared. The whole study was so pleasant and soothing.” Participant D and E noted that they did not notice changes.

[0135] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms "component," "system," "module," "controller," "framework," and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, anobject, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).

[0136] In some implementations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as embodiments of the disclosure, of the utilized features and implemented capabilities of such device or system.

[0137] As used herein, the phrase "at least one of A, B, and C" means at least one of A, at least one of B, and / or at least one of C, or any one of A, B, or C or combination of A, B, or C. A, B, and C are elements of a list, and A, B, and C may be anything contained in the Specification.

[0138] The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of theinvention.

Claims

CLAIMSWhat is claimed is:

1. A system for suppressing or reducing tinnitus perception or bothersome level of tinnitus of a subject, the system comprising: an electrical stimulation module comprising one or more electrical stimulators configured to provide electrical stimulation to the subject by producing a series of electrical pulses with an electrical pulse repetition frequency, each electrical pulse having a pulse duration and current amplitude; and an acoustic stimulation module configured to provide an acoustic stimulation to the subject by producing a soundwave having a frequency range, an acoustic stimulation duration, and frequency-specific amplitudes.

2. The system of claim 1, wherein the pulse duration is between 5 ps to 200 pS.

3. The system of claim 1, wherein the electrical pulses comprise positive monopolar electrical pulses.

4. The system of claim 1, wherein the electrical pulse repetition frequency is between 1 Hz and 200 Hz.

5. The system of claim 1, wherein the electrical pulse repetition frequency is 25 Hz.

6. The system of claim 1, wherein the series of electrical pulses comprises between 2 and 100 electrical pulses.

7. The system of claim 1, wherein the one or more electrical stimulators comprise constant current stimulators.

8. The system of claim 1, wherein the acoustic stimulation module comprises headphones or ear inserts.

9. The system of claim 1, wherein the soundwave comprises broadband noise.

10. The system of claim 1, wherein the frequency range is notched at a notch range aligned to a peak tinnitus frequency or peak range of tinnitus frequencies of the subject.

11. The system of claim 10, wherein the notch range is defined based on a peak tinnitus frequency of the subject, the notch range having a lower limit of 50% of the peak tinnitus frequency of the subject and an upper limit of 150% of the peak tinnitus frequency of the subject on an octave scale.

12. The system of claim 10, wherein the notch range is defined based on a notched Gaussian noise provide that is symmetric and centered around the most dominant tinnitus pitch of the subject, wherein the notch range is between one-third to one octave in width at 40 dB SL relative to the pure tone audiogram for the subject in a range of 0.25 kHz to 2 kHz.

13. The system of claim 1, wherein the frequency range has a lower limit of 0 kHz and an upper limit of 20 kHz.

14. The system of claim 1, wherein the frequency-specific amplitudes are set as 20 dB-SL or 40 dB-SL relative to an average pure tone audiogram from 0.25 to 2 kHz range.

15. The system of claim 1, wherein the system is portable and configured to be used outside of a clinic.

16. The system of claim 1, wherein the acoustic stimulation module is further configured to present background noise comprising a notched range of frequencies.

17. The system of claim 16, wherein the background noise is presented with an amplitude between 10 dB SL and 30 dB SL relative to different frequency ranges of a pure tone audiogram.

18. The system of claim 16, wherein the background noise is presented with an amplitude of 10 dB SL below the frequency-specific amplitudes of the acoustic stimulation.

19. A method of suppressing tinnitus perception in a subject, the method comprising: determining a first set of parameters for electrical stimulation, the first set of parameters comprising an electrical pulse repetition frequency, a number of pulses, a pulse duration, and a current amplitude; determining a second set of parameters for acoustic stimulation, the second set of parameters comprising a frequency range, an acoustic wave duration, and frequencyspecific amplitudes; using an electrical stimulation module to present electrical stimulation to the subject, the electrical stimulation being characterized by the first set of parameters; and using an acoustic stimulation module to present acoustic stimulation to the subject, the acoustic stimulation being characterized by the second set of parameters.

20. The method of claim 19, wherein the electrical stimulation module comprises one or more electrical stimulators, and wherein presenting electrical stimulation comprises placing the one or more electrical stimulators on one or more of a left ear, a right ear, a left ear region, or a right ear region of the subject.

21. The method of claim 19, wherein the electrical stimulation and acoustic stimulation are presented for a duration between 1 ms and 1 second and the electricalstimulation and acoustic stimulation are repeated after a pause period, the pause period having a pause duration being between 1 second and 10 seconds.

22. The method of claim 19, wherein the current amplitude is determined as a current amplitude at least perceivable by the subject and no greater than a maximum current amplitude tolerated by the subject.

23. The method of claim 19, wherein the pulse duration is 5 to 200 ps.

24. The method of claim 19, wherein the electrical pulses comprises positive monopolar electrical pulses.

25. The method of claim 19, wherein the electrical pulse repetition frequency is between 1 and 200 Hz.

26. The method of claim 19, wherein the number of pulses is between 2 and 100 pulses.

27. The method of claim 19, wherein the one or more electrical stimulators comprise constant current stimulators.

28. The method of claim 19, wherein the acoustic stimulation module comprises headphones or ear inserts.

29. The method of claim 19, wherein the frequency range comprises broadband noise.

30. The method of claim 19, wherein the frequency range is notched at a notch range aligned to a peak tinnitus frequency or peak range of tinnitus frequencies of the subject.

31. The method of claim 30, wherein the notch range is defined based on a peak tinnitus frequency of the subject, the notch range having a lower limit of 50% of the peak tinnitus frequency of the subject and an upper limit of 150% of the peak tinnitus frequency of the subject on an octave scale.

32. The method of claim 30, wherein the notch range is defined based on a notched Gaussian noise provide that is symmetric and centered around the most dominant tinnitus pitch of the subject, wherein the notch range is between one-third to one octave in width at 40 dB SL relative to the pure tone audiogram for the subject in a range of 0.25 kHz to 2 kHz.

33. The method of claim 19, wherein frequency range has a lower limit of 0 kHz and an upper limit of 20 kHz.

34. The method of claim 19, wherein the frequency-specific amplitudes are set as 20 dB-SL or 40 dB-SL relative to an average pure tone audiogram from 0.25 to 2 kHz range.

35. The method of claim 19, further comprising using the acoustic stimulation module to present background noise comprising a notched range of frequencies.

36. The method of claim 35, wherein the background noise is presented with an amplitude between 10 dB SL and 30 dB SL relative to different frequency ranges of a pure tone audiogram.

37. The method of claim 35, wherein the background noise is presented with an amplitude of 10 dB SL below the frequency-specific amplitudes of the acoustic stimulation.

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