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Tinnitus affects 10-15% of adults and is frequently associated with impaired quality of life, anxiety, and sleep disturbance. Conventional sound therapies based on continuous masking provide inconsistent and short-lived relief, and the neural mechanisms underlying residual inhibition (RI) remain unclear.
This study aims to determine whether 40 Hz burst stimulation with high-frequency carriers can achieve longer-lasting RI than continuous sound, and to explore its underlying neural mechanisms using EEG.
Residual inhibition (RI) refers to the temporary reduction or disappearance of tinnitus following sound stimulation and provides an important clue for identifying patients who may benefit from acoustic therapy. However, the effects of different sound stimulation strategies on RI remain poorly understood.
This study evaluates whether 40 Hz burst-modulated sound achieves stronger and longer RI compared with conventional continuous stimulation. The trial follows a four-phase design:
Phase 1: Exploratory testing of burst versus continuous tones at different frequencies.
Phase 2: Large-scale validation in 265 patients. Phase 3: Development of a personalized stimulation protocol using adaptive spectral optimization.
Phase 4: EEG investigation of neural mechanisms, focusing on gamma oscillations and functional connectivity changes.
The primary outcomes are the strength and duration of tinnitus suppression. Secondary outcomes include EEG markers such as γ-band power spectral density and phase-locking value.
By combining behavioral and neurophysiological measures, this study aims to establish 40 Hz burst stimulation as a novel rhythm-based sound therapy and to provide mechanistic insights that may enable more effective, personalized tinnitus management.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Personalized 40 Hz Broadband Stimulation | Experimental | Participants receive personalized broadband acoustic stimulation modulated at 40 Hz. An adaptive equalization algorithm, based on individual and population residual inhibition (RI) responses, is used to weight frequency components across 125 Hz-12 kHz. |
|
| 40 Hz Pure Tone Stimulation | Experimental | Participants receive pure tone stimulation at the individually optimized carrier frequency identified in earlier phases, amplitude-modulated at 40 Hz. |
|
| Continuous Broadband Noise | Active Comparator | Participants receive continuous broadband noise stimulation without 40 Hz modulation. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Personalized 40 Hz Broadband Stimulation | Other | Broadband acoustic stimulus (125 Hz-12 kHz) amplitude-modulated at 40 Hz with a 50% duty cycle. A polynomial regression and FFT-based algorithm applies individualized frequency weighting, combining population data (70%) and patient-specific responses (30%). Delivered for 60 seconds at 10 dB above the individual minimum masking level (MML). |
| Measure | Description | Time Frame |
|---|---|---|
| Tinnitus suppression strength | Residual inhibition depth, 0-100% reduction | Immediately after the sound stimulation session. |
| Residual inhibition duration | Time in seconds until tinnitus returns to baseline after stimulation | Immediately after the sound stimulation session. |
| Measure | Description | Time Frame |
|---|---|---|
| EEG spectral power changes | measured across the entire 10-minute EEG recording session (baseline, during stimulation, and post-stimulation) | |
| EEG functional connectivity changes | measured across the entire 10-minute EEG recording session (baseline, during stimulation, and post-stimulation) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Huawei Li, PhD | Eye and ENT Hospital of Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Eye & ENT Hospital of Fudan University | Shanghai | Shanghai Municipality | 200031 | China |
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| ID | Term |
|---|---|
| D014012 | Tinnitus |
| ID | Term |
|---|---|
| D006311 | Hearing Disorders |
| D004427 | Ear Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| D012678 | Sensation Disorders |
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|
| 40 Hz Pure Tone Stimulation | Other | Pure tone stimulus at the optimized frequency (matched to tinnitus characteristics or high-frequency carrier), amplitude-modulated at 40 Hz with a 50% duty cycle. Delivered for 60 seconds at 10 dB above MML. |
|
| Continuous Broadband Noise | Other | Continuous broadband noise spanning 125 Hz-12 kHz without 40 Hz modulation. Delivered for 60 seconds at 10 dB above MML as an active control condition. |
|
| D009461 |
| Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |