Residual Inhibition of 40 Hz Burst Sound in Tinnitus Patients

Neural and Clinical Effects of 40 Hz Burst Stimulation in Tinnitus: a Four-phase Self-controlled Study

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.

Study Overview

• Status: Completed
• Conditions: Tinnitus
• Intervention / Treatment: Other: Personalized 40 Hz Broadband Stimulation; Other: 40 Hz Pure Tone Stimulation; Other: Continuous Broadband Noise

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200031
      • Eye & ENT Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosed with subjective tinnitus;
2. Chronic tinnitus: tinnitus course ≥ 1 month;
3. Normal middle ear function;
4. The average hearing threshold (defined as mean of 0.5, 1, 2, and 4 kHz) of the unaffected ear < 60 dB;
5. Tinnitus can be heard under normal circumstances.
6. Subjects are able to understand the purpose of the study, volunteer to participate and cooperate with the instructors to complete the experiment, and be willing to sign the informed consent.

Exclusion Criteria:

1. Acute phase tinnitus;
2. Fluctuating tinnitus loudness;
3. Severe psychiatric disorders;
4. Inability to complete tinnitus testing;
5. Fluctuating or retrocochlear hearing loss;
6. Conductive hearing loss;
7. Currently participating in other research projects that may affect tinnitus;
8. Subjects who are not considered suitable for this clinical trial by the researchers.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized 40 Hz Broadband Stimulation; 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.	Other: Personalized 40 Hz Broadband Stimulation; 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).
Experimental: 40 Hz Pure Tone Stimulation; Participants receive pure tone stimulation at the individually optimized carrier frequency identified in earlier phases, amplitude-modulated at 40 Hz.	Other: 40 Hz Pure Tone Stimulation; 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.
Active Comparator: Continuous Broadband Noise; Participants receive continuous broadband noise stimulation without 40 Hz modulation.	Other: Continuous Broadband Noise; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Eye & ENT Hospital of Fudan University
• Investigators: Principal Investigator: Huawei Li, PhD, Eye and ENT Hospital of Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2024
• Primary Completion (Actual): July 18, 2025
• Study Completion (Actual): July 18, 2025

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Personalized medicine; Tinnitus; 40 Hz stimulation; Acoustic therapy; Residual inhibition
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Ear Diseases; Hearing Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Tinnitus
• Other Study ID Numbers: 2024087

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No