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This study aims to evaluate whether personalized gamma-frequency auditory stimulation enhances cognitive function and brain synchronization. While 40 Hz auditory stimulation has been widely studied, recent evidence suggests optimal frequencies vary by individual. Using a cross-over design with 20 healthy adults, the research compares "optimal" versus "non-optimal" frequencies over one-month intervention periods. Effectiveness is measured through EEG recordings and executive function tasks. The goal is to determine if personalized sensory intervention provides a more effective, non-invasive strategy for enhancing cognitive performance.
Previous studies have shown that 40-Hz gamma-band sensory stimulation can reduce Aβ and p-tau burden and improve memory performance in AD mouse models. However, findings from human studies remain inconsistent due to differences in intervention duration and stimulation protocols. Recent studies further suggest that the optimal frequency for inducing gamma-band neural entrainment varies across individuals. In addition, a pilot study conducted in our laboratory found that the optimal auditory stimulation frequency was not necessarily 40 Hz for all participants. Therefore, the present study aims to investigate the effects of optimal auditory frequency stimulation on cognitive performance and its relationship with electrophysiological changes measured by EEG.
The study will recruit 20 cognitively healthy adults. Participants who are willing to join the study will first undergo a screening session to determine whether they meet the inclusion and exclusion criteria and whether auditory stimulation can induce significant neural entrainment. Those who meet the eligibility criteria will proceed to the intervention stage.
This study will adopt a crossover design. All participants will receive two stages of auditory stimulation intervention. Prior to the intervention, participants will be randomly assigned in a 1:1 ratio to one of two experimental groups. One group will receive optimal auditory frequency stimulation during the first stage, while the other group will receive non-optimal auditory frequency stimulation (i.e., the frequency producing the weakest neural entrainment effect). Each group will include 10 participants. During the second intervention stage, the two groups will switch experimental conditions (optimal/non-optimal auditory frequency stimulation).
Each stage will last for one month, with stimulation lasts five days per week and one hour per day. After each intervention session, participants will complete an experimental log form to record adverse effects. A one-month washout period will be implemented between the two intervention stages.
EEG recordings will be conducted before and after each intervention stage, including resting-state EEG, optimal auditory stimulation EEG recordings, and cognitive tasks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Personalized optimal gamma auditory frequency stimulation | Experimental | The patient receives optimal gamma auditory frequency stimulation at home for 1 month, 5 days per week, and 1 hour per day. The stimulation frequency is selected based on the frequency that produces the strongest neural entrainment. |
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| Non-optimal gamma auditory frequency stimulation | Active Comparator | The patient receives non-optimal gamma auditory frequency stimulation at home for one month, five days per week, and one hour per day. The stimulation frequency is selected based on the frequency that produces the weakest neural entrainment. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Gamma auditory frequency stimulation | Device | Participants will receive auditory stimulation using our app downloaded in the mobile device to play the sound for 1 hour per day, 5 days a week, over 1 month. |
| Measure | Description | Time Frame |
|---|---|---|
| changes in neurophysiological function | EEG oscillation within the gamma band obtained during resting-state and the periods of optimal and non-optimal auditory stimulation will be analyzed to evaluate and compare the neurophysiological changes. | Stage 1 baseline (T1), post one-month intervention of stage 1 (T2), stage 2 baseline (T3), post one-month intervention of stage 2 (T4) |
| changes in working memory performance | Behavioral performance and electrophysiological activity will be evaluated via a working memory task. | Stage 1 baseline (T1), post one-month intervention of stage 1 (T2), stage 2 baseline (T3), post one-month intervention of stage 2 (T4) |
| changes in inhibitory control performance | Behavioral performance and electrophysiological activity will be evaluated via an inhibitory control task. | Stage 1 baseline (T1), post one-month intervention of stage 1 (T2), stage 2 baseline (T3), post one-month intervention of stage 2 (T4) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chia-Hsiung Cheng, Ph.D. | Contact | +886-3-211800 | 3854 | ch.cheng@mail.cgu.edu.tw |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chang Gung University | Taoyuan | Guishan | 33302 | Taiwan |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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