Combined Regulatory Effects of 40 Hz eTNS and Multisensory Stimulation on Brain Networks

The purpose of this study is to investigate the independent and interactive effects of 40Hz auditory, visual, and external trigeminal nerve stimulation (eTNS) on brain state dynamics and functional connectivity. While 40Hz visual and auditory sensory stimulation have been explored for potential cognitive and therapeutic benefits, the underlying mechanisms on large-scale brain networks and the potential effects of combining multiple modalities remain unclear. This study aims to determine whether multimodal co-stimulation genuinely compounds network-level effects or if targeted dual-pairings are more efficient for brain network reorganization. In this within-subject study, 23 participants will receive all eight possible combinations of 40Hz auditory, visual, and eTNS (targeting the maxillary branch) in a randomized order. Each stimulation condition will last for 5 minutes, separated by 1-minute inter-stimulus intervals. Continuous electroencephalography (EEG) will be recorded throughout the procedures to evaluate brain responses. The collected EEG data will be analyzed using microstate analysis, functional connectivity analysis, and graph-theoretic network analysis. Ultimately, the study seeks to understand how these non-invasive stimulation techniques, independently and together, drive large-scale network reorganization and optimize the balance between local specialization and global integration in the brain.

Inclusion Criteria: * Healthy adults aged ≥18 years old. * Normal or corrected-to-normal vision and hearing (essential for 40Hz visual and auditory stimulation). * Right-handedness. * Willing to participate in the study and capable of providing written informed consent. Exclusion Criteria: * Personal or family history of epilepsy or seizures (crucial safety criteria for 40Hz flicker and electrical stimulation). * History of any neurological or psychiatric disorders. * Presence of metallic implants in the head, cardiac pacemakers, or other implanted electronic medical devices. * Skin lesions, infections, or hypersensitivity at the eTNS stimulation site (maxillary branch of the trigeminal nerve). * Current use of psychoactive medications or substances that may significantly alter EEG signals or brain state dynamics. * Pregnant or lactating individuals. * Poor sleep quality or irregular sleep-wake cycles prior to the experiment.