Frequency-Dependent Effects of Transcranial Photobiomodulation on Cortical Excitability

This study aims to investigate the frequency-dependent effects of near-infrared (NIR) transcranial photobiomodulation (tPBM) on human cortical excitability and fine motor performance. A cohort of 20 healthy adult volunteers (aged 18-35 years) will participate in a randomized, double-blind, sham-controlled, single-center study utilizing a within-subject, five-arm crossover design. Each participant will undergo five distinct experimental conditions separated by a strict washout period: active Continuous Wave (CW) tPBM, active pulsed tPBM at three neural oscillation frequencies (10 Hz, 40 Hz, and 100 Hz), and an inactive Sham comparator. All interventions will be delivered using a clinical-grade near-infrared device. To isolate the specific effects of pulse frequency from overall energy delivery, the total energy dose (cumulative Joules) and total exposure time will be held perfectly constant across all active arms. The pulsed conditions will keeps the average irradiance and cumulative fluence identical to the continuous wave mode. Cortical excitability will be assessed via single- and paired-pulse Transcranial Magnetic Stimulation (TMS) protocols over the primary motor cortex (M1). Fine motor performance will be quantified using a smartphone-based Finger Tapping Test (FTT). Safety and systemic parameters will be tracked using the Systematic Assessment for Treatment Emergent Events - Systematic Inquiry (SAFTEE-SI) and vital signs. The central hypothesis is that distinct modulation frequencies will differentially influence corticospinal excitability and motor execution, independent of the total energy delivered.

Inclusion Criteria: * Voluntary Participation: Participants who are clear of their cognitive faculties, capable of understanding all experimental procedures, and who provide written informed consent prior to enrollment. * Neurologically and Psychiatrically Healthy Status: Individuals with no current or prior history of neurological, neurodevelopmental, or psychiatric conditions; * Age Range: Young adult volunteers aged between 18 and 35 years. Exclusion Criteria: * Use of any continuous psychotropic medication within the past 12 months. * Any current psychiatric diagnosis based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). * Diagnosis of any neurological disorder capable of altering cortical excitability (e.g., seizures/epilepsy, cerebrovascular accidents/stroke, brain tumors). * Any clinical, psychological, or social condition that, in the investigator's opinion, places the participant at an increased risk, compromises participant safety, or precludes full compliance and successful completion of the study protocol. * Presence of any intracranial devices or implants, including cochlear implants and aneurysm clips. * Severe or uncompensated systemic medical illness that could interfere with study participation or confound physiological outcomes. * Participation in any other interventional neuromodulation study within the preceding 6 months.