About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Crossover
Treatments tested in this trial
Transcranial Photobiomodulation
Combination productTranscranial photobiomodulation (tPBM) is a non-invasive, non-thermal neuromodulatory modality that utilizes low-power coherent (laser) or non-coherent (light-emitting diodes, LEDs) light sources within the red (lambda = 600-700 nm) and near-infrared (NIR; lambda = 700-1100 nm) spectral windows to modulate cortical function. Structurally tailored to penetrate superficial anatomical barriers-including the scalp, skull, and meninges-tPBM delivers photons directly to the cerebral cortex.
Treatment groups
Trial outcomes
Primary outcomes
Motor Evoked Potential (MEP) Amplitude - TMS
Single-pulse TMS will be applied over the primary motor cortex (M1) hotspot to elicit Motor Evoked Potentials (MEPs) recorded via electromyography (EMG) from the target muscle (e.g., first dorsal interosseous, FDI). Peak-to-peak MEP amplitude (mV) will be measured at a stimulation intensity adjusted to evoke a baseline response of approximately 1 mV. This outcome reflects overall baseline corticospinal excitability and its modulation following the tPBM protocol.
Intracortical Facilitation (ICF) - TMS
Evaluated using a paired-pulse TMS protocol consisting of a subthreshold conditioning stimulus (80% of resting motor threshold, RMT) followed by a suprathreshold test stimulus (120% RMT) at a long interstimulus interval (ISI) of 10 ms. The outcome is expressed as the ratio of the conditioned MEP amplitude to the unconditioned test MEP amplitude. ICF is primarily mediated by cortical glutamatergic circuits and NMDA receptor activity.
Short-Interval Intracortical Inhibition (SICI) - TMS
Assessed via a paired-pulse TMS paradigm using a subthreshold conditioning stimulus (80% RMT) followed by a suprathreshold test stimulus (120% RMT) at a short interstimulus interval (ISI) of 3 ms. The resulting SICI value is quantified as the percentage of inhibition of the conditioned MEP relative to the unconditioned test MEP. This parameter indexes local intracortical inhibitory interneuron activity mediated by GABA\_A receptors.
Cortical Silent Period (CSP) - TMS
Induced by applying a single suprathreshold TMS pulse (120% RMT) over the M1 hotspot while the participant maintains a stable, isometric voluntary contraction of the target muscle (e.g., 20% of maximum voluntary contraction). The CSP duration (ms) is measured from the onset of the MEP to the return of rectified background EMG activity. CSP duration provides a precise marker of interhemispheric and intracortical inhibition mediated by GABA\_B receptors.
Secondary outcomes
Total Number of Taps - FTT
The cumulative count of valid screen contacts executed by the participant's index finger within a fixed, standardized testing interval (e.g., 30 seconds). This metric serves as a behavioral index of maximal motor execution speed and tapping frequency.
Variability of the Inter-Tap Interval (vITI) - FTT
Calculated as the standard deviation (or coefficient of variation) of the temporal intervals between consecutive screen contacts (in milliseconds). This outcome quantifies the temporal rhythmic precision and stability of the central motor program.
Spatial Resultant Sum (Σ||Δr||) - FTT
The cumulative Euclidean distance calculated across all sequential tap coordinates on the 2D Android screen interface. This parameter reflects spatial dispersion and motor drift, tracking the continuous precision of the targeted finger-pointing trajectory.
95% Confidence Ellipse Area (X,Y) - FTT
Computed as the total geometric surface area (in squared millimeters, mm2) of the bivariate error ellipse that encompasses 95% of the coordinates of all performed taps on the horizontal (X) and vertical (Y) axes. This spatial metric quantifies overall motor accuracy and targeting consistency.
Other outcomes
Systolic Blood Pressure (SBP)
Systemic systolic blood pressure will be quantified in millimeters of mercury (mmHg) using a calibrated, digital oscillometric upper-arm sphygmomanometer. Measurements will be recorded under standardized resting conditions at pre-intervention (baseline) and immediately post-intervention across all five crossover arms to monitor potential acute alterations in peak arterial pressure induced by transcranial photobiomodulation.
Diastolic Blood Pressure (DBP)
Systemic diastolic blood pressure will be quantified in millimeters of mercury (mmHg) using the same automated oscillometric system. Measurements will be recorded concurrently with the systolic parameters at baseline and immediately post-intervention across all five crossover sessions to evaluate potential shifts in minimum arterial pressure during cardiac relaxation.
Heart Rate (HR)
Heart rate will be quantified in beats per minute (bpm) concurrently with the blood pressure evaluation using the same automated digital system. This parameter serves as an acute physiological indicator of autonomic nervous system balance (sympathovagal tone) before and after the application of continuous or sinusoidal pulsed photobiomodulation protocols.
Sponsors and contacts
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Hospital de Clinicas de Porto Alegre
Lead sponsor
Federal University of Rio Grande do Sul
Collaborator
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.
Collaborator
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