Frequency-Dependent Effects of Transcranial Photobiomodulation on Cortical Excitability

NCT07707284 | Not Yet Recruiting Phase 1

• 1 other identifier: 2025-0082
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cortical Excitability; Healthy Volunteers (HV); Transcranial Photobiomodulation

Keywords

Transcranial photobiomodulation; Cortical excitability; Healthy volunteers; Finger Tapping Test

Outcome Measures

Primary Outcomes (4)

• 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.

  Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)

• 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.

  Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)

• 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.

  Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)

• 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.

  Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)

Secondary Outcomes (5)

• Total Number of Taps - FTT

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• Variability of the Inter-Tap Interval (vITI) - FTT

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• Spatial Resultant Sum (Σ||Δr||) - FTT

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• 95% Confidence Ellipse Area (X,Y) - FTT

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• Adverse Events and Tolerability (SAFTEE-SI)

  Baseline, before all interventions and one week after the intervention

Other Outcomes (3)

• Systolic Blood Pressure (SBP)

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• Diastolic Blood Pressure (DBP)

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

• Heart Rate (HR)

  Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention)

Study Arms (5)

Continuous Wave (CW) tPBM

EXPERIMENTAL

Active near-infrared (NIR) transcranial photobiomodulation delivered in Continuous Wave (CW) mode using the NIR device, providing a constant baseline irradiance to achieve the target total energy dose (J).

Combination Product: Transcranial Photobiomodulation

10 Hz Pulsed tPBM

EXPERIMENTAL

Active NIR light delivered in pulsed mode at a frequency of 10 Hz. It matched across frequencies to ensure that the average irradiance (mW/cm2) and total energy dose (J) remain identical to the CW baseline within the same exposure time.

Combination Product: Transcranial Photobiomodulation

40 Hz Pulsed tPBM

EXPERIMENTAL

Active NIR light delivered in pulsed mode at a frequency of 40 Hz. It matched across frequencies to ensure that the average irradiance (mW/cm2) and total energy dose (J) remain identical to the CW baseline within the same exposure time.

Combination Product: Transcranial Photobiomodulation

100 Hz Pulsed tPBM

EXPERIMENTAL

Active NIR light delivered in pulsed mode at a frequency of 100 Hz. It matched across frequencies to ensure that the average irradiance (mW/cm2) and total energy dose (J) remain identical to the CW baseline within the same exposure time.

Combination Product: Transcranial Photobiomodulation

Sham Comparator (Sham tPBM)

SHAM COMPARATOR

Inactive transcranial photobiomodulation (tPBM) delivered near-infrared device. To ensure successful participant blinding, the device will be programmed to deliver a minimal, non-therapeutic power output of visible red light (660 nm), which serves as a visual guide mimic but delivers negligible energy to the cortical tissue (0 J of active near-infrared light). Total exposure time, acoustic signals, and equipment interface will be identical to the active arms.

Combination Product: Transcranial Photobiomodulation

Interventions

Transcranial Photobiomodulation COMBINATION_PRODUCT

Transcranial 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.

10 Hz Pulsed tPBM; 100 Hz Pulsed tPBM; 40 Hz Pulsed tPBM; Continuous Wave (CW) tPBM; Sham Comparator (Sham tPBM)

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• Federal University of Rio Grande do Sul: collaborator
• Coordenação de Aperfeiçoamento de Pessoal de Nível Superior.: collaborator

Study Sites (1)

Hospital de Clínicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Location

Study Officials

• Marco A Caldieraro, Doctor

  Federal University of Health Science of Porto Alegre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marco A Caldieraro, MD PhD

CONTACT

+555199109-5177; mcaldieraro@hcpa.edu.br

Victor CS Araújo, MD Msc

CONTACT

+5551997360799; vcaraujo@hcpa.edu.br

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: To evaluate the integrity of the blinding procedure, a Blinding Index assessment will be conducted at the end of each participant's final experimental session. Participants and the primary investigator will complete a forced-choice questionnaire to guess which intervention (Active or Sham) was administered in each of the five sessions. The success of the blinding protocol will be statistically confirmed if the distribution of correct guesses does not significantly deviate from random chance (p \> 0.05 via chi-square analysis).
• Purpose: DEVICE FEASIBILITY
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a randomized, double-blind, sham-controlled, single-center clinical trial utilizing a five-arm crossover assignment design to evaluate the frequency-dependent effects of near-infrared (NIR) transcranial photobiomodulation (tPBM) on human cortical excitability. By implementing a within-subject crossover design with a sample of 20 healthy participants, each volunteer will serve as their own control, drastically reducing inter-individual neuroanatomical and neurophysiological variance. All 20 participants will undergo all five experimental conditions in a randomized and counterbalanced order to mitigate any potential order or carryover effects. To ensure complete elimination of residual neuromodulatory effects, a minimum washout period of 7 days will be strictly enforced between consecutive experimental sessions.

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: July 16, 2026
• Study Start (Estimated): May 1, 2027
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: July 28, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)