Frequency-Dependent Effects of Transcranial Photobiomodulation With Same Peak Irradiance on Cortical Excitability and Fine Motor Performance: A Randomized, Double-Blind, Sham-Controlled, Within-Subject Crossover Trial
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Motor Evoked Potential (MEP) Amplitude - TMS
研究概览
简要总结
This study investigates the frequency-dependent neuromodulatory effects of transcranial photobiomodulation (tPBM) over the primary motor cortex (M1) on cortical excitability and fine motor performance in healthy young adults. Using a randomized, double-blind, sham-controlled, 5-arm crossover design, 20 healthy participants will undergo five experimental conditions separated by a mandatory 7-day washout period: Continuous Wave (CW), 10 Hz pulsed tPBM, 40 Hz pulsed tPBM, 100 Hz pulsed tPBM, and a Sham control. To isolate pulse frequency while holding peak intensity constant, all active interventions will utilize an identical peak irradiance, with pulsed modes operating at a 50% duty cycle (delivering 50% of the cumulative energy dose relative to CW). Primary outcomes include corticospinal excitability measured via single- and paired-pulse Transcranial Magnetic Stimulation (TMS), alongside fine motor speed and dexterity assessed via a computerized finger-tapping task.
详细描述
Transcranial photobiomodulation (tPBM) has emerged as a promising non-invasive tool to modulate neural activity through the absorption of near-infrared (NIR) photons by mitochondrial cytochrome c oxidase (CCO). However, whether the biological effects on the human cortex are driven solely by cumulative energy delivery or are significantly modulated by pulse frequency remains a critical question in neurophysiology. This study implements a rigorous within-subject crossover design to systematically isolate the effects of pulse frequency from total dosimetric parameters. Participants and Screening: A sample of 20 healthy volunteers (aged 18-35) will be recruited. Potential candidates will undergo a strict screening protocol to ensure safety and baseline homogeneity. Exclusion criteria include any contraindications to magnetic fields assessed by the Transcranial Magnetic Stimulation Adult Safety Screen (TASS; Rossi et al., 2021), psychiatric conditions according to DSM-5, a history of neurological disorders, the use of psychotropic medications within the last 12 months, or prior participation in an interventional neuromodulation study within the preceding 6 months. Experimental Design & Intervention: Enrolled participants will complete five experimental sessions in a randomized, counterbalanced order to eliminate carryover or sequence effects, separated by a mandatory washout period to ensure the return of cortical excitability to baseline. In each session, a clinical-grade near-infrared system will be applied over the primary motor cortex (M1) hot spot. The five experimental arms consist of: Continuous Wave (CW) tPBM - NIR light delivered continuously at baseline peak irradiance, 1x total cumulative energy dose; 10 Hz Pulsed tPBM - NIR light pulsed at 10 Hz with identical peak irradiance as CW and a 50% duty cycle, 0.5x total dose relative to CW; 40 Hz Pulsed tPBM - NIR light pulsed at 40 Hz with identical peak irradiance as CW and a 50% duty cycle, 0.5x total dose relative to CW; 100 Hz Pulsed tPBM - NIR light pulsed at 100 Hz with identical peak irradiance as CW and a 50% duty cycle, 0.5x total dose relative to CW; sham Control - a dedicated low-intensity red light photobiomodulation device emitting visible red light at sub-therapeutic levels to maintain participant blinding. Double-blinding will be enforced for the participant and investigator. Alphanumeric codes will mask the active protocols on the user interface, and participants will wear opaque safety goggles. Outcome Measures: Multiple neurophysiological, behavioral, and safety endpoints will be collected immediately pre-intervention (baseline) and post-intervention. Neurophysiology (TMS): Motor Evoked Potential (MEP) amplitude (primary excitability index); Intracortical Facilitation (ICF); Short-Interval Intracortical Inhibition (SICI); and Cortical Silent Period (CSP). Behavioral Performance (FTT): Evaluated via a dedicated Android application tracking total number of taps, variability of the inter-tap interval (vITI), spatial resultant sum (Σ||Δr||), and the 95% confidence ellipse area (X,Y).Safety and Hemodynamics: Systemic tolerability will be recorded via the Systematic Assessment for Treatment Emergent Events - Systematic Inquiry (SAFTEE-SI). Hemodynamic variations will be closely monitored through independent analyses of Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR). Data will be processed using Linear Mixed-Effects Models to account for the repeated-measures structure of the crossover design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
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).
入排标准
- 年龄范围
- 18 Years 至 35 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Continuous Wave (CW tPBM)
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).
干预措施: Transcranial Photobiomodulation (Combination Product)
10 Hz Pulsed tPBM
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.
干预措施: Transcranial Photobiomodulation (Combination Product)
40 Hz Pulsed tPBM
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.
干预措施: Transcranial Photobiomodulation (Combination Product)
100 Hz Pulsed tPBM
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.
干预措施: Transcranial Photobiomodulation (Combination Product)
Sham Comparator (Sham tPBM)
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.
干预措施: Transcranial Photobiomodulation (Combination Product)
结局指标
主要结局
Motor Evoked Potential (MEP) Amplitude - TMS
时间窗: Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)
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
时间窗: Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)
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
时间窗: Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)
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
时间窗: Immediately before the intervention (pre-intervention) and 20 minutes after the intervention (post-intervention)
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.
次要结局
- Variability of the Inter-Tap Interval (vITI) - FTT(Immediately before the intervention (pre-intervention) and immediately after the intervention (post-intervention))
- Total Number of Taps - 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 last intervention)