Effect of Different Currents for Transcranial Modulation of the Sensorimotor Corticospinal Pathway in Healthy Subjects (CURRENT-Flow)

Participants receive active transcranial direct current stimulation over the primary motor cortex (M1) during the intervention sessions.

Stimulation is delivered using two sponge electrodes (5 × 7 cm) mounted on a neoprene cap. The electrodes are positioned on the scalp according to the international 10-20 system. The anode is placed at position C3 (left primary motor cortex, M1) and the cathode over the ipsilateral clavicular region. The sinusoidal current intensity per channel ranges from ±2 mA. The session duration is 20 minutes.

• tDCS

Participants receive active transcranial alternating current stimulation over the primary motor cortex (M1) during the intervention sessions.

Single session of active gamma transcranial alternating current stimulation delivered for 30 minutes using a battery-powered external stimulator. Stimulation is applied through two sponge electrodes (5 × 7 cm) mounted on a neoprene cap. The stimulation frequency is 40 Hz, based on previous gamma-band transcranial alternating current stimulation (tACS) studies. The anode is positioned at C3 (left primary motor cortex, M1), and the cathode over the ipsilateral clavicular region.

• tACS

Participants receive active transcranial random noise stimulation over the primary motor cortex (M1) during the intervention sessions.

Stimulation is delivered using two sponge electrodes mounted on a neoprene cap. The anode is positioned at C3 (left primary motor cortex, M1), and the cathode over the ipsilateral clavicular region. A random current level is generated for each sample at a sampling rate of 1280 samples per second. The random values are normally distributed, following a bell-shaped probability density function. The noise signal contains all frequencies up to half the sampling rate (maximum 640 Hz) and has no DC offset.

• tRNS

Participants undergo sham stimulation, experiencing the same setup as active stimulation without actual current delivery.

During the sham stimulation session, the tDCS device ramps up the current to 2 mA over 30 seconds and then is immediately turned off. This procedure mimics the sensations of active stimulation without delivering therapeutic current for the remainder of the session.

• Schein

Participants remain seated with their eyes open for 20 minutes during the rest session, without performing any other task.

Electroencephalography (EEG) will be used to quantify neuronal activity through quantitative EEG (qEEG) analysis. Resting-state EEG power spectra will be analyzed across delta, theta, alpha, beta, and gamma frequency bands, reflecting synchronized neuronal oscillations. EEG data will be recorded using a 20-electrode montage according to the international 10-20 system during an 8-minute resting-state paradigm with alternating eyes-open and eyes-closed conditions. Cortical source localization will be performed using standardized Low-Resolution Brain Electromagnetic Tomography (sLORETA).

Corticospinal excitability will be assessed using single-pulse transcranial magnetic stimulation (TMS) applied over the left primary motor cortex. Motor evoked potentials (MEPs) will be recorded from the right first dorsal interosseous muscle, and measures will include resting motor threshold (RMT) and MEP amplitude, with MEPs obtained at 130% of the motor threshold.

Functional connectivity of the motor cortex will be assessed using functional near-infrared spectroscopy (fNIRS) with a continuous-wave NirScout® system. Optodes will be positioned according to the international 10-10 system to cover the bilateral motor cortex. Data will be acquired during resting-state conditions and during the cold pressor task. Functional connectivity will be analyzed within predefined motor cortex regions of interest.

Heat pain threshold will be assessed via quantitative sensory testing (QST) on the left forearm using a thermode that increases temperature from 30°C to 52°C at a rate of 1°C per second. The pain threshold is calculated as the average temperature at which pain is first reported across three trials. Higher values indicate greater pain threshold.

The function of the descending pain inhibitory system will be assessed using the Conditioned Pain Modulation Test (CPM-test). Pain intensity is rated using a verbal numerical rating scale (0 = no pain to 10 = worst possible pain) before (T0) and during (T1) cold-water immersion. The CPM effect is calculated as the difference between pain ratings at T0 and T1, with greater reductions indicating more effective pain inhibition.

Pain intensity and tolerance will be assessed using the Cold Pressor Test, in which participants immerse the non-dominant hand in ice-saturated water (~1°C) for up to 2 minutes. Pain intensity will be continuously rated using an electronic visual analog scale, allowing calculation of peak pain, mean pain, and area under the curve (AUC) over the test duration.