Effects of Transcranial Direct Current Stimulation Associated With Physical Exercise: a Metaplasticity Study

Before the two phases of the study, the subjects will be evaluate in the following aspects: anxiety by the beck anxiety inventory; depression by the beck depression inventory; level of physical exercise by the international physical activity questionnaire; stress by the stress perceived scale 10.

In the first phase, the subjects will be undergo to 4 conditions: (i) 15 minutes of physical exercise with moderate intensity; (ii) 10 minutes of physical exercise with high intensity; (iii) 30 minutes of physical exercise with mild intensity; (iv) 15 or 30 minutes of rest. Before each condition, cortical excitability will be measure through the Transcranial magnetic stimulation by motor evoked potential (MEP); the blood glucose level will be evaluate by glucometer. The MEP also will be done immediately after the physical exercise and in every 5 min for 30 after the end of exercise/rest. The blood glucose level will be done immediately after the exercise..

In the second phase, the subjects will be undergo to 6 conditions: (i) anodal tDCS + physical exercise 1; (ii) anodal tDCS + physical exercise 2; (iii) cathodal tDCS + physical exercise 1; (iv) cathodal tDCS + physical exercise 2; (v) sham tDCS + physical exercise 1; (vi) sham tDCS + physical exercise 2. The intensity and time of physical exercise depends of the results of the previous phase and will be determine after the end of phase 1. In this phase, the blood glucose level will be evaluate before and immediately the physical exercise. The cortical excitability will be evaluate through the Transcranial magnetic stimulation by the following measures: motor evoked potential - before the tDCS,after tDCS, immediately , 10, 20, 30, 60, 90 minutes after the exercise; resting motor threshold - before tdcs, immediately and 90 minutes after the exercise; recruitment curve - before tdcs, immediately and 90 minutes after the exercise.

tDCS condition During tDCS application, patients will be seated in a comfortable chair with head and arms rests. Current will be applied by a DC stimulator (NeuroConn, Germany) using a pair of saline-soaked sponge electrodes (surface 35 and 36cm²).

tDCS will be applied to Cz and Oz according to International 10-20 EEG system. In the anodal tDCS, the anode will be placed in Cz and cathode in Oz. In the cathodal tDCS the inverse position will be done. Parameters of current intensity and duration (dose) used were previously established in poststroke patients: 2 mA stimulation intensity for 20 minutes with current ramping up and down of 10 seconds each.

Sham tDCS has been used in several studies to evaluate the effect of active tDCS. For sham, the same position of anodal tDCS will be assumed, however, current duration is only 30 seconds, with current ramping up and down of 10 seconds each. Moreover, the electrostimulation device is automatically turned off without patient's perception. Thus, patients experience early sensations (mild to moderate tingling) in stimulation site without inducing effect. Moreover, after each tDCS session, patients will answer adverse effects questionnaire.

Physical exercise condition The intensity of physical exercise will be determine by the maximum heart rate (max HR) using the formula (220 - age). For the high intensity, the intensity will between xx and xx% of maxHR; moderate intensity, 64-76% of maxHR; mild intensity, 57-63% of maxHR. Furthermore, during the physical exercise the heart rate will be continuous evaluate by the POLAR and the rate perceived scale will be register in each 3 minutes by the modified Borg scale Outcome measures Evaluation of brain activity will be performed using single-pulse transcranial magnetic stimulation (TMS-p). Magnetic stimulation (Neurosoft, Russia) will be applied through a figure-8 coil to determine motor cortex representation of right tibial anterior muscle (hotspot) and performed the following electrophysiological measures to assess cortical activity: (i) Motor Evoked Potential (MEP); (ii) resting motor threshold (RMT) and (iii) Recruitment curve (RC).

Firstly, patients will be instructed to sit in a chair and to search a comfortable position. The hotspot will be considered the most excitable area, with more intense motor evoked potential (MEP), measured by electromyography.

The following electrophysiological measures will be performed in left cerebral hemisphere to assess cortical activity:

(i) Motor Evoked Potential (MEP) : the intensity of magnetic stimulator is adjusted to produce an average MEP of 0.4 mV. TMS-p will be applied in the area of cortical representation of the tibial anterior and mean responses to stimuli should reach 0.4 to 0.6 mV.

(ii) Resting motor threshold (RMT) : will be request to the patient to perform contraction of the tibial anterior muscle and then, will be given ten pulses by TMS-p to determinate resting motor threshold. Motor threshold corresponds to the lowest intensity of TMS-p to produce a MEP of 50μV in 50% of the pulses applied to the hotspot.

(iii) Recruitment curve (RC): Five stimuli were applied at each of the following intensities: 5% below resting motor threshold (RMT), RMT, 5% above RMT, 10% above RMT, 20% above RMT, 30% above RMT, 35% above RMT and at 100% of stimulator output. The five stimuli at each intensity were delivered in a block, but the order of stimulation intensity changes was random. The interval between successive TMS stimuli was between 5.5 to 6.5 s.