None of them had a history of psychiatric or neurological conditions, and all had normal VE-822 neurological and medical examinations, and Mini Mental State Examination scores in the normal range (27–30). Participants were not taking any medication known to affect motor cortical excitability at the time of the study and did not have any contraindications to TMS. All tolerated the TMS without any side effect or complication. All gave their

written informed consent to the study, which followed international guidelines and recommendations for the safe use of TMS (Rossi et al., 2009), had been approved by the local Institutional Review Board (Beth Israel Deaconess Medical Center, Boston, USA) and was conducted in adherence with the Declaration of Helsinki. We evaluated the effects of cTBS, a repetitive TMS intervention. Before and after cTBS, corticospinal excitability was assessed by recording MEPs in response to single-pulse TMS. EEG was recorded

concurrently, and TMS-induced electroencephalographic potentials and spectrum perturbation were evaluated. Finally, resting eyes-closed EEG was also evaluated. The stimulation set-up consisted of a Nexstim stimulator (Nexstim Ltd, Helsinki, Finland) for single-pulse TMS and a MagPro stimulator (MagVenture A/S, Farum, Denmark) for the cTBS intervention. We used figure-of-eight TMS coils delivering biphasic pulses (for Nexstim – mean diameter 50 mm and outer diameter 70 mm, each wing; for MagPro – inner diameter 35 mm and outer diameter Bafetinib in vitro 75 mm, each wing). In all instances, the Nexstim neuronavigation system was used, ensuring reproducible and reliable coil placement within each experimental session. All participants underwent a brain magnetic resonance imaging (MRI) scan to rule out structural brain lesions and generate a high-resolution, anatomical

brain image to guide the TMS using the Nexstim neuronavigation system. A 3-Tesla scanner (GE) was used for MRI acquisition. For MEP measurement, surface electromyography (EMG) was recorded using pre-gelled, disposable Ag/AgCl electrodes with the active electrode over the first dorsal interosseus muscle (FDI), the reference electrode over the metacarpophalangeal joint and the ground electrode over the wrist. The EMG signal was acquired at 3 kHz, SPTLC1 filtered (10–500 Hz), amplified, displayed and stored for off-line analysis. Electroencephalography was recorded with a 60-channel TMS-compatible EEG system (eXimia EEG, Nexstim Ltd). This system is designed to avoid amplifier saturation after TMS pulses by using a sample-and-hold circuit that keeps the input of the amplifiers constant from 100 μs prestimulus to 2 ms poststimulus (Virtanen et al., 1999). The signals were sampled at 1450 Hz with 16-bit resolution and referenced to an electrode placed on the forehead. Impedance of each electrode was kept below 5 kΩ. Vertical electrooculogram (EOG) was recorded by two extra sensors.