Rapid stimulator

Magnetic stimulation was applied to the left motor area M1 by means of a Magstim Rapid stimulator and a flat alpha coil (D70 Alpha Flat Coil, Magstim Company, Whitland, Dyfed, UK) being held by a support stand (Magstim AFC Support Stand, Magstim Company, Whitland, Dyfed, UK). The coil was oriented at ∼45°, inducing a posterior-to-anterior current flow across the motor cortex, and moved across the left motor cortex while delivering stimulation in order to locate the optimal coil position to stimulate FCR (Rossini et al. 2015 (link)). The position was marked with a non-permanent marker to ensure consistency of recordings over the session. The positions and orientations of the coil was monitored continuously, and if necessary, adjusted to align with the scalp markings. During all the interventions, the stimulation was controlled through Spike2 (Cambridge Electronic Design, Cambridge, UK) software. We estimated for each subject an individual resting MT, the smallest intensity of stimulation necessary to elicit peak-to-peak MEP amplitudes of at least 50 μV in at least 5 out of 10 trials with 5 s IPIs, following the relative frequency method (Rossini et al. 1994 (link)). MT values were used to calculate the intensities to be set during the recording phase.

The same stimulation parameters were used as in experiment 1. However, in this experiment, participants received both DLPFC and vertex stimulation in a blocked manner. The stimulation was delivered using a Magstim Rapid stimulator with a figure-of-eight coil (magstim; www.magstim.com). Prior to the main experiment, individual T1-weighted MRI scans were acquired using a 3T Philips Achieva MRI scanner. In order to assure precise stimulation, individual MRI scans were coregistered with the position of the rTMS coil, and the stimulation was guided by a neuronavigation system (Brainsight; Rogue Resolutions; https://www.rogue-resolutions.com). The coil was held in place manually, and the precision of the stimulation was monitored throughout the experiment. The same MNI coordinates as in experiment 1 were used.

Repetitive Transcranial Magnetic Stimulation was administered with the Magstim Rapid Stimulator (Magstim Company Ltd., Whitland, UK) using a 70-mm, 8-shaped coil. Stimulation parameters were 15 Hz, 2,400 pulses/day at 100% of resting motor threshold (MT), once a day, 6 days/week for 4 weeks (24 sessions total). Stimulation was applied on the left DLPFC, identified for each subject through neuronavigation. Resting MT was defined as the minimum magnetic flux needed to elicit a response in a resting target muscle (abductor pollicis brevis) in 5/10 trials using single-pulse TMS administered to the contralateral primary motor cortex.

Magstim Rapid stimulator (Magstim Company, Whitland, Wales, UK) was used along with H4-Coil (Brainsway Ltd., Jerusalem, Israel) specifically designed to stimulate bilateral PFC and insula symmetrically (34 (link), 35 (link)). Subjects received 20 stimulations over 4 weeks as previously described (23 (link)). ITBS protocol consisted of bursts containing 3 pulses at 50 Hz repeated at 200-ms intervals for 2 s (i.e., at 5 Hz). A 2-s train of iTBS was repeated every 10 s for 190 s and 600 pulses (26 (link)). The intensity was set at 100% of the visual resting motor threshold (RMT). For maintenance treatment 1 weekly session of iTBS was administered for 2 months.