Clinical Research Directory

The d-TMS protocol will be performed at the treatment-resistant disorders clinic, IRCCS San Gerardo Monza, and will consist of 5 weeks of daily treatments, 5 days a week and 4 treatments during the 6th week, and a 4-week follow-up phase, following most recent clinical studies. d-TMS will be administered using a TMS stimulator equipped with an H-shaped coil (Harmelech et al., 2021). The coil will be placed 4 cm anterior to the foot motor cortex and used at 100% of the leg resting motor threshold (RMT), defined as the coil position that elicited the minimal involuntary contractions of the feet (3 of 6 attempts). The stimulation of the area localized 4 cm anterior to the foot motor cortex targets the dorsal medial prefrontal cortex (mPFC) and the anterior cingulate cortex (ACC) bilaterally. Patients will receive 20 Hz d-TMS at 100% of RMT, with 2-second pulse trains and 20-second intertrain intervals, for a total of 50 trains and 2,000 pulses per session.

TBS will be administered using a Magstim Rapid2 stimulator. 3-pulse 50-Hz bursts will be given to patients' left orbitofrontal cortex every 200 ms (at 5 Hz) at an intensity of 80% of the active motor threshold, defined as the coil position that elicited a right thumb movement while stimulating the left primary motor cortex. The treatment will consist of 2 sessions per day, thirty minutes apart, for 5 days in a week. Following the parameters of previous studies, each session will deliver a burst of three pulses at 50 Hz and repeated every 200 ms (at 5 Hz) for a total of 600 pulses lasting 40s (Oberman et al., 2011). A total of 1200 pulses will be delivered per day.