TMS

Participants will receive 6 weeks of daily TMS (i.e., active or sham). Prior to receiving TMS, participants will complete a motor threshold determination to determine the neurostimulation threshold to be used during treatment. The motor threshold is defined as the amount of energy administered via a coil that is required to induce movement in the contralateral hand in at least 50% of stimulations. A separate coil system is used for motor thresholds to reduce accidental unblinding. After the motor threshold is determined, each participant will begin the TMS treatment protocol.

TMS stimulation will use a triple-blind stimulation procedure as implemented in prior randomized controlled trials [47]. Prior to each TMS session, an unblinded study member will assure the setup of either an active or a sham coil according to the participants’ randomization code. Blinded study staff will administer stimulation treatment under the supervision of a blinded attending physician, and participants will not know whether they are receiving active or sham TMS. The sham stimulation coil for this study was selected because it administers sensations to the scalp that are indistinguishable from those experienced during active stimulation (e.g., [50]). To assess the integrity of the blind, participants will be asked which treatment condition they believe they were in at the end of the TMS treatment protocol. TMS treatment (both active and sham) will be delivered using a 70-mm cooled coil via a MagStim Super Rapid 2 + 1 system. Intermittent theta burst TMS will be used for this study; this option was selected because a) it is cleared by the US Food and Drug Administration for pharmacoresistant major depression, and b) each session takes approximately 3 min, thus easing the combination of stimulation and therapy. The (active or sham) coil will be positioned over the left dorsolateral prefrontal cortex using individual scalp landmarks (i.e., Beam/F3 method) [55]. We will use the coil to deliver intermittent theta burst stimulation to the treatment site for 600 pulses at 120% of motor threshold; if participants are unable to tolerate this intensity, we will utilize theta burst delivered at 80% for 1800 pulses (following guidelines from other research in this area [47]).