Robotically Delivered fMRI-Guided Personalized Transcranial Magnetic Stimulation Therapy for Treatment-Resistant Depression

Improving the outcomes of transcranial magnetic stimulation (TMS) therapy for treatment-resistant depression may be achieved by personalizing the targeting of the dorsolateral prefrontal cortex (DLPFC) and providing precise dose delivery. We recently reported the initial clinical outcomes of an open-label study using a robotically delivered functional magnetic resonance imaging (fMRI) guided, personalized TMS therapy in treatment-resistant depression. Here, we describe the protocol used in the clinical implementation of personalized TMS for treatment-resistant depression. This protocol has been clinically implemented since November 2021. Patients with treatment-resistant depression are assessed and consented for TMS therapy. Eligible patients undertake an anatomical and 15 min eyes-open, resting-state MRI. Anatomical and functional data are uploaded to a cloud-based platform to calculate the optimal TMS target within the left dorsolateral prefrontal cortex (DLPFC) via an established approach. The output of this processing pipeline identifies brain clusters characterized by the strongest anticorrelation between fMRI signals in the subgenual cingulate cortex (SGC) and DLPFC. The TMS target is refined based on individual anatomy (e.g., gyrus position) and the size of targeted cortical cluster(s). A scalp entry point for the target is calculated via neuronavigation software. Neuronavigation is used to guide a TMS coil mounted to a robotic arm, enabling precise and consistent stimulation within and across sessions. Patients undertake daily TMS sessions over 4-6 weeks using intermittent theta-burst stimulation at 120% resting motor threshold. Symptom response is assessed 2 weeks after treatment completion. This protocol demonstrates the resources and workflow required for robotically delivered fMRI-guided personalized TMS for treatment-resistant depression.