Mapsd Dual-target cTBS (Auditory Cortex and M1) for Generalized Anxiety Disorder

This study is a randomized, triple-blind, sham-controlled trial designed to evaluate the efficacy and neural mechanisms of neuronavigation-guided dual-target continuous Theta Burst Stimulation (cTBS) in patients with Generalized Anxiety Disorder (GAD). A total of participants diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) will be recruited. After providing informed consent, participants will be randomized in a 1:1 ratio to receive either active dual-target cTBS or sham cTBS. The active intervention involves stimulating two sequential targets using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil: Target 1 (Auditory Cortex): The first target is the left auditory association cortex (posterior superior temporal sulcus), located using a Brainsight neuronavigation system based on individual MRI scans transformed from MNI coordinates (-62, -40, 10). Target 2 (M1): The second target is the primary motor cortex (M1), located at the site where the resting motor threshold (RMT) is determined. Stimulation of the auditory cortex target will be immediately followed by stimulation of the M1 target. The cTBS protocol for each target consists of 3-pulse bursts at 50 Hz, repeated at a 5 Hz frequency, for a total of 600 pulses (40 seconds duration) per target. The stimulation intensity will be set at 100% of the individual's RMT. To achieve cumulative aftereffects, this dual-target protocol will be repeated three times per day with 15-minute intervals between sessions, for seven consecutive days. The sham intervention will utilize an identical-looking sham coil that produces similar sounds and scalp sensations without inducing a significant magnetic field. The procedure, including neuronavigation, coil placement, and duration, is identical to the active group to maintain the triple-blind design (masking for participants, investigators, and outcomes assessors). All participants will undergo comprehensive assessments at baseline, post-intervention, and follow-up. Assessments include clinical scales such as the Hamilton Anxiety Rating Scale (HAMA) and multimodal MRI (structural, rs-fMRI, and DTI) to examine neural network dynamics.