Navigated cTBS for the Treatment of Generalized Anxiety Disorder

This study is a randomized, triple-blind, sham-controlled trial designed to evaluate the efficacy and neural mechanisms of neuronavigation-guided continuous Theta Burst Stimulation (cTBS) in patients with Generalized Anxiety Disorder (GAD). A total of 40 patients diagnosed with GAD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) will be recruited from the First and Second Affiliated Hospitals of Anhui Medical University. After providing informed consent, participants will be randomized in a 1:1 ratio to receive either active cTBS or sham cTBS. The stimulation target is the left auditory association cortex (posterior superior temporal sulcus), with coordinates derived from previous literature (Neri et al., 2024; MNI coordinates: -62, -40, 10). The TMStarget software will be used to transform these coordinates into each participant's native brain space, and a Brainsight neuronavigation system will guide coil placement for precise targeting. The active intervention will be delivered using a MagStim Rapid2 stimulator with a 70mm air-cooled figure-of-eight coil. Stimulation intensity will be set at 100% of the individual's resting motor threshold (RMT). The cTBS protocol consists of 3-pulse bursts at 50 Hz, repeated at a 5 Hz frequency, for a total of 600 pulses per session (duration of approximately 41 seconds). The sham intervention will utilize an identical-looking sham coil that produces similar sounds without inducing a significant magnetic field, ensuring the integrity of the blinding. The treatment schedule consists of three sessions per day, with a 15-minute interval between sessions, for seven consecutive days (from Day 2 to Day 8 of the study protocol). All participants will undergo comprehensive assessments at baseline (Day 1) and immediately after the final treatment session (Day 9). Assessments include a battery of clinical scales and multimodal magnetic resonance imaging (MRI). The MRI protocol includes high-resolution structural (3D-T1), resting-state functional MRI (rs-fMRI), Diffusion Tensor Imaging (DTI), and specific sequences targeting the Locus Coeruleus. A follow-up assessment of clinical symptoms will be conducted two weeks after the end of the intervention.