The purpose of this study is to investigate the effectiveness of a dual-target non-invasive brain stimulation technique called continuous Theta Burst Stimulation (cTBS) for treating Generalized Anxiety Disorder (GAD). The researchers will use a neuronavigation system, which acts like a GPS for the brain, to guide the stimulation to two specific targets: the left auditory association cortex and the primary motor cortex (M1).

Participants will be randomly assigned to one of two groups. One group will receive active dual-target cTBS treatment, while the other will receive a sham (placebo) stimulation that feels similar but has no therapeutic effect. The treatment will be given three times a day for seven consecutive days. Before and after the treatment period, all participants will complete clinical questionnaires to measure their anxiety and undergo Magnetic Resonance Imaging (MRI) scans to help researchers understand how cTBS affects brain activity.

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.

Inclusion Criteria:

1. Diagnosis of Generalized Anxiety Disorder (GAD) according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), confirmed by at least two psychiatrists.
2. Hamilton Anxiety Rating Scale (HAMA) score > 14.
3. Age between 18 and 60 years.
4. Right-handed.
5. More than 5 years of education.
6. Patients are either medication-free or maintain a consistent medication regimen during cTBS treatment.
7. Willing and able to provide written informed consent.
8. Normal or corrected-to-normal visual acuity and hearing.

Exclusion Criteria:

1. Presence of other psychiatric disorders, such as substance abuse, schizophrenia, schizoaffective disorder, hysteria, autism, or bipolar disorder.
2. History of epilepsy, seizures, or severe neurological diseases (e.g., stroke, organic brain lesions).
3. Presence of severe somatic diseases, such as severe heart, liver, or renal insufficiency.
4. Pregnant or lactating women.
5. Contraindications to Transcranial Magnetic Stimulation (TMS) or Magnetic Resonance Imaging (MRI), such as the presence of a cardiac pacemaker, cochlear implant, cerebrovascular metal stent, or metal dentures.
6. Inability to cooperate with experimental procedures due to conditions such as severe claustrophobia.