Temporal Interference Transcranial Alternating Current Stimulation Targeting the BNST or Amygdala for Generalized Anxiety Disorder

This randomized controlled trial will use a three-arm, parallel-group design to evaluate the efficacy and safety of 5-Hz Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in adults with generalized anxiety disorder (GAD). A total of 75 participants will be randomized in a 1:1:1 ratio to receive stimulation targeting the right bed nucleus of the stria terminalis (BNST), stimulation targeting the right amygdala, or sham stimulation. Participants will receive three 20-minute sessions per day, with 1-hour intervals between sessions, for 7 consecutive days (21 sessions in total). The primary outcome is the change in Hamilton Anxiety Rating Scale (HAMA) total score from baseline to Week 1. Secondary and exploratory assessments will include clinical symptoms, intolerance of uncertainty and related cognitive characteristics, treatment tolerability, adverse events, and EEG and MRI measures. Follow-up assessments will be conducted at Week 1, Week 4, and Week 8 from baseline to assess the durability of clinical effects and safety.

Inclusion Criteria: 1. Aged 18 to 55 years, inclusive, of any sex; 2. Diagnosis of generalized anxiety disorder (GAD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features; 3. Hamilton Anxiety Rating Scale (HAMA) total score of 14 or higher at screening; 4. Has completed at least junior high school education and has sufficient hearing, reading, writing, and comprehension abilities to complete study assessments; 5. Is willing and able to provide written informed consent and comply with study visits, treatment procedures, laboratory tests, and other study requirements. Exclusion Criteria: 1. Participants with a current or previous diagnosis of a major psychiatric disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), such as schizophrenia spectrum and other psychotic disorders or bipolar and related disorders; 2. Pregnancy or lactation; 3. Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma); 4. History of significant head injury or coma; 5. Received any standardized neuromodulation therapy targeting the nervous system within the past 6 months before enrollment, including but not limited to electroconvulsive therapy (ECT), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), or vagus nerve stimulation (VNS); 6. Suspected or confirmed history of alcohol or substance dependence; 7. Current severe suicidal ideation or recent suicide attempt; 8. Current participation in another clinical trial or recent use of prohibited psychotropic medications; 9. Positive urine drug screening or abnormal thyroid function tests; 10. Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG); 11. Inability to provide fully informed consent.