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

Generalized anxiety disorder (GAD) is characterized by persistent and excessive anxiety and worry. Intolerance of uncertainty is an important cognitive feature associated with pathological worry. The amygdala and bed nucleus of the stria terminalis (BNST) contribute to threat processing, with evidence suggesting differences in their responses to brief and sustained threats. Comparing interventions targeting these regions may help clarify their contributions to anxiety symptoms, intolerance of uncertainty, and persistent worry. Temporal interference stimulation uses two kilohertz-frequency alternating currents with a small frequency difference to generate an amplitude-modulated electric field envelope at the difference frequency. This study will compare right BNST-targeted and right amygdala-targeted stimulation using a 5-Hz envelope, with sham stimulation as the control. Individualized head models will be constructed from each participant's T1-weighted magnetic resonance images. Electric field modeling will guide scalp electrode placement for the assigned target. Stimulation intensity will be individually adjusted according to participant tolerability within a range of 1.5-3.5 mA per channel, expressed as zero-to-peak amplitude. Electroencephalography and magnetic resonance imaging will be used to investigate changes in theta-band activity and functional connectivity within anxiety-related networks. Associations between these changes and improvements in clinical symptoms and cognitive measures will be examined to explore the neural mechanisms of stimulation at the two targets. Peripheral blood samples will be collected at baseline, Week 1, and Week 8 and stored for future exploratory biomarker analyses related to GAD and treatment response.