Transcranial Alternating Current Stimulation to Enhance Mindfulness Therapy in Generalized Anxiety Disorder

Generalized anxiety disorder is characterized by excessive and difficult-to-control worry, often accompanied by physical symptoms and impaired daily functioning. Mindfulness-based therapy may help patients observe worry and anxiety-related bodily sensations with greater awareness and acceptance. Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that may modulate neural oscillations related to cognitive control and emotion regulation. This study will enroll 99 adults with generalized anxiety disorder. Eligible participants will be randomly assigned in a 1:1:1 ratio to one of three intervention groups: synchronous tACS plus mindfulness therapy, desynchronous tACS plus mindfulness therapy, or sham tACS plus mindfulness therapy. All groups will receive the same standardized mindfulness therapy program. The active tACS conditions will target the frontoparietal network, with stimulation parameters individualized according to each participant's alpha-band neurophysiological characteristics. The sham stimulation condition will mimic the initial and final sensation of stimulation while delivering no active current during the main stimulation period. Clinical, behavioral, and neurophysiological assessments will be collected at baseline and follow-up visits. Outcome assessments will include anxiety severity, depressive symptoms, worry, mindfulness, attention control, cognitive performance, adverse effects related to tACS, and multimodal measures such as electroencephalography, magnetic resonance imaging, and eye tracking. The study aims to determine whether individualized alpha-frequency tACS can improve the therapeutic effects of mindfulness therapy and to explore potential neural mechanisms underlying treatment response.