Investigating the feasibility and safety of transcranial infraslow gray noise stimulation as a potential treatment for generalized anxiety disorder.

Anxiety is a beneficial behavior that assists survival, although when high levels of anxiety persist it can hinder normal functioning. Despite numerous treatment options most individuals with Generalized Anxiety Disorder (GAD) continue to suffer from the disorder. A novel neuromodulatory treatment that safely and non-invasively alters pathological neural circuitry associated with GAD is required. Therefore, this study investigates the feasibility, safety, and effect of a new innovative High-Definition Transcranial Infraslow Gray Noise Stimulation (HD-tIGNS) targeting the anxiety network in people with GAD, in a delayed-start double-blinded randomized sham-controlled pilot trial (N = 22). HD-tIGNS was applied three times per week for three [delayed-start (following 3-weeks of actisham)], or six weeks (early-start). Anxiety questionnaires and electroencephalography were taken at baseline, mid-treatment, and post-treatment. On average, six participants were recruited per month with a mean treatment adherence of 99.5%, and an 8.3% dropout rate of enrolled participants. Clinically meaningful changes in GAD-7 were observed in 45% (early-start group) and 36% (delayed-start group) of participants following 6-weeks and 3-weeks of intervention respectively. No significant differences in brain activity or functional connectivity were observed. This study provides evidence supporting HD-tIGNS as a safe and feasible treatment approach for GAD, however future research should consider alternate network targets.