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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                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u200922). 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.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-27624-3","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T09:36:12Z","timestamp":1765964172000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the feasibility and safety of transcranial infraslow gray noise stimulation as a potential treatment for generalized anxiety disorder"],"prefix":"10.1038","volume":"15","author":[{"given":"Cindy","family":"van Sleeuwen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Adhia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Glue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"De Ridder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"27624_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1037\/0033-295X.105.2.325","volume":"105","author":"JB Rosen","year":"1998","unstructured":"Rosen, J. 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