Focused Ultrasound for Behavioral Health

Following a remote pre-screen and an in-person screening/baseline visit (Visit 0), at which informed consent is obtained, eligibility is confirmed, baseline clinical scales are administered, optional biospecimens are collected from participants who consent to them, a multi-sequence brain MRI is acquired for targeting, and monitoring devices are fitted, each participant receives between 3 and 10 ATTN201 stimulation sessions spaced approximately 7 days apart. Each stimulation visit serves as the pre-stimulation baseline for that session, the 1-week post-stimulation measurement for the prior session, and the 2-week post-stimulation measurement for the session before that. A platform-administered scale battery at day 7 after the last stimulation captures the 1-week measurement for the final session; a remote final treatment-period follow-up approximately 2 weeks after the last stimulation captures the 2-week measurement. A remote 3-month post-treatment check-in captures durability and any delayed adverse events. The trial uses a two-stage architecture. In Stage 1, visits are allocated across all seven candidate targets. After approximately 300 visits, the Sponsor and ARPA-H convene a joint review and select 3-5 targets for continued Bayesian optimization in Stage 2. Monitoring during enrollment includes validated clinical scales (PHQ-9, GAD-7, OCI-R) at baseline, before each stimulation visit, at the final treatment-period follow-up, and at the 3-month follow-up; transdiagnostic visual analog scales, a morning sleep diary, and brief voice recordings prompted through the Attune platform during monitoring blocks; optional nightly ambulatory EEG; and a smart watch worn from Visit 0 through device return. All scheduled platform prompts are voluntary at the individual-prompt level. Blinding: A single on-site research associate positions the device, runs the stimulation session, and administers participant-facing assessments, and is blinded to the brain target and parameter combination; this individual occupies both the care provider and the outcomes assessor role. The stimulation condition is selected by the Bayesian optimization algorithm and pushed to the device as a sealed session. The Lead Principal Investigator and the optimization team are unblinded as required to operate the adaptive design and do not deliver stimulation or administer participant-facing assessments. The independent Medical Monitors and the Data Safety and Monitoring Board receive unblinded safety data.