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To overcome these limitations, we developed an invasive brain mapping paradigm in which electrodes were implanted across the OCD cortico-striato-thalamo-cortical circuit in a single individual. We then performed extensive stimulation mapping during a multi-day inpatient stay to identify personalized therapeutic targets and characterize their downstream circuit effects. We found two targets within the right ventral capsule (VC) that acutely reduced OCD symptoms. Prolonged VC stimulation suppressed high frequency activity within the structurally and functionally connected orbitofrontal cortex, which encoded the severity of OCD symptoms. These VC sites were implanted for DBS and combined stimulation of these targets led to a rapid therapeutic response. This case provides the first proof-of-concept that invasive brain mapping can be used to guide a novel personalized, multi-site neuromodulation approach to treat refractory OCD.<\/jats:p>","DOI":"10.1101\/2025.03.14.25323348","type":"posted-content","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T06:38:18Z","timestamp":1742452698000},"source":"Crossref","is-referenced-by-count":0,"title":["Invasive Brain Mapping Identifies Personalized Therapeutic Neuromodulation Targets for Obsessive-Compulsive Disorder"],"prefix":"10.64898","author":[{"given":"A","family":"Moses Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Kist","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Alvarez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin K","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ankit N","family":"Khambhati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo P","family":"Sugrue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee B","family":"Reid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Kadlec","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joline M","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anusha B","family":"Allawala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline A","family":"Racine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tenzin","family":"Norbu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dani","family":"Astudillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra G","family":"Tremblay-McGaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Alhourani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip A","family":"Starr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward F","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew D","family":"Krystal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025032100474744000_2025.03.14.25323348v1.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0133591"},{"key":"2025032100474744000_2025.03.14.25323348v1.2","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19060656"},{"key":"2025032100474744000_2025.03.14.25323348v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-01175-8"},{"key":"2025032100474744000_2025.03.14.25323348v1.4","doi-asserted-by":"crossref","unstructured":"Shirvalkar, P. , et al., A Deep Brain Stimulation Trial Period for Treating Chronic Pain. 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