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One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital\/Rhode Island Hospital\/Alpert Medical School of Brown University) and S\u00e3o Paulo, Brazil (University of S\u00e3o Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size\/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (\u226535% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal\u2013ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.<\/jats:p>","DOI":"10.1038\/s41398-023-02425-2","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T03:26:50Z","timestamp":1682479610000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response"],"prefix":"10.1038","volume":"13","author":[{"given":"N. C. R.","family":"McLaughlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-0603","authenticated-orcid":false,"given":"J. 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NCRM has received research support from the NIH (5K23MH100607) and the National Institute of General Medical Sciences (5P20GM130452). SAS acknowledges support from the McNair Foundation and Dana Foundation and is a consultant for Boston Scientific, Zimmer Biomet, Abbott, and Neuropace. SS has no relevant disclosures related to the current work. He receives research support for the conduct of clinical trials from Lilly, Biogen, Genentech, Avid, Roche, Eisai, and Novartis. He was a site PI for the PRIME, ENGAGE, Clarity, and Trailblazer 1 trials. He is a co-chair of the investigator steering committee for the aducanumab phase 3 program and he is the Project Arm Leader for gantenerumab in the DIAN-TU study. He is a consultant to Lilly, Biogen, Roche, Genentech, Eisai, Bolden, Amylyx, NovoNordisk, Prothena, Ono and Alnylam. He owns no stocks or equity in any pharmaceutical company and has no patents or royalties. BDG has received research funding from the Dana Foundation, and research funding from Neurolief, Inc. WFA has research support through the Medtronic External Research Program, and is a site PI for multi-site clinical trials supported by Functional Neuromodulation Inc., Vivonics Inc. and Biogen Inc. All other authors report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"134"}}