Mapping Lesions That Cause Psychosis to a Human Brain Circuit and Proposed Stimulation Target

作者：Andrew R. Pines, Summer Frandsen, William Drew, Garance M. Meyer, Calvin Howard, Stephan Palm, Frédéric Schaper, Christopher Lin, Konstantin Butenko, Michael A. Ferguson, Maximilian Friedrich, Jordan Grafman, Ari D. Kappel, Clemens Neudorfer, Natalia S. Rost, Lauren L. Sanderson, Joseph J. Taylor, Ona Wu, Isaiah Kletenik, Jacob W. Vogel, Alexander L. Cohen, Andreas Horn, Michael Fox, David Silbersweig, Shan Siddiqi · 发表于：JAMA Psychiatry · 年份：2025 · DOI：10.1001/jamapsychiatry.2024.4534 · 被引用次数：32 · 研究领域：Schizophrenia research and treatment、Neurological disorders and treatments、Mental Health and Psychiatry

Importance: Identifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia. Objective: To assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit. Design, Setting, and Participants: This case-control study mapped functional connections of published cases of lesions causing secondary psychosis compared with control lesions unassociated with psychosis. Published cases of lesion-induced psychosis were analyzed in a computational laboratory. Participants had documented brain lesions associated with new-onset psychotic symptoms without a history of psychosis. Control cases included 1156 patients with lesions not associated with psychosis. Generalizability across lesional datasets was assessed using an independent cohort of 181 patients with brain lesions who subsequently underwent neurobehavioral testing. Data were analyzed from June 2022 to April 2024. Exposures: Lesions causing secondary psychosis. Main Outcomes and Measures: Psychosis or no psychosis. Results: A total of 153 lesions from published cases were determined to be causal of psychosis, 42 of which were described as schizophrenia or schizophrenia-like (71 [46%] patients were male, 82 [54%] female; mean [SD] age, 50.0 [20.8] years). Lesions that caused secondary psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus (84% functional overlap, family...