Lesions that Cause Psychosis Map to a Common Brain Circuit in the Hippocampus

Identifying the anatomy of circuits causal of psychosis could inform treatment targets for schizophrenia. We identified 155 published case reports of brain lesions that caused new- onset psychosis. We mapped connectivity of these lesions using a normative human fMRI connectome. Lesions causing psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus. This circuit was consistent both across individual symptoms of psychosis (delusions, hallucinations, and thought disorders), and when excluding lesions that touched the hippocampus. In an independent observational study (n=181), lesions connected to this circuit were preferentially associated with psychotic symptoms. A location in the rostromedial prefrontal cortex with high connectivity to this psychosis circuit was identified as a potential target for transcranial magnetic stimulation. Based on these results, we conclude that lesions that cause psychosis have common functional connections to the posterior subiculum of the hippocampus. ### Competing Interest Statement MDF has served as a scientific consultant for Magnus Medical and is owner of intellectual property involving the use of functional connectivity to target TMS, which was not used in the present study. SS is an owner of intellectual property involving the use of brain connectivity to target TMS; has served as a scientific consultant for Magnus Medical; has received investigator-initiated research funding from Neuronetics and Brainsway; has received speaking fees from Brainsway and Otsuka (for [PsychU.org][1]); and is a shareholder in Brainsway (publicly traded) and Magnus Medical (not publicly traded). All other authors declare they have no competing interests. [1]: https://PsychU.org