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Lesion network localization of functional and somatic symptoms

Milano, B. A.; Palm, S.; Burke, M. J.; Drew, W.; Kletenik, I.; Pines, A.; Corbetta, M.; Grafman, J.; Downar, J.; Siddiqi, S. H.

2025-03-07 psychiatry and clinical psychology
10.1101/2025.03.06.25323494 medRxiv
Show abstract

Functional and somatic symptoms with no detectable structural abnormalities are a common cause of disability. These symptoms are widely believed to have neuropsychiatric origins, and thus may respond to network-targeted brain stimulation. To derive a network-based target, we studied functional and somatic disability after focal brain lesions. Using a normative human connectome database (n=1000), we mapped the circuitry functionally connected to lesions that selectively influence such symptoms in two datasets. First, in ischemic stroke (n=101), we mapped a network causally associated with self-reported functional disability, independent of individual measures of disability. In an independent sample with penetrating head trauma (n=181), lesions connected to our network were associated with greater somatic concern (p=0.001). Across both datasets, functional and somatic symptoms were most associated with lesions connected to the orbitofrontal cortex (pFWE<0.01) and dorsal anterior cingulate, which we propose as potential brain stimulation targets.

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