TY - JOUR AU - Cotovio, Gonçalo AU - Talmasov, Daniel AU - Barahona-Corrêa, J. Bernardo AU - Hsu, Joey AU - Senova, Suhan AU - Ribeiro, Ricardo AU - Soussand, Louis AU - Velosa, Ana AU - Silva, Vera Cruz e AU - Rost, Natalia AU - Wu, Ona AU - Cohen, Alexander L. AU - Oliveira-Maia, Albino J. AU - Fox, Michael D. T1 - Mapping mania symptoms based on focal brain damage PY - 2020/10/01/ AB - BACKGROUND Although mania is characteristic of bipolar disorder, it can also occur following focal brain damage. Such cases may provide unique insight into brain regions responsible for mania symptoms and identify therapeutic targets.METHODS Lesion locations associated with mania were identified using a systematic literature search (n = 41) and mapped onto a common brain atlas. The network of brain regions functionally connected to each lesion location was computed using normative human connectome data (resting-state functional MRI, n = 1000) and contrasted with those obtained from lesion locations not associated with mania (n = 79). Reproducibility was assessed using independent cohorts of mania lesions derived from clinical chart review (n = 15) and of control lesions (n = 490). Results were compared with brain stimulation sites previously reported to induce or relieve mania symptoms.RESULTS Lesion locations associated with mania were heterogeneous and no single brain region was lesioned in all, or even most, cases. However, these lesion locations showed a unique pattern of functional connectivity to the right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole. This connectivity profile was reproducible across independent lesion cohorts and aligned with the effects of therapeutic brain stimulation on mania symptoms.CONCLUSION Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that lends insight into localization of mania symptoms and potential therapeutic targets.FUNDING Fundação para a Ciência e Tecnologia (FCT), Harvard Medical School DuPont-Warren Fellowship, Portuguese national funds from FCT and Fundo Europeu de Desenvolvimento Regional, Child Neurology Foundation Shields Research, Sidney R. Baer, Jr. Foundation, Nancy Lurie Marks Foundation, Mather’s Foundation, and the NIH. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI136096 VL - 130 IS - 10 UR - https://doi.org/10.1172/JCI136096 SP - 5209 EP - 5222 PB - The American Society for Clinical Investigation ER -