TY - JOUR
T1 - Mapping mania symptoms based on focal brain damage
AU - Cotovio, Gonçalo
AU - Talmasov, Daniel
AU - Bernardo Barahona-Corrêa, J.
AU - Hsu, Joey
AU - Senova, Suhan
AU - Ribeiro, Ricardo
AU - Soussand, Louis
AU - Velosa, Ana
AU - Cruz e Silva, Vera
AU - Rost, Natalia
AU - Wu, Ona
AU - Cohen, Alexander L.
AU - Oliveira-Maia, Albino J.
AU - Fox, Michael D.
PY - 2020/10/1
Y1 - 2020/10/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85092239906&partnerID=8YFLogxK
U2 - 10.1172/JCI136096
DO - 10.1172/JCI136096
M3 - Article
C2 - 32831292
AN - SCOPUS:85092239906
SN - 0021-9738
VL - 130
SP - 5209
EP - 5222
JO - The Journal of Clinical Investigation (JCI)
JF - The Journal of Clinical Investigation (JCI)
IS - 10
ER -