Mapping mania symptoms based on focal brain damage
Gonçalo Cotovio, … , Albino J. Oliveira-Maia, Michael D. Fox
Gonçalo Cotovio, … , Albino J. Oliveira-Maia, Michael D. Fox
Published August 24, 2020
Citation Information: J Clin Invest. 2020;130(10):5209-5222. https://doi.org/10.1172/JCI136096.
View: Text | PDF
Clinical Research and Public Health Neuroscience

Mapping mania symptoms based on focal brain damage

Abstract

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.

Authors

Gonçalo Cotovio, Daniel Talmasov, J. Bernardo Barahona-Corrêa, Joey Hsu, Suhan Senova, Ricardo Ribeiro, Louis Soussand, Ana Velosa, Vera Cruz e Silva, Natalia Rost, Ona Wu, Alexander L. Cohen, Albino J. Oliveira-Maia, Michael D. Fox

×

Figure 5

Stability of mania lesion network when controlling for various confounds.

Options: View larger image (or click on image) Download as PowerPoint
Stability of mania lesion network when controlling for various confounds...
The combined mania lesion network, using data from literature and clinical cohorts, remained similar when it was recomputed controlling for lesion size (n = 56 vs. n = 569 mania vs. control lesions) (A), when using a different set of control lesions (n = 56 vs. n = 409 mania vs. control lesions; see Methods for details) (B), and when using a subset of mania cases with shorter temporal association between lesion and symptom onset (n = 28 vs. n = 569 mania vs. control lesions) (C) or the remaining mania cases (n = 28 vs. n = 569 mania vs. control lesions; see Methods for details) (D). The lesion network was also similar when restricting analyses to subsets of lesional mania cases presenting with all core mania symptoms as listed in DSM 5 (n = 46 vs. n = 569 mania vs. control lesions) (E), with no personal or family history of relevant neuropsychiatric syndromes (n = 39 vs. n = 569 mania vs. control lesions) (F), caused by ischemic stroke (n = 23 vs. n = 569 mania vs. control lesions) (G), or accumulating all of the restrictions mentioned in E–G (n = 19 vs. n = 569 mania vs. control lesions) (H). Connectivity maps were obtained using a voxel-wise permutation-based 2-sample t test performed within FSL PALM (2000 permutations) and are displayed at an FWE-corrected level of P < 0.05, at MNI space z = –18. Regions more connected to mania lesions are shown in warm colors, while regions more connected to control lesions are shown in cool colors.