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.

Functional neuroanatomy of mania

“…Lesion network mapping is a recently developed neuroimaging methodology, developed to address this phenomenon [ 107 ], that takes advantageous of normative connectomes [ 108 , 109 ] to highlight regions that are functionally connected to each lesion location, thus resulting in brain network maps. Two studies have applied this approach to lesional mania [ 110 , 111 ]. Lee and colleagues showed that the temporal lobe and OFC, on both sides of the brain, were more functionally connected to lesion locations associated with mania than control lesions, with the possibility of negative connectivity with the DLPFC, also bilaterally, suggested.…”

Resting State Functional Connectivity Biomarkers of Treatment Response in Mood Disorders: A Review

“…There has been some recent progress in understanding mania as a state, although symptom specificity remains a challenge. For example, lesions associated with mania show a specific connectivity pattern that includes right orbitofrontal cortex, right inferior temporal gyrus, and right frontal pole ( 168 ). Future studies will continue to refine understanding of how mood is regulated throughout structurally or functionally connected brain networks.…”

A case of Sars-Cov-2-related mania with prominent psychosis>

“…It is conceivable that a transient inflammation, as well as direct neuroinvasion, had triggered - in a subject with a genetic predisposition - a cascade of events culminating in the alteration of excitatory and inhibitory circuits, ultimately leading to the onset of mania or other psychiatric disorders ( DeLisi, 2021 ) . Of note, the Sars-Cov-2-driven retrograde neuroinvasion through the olfactory pathway may favor access to the adjacent orbitofrontal cortex ( Le Guennec et al, 2020 ), a region whose dysregulation is known to be involved in manic disorders ( Cotovio et al, 2020 ).…”