Lesion network mapping of mania symptoms caused by focal brain lesions [Meeting Abstract]
Background: While mania is characteristic of Bipolar I Disorder, it has been reported following focal brain lesions for nearly a century. The localization of secondary manic symptoms is poorly understood, as mania has been reported following damage to multiple brain locations.
Objective(s): We utilize the human connectome to study cases of mania following focal brain lesions, provide insight into brain regions responsible for manic symptoms, and identify potential therapeutic targets.
Method(s): We identified two independent patient cohorts with mania attributed to focal brain lesions; a literature cohort from published case-reports (n=41) and a clinical cohort from chart review (n=15). Lesion locations were 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 fMRI, n=1000). Results were compared to lesion locations not associated with mania (n=569), lesion locations associated with symptoms potentially related to mania (n=274), and transcranial magnetic stimulation sites reported to induce/relieve mania symptoms.
Result(s): Lesion locations associated with mania were heterogeneous; no single brain region was lesioned in all or even most cases. However, these lesion locations showed a unique pattern of connectivity to the right-sided orbitofrontal cortex, right inferior temporal gyrus and right frontal pole. This connectivity profile was reproducible across independent cohorts, matched that of lesions associated with co-morbid symptoms, and aligned with effects of therapeutic brain stimulation on mania symptoms.
Conclusion(s): Brain lesions associated with mania are characterized by a specific pattern of brain connectivity that appears relevant for understanding co-morbid symptoms and identifying therapeutic targets