Neuroanatomical Dysconnectivity Underlying Cognitive Deficits in Bipolar Disorder

Abstract

Background: Graph theory applied to brain networks is an emerging approach to understand the brains' topological associations with human cognitive ability. Despite well-documented cognitive impairments in bipolar disorder (BD) and recent reports of altered anatomical network organisation, the association between connectivity and cognitive impairments in BD remains unclear. Methods: We examined the role of anatomical network connectivity derived from T1and diffusion-weighted magnetic resonance imaging in impaired cognitive performance in individuals with BD (n=32) compared to healthy controls (n=38). Fractional anisotropy-and number of streamlines-weighted anatomical brain networks were generated by mapping constrained spherical deconvolutionreconstructed white matter between 86 cortical/subcortical bilateral brain regions delineated in the individual's own coordinate space. Intelligence and executive function were investigated as distributed functions using measures of global, rich-club and interhemispheric connectivity while memory and social cognition were examined in relation to subnetwork connectivity. Results: Lower executive functioning related to higher global clustering coefficient in bipolar participants, and lower IQ performance may present with a differential relationship between global and interhemispheric efficiency in BD relative to controls. Spatial recognition memory accuracy and response times were similar between diagnostic groups and associated with basal ganglia and thalamus interconnectivity and connectivity within extended anatomical subnetworks in all participants. No anatomical subnetworks related to episodic memory, short-term memory or social cognition generally or differently in BD. Conclusions: Results demonstrate selective influence of subnetwork patterns of connectivity in underlying cognitive performance generally and abnormal global topology underlying discrete cognitive impairments in BD.

Along-Tract Statistical Mapping of Microstructural Abnormalities in Bipolar Disorder: A Pilot Study

“…Intriguingly, significant group differences were found within posterior-cerebellar pathways in BD; these differences, may represent a compensatory mechanism to the dysconnectivity observed across fronto-limbic and inter-hemispheric projections when accounting for the microstructural organization of the bundle. The tracts implicated here connect regions that play important functional roles in the regulation of emotions, motivation, decision-making, and cognitive control [15], [18], which are impaired in BD. This pilot study, which requires replication, suggests that WM microstructure abnormalities in BD vary across an individual tract.…”

“…Graph-theory tools have been applied to whole-brain networks, with findings consistent with morphological disturbances in the corpus callosum, implicating inter-hemispheric structural dysconnectivity. Local structural and functional network alterations have been reported in prefrontal and limbic areas [6], [14], [15]. Network-based analyses (structural and functional) have also highlighted disturbances in broader circuit and network mechanisms that integrate cognitive control, affective and reward-systems of the brain [16]- [18].…”