Large-Scale Exploration of Whole-Brain Structural Connectivity in Anorexia Nervosa: Alterations in the Connectivity of Frontal and Subcortical Networks

Background: Anorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding eating and weight. The severity of AN combined with the absence of localized brain abnormalities suggests distributed, systemic underpinnings that may be identified using diffusion-weighted magnetic resonance imaging and tractography to reconstruct white matter pathways.

Methods: Diffusion-weighted magnetic resonance imaging data acquired from female patients with AN (n= 147) and female healthy control (HC) participants (n = 119), ages 12 to 40 years, were combined across 5 studies. Probabilistic tractography was completed, and full-cortex connectomes describing streamline counts between 84 brain regions were generated and harmonized. Graph theory methods were used to describe alterations in network organization in AN. The network-based statistic tested between-group differences in brain subnetwork connectivity. The metrics strength and efficiency indexed the connectivity of brain regions (network nodes) and were compared between groups using multiple linear regression.

Results: Individuals with AN, relative to HC peers, had reduced connectivity in a network comprising subcortical regions and greater connectivity between frontal cortical regions (p < .05, familywise error corrected). Node-based analyses indicated reduced connectivity of the left hippocampus in patients relative to HC peers (p < .05, permutation corrected). Severity of illness, assessed by body mass index, was associated with subcortical connectivity (p < .05, uncorrected).

Conclusions: Analyses identified reduced structural connectivity of subcortical networks and regions, and stronger cortical network connectivity, among individuals with AN relative to HC peers. These findings are consistent with alterations in feeding, emotion, and executive control circuits in AN, and may direct hypothesis-driven research into mechanisms of persistent restrictive eating behavior.