Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis

Abstract

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

Figure 1

Connection strength results. ACC, anterior cingulate cortex; AN, anorexia nervosa; BLA, basolateral amygdala; BN, bulimia nervosa; CNA, central nucleus of the amygdala; CW, Controls; Dors Ant Insula, dorsal anterior insula; Front Oper, frontal operculum; Inf OFC, inferior orbitofrontal cortex; L, left; Med OFC, medial orbitofrontal Cortex; Medial PFC, BA 10, medial prefrontal cortex, Brodmann Area 10; Mid OFC, middle orbitofrontal cortex; Post Insula, posterior insula; R, right; Rectus, gyrus rectus; SN, substantia nigra; Ventr Ant Insula, ventral anterior insula; VS, ventral striatum; VMP Thalamus, ventral posterior medial thalamus.

Figure 2

Effective connectivity. ACC, anterior cingulate cortex; AN, anorexia nervosa; BLA, basolateral amygdala; BN, bulimia nervosa; CNA, central nucleus of the amygdala; CW, Controls; Dors Ant Insula, dorsal anterior insula; Front Oper, frontal operculum; Inf OFC, inferior orbitofrontal cortex; L, left; Med OFC, medial orbitofrontal cortex; Medial PFC, BA 10, medial prefrontal cortex, Brodmann Area 10; Mid OFC, middle orbitofrontal cortex; Post Insula, posterior insula; R, right; Rectus, gyrus rectus; SN, substantia nigra; Ventr Ant Insula, ventral anterior insula; VMP Thalamus, ventral posterior medial thalamus; VS, ventral striatum. For AN and BN, solid lines indicate similar pattern and dashed lines indicate different pattern between AN and BN groups. Yellow lines are used for left- and right-sided connections in the CW. For the AN and BN groups, red lines indicate left-sided connections and purple lines indicate right-sided connections.