Central Autonomic Network Alterations in Anorexia Nervosa Following Peripheral Adrenergic Stimulation

Abstract

Background: Anorexia nervosa (AN) is characterized by low body weight, disturbed eating, body image disturbance, anxiety, and interoceptive dysfunction. However, the neural processes underlying these dysfunctions in AN are unclear. This investigation combined an interoceptive pharmacological probe, the peripheral β-adrenergic agonist isoproterenol, with resting-state functional magnetic resonance imaging to examine whether individuals with AN relative to healthy comparison participants show dysregulated neural coupling in central autonomic network brain regions.

Methods: Resting-state functional magnetic resonance imaging was performed in 23 weight-restored female participants with AN and 23 age- and body mass index-matched healthy comparison participants before and after receiving isoproterenol infusions. Whole-brain functional connectivity (FC) changes were examined using central autonomic network seeds in the amygdala, anterior insular cortex, posterior cingulate cortex, and ventromedial prefrontal cortex after performing physiological noise correction procedures.

Results: Relative to healthy comparison participants, adrenergic stimulation caused widespread FC reductions in the AN group between central autonomic network regions and motor, premotor, frontal, parietal, and visual brain regions. Across both groups, these FC changes were inversely associated with trait anxiety (State-Trait Anxiety Inventory-Trait), trait depression (9-item Patient Health Questionnaire), and negative body image perception (Body Shape Questionnaire) measures, but not with changes in resting heart rate. These results were not accounted for by baseline group FC differences.

Conclusions: Weight-restored females with AN show a widespread state-dependent disruption of signaling between central autonomic, frontoparietal, and sensorimotor brain networks that facilitate interoceptive representation and visceromotor regulation. Additionally, trait associations between central autonomic network regions and these other brain networks suggest that dysfunctional processing of interoceptive signaling may contribute to affective and body image disturbance in AN.

Keywords: Autonomic; Eating disorders; Functional connectivity; Imaging; Interoception; Sympathetic arousal.

Figure 1.

Location of central autonomic network (CAN) seed regions of interest: ventromedial prefrontal cortex (orange), posterior cingulate cortex (green), amygdala (left and right, red), and anterior insular cortex (left and right, blue).

Figure 2.

Top: T-maps of group x time interaction for the left anterior insula (blue), left amygdala (red), vmPFC (yellow) and PCC (green). Bottom: Interaction plots for selected clusters with connectivity values before (T₁) and after isoproterenol infusion (T₂), specifically for (A) the left anterior insula to mPFC, (B) the left amygdala to right insula, (C) the vmPFC to left parietal cortex. Abbreviations: AN, anorexia nervosa; HC, healthy comparison; mPFC, medial prefrontal cortex; PCC, posterior cingulate cortex; vmPFC, ventromedial prefrontal cortex.

Figure 3.

Regional associations between changes in FC with trait measures of anxiety (STAI-Trait) and body image (BSQ) across AN and HC groups. For illustrative purposes, selected relationships are displayed: each scatterplot shown reflects the FC-trait association indicated by the black arrow in the adjacent glass brain. The black line in each plot indicates the correlation slope. Blue diamonds represent healthy individuals, and red circles represent AN individuals. All reported p-values are Bonferroni-corrected and two-tailed. Abbreviations: AIns, anterior insula; BSQ, Body Shape Questionnaire; IFG, inferior frontal gyrus; IP, inferior parietal; M1, primary motor cortex; PCC, posterior cingulate cortex; OFG, orbitofrontal gyrus; S1, primary somatosensory cortex; STAI: State Trait Anxiety Inventory; V1, primary visual cortex; vmPFC, ventromedial prefrontal cortex.

Figure 4.

FC differences between AN and HC for the PCC seed region at baseline (i.e., before receiving the isoproterenol infusion). A cluster of reduced functional connectivity was observed between the PCC seed and an anterior medial PFC cluster in AN. The cluster is significant at α < 0.05 after cluster-based correction (> 130 contiguous voxels as determined by AFNI’ 3dClustSim) with voxel-wise p < 0.001. For visualization purposes, the violin plot indicates the FC values of each group in the cluster. Abbreviations: FC, functional connectivity.