Altered Insula Activity during Visceral Interoception in Weight-Restored Patients with Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is a devastating psychiatric illness that is associated with significant morbidity and mortality. Aberrant visceral interoceptive processing within the insula has been hypothesized to be an important mechanism in AN's pathophysiology due to the theoretical link between interoception and emotional experience. We therefore utilized functional magnetic resonance imaging (fMRI) to examine whether altered insula functioning underlies visceral interoception in AN. Fifteen females with restricting-type AN and 15 healthy control females underwent fMRI while performing an interoceptive attention task during which they focused on sensations in their heart, stomach, and bladder. Participants also performed an anxious rumination task while in the scanner. AN participants were weight-restored and free of psychotropic medications. Two distinct regions of the insula-anterior insula and dorsal mid-insula-exhibited a significant (p<0.05) interaction between group and interoceptive modality. The post hoc analyses revealed that in the dorsal mid-insula the interaction was driven by group differences during stomach interoception (p=0.002, Bonferroni corrected), whereas in the anterior insula the interaction was driven by group differences during heart interoception (p=0.03, Bonferroni corrected). In addition, individuals with AN displayed increased activation during anxious rumination in the dorsal mid-insula, and activation in this region during stomach interoception was correlated with measures of anxiety and psychopathology. This relationship between altered visceral interoception and clinical symptoms in AN suggests an important mechanism for the disorder. Additional research is needed to examine whether interventions targeting visceral interoception may increase the efficacy of treatments for AN.

Figure 1

Focused awareness task design. The focused awareness task consisted of three types of trials: interoceptive attention (IA), anxious rumination trials, and exteroceptive trials. During IA trials, participants focused on the body part indicated by the word on the screen (stomach, heart, or bladder). During anxious rumination trials, participants ruminated about worrisome situations related to the word presented on the screen (peers, family, or academics). Exteroceptive trials were used as a baseline condition for the interoceptive trials. During exteroceptive trials, the font color of the word ‘TARGET' repeatedly changed to a lighter shade of gray, and participants focused on the intensity of the color change. Half of the trials in each condition were followed by a rating scale on which participants rated their experience (intensity of bodily sensations, anxious rumination, or color change) during that trial.

Figure 2

Altered insula activity during visceral interoception in patients with anorexia nervosa. A region-of-interest analysis (voxel-wise threshold p<0.005, cluster size corrected for multiple comparisons at p<0.05) revealed two separate insula regions—the dorsal mid-insula and anterior insula—that exhibited a significant Group (AN, HC) × Interoceptive Modality (heart, stomach, bladder) interaction. The post hoc simple effects analyses revealed that the interaction in the dorsal mid-insula was because of group differences during stomach interoception (p<0.002, Bonferroni corrected), whereas in the anterior insula the interaction resulted from group differences during heart interoception (*p<0.03, Bonferroni corrected).

Figure 3

Anorexia nervosa is associated with aberrant activation in the dorsal mid-insula during anxious rumination. A region-of-interest analysis of activation during anxious rumination in the two insula clusters that exhibited an interaction during visceral interoception revealed significant group differences in the dorsal mid-insula (*p<0.04) but not the anterior insula (p=0.20).