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 (po0.05) 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.

How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia

“…The necessity of this pathway for intact drugseeking behavior is supported by translational research in rodents, where temporary inactivation of the interoceptive insula disrupts drug-induced place preference (Contreras et al, 2007) and drug self-administration (Forget et al, 2010), and by clinical research in human patients identifying that insula lesions disrupt addiction (Naqvi et al, 2007). Similarly, in psychiatric disorders such as anorexia and major depression, abnormal interoceptive insula activity is associated with abnormal feeding behavior (Avery et al, 2014;Kerr et al, 2016;Simmons et al, 2016). Taken together, the identification of this relationship between craving and interoceptive activity in the insula may serve to identify specific neural targets for interventions to help humans discontinue unhealthy, but rewarding, behaviors (see Supplementary Materials for limitations and additional discussion).…”

Influence of Visceral Interoceptive Experience on the Brain's Response to Food Images in Anorexia Nervosa

“…Likewise, this same study demonstrated that numerous behavioral markers of illness severity were linearly related to atypical activity in the insula during stomach interoception, but not heart or bladder interoception. These findings are important in light of other evidence demonstrating that gastric sensations are both readily paired with food cues (2) and are related to activity in the mid-insula (1,3), and homeostatic signals related to energy availability modulate the response of interoceptive insula cortex to food (4). Indeed, the mid-insula has long been known to activate to the sight of food (5–9), suggesting that it may play an important role in inferences about the interoceptive consequences of visually perceived foods.…”

“…Although food avoidance may be driven by a number of factors, including a fear of fatness or desire for control, it may also be that individuals with AN have fundamentally altered interoceptive (i.e., brain-body) signaling that causes them to experience sensations from their bodies (particularly their stomachs) differently, thereby altering the homeostatic significance of food stimuli. Indeed, a recent study provides evidence that individuals with AN exhibit altered activity in the mid-insula, a key interoceptive region in the brain, while attending to stomach sensations (1). Likewise, this same study demonstrated that numerous behavioral markers of illness severity were linearly related to atypical activity in the insula during stomach interoception, but not heart or bladder interoception.…”

Psychological risk factors, cognitive-contextual approaches and neural correlates in eating disorders: an integrative review

“…Moreover, it is thought that interoceptive awareness is altered in ED patients, as these patients may be hypersensitive to interoceptive sensations due to its constant monitoring [41]. Dorsal mid-insula activity was found to be increased in AN compared to controls specifically to stomach sensations but not to other interoceptive attention types, with this activation being negatively correlated with measures of trait and state anxiety, and harm avoidance.…”