Neural representations of anxiety in adolescents with anorexia nervosa: a multivariate approach

Abstract

Anorexia nervosa (AN) is characterized by low body weight, fear of gaining weight, and distorted body image. Anxiety may play a role in the formation and course of the illness, especially related to situations involving food, eating, weight, and body image. To understand distributed patterns and consistency of neural responses related to anxiety, we enrolled 25 female adolescents with AN and 22 non-clinical female adolescents with mild anxiety who underwent two fMRI sessions in which they saw personalized anxiety-provoking word stimuli and neutral words. Consistency in brain response patterns across trials was determined using a multivariate representational similarity analysis (RSA) approach within anxiety circuits and in a whole-brain voxel-wise searchlight analysis. In the AN group there was higher representational similarity for anxiety-provoking compared with neutral stimuli predominantly in prefrontal regions including the frontal pole, medial prefrontal cortex, dorsolateral prefrontal cortex, and medial orbitofrontal cortex, although no significant group differences. Severity of anxiety correlated with consistency of brain responses within anxiety circuits and in cortical and subcortical regions including the frontal pole, middle frontal gyrus, orbitofrontal cortex, thalamus, lateral occipital cortex, middle temporal gyrus, and cerebellum. Higher consistency of activation in those with more severe anxiety symptoms suggests the possibility of a greater degree of conditioned brain responses evoked by personally-relevant emotional stimuli. Anxiety elicited by disorder-related stimuli may activate stereotyped, previously-learned neural responses within- and outside of classical anxiety circuits. Results have implications for understanding consistent and automatic responding to environmental stimuli that may play a role in maintenance of AN.

Multivariate Neural Patterns of Reward and Anxiety in Adolescents with Anorexia Nervosa

“…Our previous work [20] found higher representational similarity in AN for anxiety-provoking compared to neutral stimuli in prefrontal regions, including the frontal pole, medial prefrontal cortex, dorsolateral prefrontal cortex (dlPFC), and mOFC. These results clarify which nodes within a larger anxiety network are contributing to consistent responses to anxiety-inducing word stimuli, supporting theories that altered mechanisms of cognitive control could be engaged by frontal brain areas in AN in an anxious state [21].…”

“…Previous research has suggested that high anxiety might 'hijack' the reward response, a concept explored in various contexts [22][23][24], but which has not been tested in AN. Given the high salience of disorder-specific anxiety-inducing stimuli in AN [9], and previously found consistent responses to anxiety provocation [20], we hypothesized that AN individuals would exhibit more consistent reward responses. This would be due to consistent effects trialby-trial of induced anxiety on reward responses, reflected in higher RS in reward regions in AN compared to controls.…”