Altered brain response to reward and punishment in adolescents with Anorexia nervosa

Abstract

Adults recovered from Anorexia nervosa (AN) have altered reward modulation within striatal limbic regions associated with the emotional significance of stimuli, and executive regions concerned with planning and consequences. We hypothesized that adolescents with AN would show similar disturbed reward modulation within the striatum and the anterior cingulate cortex, a region connected to the striatum and involved in reward-guided action selection. Using functional magnetic resonance imaging, twenty-two adolescent females (10 restricting-type AN, 12 healthy volunteers) performed a monetary guessing task. Time series data associated with monetary wins and losses within striatal and cingulate regions of interest were subjected to a linear mixed effects analysis. All participants responded more strongly to wins versus losses in limbic and anterior executive striatal territories. However, AN participants exhibited an exaggerated response to losses compared to wins in posterior executive and sensorimotor striatal regions, suggesting altered function in circuitry responsible for coding the affective context of stimuli and action selection based upon these valuations. As AN individuals are particularly sensitive to criticism, failure, and making mistakes, these findings may reflect the neural processes responsible for a bias in those with AN to exaggerate negative consequences.

Keywords: Anorexia nervosa; Cingulate; Functional magnetic resonance imaging; Reward; Striatum.

Figure 1

Overview of striatal and cingulate regions of interest (ROI) projections and response patterns in left) CA and right) AN. Black lines within the ROIs demonstrate approximate boundaries of each ROI. Colors indicate functional connectivity between subregions of the cingulate with the striatum, with reddish areas mainly associated with limbic function, orange/yellow mainly with executive function, and green/blue mainly with motor function. Monetary wins, being appetitive, were considered rewarding; monetary losses were considered punishment, as they represented the loss of an appetitive stimulus following an incorrect choice. + symbol: region responded more strongly to wins than to losses; − symbol: region responded more strongly to losses than to wins; ACC: anterior cingulate cortex; AN: ill adolescent females with anorexia nervosa; CA: healthy comparison adolescent females; Cd: caudate; IC: internal capsule; Nacc: nucleus accumbens; Put: putamen.

Figure 2

Limbic regions of interest showing a significant main effect of condition (win > loss). For each region, the left panel shows the region of interest mask overlaying the voxelwise analysis for visualization purposes; the right panel shows the mean percent signal change calculated across the entire region of interest. A) Left nucleus accumbens; B) left rostral anterior cingulate. Hot colors indicate voxels reflecting a greater response to wins relative to losses within the regions of interest. C) Analysis of variance showing a significant main effect of condition and the post hoc comparisons revealing directionality of the effect within limbic areas. The group x condition interaction was not significant. Where different, lowercase letters on the barplot indicate a significant difference of mean percent signal for the main effect of win > loss. AN: ill adolescent females with anorexia nervosa; CA: control adolescent females; FDR: false discovery rate.

Figure 3

Anatomical location and mean percent signal change for executive regions of interest demonstrating either a main effect of condition or a group x condition interaction. A) Left anterior caudate nucleus; B) left posterior caudate nucleus; C) right anterior putamen; D) left cognitive anterior cingulate cortex. Hot colors indicate voxels reflecting a greater response to wins relative to losses (or the group x condition interaction if the main effect of condition was not significant) within the regions of interest. E) Table of significant analysis of variance main effects, interactions, and post hoc comparisons. Where different, lowercase letters on the barplot indicate a significant difference of mean percent signal for the main effect of win > loss. AN: ill adolescent females with anorexia nervosa; CA: control adolescent females; FDR: false discovery rate. *p < 0.05; ****p < 0.0001

Figure 4

Anatomical location and mean percent signal change within sensorimotor regions of interest demonstrating a group by condition interaction for A) right posterior putamen; B) left motor cingulate. Hot colors indicate voxels reflecting a greater response to the group x condition interaction within the regions of interest. C) Analysis of variance reported a lack of a main effect of condition within sensorimotor areas. The group x condition interaction, however, was significant within the bilateral posterior putamen and motor cingulate. Only significant post hoc comparisons are shown. AN: ill adolescent females with anorexia nervosa; CA: control adolescent females; FDR: false discovery rate. *p < 0.05; ***p < 0.005.