Valuation and Cognitive Circuitry in Anorexia Nervosa: Disentangling Appetite from the Effort to Obtain a Reward

Abstract

Motivation is classically defined as the amount of effort one is willing to expend to acquire a reward. In humans, rewards may range from basic or primary (e.g., drugs of abuse, sex, money, palatable food) to more complex, personal ones (e.g., social engagement or reciprocity, entertainment, hobbies), and working toward those rewards, whether immediate or distant, often guides the choices we make daily. Findings in healthy populations have identified key neural regions involved in anticipation, evaluation, and decision making during reward processing and demonstrated the impact of internal states modulating these, including stress (1) and sleep (2), among others. Disruption in these circuits underlies the pathophysiology of several neuropsychiatric conditions (i.e., addiction to substances, sex, and gambling; eating disorders; major depression and anxiety; autism). Of these conditions, anorexia nervosa (AN), marked by a refusal to consume adequate nutrients in a state of severe starvation, is one of the most difficult to treat and deadly (3). This fact owes largely to the necessity of the primary reward in question (food) to sustain health and, ultimately, life. Mounting evidence of neurohormonal dysfunction contributes to aberrant food reward and appetite in AN, but there is little clinical application of these findings to treatment. A study by Wierenga et al. (4) in this issue of Biological Psychiatry may have implications for enhancing efficacy of treatment for AN. Their study focuses on the impact of internal appetitive drive on brain activity during decision making for monetary cues in women remitted from AN (RAN) compared with healthy control (HC) women. This clever and wellformulated design sidesteps numerous potential confounders in identifying brain activity deficits in AN. In particular, rather than food cues, the authors used a robust delay discounting paradigm to assess immediate versus future valuation of monetary rewards; this design avoids the use of stimuli which commonly elicits anxiety in this population. The task simultaneously evokes neural response to reward and cognitive control, both of which are abnormal in AN. In a group of subjects (23 RAN women, 17 HC women) who were carefully phenotyped and medication-free, one of the novel features of the design was the counterbalanced task administration across two states of appetitive motivation: hunger (after 16-hour fast) and satiety (meal consumption 2 hours before the scan). The authors showed enhanced activity to immediate rewards in valuation circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during hunger in HC women compared with satiety but no differences across appetitive states in RAN women, who tended to show hyperactivity in these regions during satiation compared with HC women. The opposite trend emerged in HC women during decision making, with