Project Summary Anorexia Nervosa (AN) is a serious eating disorder with a mortality rate among the highest of any psychiatric illness. Identifying modifiable targets for the development of novel AN interventions is crucial because leading treatments achieve remission rates of less than 50%, and relapse is common. One aspect of AN that likely contributes to poor long-term outcomes is maladaptive food choice, i.e., the persistent and stereotyped choice of low-calorie, low-fat foods. Food choice requires individuals to construct the subjective value of foods from a number of attributes. Yet, despite the centrality of food choice in AN, little is known about how people with AN construct the subjective values placed on foods, leading to maladaptive food-choice behavior. The overall goal of this research is to elucidate the cognitive and neural mechanisms that contribute to subjective food valuation in AN. Leveraging fMRI, eyetracking, and computational models that have advanced understanding of decision-making in healthy individuals, we propose two studies to examine: (1) how individuals with AN combine across attributes to construct subjective value for food; (2) how the cognitive and neural mechanisms that contribute to valuation and food choice differ between individuals with AN and healthy controls (HC); and (3) how the value construction process can be biased to influence food choice. Study 1 will examine choices, reaction times, eyetracking, and fMRI measures obtained while individuals with AN (n=75) and HC (n=75) perform a novel multi-attribute decision task during which they will rate food items on attributes such as healthiness, tastiness, and savoriness, and then choose between 2 “meals” each composed of three different food items from different categories. We hypothesize that compared to HC, individuals with AN will base their subjective valuation of meal options largely on healthiness-related attributes and attend more to healthiness- related attributes. We also hypothesize that representations of healthiness in patterns of BOLD activity in the orbitofrontal cortex (OFC) will be more related to food choice in AN than HC. Study 2 will use cue-approach training (CAT), which has shown that the mere association of a cue and an action (a button press) with an image leads to enduring preference changes and attentional biases in favor of cued items. We will combine CAT with multi-attribute choices used in Study 1 and cue highly tasty foods for all participants. We hypothesize that attentional bias following CAT will alter the value construction process in AN (but not HCs) by increasing the value of tastiness attributes, and that healthiness representations in patterns of BOLD activity in AN OFC will be no more related to meal choices than tastiness representations. This research is the first effort to identify mechanisms underlying subjective food valuation in AN, and test whether value construction can be altered to normalize food-choice behavior. Results will inform the development of novel, neuroscience-based interventions designed to modify food preferences in AN and enhance the efficacy of existing treatments.

Project Narrative Anorexia Nervosa (AN) is a serious and sometimes deadly psychiatric illness characterized by distortions in valuation for food that drive rigid and stereotyped food choices and lead to dangerously low body weight. We propose to examine the cognitive and neural mechanisms that underlie subjective food value construction that drive maladaptive food choices in AN using state-of-the-art cognitive neuroscience methods and computational modeling to determine how this process arises and how it can be biased to normalize decisions about what to eat. The proposed studies will develop a new pathway for understanding and treating the salient behavior of restrictive eating that contributes to the significant disease burden of Anorexia Nervosa.