PROJECT SUMMARY The dominant source of calories in the American diet is now ultra-processed (UP) foods that are composed of mostly cheap industrial sources of dietary energy and nutrients plus additives. UP foods are capable of triggering addictive-like changes in the brain and are strongly associated with indicators of substance use disorders (SUD), including an escalating, compulsive pattern of intake that occurs despite negative consequences. The ability of UP foods to trigger withdrawal has received little study in humans, despite compelling animal model evidence. Withdrawal in SUD is marked by the emergence of aversive physical, cognitive and affective symptoms and increased motivational salience of substance-related cues during abstinence in chronic users. If UP foods are capable of triggering a similar response, aversive withdrawal symptoms and increased motivational salience to UP food cues may be a significant obstacle to dietary change and a novel intervention target. Investigating whether reducing UP food intake results in withdrawal could also inform the ongoing scientific debate of whether UP foods are addictive, which has important theoretical and practical implications. Our overall objectives in this application are to determine whether a reduction in UP food intake: 1) causes withdrawal symptoms, and 2) increases the motivational salience of UP food cues and, if so, whether these factors undermine maintenance of a low-UP diet. We will achieve our objectives by testing the following specific aims using a within-subject design in 200 high-risk individuals: Aim 1: To investigate whether aversive physical, cognitive, and affective withdrawal symptoms emerge in response to reduced UP food intake compared to a calorically equivalent high-UP diet, and whether this predicts failure to maintain a low-UP diet. H1a: Reducing UP food intake will result in aversive physical, cognitive, and affective withdrawal symptoms, as indicated by 1) Ecological Momentary Assessment (EMA) reports of aversive withdrawal symptoms, and 2) heart rate reactivity and subjective distress to an in-lab stressor. H1b: Aversive symptoms of UP food withdrawal will predict greater UP food intake and higher blood glucose levels during dietary maintenance. Aim 2: To investigate whether increased motivational salience of UP food cues emerges in response to reduced UP food intake, and whether this predicts failure to maintain a low-UP diet. H2a: Reducing UP food intake will result in increased motivational salience of UP food cues, as indicated by 1) EMA reports of UP food craving, 2) heart rate reactivity and subjective craving in a simulated fast-food restaurant, 3) attentional biases for UP foods, and 4) greater reward-related neural response to UP food cues. H2b: Increased motivational salience of UP food cues will predict greater UP food intake and higher blood glucose levels during dietary maintenance.