Rule-Based Decision-Making: A Novel Neuroeconomic Mechanism of Anorexia Nervosa

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PROJECT SUMMARY/ABSTRACT Cognitive and behavioral inflexibility are key features of many severe psychiatric disorders. One particularly dangerous prototype of behavioral rigidity is evident in the relentless pursuit of weight loss in anorexia nervosa (AN), a disorder with alarmingly high morbidity and mortality rates. Prior efforts to intervene upon psychological inflexibility in AN have been ineffective. This may be due to inflexibility encompassing a broad set of cognitive and behavioral processes that can result from multiple distinct decision dysfunctions that require different interventions. Decision Neuroscience, which integrates translational and computational neuroscience with economics, offers a promising new paradigm for enhancing the precision of mechanistic science for psychiatric disorders. This approach posits that mental illnesses result from unique miscalculations performed by neurally- separable decision systems that can be probed with neuroeconomic paradigms. This approach holds promise for identifying precise treatment targets suited for different forms of psychiatric illness. Our pilot data derived from a Decision Neuroscience approach using a novel neuroeconomic paradigm (the Web-Surf task) have provided several insights into unique decision-making processes in AN. First, on this task, individuals with AN showed a distinct decision dysfunction suggesting overreliance on a rule-based decision system, reflected through rapid decision-making focused on maximizing long-term goals. This approach can lead to behavior that is inflexible and insensitive to current context. Second, this decision system appeared to be supported by hyperactivity within the frontoparietal cognitive control circuit (e.g., dorsolateral and ventrolateral prefrontal cortex), which is involved in long-term rule-following. Third, these biobehavioral patterns were linked to BMI and short-term weight-control behavior in AN. This frontoparietal-driven rule-based decision process differs from other decision-making patterns (e.g., fronto-dorsal striatal habit learning) that have been implicated in promoting behavioral rigidity in other psychiatric disorders, such as OCD. To extend this research to establish whether decision patterns distinguish AN from non-clinical and related clinical groups, we will recruit: a) AN; b) healthy comparison (HC); and (c) OCD (clinical comparison) groups. OCD represents a similar phenotype to AN hypothesized to be promoted through different decision processes. During fMRI, subjects will complete the Web-Surf task to identify neuroeconomic decision patterns (e.g., rule- based, reward-based, or habitual decision-making) in each group; these will be validated against other decision tasks. Participants will then provide data on symptoms via interviews and ecological momentary assessment at baseline and 12-month follow-up to examine the influence of distinct decision processes on AN and OCD symptoms. This study will evaluate the specificity with which AN is maintained by over-reliance on a frontoparietal rule-based decision system. This will permit first steps towards informing precision neuroscience- based psychiatric treatments informed by decision mechanisms, rather than solely by phenotypic presentation.