Dynamic Neural Computations Underlying Cognitive Control in Bulimia Nervosa

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PROJECT SUMMARY/ABSTRACT Bulimia nervosa (BN) is a disabling and often chronic eating disorder associated with medical complications and premature death. There is an acute need to identify the mechanisms that maintain BN and that may serve as targets for new treatments. Most studies have assumed that BN is perpetuated by stable, trait-like factors, including self-reported impulsivity and deficits in the ability to exert cognitive control. However, the out-of-control excessive intake and compensatory behaviors characteristic of BN are episodic and tend to alternate with periods of restricted intake or even fasting, suggesting intermittent oscillations in control. In addition, emerging work in behavioral economics and cognitive neuroscience suggests that failures to ultimately exert cognitive control depend on numerous neural computations, including: updating predictions about whether control will be needed in the next moment, and deciding whether trying to exert control is worth the costly cognitive effort. The overarching goal of this R01 is to clarify how these cognitive control computations may fluctuate across fasted and fed states in BN, potentially maintaining the cyclical nature of the disorder. Specifically, the proposed study combines functional magnetic resonance imaging (fMRI), computational modeling, and real-time mobile assessments to examine whether food consumption abnormally impairs frontostriatal function and associated control-related updating and effort-valuation processes in BN. We propose that the impairment of these processes in the fed state and relative improvement of these processes in the fasted state perpetuate out-of- control binge/purge episodes alternating with periods of dietary restriction. We will compare behavioral and neural responses of women with BN to those of group-matched healthy women during an inhibitory control paradigm to assess control-related prediction updating (Aim 1) and during a cognitive effort discounting paradigm to assess control-related effort valuation (Aim 2) in two states: after a 16-h fast and after a standardized meal. Aim 3 will use multi-modal symptom measures to examine main effects and potential interactions of state-specific updating and valuation processes on binge eating, purging, and restriction severity at baseline and at 6-month follow-up. The research team includes experts in BN-focused research, neuroimaging, computational neuroscience and psychiatry, advanced statistical methods, and ecological momentary assessment. The project innovatively 1) applies a neurocomputational framework to examine the roles of understudied subcomponents of cognitive control in BN; 2) assesses the influence of metabolic state (fasted, fed) on these subcomponents; and 3) relates the dynamics of these subcomponents in the laboratory to real-world, state-specific experiences and symptoms at baseline and over time. Data from this project will pinpoint altered elements of the control process that may represent prognostic biomarkers. Results will also identify the potential optimal patient state (i.e., fasted or fed) for control-focused interventions. Therefore, this study will yield vital data to inform urgently needed, precisely targeted treatments for cycles of binge eating, purging, and restriction.