PROJECT SUMMARY/ABSTRACT Binge-eating disorder (BED) is more common than any other eating disorder in the US and is associated with high rates of medical morbidity, disability, and suicidality. As roughly half of patients with BED remain symptomatic after current first-line treatments, there is a critical need to identify brain-based factors that perpetuate BED symptoms and that may serve as mechanistic targets for novel treatments. Current theoretical models posit that the recurrent, distressing, and out-of-control overeating that characterizes BED arises after a transition from ventral to dorsal corticostriatal circuit control over decision-making, and a corresponding shift from goal-oriented to habitual behavior. However, individuals with BED present with a co-occurrence of seemingly contradictory decision-making problems—impulsivity and perseveration—and a wide range of binge-eating severity. Neurobiological research to date has failed to account for this within-person combination of cognitive deficits or this between-person variability in symptoms. The goal of this R21 project is to test a neurocomputational model of BED that provides a more comprehensive account of symptoms and severity. This model expands on previous theories and links behavior to effective connectivity in corticostriatal circuits underlying decision-making. Specifically, the proposed study combines computational modeling of behavior with dynamic causal modeling (DCM) of neural connectivity to examine whether aberrant within- and between- circuit dynamics relate to cognitive and clinical symptom profiles in BED. We will compare effective connectivity of 28 adults with BED to that of 28 group-matched healthy controls during two decision-making paradigms. We will test two overarching predictions that are informed by our simulations of corticostriatal circuit dynamics and associated behavior: 1) In individuals with BED, aberrant within-circuit dynamics, specifically overstability (high “gain”) within dorsal and ventral corticostriatal circuits, result in overweighting of initial evidence (leading to impulsivity) and promote choice selections that are insensitive to changes in the environment (perseveration); 2) In individuals with BED, aberrant between-circuit dynamics, specifically an over-influence of one corticostriatal circuit on the other (dorsal on ventral or vice-versa), promote more severe binge eating. These model predictions can explain the impulsive, out-of-control initiation of binge eating, why individuals with BED continue to binge eat despite fullness and distress (i.e., perseverate), and why some individuals with BED are more likely than others to more frequently initiate binge eating episodes. As such, data from this proof-of- concept pilot study will substantiate a novel neurocomputational model of BED symptoms and characterize alterations in neural circuit dynamics, not just neural activation, in BED. In addition, the data will support a future R01 application focused on testing the model among a wider diagnostic spectrum of individuals who binge eat. This work can ultimately inform new interventions with circuit-based targets to more effectively interrupt entrenched patterns of binge eating.
|Effective start/end date||1/12/22 → 30/11/23|
- NATIONAL INSTITUTE OF MENTAL HEALTH: $253,500.00
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