An insula‐driven network computes decision uncertainty and promotes abstinence in chronic cocaine users

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  • Ju‐Chi Yu
    School of Behavioral and Brain Sciences University of Texas at Dallas Richardson TX USA
  • Vincenzo G. Fiore
    Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA
  • Richard W. Briggs
    Department of Aging and Geriatric Research University of Florida Gainesville FL USA
  • Jacquelyn Braud
    Department of Psychiatry University of Texas Southwestern Medical Center Dallas TX USA
  • Katya Rubia
    Institute of Psychiatry, Psychology and Neuroscience King's College London London UK
  • Bryon Adinoff
    Department of Psychiatry University of Texas Southwestern Medical Center Dallas TX USA
  • Xiaosi Gu
    Department of Psychiatry Icahn School of Medicine at Mount Sinai New York NY USA

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<jats:title>Abstract</jats:title><jats:p>The anterior insular cortex (AIC) and its interconnected brain regions have been associated with both addiction and decision‐making under uncertainty. However, the causal interactions in this uncertainty‐encoding neurocircuitry and how these neural dynamics impact relapse remain elusive. Here, we used model‐based fMRI to measure choice uncertainty in a motor decision task in 61 individuals with cocaine use disorder (CUD) and 25 healthy controls. CUD participants were assessed before discharge from a residential treatment program and followed for up to 24 weeks. We found that choice uncertainty was tracked by the AIC, dorsal anterior cingulate cortex (dACC) and ventral striatum (VS), across participants. Stronger activations in these regions measured pre‐discharge predicted longer abstinence after discharge in individuals with CUD. Dynamic causal modeling revealed an AIC‐to‐dACC‐directed connectivity modulated by uncertainty in controls, but a dACC‐to‐AIC connectivity in CUD participants. This reversal was mostly driven by early relapsers (<30 days). Furthermore, CUD individuals who displayed a stronger AIC‐to‐dACC excitatory connection during uncertainty encoding remained abstinent for longer periods. These findings reveal a critical role of an AIC‐driven, uncertainty‐encoding neurocircuitry in protecting against relapse and promoting abstinence.</jats:p>

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