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

Ju Chi Yu, Vincenzo G. Fiore, Richard W. Briggs, Jacquelyn Braud, Katya Rubia, Bryon Adinoff, Xiaosi Gu

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Pages (from-to)4923-4936
Number of pages14
JournalEuropean Journal of Neuroscience
Issue number12
StatePublished - Dec 2020


  • addiction
  • anterior cingulate
  • anterior insula
  • relapse


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