Distress tolerance among substance users is associated with functional connectivity between prefrontal regions during a distress tolerance task

Addict Biol. 2017 Sep;22(5):1378-1390. doi: 10.1111/adb.12396. Epub 2016 Apr 2.


Distress tolerance (DT), defined as the ability to persist in goal directed behavior while experiencing affective distress, is implicated in the development and maintenance of substance use disorders. While theory and evidence indicate that cortico-limbic neural dysfunction may account for deficits in goal directed behavior while experiencing distress, the neurobiological mechanisms of DT have yet to be examined. We modified a computerized DT task for use in functional magnetic resonance imaging (fMRI), the Paced Auditory Serial Addition Task (PASAT-M), and examined the neural correlates and functional connectivity of DT among a cohort of substance users (n = 21; regular cocaine and nicotine users) and healthy controls (n = 25). In response to distress during the PASAT-M, we found greater activation in a priori cortico-limbic network ROIs, namely the right insula, anterior cingulate cortex (ACC), bilateral medial frontal gyrus (MFG), right inferior frontal gyrus (IFG) and right ventromedial prefrontal cortex (vmPFC) significantly predicted higher DT among substance users, but not healthy controls. In addition, greater task-specific functional connectivity during distress between the right MFG and bilateral vmPFC/sgACC was associated with higher DT among substance users, but not healthy controls. The observed positive relationship between DT and neural activation in cortico-limbic structures, as well as functional connectivity between the rMFG and vmPFC/sgACC, is in line with theory and research suggesting the importance of these structures for persisting in goal directed behavior while experiencing affective distress.

Keywords: distress tolerance; emotion regulation; fMRI; prefrontal cortex; substance use disorder.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cocaine-Related Disorders / diagnostic imaging*
  • Cocaine-Related Disorders / psychology
  • Cohort Studies
  • Female
  • Functional Neuroimaging
  • Gyrus Cinguli / diagnostic imaging*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Neural Pathways
  • Prefrontal Cortex / diagnostic imaging*
  • Stress, Psychological / diagnostic imaging*
  • Stress, Psychological / psychology
  • Substance-Related Disorders / diagnostic imaging
  • Substance-Related Disorders / psychology
  • Tobacco Use Disorder / diagnostic imaging*
  • Tobacco Use Disorder / psychology