Hypoactive ventromedial prefrontal cortex (VmPFC) response to stress, alcohol craving, and relapse risk. (A) Hypoactive VmPFC response to stress but hyperactive response to neutral-relaxing condition in 30 patients with alcohol use disorder (AUD) compared with 30 healthy control subjects. AUD patients showed hypoactive VmPFC and anterior cingulate cortex (ACC) response to stress compared with demographically matched healthy control subjects (P < 0.05; whole-brain familywise error correction [FWE] corrected). (B) Neural correlates of alcohol craving and relapse in 45 AUD patients. (B-1) Whole-brain correlation analyses indicated that hypoactive VmPFC/ACC response to stress, compared with a neutral condition, was associated with increased alcohol craving during stress (r = −0.55; R2 = 0.30; P < 0.01 whole-brain FWE corrected). No other regions were significantly associated with craving in this whole-brain voxel-based analysis. (B-2) Estimated survival functions for time to initial alcohol relapse are presented to illustrate the increasing risk of relapse with signal changes in the VmPFC hypoactivity during stress relative to the neutral condition: mean (in red) +1 (green) and +2 (gray) standard deviation (SD) above the mean, and −1 (blue) and −2 (black) SD below the mean. Cox proportional hazards regression analysis also indicates that hypoactive response during stress-neutral predicted a shorter time to initial alcohol use (χ2 = 5.37, P < 0.05; hazard ratio [HR] = 0.22, confidence interval [CI] = 0.06–0.79) as well as heavy-drinking relapse (χ2 = 5.5, P < 0.05; HR = 0.21, CI = 0.06–0.77). S-N = stress-neutral.NOTE: This figure is reproduced with the permission of the American Medical Association (Seo et al. 2013).
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