Neuroplasticity and Predictors of Alcohol Recovery

Abstract

Chronic alcohol-related neuroadaptations in key neural circuits of emotional and cognitive control play a critical role in the development of, and recovery from, alcoholism. Converging evidence in the neurobiological literature indicates that neuroplastic changes in the prefrontal-striatal-limbic circuit, which governs emotion regulation and decisionmaking and controls physiological responses in the autonomic nervous system and hypothalamic-pituitary-adrenal axis system, contribute to chronic alcoholism and also are significant predictors of relapse and recovery. This paper reviews recent evidence on the neuroplasticity associated with alcoholism in humans, including acute and chronic effects, and how these neurobiological adaptations contribute to alcohol recovery, along with the discussion of relevant clinical implications and future research directions.

Figure 1

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).

Figure 2

Hyperactive ventromedial prefrontal cortex (VmPFC) response to the neutral-relaxing condition, alcohol craving, and relapse risk. (A) In 45 patients with alcohol use disorder (AUD), hyperactive response in the VmPFC and anterior cingulate cortex (ACC) when they are exposed to neutrally relaxing situations during brief guided imagery was significantly associated with high alcohol craving during alcohol cue imagery (R = 0.56; R ² = 0.31, P < 0.01 whole-brain FWE corrected). (B) Estimated survival functions for time to initial alcohol relapse, showing that the more VmPFC hyperactivity during the neutral condition, the shorter the time to subsequent initial relapse and heavy drinking relapse: 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 indicates that hyperactive VmPFC response during the neutral condition predicted a shorter time to initial alcohol use (χ² = 6.39, P = 0.01; hazard ratio [HR] = 8.45, confidence interval [CI] = 1.6–44.2) as well as heavy drinking relapse (χ² = 7.39, P < 0.01, HR = 8.68, CI = 1.8–41.2). I-B = imagery minus baseline ratings. SOURCE: This figure is reproduced with the permission of the American Medical Association (Seo et al. 2013).