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Neuroplasticity and Predictors of Alcohol Recovery.

Seo D, Sinha R - Alcohol Res (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.

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.

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Related in: MedlinePlus

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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f1-arcr-37-1-143: 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).

Mentions: During stress, ANS and HPA axis function are under the regulatory control of the VmPFC (Figueiredo et al. 2003; Radley 2006). Preclinical studies demonstrate decreased HPA axis response to stress following VmPFC lesions (Radley 2006) and find that the VmPFC maintains stress-related inhibitory control over HPA axis arousal (Figueiredo et al. 2003). In addition, a meta-analysis of studies in humans reported significant associations between brain activity in the VmPFC and amygdala and ANS function indexed by heart rate variability (Thayer et al. 2012). Given that chronic alcoholism is associated with HPA axis and ANS system dysfunctions, as discussed earlier, these findings on the VmPFC regulation over stress-related HPA axis and ANS arousal suggest that individuals with chronic alcoholism may have underlying VmPFC dysfunction in response to stress. Consistent with this hypothesis, a recent fMRI study (Seo et al. 2013) found lowered activity in the stress modulatory regions involving VmPFC/ACC during stress exposure in 30 AUD patients engaged in inpatient treatment and abstinent for 4 weeks, compared with 30 matched healthy control subjects (figure 1A). Interestingly, the researchers observed an opposite pattern when the subjects were relaxed: AUD patients showed hyperactive VmPFC/ACC compared with control subjects (figure 1A). More importantly, to prospectively assess relapse and early recovery, these researchers followed the same 30 AUD patients, plus 15 others, after they completed inpatient treatment. Results indicated that lowered VmPFC activity in response to stress exposure relative to the response when patients were relaxed was significantly associated with stress-induced alcohol craving and also predicted a shorter time to future relapse (see figure 1B) (Seo et al. 2013). In addition, lower VmPFC activity and insula response to stress was significantly correlated with more days of alcohol use during subsequent followup, emphasizing the contribution of altered stress neural circuitry to relapse susceptibility (Seo et al. 2013).


Neuroplasticity and Predictors of Alcohol Recovery.

Seo D, Sinha R - Alcohol Res (2015)

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).
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476600&req=5

f1-arcr-37-1-143: 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).
Mentions: During stress, ANS and HPA axis function are under the regulatory control of the VmPFC (Figueiredo et al. 2003; Radley 2006). Preclinical studies demonstrate decreased HPA axis response to stress following VmPFC lesions (Radley 2006) and find that the VmPFC maintains stress-related inhibitory control over HPA axis arousal (Figueiredo et al. 2003). In addition, a meta-analysis of studies in humans reported significant associations between brain activity in the VmPFC and amygdala and ANS function indexed by heart rate variability (Thayer et al. 2012). Given that chronic alcoholism is associated with HPA axis and ANS system dysfunctions, as discussed earlier, these findings on the VmPFC regulation over stress-related HPA axis and ANS arousal suggest that individuals with chronic alcoholism may have underlying VmPFC dysfunction in response to stress. Consistent with this hypothesis, a recent fMRI study (Seo et al. 2013) found lowered activity in the stress modulatory regions involving VmPFC/ACC during stress exposure in 30 AUD patients engaged in inpatient treatment and abstinent for 4 weeks, compared with 30 matched healthy control subjects (figure 1A). Interestingly, the researchers observed an opposite pattern when the subjects were relaxed: AUD patients showed hyperactive VmPFC/ACC compared with control subjects (figure 1A). More importantly, to prospectively assess relapse and early recovery, these researchers followed the same 30 AUD patients, plus 15 others, after they completed inpatient treatment. Results indicated that lowered VmPFC activity in response to stress exposure relative to the response when patients were relaxed was significantly associated with stress-induced alcohol craving and also predicted a shorter time to future relapse (see figure 1B) (Seo et al. 2013). In addition, lower VmPFC activity and insula response to stress was significantly correlated with more days of alcohol use during subsequent followup, emphasizing the contribution of altered stress neural circuitry to relapse susceptibility (Seo et al. 2013).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.

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.

Show MeSH
Related in: MedlinePlus