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NIAAA P01

Project 1: Human Studies

Functional Brain Networks and Alcohol Composition: Associations with Age, Stress, and Cognitio

Principal Investigator: Paul Laurenti, PhD

The goal of this project was to establish new approaches at Wake Forest School of Medicine to study behavioral and neurobiological correlates of alcohol addiction vulnerability in human subjects.  This project leveraged resources of a small alcohol study led by Dr. Paul Laurienti, a neuroimaging expert, and a student supported by our institutional NIAAA T32 Training Grant. This component had two distinct projects. The first evaluated the effects of moderate-to-heavy alcohol consumption on cognitive and brain function in older adults. The primary hypothesis was that moderate-to-heavy alcohol consumers would exhibit increases in age-related cognitive decline. It was also predicted that changes in functional brain networks would be identified that would parallel the cognitive changes. This study enrolled and performed cognitive testing and brain imaging on 63 participants (22 young and 41 older). Interestingly, moderate-to-heavy drinkers did not exhibit increased cognitive decline relative to light drinkers (Moussa et al., 2014). While there were no differences in cognitive function, there were differences in functional brain network connectivity measured during a working memory task (Mayhugh et al., 2016). Future work will be required to determine if the brain connectivity changes are merely compensatory or are an early marker of cognitive decline.

Fig. 3 Effect of abstinence on mPFC connectivity. Abstinence resulted in significant decreases in connectivity in the striatum and amygdala. Although connectivity was reduced throughout the striatum, note that the ventral striatum, or nucleus accumbens, exhibited the greatest reductions.  Color map represents the magnitude of connection efficiency to the PFC (number of network steps to between the PFC and the regions of interest). The second project explored the innovative hypothesis that moderate-heavy drinkers without alcohol use disorder (AUD) may exhibit individual differences in alcohol craving, and that there may be a neural signature associated with these differences. High levels of stress-induced craving are one of the most robust predictors of relapse in recovering alcoholics (Seo and Sinha, 2014), but little attention has focused on the possibility that craving measures may be associated with AUD vulnerability. To address this issue, this study examined the effects of abstinence and stress on brain network connectivity in 34 regular alcohol consumers 30 to 60 years old who regularly consume moderate to heavy amounts of alcohol (1-3 drinks for women and 2-4 drinks for men). Each participant completed two MRI scan sessions. One session occurred after 3 days of normal alcohol consumption, and the other session occurred after 3 days of abstinence. iPhones and mobile breath testing were used to monitor abstinence and ecological momentary assessment to assess stress and craving in real time. Significant differences in “craving relief following drinking” occurred between those with low and high scores on the Alcohol Craving Experience (ACE) Questionnaire (Statham et al., 2011). The manuscript describing these findings is currently in review. Preliminary brain imaging analyses from 23 participants are completed; abstinence significantly decreased connectivity between the medial prefrontal cortex (mPFC) and both the striatum and amygdala (Fig. 3). Connectivity was also increased between mPFC and the remainder of the default-mode network after abstinence (for details, see Project 1 of this application). Initial data suggest that these changes are associated with increased craving during abstinence.

References Cited

Mayhugh avy Alcohol Consumption Lifestyle in Older Adults Is Associated with Altered Central Executive NRE, Moussa MN, Simpson SL, Lyday RG, Burdette JH, Porrino LJ, Laurienti PJ (2016) Moderate-Heetwork Community Structure during Cognitive Task. PloS one 11:e0160214.

Moussa MN, Simpson SL, Mayhugh RE, Grata ME, Burdette JH, Porrino LJ, Laurienti PJ (2014) Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults. Front Aging Neurosci 6:341.

Seo D, Sinha R (2014) The neurobiology of alcohol craving and relapse. Handb Clin Neurol 125:355-368.

Statham DJ, Connor JP, Kavanagh DJ, Feeney GF, Young RM, May J, Andrade J (2011) Measuring alcohol craving: development of the Alcohol Craving Experience questionnaire. Addiction 106:1230-1238.

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