Alcohol use disorder (AUD) is a multifaceted, chronic relapsing disorder suffered by millions of men and women in the United States. AUD is associated with disrupted sleep continuity and architecture, including an abnormally high level of rapid eye movement (REM) sleep that persists long into abstinence, and which is a significant predictor of relapse. Emotion deficits, including affective flattening and mesocorticolimbic hypo-responsiveness to emotional stimuli, are consistent findings in AUD and also predict relapse. Here, we bring these two components together, building on an emerging literature showing that REM sleep is important for neural emotion regulation, calibrating emotions to promote next-day adaptive emotional functioning. We propose that the REM sleep-emotion pathway is dysfunctional in AUD, contributing to the deficits in emotion regulation in AUD shown by us and others, which lead to increased craving and relapse. Here, multidisciplinary researchers (Baker, M?ller-Oehring) with combined expertise in AUD, sleep, fMRI, and emotion, aim to investigate the role of REM sleep in next-day emotional functioning in AUD. A novel counterbalanced, mixed-measures experimental design is applied in abstinent male and female AUD patients compared to age- and gender-matched healthy controls, all undergoing two experimental night conditions: uninterrupted sleep and selective REM sleep reduction, each followed by functional neuroimaging with emotion reactivity and emotion regulation tasks the following morning.
We aim to (1) Determine relationships between REM sleep qualities (duration and intensity) and next-day neural emotional reactivity in AUD; (2) Determine specific effects of experimental REM sleep reduction on next-day neural emotional reactivity in AUD compared to healthy controls and compared to an uninterrupted sleep condition. We will also explore to what extent the sleep-emotion regulation link is adjustable with a REM sleep reduction protocol towards a more functionally-intact system that contributes to normalization of behavioral measures of emotion functioning and less alcohol craving in AUD. These studies open up new avenues into a mechanistic understanding of links between sleep processes and emotional brain function in AUD. Findings will inform a R01 application aimed at investigating the effects of sleep manipulation as a pathway to reset neural emotion regulation circuits, fracture the cycle of relapse, and improve management of AUD.

Public Health Relevance

The proposed research will serve the mission of the National Institute on Alcohol Abuse and Alcoholism by expanding knowledge of the functional inter-connections between sleep and emotion regulation, both contributors to relapse in individuals with alcohol use disorder (AUD). Using EEG and brain MR imaging methods, we will measure sleep physiology and neural emotion regulation pathways in AUD to determine whether the sleep-emotion regulation link is dysfunctional in AUD, and is adjustable with a rapid eye movement sleep reduction protocol towards a more functionally-intact system that contributes to lower alcohol craving in AUD. Knowledge gained from this proposal could lead to the development of tools to potentially harness the power of sleep to restore emotional balance and ultimately lead to better management of AUD.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA028617-01
Application #
10041719
Study Section
National Institute on Alcohol Abuse and Alcoholism Initial Review Group (AA)
Program Officer
Regunathan, Soundar
Project Start
2020-09-05
Project End
2022-08-31
Budget Start
2020-09-05
Budget End
2021-08-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Sri International
Department
Type
DUNS #
009232752
City
Menlo Park
State
CA
Country
United States
Zip Code
94025