Maladaptive brain organization at 1 month into abstinence as an indicator for future relapse in patients with alcohol use disorder

Abstract

Abstinence is a lifelong endeavor, and the risk of a relapse is always present for patients with Alcohol Use Disorder (AUD). The aim of the study was to better understand specific characteristics of the intrinsic whole‐brain‐network architecture of 34 AUD patients that may support abstinence or relapse. We used Graph Theory Analysis (GTA) of resting‐state fMRI data from treatment seekers at 1 month of abstinence and their follow‐up data as abstainers or relapsers 3 months later, together with data from 30 light/non‐drinking controls scanned at the same interval. We determined the group‐specific intrinsic community configurations at both timepoints as well as the corresponding modularity Q, a GTA measure that quantifies how well individual network communities are separated from each other. Both AUD groups at both timepoints had community configurations significantly different from those of controls, but the three groups did not significantly differ in their Q values. However, relapsers showed a maladaptive community configuration at baseline, which became more similar to the controls’ community organization after the relapsers had started consuming alcohol again during the study interval. Additionally, successful recovery from AUD was not associated with re‐gaining the intrinsic brain organization found in light/non‐drinkers, but with a re‐configuration resulting in a new brain organization distinctly different from that of healthy controls. Resting‐state fMRI provides useful measures reflecting neuroplastic adaptations related to AUD treatment outcome.

Frontocerebellar gray matter plasticity in alcohol use disorder linked to abstinence

“…This brain structure not only relays first-order sensory information to the cortex ( Habas et al, 2019 , Halassa and Sherman, 2019 , Sherman, 2007 , Sherman, 2017 , Sherman, 2016 , Usrey and Sherman, 2019 ), but it is also involved in a wide variety of higher-order cognitive functions ( Habas et al, 2019 , Pergola et al, 2018 ), with its subunits capable of dynamically integrating multimodal information from diverse networks ( Garrett et al, 2018 , Hwang et al, 2017 ). The importance of the functional integrity of the thalamus for successful alcohol abstinence was recently also demonstrated in a resting-state fMRI study by our team with an AUD patient group similar to that described here: One month into treatment, future relapsers differed from healthy controls and future abstainers in the way the thalamus interacted with major resting-state networks ( Muller and Meyerhoff, 2021 ).…”

Alcohol dependence modifies brain networks activated during abstinence and reaccess: a c-fos-based analysis in mice

“…The copyright holder for this preprint this version posted August 26, 2022. ; https://doi.org/10.1101/2022.08.26.505400 doi: bioRxiv preprint to similar configurations as controls following relapse (35). However, modularity was not different in drinkers relative to controls either before or after relapse.…”

“…Similarly, we observed a significantly elevated diversity coefficient in abstinent HD mice in PL, ILA, and ACA, rodent correlates of human PFC (34); while reaccess tended to attenuate these diversity measures in high drinkers, this finding did not reach significance. In another human imaging study, basal ganglia and thalamic nodes had different community associations in heavy drinkers compared to controls during abstinence, and returned to similar configurations as controls following relapse (35). However, modularity was not different in drinkers relative to controls either before or after relapse.…”

Desire and craving measured using behavioral ratings and brain network topology differ significantly among moderate to heavy alcohol consumers

“…A wide body of research has shown the important role craving plays in alcohol use: craving is a driving factor of alcohol consumption (Kozlowski et al, 1989; Ludwig, 1986; May et al, 2014; Mayhugh, Laurienti, et al, 2018; Mayhugh, Rejeski, et al, 2018; Rankin et al, 1979), a diagnostic feature of Alcohol Use Disorder (AUD) (APA, 2013), a symptom of alcohol withdrawal (Sullivan et al, 1989), and a key predictor of relapse in patients with an AUD (Breese et al, 2006; Gordon et al, 2006; Miller & Gold, 1994; Moos & Moos, 2006; Muller & Meyerhoff, 2020; Seo et al, 2013; Sinha, 2007, 2011, 2012; Tuithof et al, 2014; Volkow & Baler, 2013). In 1955, the World Health Organization convened to define craving as a central part of the “alcoholic experience” (WHO, 1955), where vernacular use of “craving” conveyed “urgent and overpowering desire,” an “irresistible impulse,” or “a strong desire or intense longing” (Fowler & Fowler, 1964; Kozlowski & Wilkinson, 1987).…”