Functional Connectivity of Nucleus Accumbens and Medial Prefrontal Cortex With Other Brain Regions During Early-Abstinence Is Associated With Alcohol Dependence and Relapse: A Resting-Functional Magnetic Resonance Imaging Study

Abstract

Background: Alcohol dependence (AD) is a chronic recurrent brain disease that causes a heavy disease burden worldwide, partly due to high relapse rates after detoxification. Verified biomarkers are not available for AD and its relapse, although the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) may play important roles in the mechanism of addiction. This study investigated AD- and relapse-associated functional connectivity (FC) of the NAc and mPFC with other brain regions during early abstinence.Methods: Sixty-eight hospitalized early-abstinence AD male patients and 68 age- and education-matched healthy controls (HCs) underwent resting-functional magnetic resonance imaging (r-fMRI). Using the NAc and mPFC as seeds, we calculated changes in FC between the seeds and other brain regions. Over a follow-up period of 6 months, patients were measured with the Alcohol Use Disorder Identification Test (AUDIT) scale to identify relapse outcomes (AUDIT ≥ 8).Results: Thirty-five (52.24%) of the AD patients relapsed during the follow-up period. AD displayed lower FC of the left fusiform, bilateral temporal superior and right postcentral regions with the NAc and lower FC of the right temporal inferior, bilateral temporal superior, and left cingulate anterior regions with the mPFC compared to controls. Among these FC changes, lower FC between the NAc and left fusiform, lower FC between the mPFC and left cingulate anterior cortex, and smoking status were independently associated with AD. Subjects in relapse exhibited lower FC of the right cingulate anterior cortex with NAc and of the left calcarine sulcus with mPFC compared to non-relapsed subjects; both of these reductions in FC independently predicted relapse. Additionally, FC between the mPFC and right frontal superior gyrus, as well as years of education, independently predicted relapse severity.Conclusion: This study found that values of FC between selected seeds (i.e., the NAc and the mPFC) and some other reward- and/or impulse-control-related brain regions were associated with AD and relapse; these FC values could be potential biomarkers of AD or for prediction of relapse. These findings may help to guide further research on the neurobiology of AD and other addictive disorders.

Comparing the test–retest reliability of resting‐state functional magnetic resonance imaging metrics across single band and multiband acquisitions in the context of healthy aging

“…This is partially in line with Our present findings revealed that future studies using MB factor 4 with no in-plane acceleration would help build upon existing psychiatric research aiming to identify biomarkers targeting specific cortical structures. Atypical FC of the AI has previously been associated with autism spectrum disorders (Ebisch et al, 2011), while impaired FC of the medial prefrontal cortex has been proposed as a potential biomarker for alcohol dependence (Yang et al, 2021). In contrast, commonly used conventional single band sequences may be preferable for studies focusing on the FC of the nucleus accumbens, which has formerly been examined in the context of anorexia nervosa (Haynos et al, 2019) and major depressive disorder (Liu et al, 2021).…”

“…For all three analyses described below, we specifically focused on three rs‐fMRI metrics which have previously been used to gain a better understanding of psychiatric disorders: ALFF, seed‐to‐voxel and ROI‐to‐ROI measures (Ebisch et al, 2011 , Lei et al, 2017 ; Yang et al, 2021 , Zhang et al, 2021 ). All fMRI analyses were carried out using MR images after denoizing.…”

“…Eleven ROIs were identified a priori based on their implication in a range of psychiatric and neurological disorders (Ebisch et al, 2011 ; Ellard et al, 2018 ; Lei et al, 2017 ; Liu et al, 2021 ; Uddin et al, 2013 ; Wu et al, 2021 ; Yang et al, 2021 ; see Bao et al, 2021 , Briley et al, 2022 and Wang et al, 2020 for meta‐analyses focusing on posttraumatic stress disorder, anxiety and depression, and bipoler disorder, respectively). The ROI name, MNI coordinates of the center of gravity of each ROI and rendering of all 11 ROIs are provided in Table 2 and Figure 1 .…”

“…2021;Uddin et al, 2013;Wu et al, 2021;Yang et al, 2021; see Bao et al, 2021, Briley et al, 2022and Wang et al, 2020 for meta-analyses focusing on posttraumatic stress disorder, anxiety and depression, and bipoler disorder, respectively). The ROI name, MNI coordinates of the center of gravity of each ROI and rendering of all 11 ROIs are provided in…”

Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder

“…Excessive craving and motivation to drink, along with challenges in moderating consumption are key symptoms associated with AUDs. Clinical studies have consistently associated the prefrontal cortex (PFC) function with these behaviors and symptoms (Grusser et al, 2004 ; Koob, 2014 ; Courtney et al, 2016 ; Blaine et al, 2020 ; Yang et al, 2021 ). In addition, population-level analyses have linked the PFC structure and function with heavy drinking and/or AUD diagnosis (Medina et al, 2008 ; Sorg et al, 2012 ; Wang et al, 2016 ).…”