UNASSIGNED: Working memory refers to a process of temporary storage and manipulation of information to support planning, decision-making, and action. Frequently comorbid alcohol misuse and sleep deficiency have both been associated with working memory deficits. However, how alcohol misuse and sleep deficiency interact to impact working memory remains unclear. In this study, we aim to investigate the neural processes inter-relating alcohol misuse, sleep deficiency and working memory.
UNASSIGNED: We curated the Human Connectome Project (HCP) dataset and investigated the neural correlation of working memory in link with alcohol use severity and sleep deficiency in 991 young adults (521 women). The two were indexed by the first principal component (PC1) of principal component analysis of all drinking metrics and Pittsburgh Sleep Quality Index (PSQI) score, respectively. We processed the imaging data with published routines and evaluated the results with a corrected threshold. We used path model to characterize the inter-relationship between the clinical, behavioral, and neural measures, and explored sex differences in the findings.
UNASSIGNED: In whole-brain regression, we identified β estimates of dorsolateral prefrontal cortex response (DLPFC β) to 2- vs. 0-back in correlation with PC1. The DLPFC showed higher activation in positive correlation with PC1 across men and women (r=0.16, P<0.001). Path analyses showed the model PC1 → DLPFC β → differences in reaction time (2- minus 0-back; RT2-0) of correct trials → differences in critical success index (2- minus 0-back; CSI2-0) with the best fit. In women alone, in addition to the DLPFC, a cluster in the superior colliculus (SC) showed a significant negative correlation with the PSQI score (r=-0.23, P<0.001), and the path model showed the inter-relationship of PC1, PSQI score, DLPFC and SC β\'s, and CSI2-0 in women.
UNASSIGNED: Alcohol misuse may involve higher DLPFC activation in functional compensation, whereas, in women only, sleep deficiency affects 2-back memory by depressing SC activity. In women only, path model suggests inter-related impact of drinking severity and sleep deficiency on 2-back memory. These findings suggest potential sex differences in the impact of drinking and sleep problems on working memory that need to be further investigated.

The relationship between fibrosis-4 (FIB-4) index and all-cause mortality in critically ill patients with alcohol use disorder (AUD) is unclear. The present study aimed to investigate the predictive ability of FIB-4 for all-cause mortality in critically ill AUD patients and the association between them.
A total of 2528 AUD patients were included using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. FIB-4 was calculated for each patient using the existing formula. The patients were equally divided into four groups based on the quartiles of FIB-4. Multivariate logistic regression and Cox proportional hazard model were used to evaluate the association of FIB-4 with in-hospital mortality, 28-day mortality and 1-year mortality. Kaplan-Meier curves were used to analyse the incidence of 28-day mortality among four groups.
FIB-4 was positively associated with 28-day mortality of AUD patients with hazard ratio (HR) of 1.354 [95% confidence interval (CI) 1.192-1.538]. There were similar trends in the in-hospital mortality [odds ratio (OR): 1.440, 95% CI (1.239-1.674)] and 1-year mortality [HR: 1.325, 95% CI (1.178-1.490)].
Increased FIB-4 is associated with greater in-hospital mortality, 28-day mortality and 1-year mortality in critically ill AUD patients.

It has yet to be determined whether medication overuse headache (MOH) is an independent disorder or a combination of primary headache and substance addiction. To further explore the causes of MOH, we compared MOH with substance use disorder (SUD) in terms of the brain regions involved to draw more targeted conclusions. In this review, we selected alcohol use disorder (AUD) as a representative SUD and compared MOH and AUD from two aspects of neuroimaging and basic research. We found that in neuroimaging studies, there were many overlaps between AUD and MOH in the reward circuit, but the extensive cerebral cortex damage in AUD was more serious than that in MOH. This difference was considered to reflect the sensitivity of the cortex structure to alcohol damage. In future research, we will focus on the central amygdala (CeA), prefrontal cortex (PFC), orbital-frontal cortex (OFC), hippocampus, and other brain regions for interventions, which may have unexpected benefits for addiction and headache symptoms in MOH patients.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain\'s \"scale-free\" networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

Alcohol misuse is associated with externalizing behaviors, including rule breaking. Studies have implicated altered reward processing in externalizing behaviors and alcohol misuse. Here, we investigated whether reward or punishment reactivity more significantly influenced alcohol use severity and rule-breaking behavior in young adult drinkers.
We curated data from the Human Connectome Project and identified 181 binge (132 men) and 288 nonbinge (97 men) drinkers performing a gambling task during brain imaging. Alcohol use severity was quantified by the first principal component of principal-component analysis of all drinking measures. We analyzed the imaging data using published routines and evaluated the results at a corrected threshold. We examined the interrelationship between imaging and clinical metrics with mediation and path analyses.
Compared with nonbingers, bingers showed more severe rule-breaking behavior and responded significantly faster during post-loss than during post-win trials. Compared with nonbingers, bingers demonstrated greater inferior/middle frontal gyrus and cerebellum activations in loss-predominating blocks but no differences in regional responses to win-predominating blocks, relative to an interblock baseline. The right caudate body showed loss reactivity that was positively correlated with the rule-breaking score. No regional responses to wins were significantly correlated with the rule-breaking score. Mediation and path analyses demonstrated significant models with inferior/middle frontal gyrus and caudate reactivity to loss interrelating rule breaking and alcohol use severity.
Punishment rather than reward reactivity was associated with alcohol use severity and rule breaking in young adults. The findings highlight the roles of negative emotions in psychological models of externalizing behaviors and alcohol misuse.

UNASSIGNED: The purpose of this study is to explore the association of P300 components with clinical characteristics and efficacy of pharmacotherapy in alcohol use disorder (AUD).
UNASSIGNED: One hundred fifty-one AUD patients and 96 healthy controls were recruited and evaluated for the symptoms of depression, anxiety, sleep, and cognitive function by the Alcohol Use Disorders Identification Test (AUDIT), the 9-item Patient Health Questionnaire (PHQ-9), the 7-item Generalized Anxiety Disorder scale (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), Digit Symbol Substitution test (DSST), and event-related potential P300, which is one of the averaged scalp electroencephalography responses time-locked to specific events. Among the AUD group, 101 patients finished an 8-week pharmacotherapy and were evaluated for the above data at post-intervention.
UNASSIGNED: 1. At baseline, AUD patients had higher scores of AUDIT, PHQ-9, GAD-7, PSQI, and P300 latency at Cz, Pz, and Fz and lower DSST score and smaller P300 amplitudes at Fz, Cz, and Pz compared with controls. P300 components correlated significantly with alcohol dose and score of AUDIT, PHQ-9, GAD-7, PSQI, and DSST. 2. After 8 weeks\' treatment, there were significant changes for the P300 components; alcohol dose; and score of AUDIT, PHQ-9, GAD-7, PSQI, and DSST. Variables at baseline, including P300 amplitudes at Fz, Cz, and Pz; latency of Fz and Pz; alcohol dose; and scores of PHQ-9, GAD-7, PSQI, and DSST, were significantly associated with changes of reduction rate of AUDIT scores. However, P300 amplitudes at Fz, Cz, and Pz in AUD patients after 8-week treatment were still significantly shorter than healthy controls (HCs), and P300 latencies at Fz, Cz, and Pz were significantly longer than HCs. 3. When validated area under the receiver operating characteristic curve (AUC) was over 0.80, the baseline variables including amplitudes at Cz and Pz, alcohol dose, and scores of PSQI could predict the changes of reduction rate of AUDIT score.
UNASSIGNED: P300 amplitudes and latencies at Fz, Cz, and Pz could be used as biological markers for evaluating the clinical characters and severity of AUD. P300 amplitudes at Cz and Pz, sleep condition, and cognitive function at baseline could predict the efficacy of pharmacotherapy for AUD patients.

Alcohol use disorder (AUD), which combines the criteria of both alcohol abuse and dependence, contributes as an important causal factor to multiple health and social problems. Given the limitation of current treatments, novel medications for AUD are needed to better control alcohol consumption and maintain abstinence. It has been well established that the intracellular signal transduction mediated by the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) crucially underlies the genetic predisposition, rewarding properties, relapsing features, and systemic toxicity of compulsive alcohol consumption. On this basis, the upstream modulators phosphodiesterases (PDEs), which critically control intracellular levels of cyclic nucleotides by catalyzing their degradation, are proposed to play a role in modulating alcohol abuse and dependent process. Here, we highlight existing evidence that correlates cAMP and cGMP signal cascades with the regulation of alcohol-drinking behavior and discuss the possibility that PDEs may become a novel class of therapeutic targets for AUD.

Screening alcohol use disorder (AUD) patients has been challenging due to the subjectivity involved in the process. Hence, robust and objective methods are needed to automate the screening of AUD patients. In this paper, a machine learning method is proposed that utilized resting-state electroencephalography (EEG)-derived features as input data to classify the AUD patients and healthy controls and to perform automatic screening of AUD patients. In this context, the EEG data were recorded during 5 min of eyes closed and 5 min of eyes open conditions. For this purpose, 30 AUD patients and 15 aged-matched healthy controls were recruited. After preprocessing the EEG data, EEG features such as inter-hemispheric coherences and spectral power for EEG delta, theta, alpha, beta and gamma bands were computed involving 19 scalp locations. The selection of most discriminant features was performed with a rank-based feature selection method assigning a weight value to each feature according to a criterion, i.e., receiver operating characteristics curve. For example, a feature with large weight was considered more relevant to the target labels than a feature with less weight. Therefore, a reduced set of most discriminant features was identified and further be utilized during classification of AUD patients and healthy controls. As results, the inter-hemispheric coherences between the brain regions were found significantly different between the study groups and provided high classification efficiency (Accuracy = 80.8, sensitivity = 82.5, and specificity = 80, F-Measure = 0.78). In addition, the power computed in different EEG bands were found significant and provided an overall classification efficiency as (Accuracy = 86.6, sensitivity = 95, specificity = 82.5, and F-Measure = 0.88). Further, the integration of these EEG feature resulted into even higher results (Accuracy = 89.3 %, sensitivity = 88.5 %, specificity = 91 %, and F-Measure = 0.90). Based on the results, it is concluded that the EEG data (integration of the theta, beta, and gamma power and inter-hemispheric coherence) could be utilized as objective markers to screen the AUD patients and healthy controls.