Alcohol Use Disorder Patients Research Articles

A Study to Assess the Efficacy of Audio-Visual Psychoeducation on Level of Knowledge and Attitude Regarding Harmful Effects of Alcohol among Alcohol use Disorder Patients Admitted to Mental Health Units of Selected Hospitals of Western Maharashtra

Introduction: Alcohol use disorder (AUD) has emerged as a global concern in the world, due to its harmful impact on health, social, economic, and legal aspects. Several established treatment approaches, both pharmacological and nonpharmacological are available but have only modest success. Relapse in alcohol use is noted to be common following treatment, hence efficacy of newer modalities of treatment or therapies is needed. Aim: This study aims to assess the efficacy of audiovisual psychoeducation on the level of knowledge and attitude of harmful effects of alcohol among AUD patients admitted to mental health units of selected hospitals of Western Maharashtra. Materials and Methodology: A quantitative research approach with pretest-posttest control design was adopted in the study. The sample size was estimated to be 70 based on the pilot study and settings were mental health units of selected hospitals in Western Maharashtra. A simple random sampling technique was used with random allocation of subjects into experimental group and control group by lottery method. A structured tool to assess knowledge was developed, validated by experts and reliability was tested. Alcohol Decisional Balance Scale, which is a standardized tool was used for assessing the attitude. Pretest knowledge assessment was done for control and experimental groups. Audiovisual psychoeducation was given to the experimental group. Both the groups were receiving routine care. A posttest assessment was done after 7 days of intervention. Results: Findings revealed that there is statistically significant increase in the level of knowledge from pretest mean score of 9.37 + 3.191–14.06 + 4.179 in posttest of the experimental group by Wilcoxon Z value test at the level of significance P < 0.0001 showing the efficacy of audio-visual psychoeducation in changing the level of knowledge. Similarly, postintervention attitude distribution assessment in the experimental group revealed a statistically significant difference in positive attitude from 6 (17%) in pretest to 12 (34%) in posttest with the McNemar's test at level of significance of P < 0.031. Correlation in level of knowledge with attitude revealed a weak positive correlation with r = 0.17. There was no significant association of pretest knowledge with selected socio-demographic data. Conclusion: Audiovisual psychoeducation is efficient in increasing the level of knowledge and change in attitude toward harmful effects of alcohol.

Alcohol craving and withdrawal at treatment entry prospectively predict alcohol use outcomes during outpatient treatment

ObjectiveChronic alcohol use increases risk of alcohol craving and withdrawal symptoms (AW) as well as abstinence-related distress symptoms, in those entering alcohol use disorder (AUD) treatment. Here, we examined whether AW and alcohol craving in AUD patients entering outpatient treatment prospectively predicts future heavy drinking days/week (HDD) and additional alcohol use outcomes during 8-weeks of outpatient treatment, and their relationship to abstinence symptoms of depression, anxiety and sleep difficulties. MethodsParticipants were 80 treatment-seeking adults with current DSM-5 AUD (39% female; 43% White; 20–60 years) who completed assessments of AW and alcohol craving and also alcohol abstinence symptoms of depression, anxiety, and sleep quality at treatment intake. Participants were prospectively followed using daily diaries for alcohol intake during 8-week of standardized weekly relapse prevention counseling to support recovery. ResultsAfter accounting for demographic and pre-treatment alcohol use, greater alcohol craving at treatment entry predicted higher HDD (p < .013) as well as greater drinking days (DD: p < .004), average drinks per drinking day/week (AvgD: p < .001) and relapse to heavy drinking (p < .05), while higher levels of pretreatment AW symptoms interacted with treatment week to predict greater HDD (p < .018). Abstinence symptoms of depression, anxiety, and sleep difficulties were associated with craving and AW but did not predict any drinking-related outcomes. ConclusionsThese results provide evidence that increased alcohol craving and AW may serve as prognostic indicators of greater risk of heavy drinking in outpatient treatment. Findings suggest the need to evaluate craving and AW at outpatient treatment entry and develop targeted treatments to specifically address the effects of craving and AW on drinking outcomes in outpatient AUD treatment.

Screening for depression in patients in treatment for alcohol use disorder using the Beck Depression Inventory-II and the Hopkins Symptom Checklist-10

Alcohol use disorder (AUD) and major depressive disorder (MDD) are prevalent disorders that often co-occur. The aim of the study was to investigate how the Beck Depression Inventory (BDI-II) and Hopkins Symptom Checklist (HSCL-10) perform as screening instruments for MDD in AUD patients in treatment. The study included 127 mainly AUD inpatients currently in treatment at rehabilitation clinics in Norway. Demographic and clinical variables were examined using questionnaires and clinical interviews. The factor structures of the BDI-II and HCSL-10 were examined, as well as internal consistency and receiver operating characteristic (ROC) curve analyses. The Mini International Neuropsychiatric Interview (M.I.N.I.) was used as standard for diagnosing MDD. In total, 14% of the participants were diagnosed with MDD. BDI-II factor analysis retrieved three factors; cognition, somatic complaints and affect, and factor analysis for the HSCL-10 retrieved two factors; depression and anxiety. The optimal cut-off for the BDI-II was 24.5 with sensitivity of 80% and specificity of 78%. For HSCL-10 the optimal cut-off was 2.35, giving sensitivity of 80% and specificity of 69%. Both the BDI-II and HSCL-10 may be clinically useful screening instruments for MDD in AUD patients. There was a tendency that the affect factor of the BDI-II and the depression factor of the HSCL-10 were slightly more suitable for identifying MDD than the other factors. Optimal cut-offs for both the BDI-II and the HSCL-10 in this patient group were higher than cut-offs commonly used in the general population.

Restoring an adequate dietary fiber intake by inulin supplementation: a pilot study showing an impact on gut microbiota and sociability in alcohol use disorder patients

ABSTRACT Alcohol use disorder (AUD) is a chronic relapsing disease associated with malnutrition, metabolic disturbances, and gut microbiota alterations that are correlated with the severity of psychological symptoms. This study aims at supplementing AUD patients with prebiotic fiber during alcohol withdrawal, in order to modulate the gut microbiota composition and to evaluate its effect on gastrointestinal tolerance, metabolism, and patient’s behavior. A randomized, double-blind, placebo-controlled study included 50 AUD patients assigned to inulin versus maltodextrin daily supplementation for 17 days. Biological measurements (fecal microbial 16S rDNA sequencing, serum biology), dietary intake, validated psychological questionnaires, and gastrointestinal tolerance assessment were performed before and after the intervention. Inulin significantly decreased the richness and evenness and induced changes of 8 genera (q < 0.1) including Bifidobacterium and Bacteroides. Prebiotic had minor effects on gastrointestinal symptoms and nutritional intakes compared to placebo. All patients showed an improvement in depression, anxiety, and craving scores during alcohol withdrawal regardless of the intervention group. Interestingly, only patients treated with inulin significantly improved the sociability score and had an increased serum level of brain-derived neurotrophic factor. This pilot study shows that inulin is well tolerated and modulates the gut microbiota and the social behavior in AUD patients, without further improving other psychological and biological parameters as compared to placebo. Gut2Brain study, clinicaltrial.gov: NCT03803709, https://clinicaltrials.gov/ct2/show/NCT03803709

Evaluating the Impact of Alcohol Abstinence on the Cognitive Functioning of Adults Diagnosed with Alcohol Use Disorder

Research supports the relation between chronic alcohol use and progressive cognitive impairment but alcohol rehabilitation facilities mainly focus on psycho-social factors with limited emphasis on cognitive impairment and recovery. This study evaluated the impact of alcohol abstinence on cognitive functioning; specifically, visuospatial attention, working memory and abstract reasoning on two different occasions using the WAIS-IVSA battery. A pre-test–post-test design was used to assess patients diagnosed with Alcohol Use Disorder (AUD). Differences in cognitive functioning from phase 1 (3-4 days after admission) and phase 2 (14 days after phase 1) were measured. A paired samples t-test was conducted using SPSS version 27. A statistically significant increase in AUD patients’ visuospatial scores was found when comparing phase 1 and 2 (M=7.11, SD=2.07), t(8)=3.42, p=.009. No statistically significant differences were observed for working memory and abstract reasoning. We conclude that the findings can be used to guide, and improve the development of future intervention programs to emphasize the value of cognitive recovery.

Alcohol withdrawal symptoms predict corticostriatal dysfunction that is reversed by prazosin treatment in alcohol use disorder.

Chronic alcohol use increases risk of alcohol withdrawal symptoms (AW) and disrupts stress biology and resilient coping, thereby promoting excessive alcohol intake. Chronic alcohol intake and multiple alcohol detoxifications are known to impair brain medial prefrontal cortex (mPFC) and striatal functioning, regions involved in regulating stress, craving and alcohol intake. In two related studies, we examined whether AW predicts this functional brain pathology and whether Prazosin versus Placebo treatment may reverse these effects. In Study 1, patients with Alcohol Use Disorder (AUD) (N = 45) with varying AW levels at treatment entry were assessed to examine AW effects on corticostriatal responses to stress, alcohol cue and neutral visual images with functional magnetic resonance imaging (fMRI). In Study 2, 23 AUD patients entering a 12-week randomised controlled trial (RCT) of Prazosin, an alpha1 adrenergic antagonist that decreased withdrawal-related alcohol intake in laboratory animals, participated in two fMRI sessions at pretreatment and also at week 9-10 of chronic treatment (Placebo: N = 13; Prazosin: N=10) to assess Prazosin treatment effects on alcohol-related cortico-striatal dysfunction. Study 1 results indicated that higher AW predicted greater disruption in brain mPFC and striatal response to stress and alcohol cues (p < 0.001, family-wise error [FWE] correction) and also subsequently greater heavy drinking days (HDD) in early treatment (p < 0.01). In Study 2, Prazosin versus Placebo treatment reversed mPFC-striatal dysfunction (p < 0.001, FWE), which in turn predicted fewer drinking days (p < 0.01) during the 12-week treatment period. These results indicate that AW is a significant predictor of alcohol-related prefrontal-striatal dysfunction, and Prazosin treatment reversed these effects that in turn contributed to improved alcohol treatment outcomes.

The oral microbiome in alcohol use disorder: a longitudinal analysis during inpatient treatment

ABSTRACT Background Alcohol use disorder (AUD)-induced disruption of oral microbiota can lead to poor oral health; there have been no studies published examining the longitudinal effects of alcohol use cessation on the oral microbiome. Aim To investigate the oral microbiome during alcohol cessation during inpatient treatment for AUD. Methods Up to 10 oral tongue brushings were collected from 22 AUD patients during inpatient treatment at the National Institutes of Health. Alcohol use history, smoking, and periodontal disease status were measured. Oral microbiome samples were sequenced using 16S rRNA gene sequencing. Results Alpha diversity decreased linearly during treatment across the entire cohort (P = 0.002). Alcohol preference was associated with changes in both alpha and beta diversity measures. Characteristic tongue dorsum genera from the Human Microbiome Project such as Streptococcus, Prevotella, Veillonella and Haemophilus were highly correlated in AUD. Oral health-associated genera that changed longitudinally during abstinence included Actinomyces, Capnocytophaga, Fusobacterium, Neisseria and Prevotella. Conclusion The oral microbiome in AUD is affected by alcohol preference. Patients with AUD often have poor oral health but abstinence and attention to oral care improve dysbiosis, decreasing microbiome diversity and periodontal disease-associated genera while improving acute oral health.

Effect of a nutritional modulation of the gut-brain axis in alcohol-dependent patients

Rationale: Our previous studies have shown that chronic alcohol abuse induces a leaky gut and alterations of the gut microbiota composition, which are correlated with the severity of psychological symptoms, suggesting the involvement of the gut-brain axis in the development of alcohol use disorders (AUD). The Gut2Brain study aims at supplementing AUD patients with prebiotics (inulin) in order to modulate the gut microbiota composition and to evaluate the putative effect on metabolism, inflammation and behavior.

Mental Imagery Skills in Alcohol-Dependent Subjects and Their Associations With Cognitive Performance: An Exploratory Study During Residential Rehabilitation.

People in alcohol-detoxification experience deficits in motor and non-motor functions including cognitive performance. Imagery, the cognitive process of generating visual, auditory or kinesthetic experiences in the mind without the presence of external stimuli, has been little studied in Alcohol Use Disorders (AUD). This pilot study aims to observe the cognitive abilities useful for the inspection, maintenance, generation and manipulation of images in these patients during residential rehabilitation and investigate the relationships with their cognitive performance. Thirty-six subjects who completed the 28-day rehabilitation program for alcohol addiction, completed the Mental Imagery Test (MIT) and Neuropsychological Battery (ENB-2). The global score at MIT did not show pathological scores. The 11.1% of AUD patients showed an impaired global score in the cognitive performance and the 5.7% with scoring at limits of norm. Significant correlations were found between Mental Imagery abilities and ENB-2 subscale and stepwise regression analysis showed the close association between the ability of imagery (Mental Imagery Test) and the overall cognitive performance (ENB-2) in alcohol dependent patients and this relationship is stronger than other cognitive tasks.

Learning and verbal memory: A comparison between patients with alcohol use disorder and major depressive disorder.

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p < 0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p < 0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.

Employment trajectories among those treated for alcohol use disorder: A register-based cohort study.

Employment during and following treatment for alcohol use disorder (AUD) is important for the individual's health and well-being and for reducing the societal costs associated with benefit payments. Nonetheless, this is an under-researched topic. This study aimed to identify trajectories of labour force participation among people enrolled in AUD treatment and describe the characteristics of those following contrasting pathways. Using trajectory analysis, we modelled employment trajectory groups among AUD patients during the year of treatment entry and the 4 subsequent years, applying Norwegian longitudinal register data. Norway. Patients who entered treatment with AUD as the primary diagnosis during 2009 and 2010 (9000 patients, age 20-61 years). The outcome variable 'labour force attachment' was measured as being in full-time employment, partly employed, on temporary welfare benefits or on permanent disability pension. Predictors were age, gender, education and comorbid mental health and drug use disorders. We distinguished six employment trajectories among AUD patients: 15.8% were on permanent disability pension throughout, 8.7% exited the labour force on permanent disability pension during the observation period, 32.1% had a medium attachment throughout follow-up, and 9.2% had a decreasing attachment; 23.3% had a high labour force attachment throughout, and 10.9% experienced increasing attachment. High attachment throughout was negatively associated with being female (P < 0.001), having lower educational attainment (P < 0.001), and having comorbid mental health (P < 0.001) and drug use disorders (P < 0.001). Norwegian patients treated for alcohol use disorder in 2009 and 2010 followed six employment trajectories during the 5 years following treatment entry and had lower labour force participation than the general population. Nearly a quarter had a high labour force attachment throughout treatment, which was positively associated with being male, having higher educational attainment and having fewer comorbid mental health and drug use disorders.

Use of the MoCA Combined with the Fab for the Screening of Cognitive Dysfunction in Patients with Alcohol Use Disorders

Objective: Cognitive dysfunction is common in patients with Alcohol Use Disorders (AUD). This impairment needs to be detected since it affects the quality of life of patients and compliance with therapeutic programs. As global cognitive and executive functions may be differently affected in AUD patients, we wondered whether, when diagnosing cognitive dysfunction, specific measurement of executive functioning could provide an incremental value that could be used in addition to global cognitive measurement. Methods: Cognitive status was evaluated at admission using the Montreal Cognitive Assessment (MoCA) test, the Frontal Assessment Battery (FAB) and a battery of Neuropsychological (NP) reference tests in 134 patients with AUD hospitalized in an addictions treatment unit. Results: Seventy patients (52%) had cognitive dysfunction according to the battery of Neuropsychological (NP) tests. Among these 70 patients, 59 (84%) and 38 (54%) had abnormal MoCA and FAB test results, respectively. Concordance between the MoCA and the FAB was weak (kappa = 0.27). Analysis through logistic regression showed that the Area under Curve (AUC) obtained with the MoCA test was a better single predictor of cognitive impairment (0.85) than that obtained with the FAB (0.73). Combining the two tests produced an AUC of 0.86, a value not significantly different from that obtained with the MoCA. Conclusions: The MoCA-FAB combination did not perform better than the MoCA alone as a screening tool for cognitive dysfunction among AUD patients. This confirms that the MoCA is an efficient screening tool since it can detect frontal as well as general cognitive disorders.

Management of alcohol use disorder in patients with cirrhosis in the setting of liver transplantation.

The prevalence of alcohol use disorder (AUD) has been steadily increasing over the past decade. In parallel, alcohol-associated liver disease (ALD) has been increasing at an alarming rate, especially among young patients. Data suggest that most patients with ALD do not receive AUD therapy. Although liver transplantation is the only curative therapy for end-stage ALD, transplant candidacy is often a matter of debate given concerns about patients being under-treated for AUD and fears of post-transplantation relapse affecting the allograft. In this Review, we discuss diagnosis, predictors and effects of relapse, behavioural therapies and pharmacotherapies, and we also propose an integrative, multidisciplinary and multimodality approach for treating AUD in patients with cirrhosis, especially in the setting of liver transplantation. Notably, this approach takes into account the utility of AUD pharmacotherapy in patients on immunosuppressive medications and those with renal impairment after liver transplantation. We also propose a comprehensive and objective definition of relapse utilizing contemporary biomarkers to guide future clinical trials. Future research using the proposed approach and definition is warranted with the goal of optimizing AUD treatment in patients with cirrhosis, the transplant selection process and post-transplantation care of patients with AUD.

Sedation - Effects of disorders of abuse on therapeutic efficacy (SEDATE): A retrospective cohort study.

The impact of alcohol or opioid use disorders on medication dosing for procedural sedation in the emergency department (ED) is unclear, as most of the literature is from gastrointestinal endoscopy. Exploring how these patient factors affect sedative and analgesic medications may inform more nuanced sedation strategies in the emergency department. This was a retrospective chart-review cohort study across five EDs from 2015 to 2020. Included were adult patients who underwent procedural sedation in the ED, categorized into three a priori groups: alcohol use disorder (AUD), opioid use disorder (OUD), and individuals with neither (non-SUD). Wilcoxon test was used to compare the time-averaged dose of agents between groups. Logistic regression was used to model multi-agent sedations. The propofol time-averaged dose was the primary outcome. Secondary outcomes included other agents, sedation duration, and switching to other agents. 2725 sedations were included in the analysis. 59 patients had a history of AUD, and 40 had a history of OUD. Time-averaged doses of medications did not differ significantly between AUD and non-SUD patients. Likewise, patients with OUD did not receive different doses of medications compared to non-SUD. The propofol doses for non-SUD, AUD, and OUD were 0.033 IQR 0.04; 0.042 IQR 0.05; and 0.058 IQR 0.04 mg/kg*min, respectively. Sedation duration was not different across groups. Having AUD or OUD is not associated with increased odds of requiring multiple sedative agents. Although sedation in patients with AUD or OUD may be associated with significant case bias, these patient factors did not significantly alter outcomes compared to the general population. This study suggests there is no evidence to proactively adjust medication strategy in ED patients with AUD or OUD.

Acamprosate may be safer than baclofen for the treatment of alcohol use disorder in patients with cirrhosis: a first description of use in real-world clinical practice.

Patients with alcohol use disorder (AUD) and liver cirrhosis benefit from stopping alcohol intake. Baclofen has been trialled for AUD in cirrhosis and appears to be effective. However, in patients without cirrhosis acamprosate is safer and more efficacious. Acamprosate is rarely used in cirrhosis due to safety concerns: the only published report was for 24 h in a controlled setting. Our centre uses both medications off-label in cirrhotic patients. We performed an audit to pragmatically compare the safety of acamprosate to baclofen in these patients. The electronic records of patients prescribed acamprosate or baclofen between 01/04/17 and 31/03/20 were retrospectively reviewed. Adverse events and abstinence at last follow-up were compared by Student's t-test, Mann-Whitney U or chi-square test. Confounding variables were evaluated by logistic regression. In total 48 cirrhotic patients taking acamprosate (median 84 days, range 2-524); 44 baclofen (247 days, 8-910) met inclusion criteria. At baseline, 41% had Childs-Pugh B or C cirrhosis. More patients taking baclofen had an unplanned hospital admission or attendance (23 vs 13; P = 0.013) and the mean number per patient was higher (1.6 vs 0.6; P = 0.032). Sub-group analysis revealed increased admissions in actively drinking patients prescribed baclofen to achieve abstinence (mean 2.4 vs 0.6; P = 0.020); acamprosate use was associated with a reduced chance of admission or attendance (OR, 0.284; 0.095-0.854; P = 0.025) independent of treatment length. No difference in efficacy was observed. In patients with cirrhosis, acamprosate was associated with fewer unplanned admissions than baclofen, hence may be safer despite historical concerns.

Functional and Structural Alteration of Default Mode, Executive Control, and Salience Networks in Alcohol Use Disorder.

Alcohol use disorder (AUD) has been related to aberrant functional connectivity (FC) in the salience network (SN), executive control network (ECN), and default mode network (DMN). However, there is a lack of comprehensive and simultaneous examination of these networks in patients with AUD and of their relation to potential anatomical changes. We aimed to comprehensively examine the alteration in FC in the three networks in AUD patients, and the correlation of the alteration with anatomical/structural changes (volume) in the neural areas implicated in these networks, by applying voxel-based morphometry (VBM) and region of interest-to-region of interest connectivity analysis simultaneously. In all, 22 patients with AUD and 22 healthy adults participated in the study and underwent T1 magnetic resonance imaging. Patients with AUD showed increased FCs within the DMN and SN networks, especially in terms of connectivity of the frontal areas and bilateral hippocampi. They also showed decreased FCs in the ECN. In addition, there was significant volume reduction in these areas (frontal areas and hippocampus). The increased FCs within the frontal areas or bilateral hippocampi showed a negative correlation with gray matter volume of these areas in AUD patients. Our findings add to the empirical evidence that the frontal lobe and hippocampi are critical areas that are vulnerable to functional and structural changes due to AUD.

Gender Differences among Sardinians with Alcohol Use Disorder

Sardinia is an Italian island in the Mediterranean characterized by secular isolation and the singular genetic characteristics of its inhabitants. Findings obtained in populations with diverse genetic make-up and cultural background indicate gender differences and/or similarities in drinking characteristics of patients with alcohol use disorder (AUD). Knowledge of these characteristics in AUD patients is useful to improve access to treatments. This paper investigated the drinking characteristics of 66 female and 282 male outpatients with AUD, born from 1937 to 1991, living in Sardinia, and compared their characteristics with those of AUD patients living in other countries. Most Sardinian patients were men, approximately 3 years younger than women; women consumed lower amounts of alcohol than men but did not differ from men in the severity of AUD. Men were more often single than women, while a higher proportion of women reported that their mother or spouse was affected by AUD. Anxiety and depression were more prevalent among women while a higher proportion of men were affected by substance use disorders. Women were older than men at the age of first drink, regular drinking, and onset of AUD, and progressed faster than men from regular use to AUD onset. Women did not differ from men in age at first request for care, and in the lapse from AUD onset to first request for care. Women and men waited for more than 8 and 9 years, respectively, before receiving medical treatment. Gender differences progressively decreased among younger patients. Although the scarce number of women in some cohorts limits the strength of these findings, drinking characteristics of Sardinian patients did not vary significantly from those of AUD patients living in other countries. These results suggest that the number of Sardinian women with AUD is increasing and services for treatment of AUD should (a) consider women’s specific needs, and (b) realize effective policies to reduce latency prior to accessing medical treatment for both men and women with AUD.

Convolutional Neural Network Based Frameworks for Fast Automatic Segmentation of Thalamic Nuclei from Native and Synthesized Contrast Structural MRI.

Thalamic nuclei have been implicated in several neurological diseases. Thalamic nuclei parcellation from structural MRI is challenging due to poor intra-thalamic nuclear contrast while methods based on diffusion and functional MRI are affected by limited spatial resolution and image distortion. Existing multi-atlas based techniques are often computationally intensive and time-consuming. In this work, we propose a 3D convolutional neural network (CNN) based framework for thalamic nuclei parcellation using T1-weighted Magnetization Prepared Rapid Gradient Echo (MPRAGE) images. Transformation of images to an efficient representation has been proposed to improve the performance of subsequent classification tasks especially when working with limited labeled data. We investigate this by transforming the MPRAGE images to White-Matter-nulled MPRAGE (WMn-MPRAGE) contrast, previously shown to exhibit good intra-thalamic nuclear contrast, prior to the segmentation step. We trained two 3D segmentation frameworks using MPRAGE images (n = 35 subjects): (a) a native contrast segmentation (NCS) on MPRAGE images and (b) a synthesized contrast segmentation (SCS) where synthesized WMn-MPRAGE representation generated by a contrast synthesis CNN were used. Thalamic nuclei labels were generated using THOMAS, a multi-atlas segmentation technique proposed for WMn-MPRAGE images. The segmentation accuracy and clinical utility were evaluated on a healthy cohort (n = 12) and a cohort (n = 45) comprising of healthy subjects and patients with alcohol use disorder (AUD), respectively. Both the segmentation CNNs yielded comparable performances on most thalamic nuclei with Dice scores greater than 0.84 for larger nuclei and at least 0.7 for smaller nuclei. However, for some nuclei, the SCS CNN yielded significant improvements in Dice scores (medial geniculate nucleus, P = 0.003, centromedian nucleus, P = 0.01) and percent volume difference (ventral anterior, P = 0.001, ventral posterior lateral, P = 0.01) over NCS. In the AUD cohort, the SCS CNN demonstrated a significant atrophy in ventral lateral posterior nucleus in AUD patients compared to healthy age-matched controls (P = 0.01), agreeing with previous studies on thalamic atrophy in alcoholism, whereas the NCS CNN showed spurious atrophy of the ventral posterior lateral nucleus. CNN-based segmentation of thalamic nuclei provides a fast and automated technique for thalamic nuclei prediction in MPRAGE images. The transformation of images to an efficient representation, such as WMn-MPRAGE, can provide further improvements in segmentation performance.

Increased decision latency in alcohol use disorder reflects altered resting-state synchrony in the anterior salience network

Increased decision latency in alcohol use disorder (AUD) has been generally explained in terms of psychomotor slowing. Recent results suggest that AUD patients’ slowed decision-making might rather reflect alterations in the neural circuitry underlying the engagement of controlled processing by salient stimuli. We addressed this hypothesis by testing a relationship between decision latency at the Cambridge Gambling Task (CGT) and intrinsic brain activity in 22 individuals with AUD and 19 matched controls. CGT deliberation time was related to two complementary facets of resting-state fMRI activity, i.e. coherence and intensity, representing early biomarkers of functional changes in the intrinsic brain architecture. For both metrics, we assessed a multiple regression (to test a relationship with deliberation time in the whole sample), and an interaction analysis (to test a significantly different relationship with decision latency across groups). AUD patients’ slowed deliberation time (p < 0.025) reflected distinct facets of altered intrinsic activity in the cingulate node of the anterior salience network previously associated with the “output” motor stage of response selection. Its heightened activity in AUD patients compared with controls, tracking choice latency (p < 0.025 corrected), might represent a compensation mechanism counterbalancing the concurrent decrease of its internal coherent activity (p < 0.025 corrected). These findings provide novel insights into the intrinsic neural mechanisms underlying increased decision latency in AUD, involving decreased temporal synchronicity in networks promoting executive control by behaviourally relevant stimuli. These results pave the way to further studies assessing more subtle facets of decision-making in AUD, and their possible changes with rehabilitative treatment.

Alterations of kynurenine pathway in alcohol use disorder and abstinence: a link with gut microbiota, peripheral inflammation and psychological symptoms

The gut-brain communication is mostly driven by the immune, metabolic and neural pathways which remained poorly explored in patients with alcohol use disorder (AUD). The metabolites arising from the tryptophan-kynurenine pathway have gained considerable attention since they are at the interface between intestinal bacteria, host immune response and brain functions. This study described the circulating levels of kynurenine metabolites in AUD patients, at the onset (T1) and end (T2) of a 3-week detoxification program, and tested correlations between those metabolites and inflammatory markers, the gut microbiota and the psychological symptoms. Increased concentration of the neurotoxic metabolite quinolinic acid (QUIN) and decreased levels of the neuroprotector metabolite kynurenic acid (KYNA) which both modulate glutamatergic neurotransmission were observed in AUD patients, particularly at T2. The inflammatory marker hsCRP was associated with several metabolic ratios of the kynurenine pathway. Tryptophan, KYNA and QUIN were correlated with depression, alcohol craving and reaction time, respectively. Analysis of gut microbiota revealed that bacteria known as short-chain fatty acid producers, as well as bacterial metabolites including butyrate and medium-chain fatty acids were associated with some metabolites of the tryptophan-kynurenine pathway. Targeting the glutamatergic neurotransmission through the modulation of the kynurenine pathway, by manipulating the gut microbiota, might represent an interesting alternative for modulating alcohol-related behavior.