Correlation of striatal dopamine D2/3 receptor availability with GABA level in the anterior cingulate cortex in healthy controls but not in alcohol-dependent subjects and individuals at high risk: A multimodal magnetic resonance spectroscopy and positron emission tomography study.

BACKGROUND: The association of impaired dopaminergic neurotransmission with the development and maintenance of alcohol use disorder is well known. More specifically, reduced dopamine D2/3 receptors in the striatum of subjects with alcohol dependence (AD) compared to healthy controls have been found in previous studies. Furthermore, alterations of gamma-aminobutyric acid (GABA) and glutamate (Glu) levels in the anterior cingulate cortex (ACC) of AD subjects have been documented in several studies. However, the interaction between cortical Glu levels and striatal dopamine D2/3 receptors has not been investigated in AD thus far. METHODS: This study investigated dopamine D2/3 receptor availability via 18F-fallypride positron emission tomography (PET) and GABA as well as Glu levels via magnetic resonance spectroscopy (MRS) in 19 detoxified AD subjects, 18 healthy controls (low risk, LR) controls and 19 individuals at high risk (HR) for developing AD, carefully matched for sex, age and smoking status. RESULTS: We found a significant negative correlation between GABA levels in the ACC and dopamine D2/3 receptor availability in the associative striatum of LR but not in AD or HR individuals. Contrary to our expectations, we did not observe a correlation between Glu concentrations in the ACC and striatal D2/3 receptor availability. CONCLUSIONS: The results may reflect potential regulatory cortical mechanisms on mesolimbic dopamine receptors and their disruption in AD and individuals at high risk, mirroring complex neurotransmitter interactions associated with the pathogenesis of addiction. This is the first study combining 18F-fallypride PET and MRS in AD subjects and individuals at high risk.

Multi-level prediction of substance use: Interaction of white matter integrity, resting-state connectivity and inhibitory control measured repeatedly in every-day life.

Substance use disorders are characterized by inhibition deficits related to disrupted connectivity in white matter pathways, leading via interaction to difficulties in resisting substance use. By combining neuroimaging with smartphone-based ecological momentary assessment (EMA), we questioned how biomarkers moderate inhibition deficits to predict use. Thus, we aimed to assess white matter integrity interaction with everyday inhibition deficits and related resting-state network connectivity to identify multi-dimensional predictors of substance use. Thirty-eight patients treated for alcohol, cannabis or tobacco use disorder completed 1 week of EMA to report substance use five times and complete Stroop inhibition testing twice daily. Before EMA tracking, participants underwent resting state functional MRI and diffusion tensor imaging (DTI) scanning. Regression analyses were conducted between mean Stroop performances and whole-brain fractional anisotropy (FA) in white matter. Moderation testing was conducted between mean FA within significant clusters as moderator and the link between momentary Stroop performance and use as outcome. Predictions between FA and resting-state connectivity strength in known inhibition-related networks were assessed using mixed modelling. Higher FA values in the anterior corpus callosum and bilateral anterior corona radiata predicted higher mean Stroop performance during the EMA week and stronger functional connectivity in occipital-frontal-cerebellar regions. Integrity in these regions moderated the link between inhibitory control and substance use, whereby stronger inhibition was predictive of the lowest probability of use for the highest FA values. In conclusion, compromised white matter structural integrity in anterior brain systems appears to underlie impairment in inhibitory control functional networks and compromised ability to refrain from substance use.

Regional cortical thickness recovery with extended abstinence after treatment in those with alcohol use disorder.

Several cross-sectional investigations reported widespread cortical thinning in those with alcohol use disorder (AUD). The few longitudinal studies investigating cortical thickness changes during abstinence are limited to the first month of sobriety. Consequently, cortical thickness changes during extended abstinence in those with AUD is unclear. In this study, AUD participants were studied at approximately 1 week (n = 68), 1 month (n = 88), and 7.3 months (n = 40) of abstinence. Forty-five never-smoking controls (CON) completed a baseline study, and 15 were reassessed after approximately 9.6 months. Participants completed magnetic resonance imaging studies at 1.5T, and cortical thickness for 34 bilateral regions of interest (ROI) was quantitated with FreeSurfer. AUD participants demonstrated significant linear thickness increases in 25/34 ROI over 7.3 months of abstinence. The rate of change from 1 week to 1 month was greater than 1 month to 7.3 months in 19/34 ROIs. Proatherogenic conditions were associated with lower thickness recovery in anterior frontal, inferior parietal, and lateral/mesial temporal regions. After 7.3 months of abstinence, AUD participants were statistically equivalent to CON on cortical thickness in 24/34 ROIs; the cortical thickness differences between AUD and CON in the banks superior temporal gyrus, post central, posterior cingulate, superior parietal, supramarginal, and superior frontal cortices were driven by thinner cortices in AUD with proatherogenic conditions relative to CON. In actively smoking AUD, increasing pack-years was associated with decreasing thickness recovery primarily in the anterior frontal ROIs. Widespread bilateral cortical thickness recovery over 7.3 months of abstinence was the central finding for this AUD cohort. The longitudinal and cross-sectional findings for AUD with proatherogenic suggests alterations in perfusion or vascular integrity may relate to structural recovery in those with AUD. These results support the adaptive and beneficial effects of sustained sobriety on brain structural recovery in people with AUD.

Machine Learning of Functional Connectivity to Biotype Alcohol and Nicotine Use Disorders.

BACKGROUND: Magnetic resonance imaging provides noninvasive tools to investigate alcohol use disorder (AUD) and nicotine use disorder (NUD) and neural phenotypes for genetic studies. A data-driven transdiagnostic approach could provide a new perspective on the neurobiology of AUD and NUD. METHODS: Using samples of individuals with AUD (n = 140), individuals with NUD (n = 249), and healthy control participants (n = 461) from the UK Biobank, we integrated clinical, neuroimaging, and genetic markers to identify biotypes of AUD and NUD. We partitioned participants with AUD and NUD based on resting-state functional connectivity (FC) features associated with clinical metrics. A multitask artificial neural network was trained to evaluate the cluster-defined biotypes and jointly infer AUD and NUD diagnoses. RESULTS: Three biotypes-primary NUD, mixed NUD/AUD with depression and anxiety, and mixed AUD/NUD-were identified. Multitask classifiers incorporating biotype knowledge achieved higher area under the curve (AUD: 0.76, NUD: 0.74) than single-task classifiers without biotype differentiation (AUD: 0.61, NUD: 0.64). Cerebellar FC features were important in distinguishing the 3 biotypes. The biotype of mixed NUD/AUD with depression and anxiety demonstrated the largest number of FC features (n = 5), all related to the visual cortex, that significantly differed from healthy control participants and were validated in a replication sample (p < .05). A polymorphism in TNRC6A was associated with the mixed AUD/NUD biotype in both the discovery (p = 7.3 × 10-5) and replication (p = 4.2 × 10-2) sets. CONCLUSIONS: Biotyping and multitask learning using FC features can characterize the clinical and genetic profiles of AUD and NUD and help identify cerebellar and visual circuit markers to differentiate the AUD/NUD group from the healthy control group. These markers support a new growing body of literature.

Disrupted brain state dynamics in opioid and alcohol use disorder: attenuation by nicotine use.

Substance use disorder (SUD) is a chronic relapsing disorder with long-lasting changes in brain intrinsic networks. While most research to date has focused on static functional connectivity, less is known about the effect of chronic drug use on dynamics of brain networks. Here we investigated brain state dynamics in individuals with opioid use (OUD) and alcohol use disorder (AUD) and assessed how concomitant nicotine use, which is frequent among individuals with OUD and AUD, affects brain dynamics. Resting-state functional magnetic resonance imaging data of 27 OUD, 107 AUD, and 137 healthy participants were included in the analyses. To identify recurrent brain states and their dynamics, we applied a data-driven clustering approach that determines brain states at a single time frame. We found that OUD and AUD non-smokers displayed similar changes in brain state dynamics including decreased fractional occupancy or dwell time in default mode network (DMN)-dominated brain states and increased appearance rate in visual network (VIS)-dominated brain states, which were also reflected in transition probabilities of related brain states. Interestingly, co-use of nicotine affected brain states in an opposite manner by lowering VIS-dominated and enhancing DMN-dominated brain states in both OUD and AUD participants. Our finding revealed a similar pattern of brain state dynamics in OUD and AUD participants that differed from controls, with an opposite effect for nicotine use suggesting distinct effects of various drugs on brain state dynamics. Different strategies for treating SUD may need to be implemented based on patterns of co-morbid drug use.

The disruption of white matter integrity of systemic striatal circuits in alcohol-dependent males with physiological cue reactivity.

Alcohol dependence (AD) is a chronic and relapsing disorder. Conditioned cues associated with the rewarding properties of drugs could trigger motivational/physiological reactions and render subjects vulnerable to relapse. Striatal circuit dysfunction has been implicated in alcohol addiction behaviours. However, little is known about the striatal tracts structural connectivity changes underlying cue induced reactivity in AD. In our present study, we recruited 51 patients with AD; 31 individuals had physiological response. We used seed-based classification by probabilistic tractography with nine target masks to explore the white matter integrity of striatal circuits in physiological responders (N = 31), non-responders (N = 20), and healthy controls (N = 27). Compared with healthy controls, physiological responders showed lower fractional anisotropy (FA) and/or higher mean diffusivity in the striatum-dorsolateral prefrontal cortex (dlPFC), striatum-ventral lateral prefrontal cortex, striatum-supplementary motor area (SMA), and striatum-insular. Considering age and smoking are potential nuisances to diffusion parameters, an analysis of covariance also was conducted and similar results were found. We also found the cue-induced physiological response was negatively associated with the FA of the striatum-SMA (r = -0.287; p = 0.045) and left striatum-dlPFC (r = -0.253; p = 0.079) in AD. In our study, we found abnormal integrity of striatal circuit structural connectivity in AD with physiological cue reactivity, especially trajectory from prefrontal cortex and insular. We also found the FA of striatal tracks was negatively associated with the degree of cue reactivity. Our findings provide further evidence for reduced white matter integrity of striatal circuits for cue reactivity in male individuals with AD.

N-acetylcysteine does not alter neurometabolite levels in non-treatment seeking adolescents who use alcohol heavily: A preliminary randomized clinical trial.

Current treatments for adolescent alcohol use disorder (AUD) are mainly psychosocial and limited in their efficacy. As such, pharmacotherapies are being investigated as potential adjunctive treatments to bolster treatment outcomes. N-acetylcysteine is a promising candidate pharmacotherapy for adolescent AUD because of its tolerability and demonstrated ability to modulate glutamatergic, GABAergic, and glutathione systems. The primary objective of this double-blind, placebo-controlled, within-subjects crossover preliminary investigation was to measure potential changes within glutamate + glutamine (Glx), GABA, and glutathione levels in the dorsal anterior cingulate cortex (dACC) using proton magnetic resonance spectroscopy during 10-days of N-acetylcysteine (1200 mg twice daily) compared to 10-days of placebo in non-treatment seeking adolescents who use alcohol heavily (N = 31; 55% female). Medication adherence was confirmed via video. Effects on alcohol use were measured using Timeline Follow-Back as an exploratory aim. Linear mixed effects models controlling for baseline metabolite levels, brain tissue composition, alcohol use, cannabis use, and medication adherence found no significant differences in Glx, GABA, or glutathione levels in the dACC after N-acetylcysteine compared to placebo. There were also no measurable effects on alcohol use; however, this finding was underpowered. Findings were consistent in the subsample of participants who met criteria for AUD (n = 19). The preliminary null findings in brain metabolite levels may be due to the young age of participants, relatively low severity of alcohol use, and non-treatment seeking status of the population investigated. Future studies can use these findings to conduct larger, well-powered studies within adolescents with AUD.

Association between iron accumulation in the dorsal striatum and compulsive drinking in alcohol use disorder.

RATIONALE: Brain iron accumulation has been observed in neuropsychiatric disorders and shown to be related to neurodegeneration. OBJECTIVES: In this study, we used quantitative susceptibility mapping (QSM), an emerging MRI technique developed for quantifying tissue magnetic susceptibility, to examine brain iron accumulation in individuals with alcohol use disorder (AUD) and its relation to compulsive drinking. METHODS: Based on our previous projects, QSM was performed as a secondary analysis with gradient echo sequence images, in 186 individuals with AUD and 274 healthy participants. Whole-brain susceptibility values were calculated with morphology-enabled dipole inversion and referenced to the cerebrospinal fluid. Then, the susceptibility maps were compared between AUD individuals and healthy participants. The relationship between drinking patterns and susceptibility was explored. RESULTS: Whole-brain analyses showed that the susceptibility in the dorsal striatum (putamen and caudate) among AUD individuals was higher than healthy participants and was positively related to the Obsessive Compulsive Drinking Scale (OCDS) scores and the amount of drinking in the past three months. CONCLUSIONS: Increased susceptibility suggests higher iron accumulation in the dorsal striatum in AUD. This surrogate for the brain iron level was linearly associated with the compulsive drinking pattern and the recent amount of drinking, which provides us a new clinical perspective in relation to brain iron accumulation, and also might indicate an association of AUD with neuroinflammation as a consequence of brain iron accumulation. The iron accumulation in the striatum is further relevant for functional imaging studies in AUD by potentially producing signal dropout and artefacts in fMRI images.

Association between DRD2/ANKK1 TaqIA Allele Status and Striatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder.

BACKGROUND: The association between blunted dopaminergic neurotransmission and alcohol use disorder (AUD) is well-known. In particular, the impairment of postsynaptic dopamine 2 and 3 receptors (DRD2/3) in the ventral and dorsal striatum during the development and maintenance of alcohol addiction has been investigated in several positron emission tomography (PET) studies. However, it is unclear whether these changes are the result of adaptation or genetic predisposition. METHODS: Here we investigated the association between DRD2/ankyrin repeat and kinase domain-containing 1 (ANKK1) TaqIA allele (rs1800497) status and striatal DRD2/3 availability measured by 18F-fallypride PET in 12 AUD patients and 17 sex-matched healthy controls. Age and smoking status were included as covariates. RESULTS: Contrary to our expectations, TaqIA allele status was not associated with striatal DRD2/3 availability in either group and there was no significant difference between groups, possibly due to the relatively small sample size (N = 29). CONCLUSIONS: Nonetheless, this is the first in vivo study investigating the relationship between dopamine receptor availability and genetic factors in AUD. The pitfalls of assessing such relationships in a relatively small sample are discussed. CLINICAL TRIAL REGISTRATION: The published analysis is an additional, post hoc analysis to the preregistered trial with clinical trial number NCT01679145 available on https://clinical-trials.gov/ct2/show/NCT01679145.

Intracortical myelin in individuals with alcohol use disorder: An initial proof-of-concept study.

INTRODUCTION: Disruption of cortical gray matter and white matter tracts are well-established markers of alcohol use disorder (AUD), but less is known about whether similar differences are present in intracortical myelin (ICM, i.e., highly myelinated gray matter in deeper cortical layers). The goal of this study was to provide initial proof-of-concept for using an optimized structural magnetic resonance imaging (MRI) sequence to detect differences in ICM in individuals with AUD compared to control participants reporting drinking within recommended guidelines. METHODS: This study used an optimized 3T MRI sequence for high intracortical contrast to examine ICM-related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Surface-based analytic techniques were used to quantify ICM-related MRI signal in 20 bilateral a priori regions of interest based on prior cortical thickness studies, and exploratory vertex-wise analyses were examined using Cohen's d effect size. RESULTS: The global distribution of ICM-related signal was largely comparable between groups. Region of interest analysis indicated that AUD group exhibited greater ICM-related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, and dorsolateral prefrontal cortex (Cohen's ds = 0.50-0.75). Four regions (right precuneus, ventromedial prefrontal cortex, posterior cingulate and left dorsolateral prefrontal cortex) remained significant (p < .05) after covarying for smoking status. CONCLUSION: These findings provide initial evidence of ICM differences in a moderately sized sample of individuals with AUD compared to controls, although the inflation of type 1 error rate necessitates caution in drawing conclusions. Robustly establishing these differences in larger samples is necessary. The cross-sectional design cannot address whether the observed differences predate AUD or are consequences of heavy alcohol consumption.

A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder.

INTRODUCTION: Besides the commonly described gray matter (GM) deficits, there is growing evidence of significant white matter (WM) alterations in patients with alcohol use disorder (AUD). WM changes can be assessed using volumetric and diffusive magnetic resonance imaging methods, such as voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The aim of the present meta-analysis is to investigate the spatial convergence of the reported findings on WM alterations in AUD. METHODS: Systematic literature search on PubMed and further databases revealed 18 studies eligible for inclusion, entailing a total of 462 AUD patients and 416 healthy controls (up to January 18, 2021). All studies that had used either VBM or DTI whole-brain analyzing methods and reported results as peak-coordinates in standard reference space were considered for inclusion. We excluded studies using approaches non-concordant with recent guidelines for neuroimaging meta-analyses and studies investigating patient groups with Korsakoff syndrome or other comorbid substance use disorders (except tobacco). RESULTS: Anatomical likelihood estimation (ALE) revealed four significant clusters of convergent macro- and microstructural WM alterations in AUD patients that were assigned to the genu and body of the corpus callosum, anterior and posterior cingulum, fornix, and the right posterior limb of the internal capsule. DISCUSSION: The changes in WM could to some extent explain the deteriorations in motor, cognitive, affective, and perceptual functions seen in AUD. Future studies are needed to clarify how WM alterations vary over the course of the disorder and to what extent they are reversible with prolonged abstinence.

Mapping cortical and subcortical asymmetries in substance dependence: Findings from the ENIGMA Addiction Working Group.

Brain asymmetry reflects left-right hemispheric differentiation, which is a quantitative brain phenotype that develops with age and can vary with psychiatric diagnoses. Previous studies have shown that substance dependence is associated with altered brain structure and function. However, it is unknown whether structural brain asymmetries are different in individuals with substance dependence compared with nondependent participants. Here, a mega-analysis was performed using a collection of 22 structural brain MRI datasets from the ENIGMA Addiction Working Group. Structural asymmetries of cortical and subcortical regions were compared between individuals who were dependent on alcohol, nicotine, cocaine, methamphetamine, or cannabis (n = 1,796) and nondependent participants (n = 996). Substance-general and substance-specific effects on structural asymmetry were examined using separate models. We found that substance dependence was significantly associated with differences in volume asymmetry of the nucleus accumbens (NAcc; less rightward; Cohen's d = 0.15). This effect was driven by differences from controls in individuals with alcohol dependence (less rightward; Cohen's d = 0.10) and nicotine dependence (less rightward; Cohen's d = 0.11). These findings suggest that disrupted structural asymmetry in the NAcc may be a characteristic of substance dependence.

Neuroimaging and Cognitive Evidence for Combined HIV-Alcohol Effects on the Central Nervous System: A Review.

Alcohol use disorder (AUD) among people living with HIV (PLWH) is a significant public health concern. Despite the advent of effective antiretroviral therapy, up to 50% of PLWH still experience worsened neurocognition, which comorbid AUD exacerbates. We report converging lines of neuroimaging and neuropsychological evidence linking comorbid HIV/AUD to dysfunction in brain regions linked to executive function, learning and memory, processing speed, and motor control, and consequently to impairment in daily life. The brain shrinkage, functional network alterations, and brain metabolite disruption seen in individuals with HIV/AUD have been attributed to several interacting pathways: viral proteins and EtOH are directly neurotoxic and exacerbate each other's neurotoxic effects; EtOH reduces antiretroviral adherence and increases viral replication; AUD and HIV both increase gut microbial translocation, promoting systemic inflammation and HIV transport into the brain by immune cells; and HIV may compound alcohol's damaging effects on the liver, further increasing inflammation. We additionally review the neurocognitive effects of aging, Hepatitis C coinfection, obesity, and cardiovascular disease, tobacco use, and nutritional deficiencies, all of which have been shown to compound cognitive changes in HIV, AUD, and in their comorbidity. Finally, we examine emerging questions in HIV/AUD research, including genetic and cognitive protective factors, the role of binge drinking in HIV/AUD-linked cognitive decline, and whether neurocognitive and brain functions normalize after drinking cessation.

The Relationship Between Alcohol Consumption With Vascular Structure and Arterial Stiffness in the Spanish Population: EVA Study.

BACKGROUND: Controversy exists regarding the way alcohol use is associated with vascular structure and arterial stiffness parameters. The purpose of this study is to evaluate the association between alcohol consumption with vascular structure and arterial stiffness in an adult population. METHODS: We conducted a cross-sectional study. Five hundred and one participants were recruited by random sampling from an urban population of 43,946 individuals aged 35 to 75 years, assigned from 5 healthcare centers located in Salamanca, Spain. This was a subanalysis of the EVA study. Arterial stiffness was assessed by measuring cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (ba-PWV) with the VaSera VS-1500® device, and carotid-femoral pulse wave velocity (cf-PWV) with the Sphygmocor® . Vascular structure was evaluated by measuring the carotid intima-media thickness (c-IMT) with a Sonosite Micromax® ultrasound. Alcohol consumption was calculated using a standardized questionnaire and quantified in g/wk. RESULTS: In the multiple regression analysis adjusted for sex, age, smoking status, and systolic blood pressure, the c-IMT and cf-PWV values of individuals drinking > 70 g/wk were higher than those of the reference group (nondrinkers) by 0.02 mm (p = 0.030) and 0.42 m/s (p = 0.021), respectively. The association between alcohol consumption with vascular structure and arterial stiffness only attains statistical significance for cf-PWV (p = 0.039) and c-IMT (p = 0.019), showing an association which suggests a J-shaped association. This association was not statistically significant for ba-PWV and CAVI (p = 0.446 and p = 0.141, respectively), although a similar trend was observed with ba-PWV. CONCLUSIONS: The results of this study suggest that heavy alcohol consumption (>70 g/wk) is associated with increased c-IMT and cf-PWV. Moreover, we found a J-shaped association between alcohol consumption and c-IMT and cf-PWV values as markers of vascular structure and arterial stiffness, with no association with ba-PWV and CAVI being observed.

History of Alcohol Consumption and HIV Status Related to Functional Connectivity Differences in the Brain During Working Memory Performance.

BACKGROUND: Poorer working memory function has previously been associated with alcohol misuse, Human Immunodeficiency Virus (HIV) positive status, and risky behavior. Poorer working memory performance relates to alterations in specific brain networks. OBJECTIVE: The current study examined if there was a relationship between brain networks involved in working memory and reported level of alcohol consumption during an individual's period of heaviest use. Furthermore, we examined whether HIV status and the interaction between HIV and alcohol consumption was associated with differences in these brain networks. METHODS: Fifty adults, 26 of whom were HIV positive, engaged in an n-back working memory task (0-back and 2-back trials) administered in a magnetic resonance imaging (MRI) scanner. The Kreek- McHugh-Schluger-Kellogg (KMSK) scale of alcohol consumption was used to characterize an individual's period of heaviest use and correlates well with their risk for alcohol dependence. Connectivity analyses were conducted using data collected during n-back task. RESULTS: Functional connectivity differences associated with greater alcohol consumption included negative connectivity, primarily from parietal attention networks to frontal networks. Greater alcohol consumption was also associated with positive connectivity from working memory nodes to the precuneus and paracingulate. HIV positive status was associated with more nodes of negative functional connectivity relative to alcohol consumption history alone, particularly in the frontoparietal networks. The HIV positive individuals with heavier drinking history related to negative fronto-parietal connectivity, along with positive connectivity from working memory nodes to mesolimbic regions. CONCLUSION: Findings allow for a better understanding of brain networks affected by HIV and alcohol and may provide avenues for interventions.

Cerebellar Morphometry and Cognition in the Context of Chronic Alcohol Consumption and Cigarette Smoking.

BACKGROUND: Cerebellar atrophy (especially involving the superior-anterior cerebellar vermis) is among the most salient and clinically significant effects of chronic hazardous alcohol consumption on brain structure. Smaller cerebellar volumes are also associated with chronic cigarette smoking. The present study investigated effects of both chronic alcohol consumption and cigarette smoking on cerebellar structure and its relation to performance on select cognitive/behavioral tasks. METHODS: Using T1-weighted Magnetic Resonance Images (MRIs), the Cerebellar Analysis Tool Kit segmented the cerebellum into bilateral hemispheres and 3 vermis parcels from 4 participant groups: smoking (s) and nonsmoking (ns) abstinent alcohol-dependent treatment seekers (ALC) and controls (CON) (i.e., sALC, nsALC, sCON, and nsCON). Cognitive and behavioral data were also obtained. RESULTS: We found detrimental effects of chronic drinking on all cerebellar structural measures in ALC participants, with largest reductions seen in vermis areas. Furthermore, both smoking groups had smaller volumes of cerebellar hemispheres but not vermis areas compared to their nonsmoking counterparts. In exploratory analyses, smaller cerebellar volumes were related to lower measures of intelligence. In sCON, but not sALC, greater smoking severity was related to smaller cerebellar volume and smaller superior-anterior vermis area. In sALC, greater abstinence duration was associated with larger cerebellar and superior-anterior vermis areas, suggesting some recovery with abstinence. CONCLUSIONS: Our results show that both smoking and alcohol status are associated with smaller cerebellar structural measurements, with vermal areas more vulnerable to chronic alcohol consumption and less affected by chronic smoking. These morphometric cerebellar deficits were also associated with lower intelligence and related to duration of abstinence in sALC only.

Antemortem histopathology and imaging findings in a case of Marchiafava-Bignami disease.

Marchiafava-Bignami disease (MBD) is a rare condition often associated with chronic alcohol abuse. Clinical presentation is diverse. Characteristic magnetic resonance imaging (MRI) changes in the corpus callosum are the mainstay of radiological diagnosis. We present a case of a 54-year-old man with chronic alcoholism and peripherally enhancing lesion in the body of the corpus callosum on MRI Brain. Open biopsy of the lesion showed necrosis and demyelination. He was diagnosed with Marchiafava-Bignami disease based on clinical, radiology and histopathology findings. Our case represents the only case in the literature with antemortem histopathology findings describing MBD.

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects.

OBJECTIVE: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. METHOD: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. RESULTS: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. CONCLUSIONS: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Effects of Binge Drinking on the Developing Brain.

Binge drinking is a pattern of alcohol drinking that raises a person's blood alcohol concentration to at least .08%, which amounts to consuming five alcoholic drinks for men and four alcoholic drinks for women in about 2 hours. It is the most common form of alcohol misuse in adolescents and young adults. Heavy drinking includes the same criterion as binge drinking, but with higher frequency (i.e., 5 or more days in the past 30 days). Although binge drinking or heavy drinking alone is insufficient to meet the criteria for an alcohol use disorder (AUD) diagnosis, there are neurobiological changes, as well as an increased risk of developing an AUD later in life, associated with this form of alcohol misuse. This review describes the recent neuroimaging findings in binge drinking and heavy-drinking adolescents and young adults, a developmental period during which significant neuromaturation occurs.

White matter microstructural correlates of relapse in alcohol dependence.

Identification of neural correlates of relapse to alcohol after treatment is clinically important as it may inform better substance abuse treatment. Few studies have specifically analyzed the white matter microstructure in treatment seekers as it might relate to relapse risk versus long-term abstinence. Using 4 Tesla diffusion tensor imaging, we compared two groups of one-month-abstinent treatment-seekers, who were classified based on their drinking status between six and nine months after treatment initiation. We hypothesized that subsequent relapsers had greater white matter microstructural deficits in specific brain regions than long-term abstainers. At one month of abstinence, 37 future relapsers versus 25 future abstainers had lower fractional anisotropy (a measure of axonal organization and membrane integrity) in the corpus callosum and right stria terminalis/fornix, higher diffusivity in the genu of the corpus callosum, left and right stria terminalis/fornix, and lower diffusivity in left anterior corona radiata. These differences existed despite similar lifetime and recent drinking and smoking histories in the groups. Longer smoking duration in relapsers was associated with lower fractional anisotropy in right stria terminalis/fornix. The study identified specific microstructural biomarkers of alcohol relapse risk in adults, contributing to the definition of a neurobiological relapse risk profile in alcohol use disorder.