Anterior cingulate metabolite levels, memory, and inhibitory control in abstinent men and women with alcohol use disorder.

Alcohol use disorder (AUD) has been shown to have harmful cognitive and physiological effects, including altered brain chemistry. Further, although men and women may differ in vulnerability to the neurobiological effects of AUD, the results of existing studies have been conflicting. We examined brain metabolite levels and cognitive functions in a cross-section of men with AUD (AUDm) and women with AUD (AUDw) to determine the degree of abnormalities after extended periods of abstinence (mean, 6 years) and to evaluate gender differences in neuropsychological and metabolite measures. Participants were 40 abstinent individuals with AUD (22 AUDw, 18 AUDm) and 50 age-equivalent non-AUD comparison participants (26 NCw, 24 NCm). Proton magnetic resonance spectroscopy (MRS) was employed at 3 Tesla to acquire metabolite spectra from the dorsal anterior cingulate cortex (dACC). Brain metabolites N-acetyl aspartate (NAA), choline (Cho), myo-Inositol (mI), and glutamate & glutamine (Glx) were examined relative to measures of memory and inhibitory control. Metabolite levels did not differ significantly between AUD and NC groups. Memory and inhibitory-control impairments were observed in the AUD group. There also were significant group-specific associations between metabolite ratios and measures of inhibitory control. There were no group-by-gender interactions for the four metabolite ratios. These findings demonstrate that brain metabolite levels in men and women with AUD, following long-term abstinence, do not differ from individuals without AUD. The data also provide preliminary evidence of sustained associations between metabolite levels and measures of inhibitory control, a functional domain important for curtailing harmful drinking.

On the impact of interhemispheric white matter: Age, executive functioning, and dedifferentiation in the frontal lobes.

INTRODUCTION: In middle age, declines in executive functioning (EF) are associated with decrements in the quality and/or quantity of white and grey matter. Recruitment of homologous regions has been identified as a compensatory mechanism for cognitive decline in later middle age; however, research into neural substrates of EF has yet to be guided by dedifferentiation models. We hypothesized that frontal-parietal grey matter volume, interhemispheric white matter, and intrahemispheric white matter fractional anisotropy will be predictive of EF. Further, we hypothesized that the comparative association between interhemispheric white matter and EF will increase with age, because of compensatory recruitment. METHODS: Neurocognitive test data, DTI, and T1 MPRAGE scans (n = 444) were obtained from the NKI-Rockland Sample. Structural equation modeling was used to examine the relationship between age, EF, interhemispheric white matter (forceps minor; FM), intrahemispheric white matter (superior longitudinal fasciculus; SLF), and a frontal-parietal grey matter network. EF and grey matter were modelled as latent variables, with EF examined as the criterion. Additionally, a subsample of participants aged 55 to 85 (n = 168) was analyzed to examine the influence of age related compensatory mechanisms. RESULTS: There was a significant relationship between FM, grey matter, and EF, which was fully mediated by age. There was a significant relationship between SLF and EF, which was not mediated by age. For older adults, only the age-mediated pathway from FM to EF was significant. DISCUSSION: Using structural imaging data, support was found for age-related interhemispheric mechanisms of compensation, but not intrahemispheric mechanisms.

Associations Between Personality and Drinking Motives Among Abstinent Adult Alcoholic Men and Women.

AIMS: Men and women differ in personality characteristics and may be motivated to use alcohol for different reasons. The goals of the present study were to characterize personality and drinking motives by gender and alcoholism status in adults, and to determine how alcoholism history and gender are related to the associations between personality traits and drinking motivation. METHODS: Personality characteristics were assessed with the Eysenck Personality Questionnaire, which includes Extraversion, Neuroticism, Psychoticism and Lie (Social Conforming) scales. To evaluate drinking motivation, we asked abstinent long-term alcoholic men and women, and demographically similar nonalcoholic participants to complete the Drinking Motives Questionnaire, which includes Conformity, Coping, Social and Enhancement scales. RESULTS: Patterns of personality scale scores and drinking motives differed by alcoholism status, with alcoholics showing higher psychopathology and stronger motives for drinking compared with controls. Divergent gender-specific relationships between personality and drinking motives also were identified, which differed for alcoholics and controls. CONCLUSION: Alcoholic and control men and women differed with respect to the associations between personality traits and motives for drinking. A better understanding of how different personality traits affect drinking motivations for alcoholic men and women can inform individualized relapse prevention strategies. SHORT SUMMARY: Men and women differed in their personality traits and their motivations for drinking, and these relationships differed for abstinent alcoholic and control groups. Additionally, alcoholics scored higher on Neuroticism and Psychoticism personality traits, and had lower Enhancement and Social Conformity drinking motives than nonalcoholic controls.

Associations Between Cerebellar Subregional Morphometry and Alcoholism History in Men and Women.

BACKGROUND: Alcoholism has been linked to deficits in cognitive, behavioral, and emotional functions, and the cerebellum is important for optimal functioning of these abilities. However, little is known about how individual differences such as gender and drinking history might influence regional cerebellar abnormalities. METHODS: Volumetric analyses of the cerebellum and its subregions were performed in relation to the interaction of gender and measures of drinking history. Structural magnetic resonance imaging scans of 44 alcoholic individuals (23 men) and 39 nonalcoholic controls (18 men) were obtained. In addition to measuring total cerebellar gray and white matter volumes, we measured 64 individual cerebellar parcellation units, as well as functionally defined a priori regions of interest that have been shown to correspond to functions impaired in alcoholism. RESULTS: Total cerebellar white matter volume was smaller in alcoholic relative to nonalcoholic participants. Moreover, volumes of parcellation units varied with drinking history, showing negative associations between years of heavy drinking and the anterior lobe, the vestibulocerebellar lobe, and the spinocerebellar subdivision. The negative association between anterior volume and years of heavy drinking was driven primarily by alcoholic men. Additionally, we observed larger white and gray matter volumes for alcoholic women than for alcoholic men. CONCLUSIONS: The identification of drinking-related abnormalities in cerebellar subregions lays a foundation that can be utilized to inform how cerebro-cerebellar networks are perturbed in this pathological condition. These results also provide estimates of how gender and individual differences in drinking history can predict cerebellar volumes.

Social cognition deficits and associations with drinking history in alcoholic men and women.

BACKGROUND: Previous studies have demonstrated the presence of a social cognition factor as an element of general cognition in healthy control and clinical populations. Recently developed measures of social cognition include the social perception and faces subtests of the Wechsler Advanced Clinical Solutions (ACS) Social Cognition module. While these measures have been validated on various clinical samples, they have not been studied in alcoholics. Alcoholism has been associated with emotional abnormalities and diminished social cognitive functioning as well as neuropathology of brain areas underlying social processing abilities. We used the ACS Social Perception and Faces subtests to assess alcoholism-related impairments in social cognition. METHODS: Social cognitive functioning was assessed in 77 abstinent alcoholic individuals (37 women) and 59 nonalcoholic control participants (29 women), using measures of the ACS Social Cognition module and subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) that contain a social cognition component (Picture Completion and Comprehension). Group and gender differences in ACS and WAIS-IV performance were assessed, as well as relationships between measures of alcoholism severity and social cognitive functioning. RESULTS: Alcoholics performed significantly worse than nonalcoholics on the ACS measures of Affect Naming and Faces Content. Alcoholic men were impaired relative to alcoholic women on Prosody Face Matching and Faces Content scores. Among alcoholics, longer durations of heavy drinking were associated with poorer performance on Affect Naming, and a greater number of daily drinks were associated with lower Prosody Face Matching performance. For alcoholic women, a longer duration of abstinence was associated with better performance on Affect Naming. CONCLUSIONS: Alcoholic men and women showed different patterns of associations between alcoholism indices and clinically validated social cognition assessments. These findings extend into the social cognition domain, previous literature demonstrating the presence of cognitive deficits in alcoholism, their association with alcoholism severity, and variability by gender. Moreover, because impairments in social cognition can persist despite extended abstinence, they have important implications for relapse prevention.

Drinking history associations with regional white matter volumes in alcoholic men and women.

BACKGROUND: Alcoholism has been repeatedly associated with gray and white matter pathology. Although neuroimaging has shown alcoholism-related brain volume reductions and axonal compromise, the integrity of white matter volumes in chronic alcoholism has been challenging to measure on a regional level. METHODS: We first examined the effects of alcoholism on cerebral white matter volumes by lobar and gyral subdivisions in 42 abstinent alcoholics and 42 control participants (split evenly by gender). We also examined cerebellar white matter and regions of the corpus callosum, as well as ventricular volumes. Next, relationships between white matter and ventricular volumes with measures of drinking patterns were assessed. Finally, an examination of early versus late abstinence was conducted. Within each examination, gender effects were explored. RESULTS: Differences in regional white matter volumes between alcoholics and controls were observed primarily in the corpus callosum, with a stronger group difference among men than women. Years of heavy drinking had a strong negative impact on frontal and temporal white matter among alcoholic women, and on the corpus callosum among alcoholic men. Quantity of alcohol consumption was associated with smaller corpus callosum and larger ventricular volumes among alcoholic women, whereas abstinence duration was associated with larger corpus callosum volume among alcoholic men. Preliminary data indicated that alcoholic women showed stronger positive associations between sobriety duration and white matter volume than men within the first year of abstinence, whereas men showed this association more so than women after 1 year of abstinence. CONCLUSIONS: Effects of drinking history on white matter and ventricular volumes vary by gender, with alcoholic women showing greatest sensitivity in frontal, temporal, ventricular, and corpus callosum regions, and alcoholic men showing effects mainly in the corpus callosum. Preliminary results indicate that recovery of white matter volume may occur sooner for women than for men.

Intrinsic brain functional connectivity patterns in alcohol use disorder.

Alcohol use disorder is associated with damaging effects to the brain. This study aimed to examine differences in static and dynamic intrinsic functional connectivity patterns in individuals with a history of alcohol use disorder in comparison to those with no history of alcohol abuse. A total of 55 participants consisting of 23 patients and 32 control individuals underwent neuropsychological assessments and resting-state functional magnetic resonance imaging on a 3 Tesla MRI scanner. Differences in functional connectivity between the two groups were determined using static and dynamic independent component analysis. Differences in static functional connectivity between the two groups were identified in the default mode network, attention network, frontoparietal network, frontal cortical network and cerebellar network. Furthermore, the analyses revealed specific differences in the dynamic temporal characteristics of functional connectivity between the two groups of participants, in a cluster involving key regions in reward, sensorimotor and frontal cortical functional networks, with some connections correlating with the length of sobriety and some others with the severity of drinking. The findings altogether suggest dysregulation in the intrinsic connectivity of cortico-basal ganglia-thalamo-cortical loops that may reflect persistent alcohol use disorder-related network abnormalities, compensatory recovery-related processes whereby additional neural resources are recruited to achieve normal levels of performance, or a predisposition toward developing alcohol use disorder.

Factors in the neurodevelopment of negative urgency: Findings from a community-dwelling sample.

This study investigated neuroanatomic, genetic, cognitive, sociodemographic and emotional underpinnings of the Negative Urgency subscale of the Urgency, Premeditation, Perseverance, Sensation-Seeking and Positive Urgency Impulsive Behavior Scale in a healthy developmental sample. The goal of the investigation is to contribute to the harmonisation of behavioural, brain and neurogenetic aspects of behavioural self-control. Three domains - (1) Demographic, developmental, psychiatric and cognitive ability; (2) Regional brain volumes (neurobiological); and (3) Genetic variability (single nucleotide polymorphisms) - were examined, and models with relevant predictor variables were selected. Least absolute shrinkage and selection operator and best subset regressions were used to identify sparse models predicting negative urgency scores, which revealed that variables related to emotional regulation and right cingulate volume, as well as single nucleotide polymorphisms in CADM2 and SLC6A4, were associated with negative urgency. Our results contribute to the construct and criterion validity of negative urgency and support the hypothesis that negative urgency is a result of a complex array of influences across domains whose integration furthers developmental psychopathology research.

It's about time: Linking dynamical systems with human neuroimaging to understand the brain.

Most human neuroscience research to date has focused on statistical approaches that describe stationary patterns of localized neural activity or blood flow. While these patterns are often interpreted in light of dynamic, information-processing concepts, the static, local, and inferential nature of the statistical approach makes it challenging to directly link neuroimaging results to plausible underlying neural mechanisms. Here, we argue that dynamical systems theory provides the crucial mechanistic framework for characterizing both the brain's time-varying quality and its partial stability in the face of perturbations, and hence, that this perspective can have a profound impact on the interpretation of human neuroimaging results and their relationship with behavior. After briefly reviewing some key terminology, we identify three key ways in which neuroimaging analyses can embrace a dynamical systems perspective: by shifting from a local to a more global perspective, by focusing on dynamics instead of static snapshots of neural activity, and by embracing modeling approaches that map neural dynamics using "forward" models. Through this approach, we envisage ample opportunities for neuroimaging researchers to enrich their understanding of the dynamic neural mechanisms that support a wide array of brain functions, both in health and in the setting of psychopathology.

Age-dependent relationship of cardiorespiratory fitness and white matter integrity.

Growing evidence has linked cardiorespiratory fitness (CRF) to more conserved white matter (WM) microstructure. Additional research is needed to determine which WM tracts are most strongly related to CRF and if the neuroprotective effects of CRF are age-dependent. Participants were community-dwelling adults (N = 499; ages 20-85) from the open-access Nathan Kline Institute - Rockland Sample (NKI-RS) with CRF (bike test) and diffusion tensor imaging (DTI) data. Mixed-effect modeling tested the interaction between CRF and age on global (main effect across 9 tracts) and local (individual tract effects) WM microstructure. Among older participants (age ≥ 60), CRF was significantly related to whole-brain (z-score slope = 0.11) and local WM microstructure within several tracts (| z-score slope | range = 0.13 - 0.27). Significant interactions with age indicated that the CRF-WM relationship was weaker (z-score slope ≤ 0.11) and more limited (one WM tract) in younger adults. The findings highlight the importance of aerobic exercise to maintain brain health into senescence. CRF may preferentially preserve a collection of anterior and posterior WM connections related to visuomotor function.

Brain responsivity to emotional faces differs in men and women with and without a history of alcohol use disorder.

Inclusion of women in research on Alcohol Use Disorder (AUD) has shown that gender differences contribute to unique profiles of cognitive, emotional, and neuropsychological dysfunction. We employed functional magnetic resonance imaging (fMRI) of abstinent individuals with a history of AUD (21 women [AUDw], 21 men [AUDm]) and demographically similar non-AUD control (NC) participants without AUD (21 women [NCw], 21 men [NCm]) to explore how gender and AUD interact to influence brain responses during emotional processing and memory. Participants completed a delayed match-to-sample emotional face memory fMRI task, and brain activation contrasts between a fixation stimulus and pictures of emotional face elicited a similar overall pattern of activation for all four groups. Significant Group by Gender interactions revealed two activation clusters. A cluster in an anterior portion of the middle and superior temporal gyrus, elicited lower activation to the fixation stimulus than to faces for the AUDw as compared to the NCw; that abnormality was more pronounced than the one observed for men. Another cluster in the medial portion of the superior frontal cortex elicited higher activation to the faces by AUDm than NCm, a difference that was more evident than the one observed for women. Together, these findings have added new evidence of AUD-related gender differences in neural responses to facial expressions of emotion.

White matter connectometry among individuals with self-reported family history of drug and alcohol use disorders.

Heredity is an important risk factor for alcoholism. Several studies have been conducted on small groups of alcohol naïve adolescents which show lowered fractional anisotropy of frontal white matter in individuals with a family history of alcohol and substance use disorder (FH+). We compare large adult FH+ and FH- groups using white matter connectometry, different from the previously used global tractography method, as it is more sensitive to regional variability. Imaging and behavioral data from the Human Connectome Project (WU-MINN HCP 1200) was analyzed. Groups of participants were positive (n = 109) and negative (n = 109) for self-reported alcohol and substance use disorders in at least one parent, and stringently matched. Connectometry was performed on diffusion MRI in DSI-Studio using q-space diffeomorphic reconstruction, and multiple regression was completed with 5000 permutations. Analyses showed decreased major tract (>40 mm) connectivity in the FH+ group in left inferior longitudinal fasciculus, bilateral cortico-striatal pathway, left cortico-thalamic pathway, and corpus callosum, compared to the FH- group. For cognitive tasks related to reward processing, inhibition, and monitoring, there were a number of interactions, such that the relationship between identified tracts and behavior differed significantly between groups. Self-reported family history was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and alcohol use disorder. This is the first connectometry study of FH+, and extends the neural basis of the hereditary diathesis of alcoholism beyond that demonstrated with global tractography. Regions associated with FH+ are similar to those associated with alcohol use disorder.

Hippocampal subfield volumes in abstinent men and women with a history of alcohol use disorder.

Alcohol Use Disorder (AUD) has been associated with abnormalities in hippocampal volumes, but these relationships have not been fully explored with respect to sub-regional volumes, nor in association with individual characteristics such as age, gender differences, drinking history, and memory. The present study examined the impact of those variables in relation to hippocampal subfield volumes in abstinent men and women with a history of AUD. Using Magnetic Resonance Imaging at 3 Tesla, we obtained brain images from 67 participants with AUD (31 women) and 64 nonalcoholic control (NC) participants (31 women). The average duration of the most recent period of sobriety for AUD participants was 7.1 years. We used Freesurfer 6.0 to segment the hippocampus into 12 regions. These were imputed into statistical models to examine the relationships of brain volume with AUD group, age, gender, memory, and drinking history. Interactions with gender and age were of particular interest. Compared to the NC group, the AUD group had approximately 5% smaller subiculum, CA1, molecular layer, and hippocampal tail regions. Age was negatively associated with volumes for the AUD group in the subiculum and the hippocampal tail, but no significant interactions with gender were identified. The relationships for delayed and immediate memory with hippocampal tail volume differed for AUD and NC groups: Higher scores on tests of immediate and delayed memory were associated with smaller volumes in the AUD group, but larger volumes in the NC group. Length of sobriety was associated with decreasing CA1 volume in women (0.19% per year) and increasing volume size in men (0.38% per year). The course of abstinence on CA1 volume differed for men and women, and the differential relationships of subfield volumes to age and memory could indicate a distinction in the impact of AUD on functions of the hippocampal tail. These findings confirm and extend evidence that AUD, age, gender, memory, and abstinence differentially impact volumes of component parts of the hippocampus.

Components of executive function model regional prefrontal volumes.

OBJECTIVE: Designed to measure a diversity of executive functioning (EF) through classical neuropsychological tests, the Delis-Kaplan Executive Function Scale (D-KEFS) allows for the investigation of the neural architecture of EF. We examined how the D-KEFS Tower, Verbal Fluency, Design Fluency, Color-Word Interference, and Trail Making Test tasks related to frontal lobe volumes, quantifying the regional specificity of EF components. METHOD: Adults from the Nathan Kline Institute-Rockland Sample (NKI-RS), an open-access community study of brain development, with complete MRI (3T scanner) and D-KEFS data were selected for analysis (N = 478; ages 20-85). In a mixed-effects model predicting volume, D-KEFS task, D-KEFS score, region of interest (ROI; 13 frontal, 1 occipital control), were entered as fixed effects with intercepts for participants as random effects. RESULTS: "Unitary" EF (aggregate of D-KEFS scores) was positively associated with superior frontal, rostral middle frontal, and lateral orbitofrontal volumes; a negative association was observed with frontal pole volume (| z-score slope | range = 0.040 to 0.051). "Diverse" EF skills (individual D-KEFS task scores) were differentially associated with two or three ROIs, respectively, but to a stronger extent (| z-score slope | range = 0.053 to 0.103). CONCLUSIONS: The neural correlates found for the D-KEFS support the prefrontal modularity of both unitary (aspects of EF ability common to all tasks) and diverse EF. Our findings contribute to emerging evidence that aggregate measurements of EF may serve broader but less robust frontal neural correlates than distinct EF skills. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Identifying errors in Freesurfer automated skull stripping and the incremental utility of manual intervention.

Quality assurance (QA) is vital for ensuring the integrity of processed neuroimaging data for use in clinical neurosciences research. Manual QA (visual inspection) of processed brains for cortical surface reconstruction errors is resource-intensive, particularly with large datasets. Several semi-automated QA tools use quantitative detection of subjects for editing based on outlier brain regions. There were two project goals: (1) evaluate the assumption that statistical outliers are related to errors of cortical extension, and (2) examine whether error identification and correction significantly impacts estimation of cortical parameters and established brain-behavior relationships. T1 MPRAGE images (N = 530) of healthy adults were obtained from the NKI-Rockland Sample and reconstructed using Freesurfer 5.3. Visual inspection of T1 images was conducted for: (1) participants (n = 110) with outlier values (z scores ±3 SD) for subcortical and cortical segmentation volumes (outlier group), and (2) a random sample of remaining participants (n = 110) with segmentation values that did not meet the outlier criterion (non-outlier group). The outlier group had 21% more participants with visual inspection-identified errors than participants in the non-outlier group, with a medium effect size (Φ = 0.22). Nevertheless, a considerable portion of images with errors of cortical extension were found in the non-outlier group (41%). Although nine brain regions significantly changed size from pre- to post-editing (with effect sizes ranging from 0.26 to 0.59), editing did not substantially change the correlations of neurocognitive tasks and brain volumes (ps > 0.05). Statistically-based QA, although less resource intensive, is not accurate enough to supplant visual inspection. We discuss practical implications of our findings to guide resource allocation decisions for image processing.

Alcoholism gender differences in brain responsivity to emotional stimuli.

Men and women may use alcohol to regulate emotions differently, with corresponding differences in neural responses. We explored how the viewing of different types of emotionally salient stimuli impacted brain activity observed through functional magnetic resonance imaging (fMRI) from 42 long-term abstinent alcoholic (25 women) and 46 nonalcoholic (24 women) participants. Analyses revealed blunted brain responsivity in alcoholic compared to nonalcoholic groups, as well as gender differences in those activation patterns. Brain activation in alcoholic men (ALCM) was significantly lower than in nonalcoholic men (NCM) in regions including rostral middle and superior frontal cortex, precentral gyrus, and inferior parietal cortex, whereas activation was higher in alcoholic women (ALCW) than in nonalcoholic women (NCW) in superior frontal and supramarginal cortical regions. The reduced brain reactivity of ALCM, and increases for ALCW, highlighted divergent brain regions and gender effects, suggesting possible differences in the underlying basis for development of alcohol use disorders.

Cerebral white matter sex dimorphism in alcoholism: a diffusion tensor imaging study.

Excessive alcohol consumption is associated with brain aberrations, including abnormalities in frontal and limbic brain regions. In a prior diffusion tensor magnetic resonance imaging (dMRI) study of neuronal circuitry connecting the frontal lobes and limbic system structures, we demonstrated decreases in white matter fractional anisotropy in abstinent alcoholic men. In the present study, we examined sex differences in alcoholism-related abnormalities of white matter connectivity and their association with alcoholism history. The dMRI scans were acquired from 49 abstinent alcoholic individuals (26 women) and 41 nonalcoholic controls (22 women). Tract-based spatial statistical tools were used to estimate regional FA of white matter tracts and to determine sex differences and their relation to measures of alcoholism history. Sex-related differences in white matter connectivity were observed in association with alcoholism: Compared to nonalcoholic men, alcoholic men had diminished FA in portions of the corpus callosum, the superior longitudinal fasciculi II and III, and the arcuate fasciculus and extreme capsule. In contrast, alcoholic women had higher FA in these regions. Sex differences also were observed for correlations between corpus callosum FA and length of sobriety. Our results suggest that sexual dimorphism in white matter microstructure in abstinent alcoholics may implicate underlying differences in the neurobehavioral liabilities for developing alcohol abuse disorders, or for sequelae following abuse.

Sexually dimorphic structural abnormalities in major connections of the medial forebrain bundle in alcoholism.

Background: The mesocorticolimbic system is particularly susceptible to the effects of chronic alcoholism. Disruption of this system has been linked to drug seeking and the development of Reward Deficiency Syndrome, a neurobiological framework for describing the development and relapsing patterns of addictions. In this study, we evaluated the association of alcoholism and sex with major connections of the medial forebrain bundle (MFB), a prominent mesocorticolimbic fiber pathway connecting the ventral tegmental area with the basal forebrain. Given sex differences in clinical consequences of alcohol consumption, we hypothesized that alcoholic men and women would differ in structural abnormalities of the MFB. Methods: Diffusion magnetic resonance imaging (dMRI) data were acquired from 30 abstinent long-term alcoholic individuals (ALC; 9 men) and 25 non-alcoholic controls (NC; 8 men). Major connections of the MFB were extracted using multi-tensor tractography. We compared groups on MFB volume, fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD), with hemisphere and sex as independent variables. We also evaluated associations between abnormal structural measures and drinking measures. Results: Analyses revealed significant group-by-sex interactions for FA and RD: while ALC men had lower FA and higher RD compared to NC men, ALC women had higher FA and lower RD compared to NC women. We also detected a significant negative association between FA and number of daily drinks in ALC women. Conclusion: Alcoholism is associated with sexually dimorphic structural abnormalities in the MFB. The results expand upon other findings of differences in brain reward circuitry of alcoholic men and women.

Gender dimorphism of brain reward system volumes in alcoholism.

The brain's reward network has been reported to be smaller in alcoholic men compared to nonalcoholic men, but little is known about the volumes of reward regions in alcoholic women. Morphometric analyses were performed on magnetic resonance brain scans of 60 long-term chronic alcoholics (ALC; 30 men) and 60 nonalcoholic controls (NC; 29 men). We derived volumes of total brain, and cortical and subcortical reward-related structures including the dorsolateral prefrontal (DLPFC), orbitofrontal, and cingulate cortices, and the temporal pole, insula, amygdala, hippocampus, nucleus accumbens septi (NAc), and ventral diencephalon (VDC). We examined the relationships of the volumetric findings to drinking history. Analyses revealed a significant gender interaction for the association between alcoholism and total reward network volumes, with ALC men having smaller reward volumes than NC men and ALC women having larger reward volumes than NC women. Analyses of a priori subregions revealed a similar pattern of reward volume differences with significant gender interactions for DLPFC and VDC. Overall, the volume of the cerebral ventricles in ALC participants was negatively associated with duration of abstinence, suggesting decline in atrophy with greater length of sobriety.

Alcoholism and sexual dimorphism in the middle longitudinal fascicle: a pilot study.

Alcoholism can lead to a complex mixture of cognitive and emotional deficits associated with abnormalities in fronto-cortico-striatal-limbic brain circuitries. Given the broad variety of neurobehavioral symptoms, one would also expect alterations of postrolandic neocortical systems. Thus, we used diffusion tensor imaging (DTI) to study the integrity of the middle longitudinal fascicle (MdLF), a major postrolandic association white matter tract that extends from the superior temporal gyrus to the parietal and occipital lobes, in individuals with a history of chronic alcohol abuse. DTI data were acquired on a 3 Tesla scanner in 30 abstinent alcoholics (AL; 9 men) and 25 nonalcoholic controls (NC; 8 men). The MdLF was determined using DTI-based tractography. Volume of the tract, fractional anisotropy (FA), radial (RD), and axial (AD) diffusivity, were compared between AL and NC, with sex and hemispheric laterality as independent variables. The association of DTI measures with neuropsychological performance was evaluated. Men showed bilateral reduction of MdLF volume and abnormal diffusion measurements of the left MdLF. Analyses also indicated that the left MdLF diffusion measurements in AL men were negatively associated with Verbal IQ and verbal fluency test scores. Abstinent alcoholic men display macrostructural abnormalities in the MdLF bilaterally, indicating an overall white matter deficit. Additionally, microstructural deficits of the left MdLF suggest more specific alterations associated with verbal skills in men.