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The impact of levamisole and alcohol on white matter microstructure in adult chronic cocaine users.

ABSTRACT: Previous brain imaging studies with chronic cocaine users (CU) using diffusion tensor imaging (DTI) mostly focused on fractional anisotropy to investigate white matter (WM) integrity. However, a quantitative interpretation of fractional anisotropy (FA) alterations is often impeded by the inherent limitations of the underlying tensor model. A more fine-grained measure of WM alterations could be achieved by measuring fibre density (FD). This study investigates this novel DTI metric comparing 23 chronic CU and 32 healthy subjects. Quantitative hair analysis was used to determine intensity of cocaine and levamisole exposure-a cocaine adulterant with putative WM neurotoxicity. We first assessed the impact of cocaine use, levamisole exposure and alcohol use on group differences in WM integrity. Compared with healthy controls, all models revealed cortical reductions of FA and FD in CU. At the within-patient group level, we found that alcohol use and levamisole exposure exhibited regionally different FA and FD alterations than cocaine use. We found mostly negative correlations of tract-based WM associated with levamisole and weekly alcohol use. Specifically, levamisole exposure was linked with stronger WM reductions in the corpus callosum than alcohol use. Cocaine use duration correlated negatively with FA and FD in some regions. Yet, most of these correlations did not survive a correction for multiple testing. Our results suggest that chronic cocaine use, levamisole exposure and alcohol use were all linked to significant WM impairments in CU. We conclude that FD could be a sensitive marker to detect the impact of the use of multiple substances on WM integrity in cocaine but also other substance use disorders.

SUBMITTER: Michels L

PROVIDER: S-EPMC9287079 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundMagnetic resonance imaging (MRI) studies have shown differences in volume and structure in the brains of individuals with alcohol use disorder (AUD). Most research has focused on neuropathological effects of alcohol that appear after years of chronic alcohol misuse. However, few studies have investigated white matter (WM) microstructure and diffusion MRI-based (DWI) connectivity during early stages of AUD. Therefore, the goal of this work was to investigate WM integrity and structural connectivity in emerging adulthood AUD subjects using both conventional DWI metrics and a novel connectomics approach.MethodsTwenty-two AUD and 18 controls (CON) underwent anatomic and diffusion MRI. Outcome measures were scalar diffusion metrics and structural network connectomes. Tract-Based Spatial Statistics was used to investigate group differences in diffusion measures. Structural connectomes were used as input into a community structure procedure to obtain a coclassification index matrix (an indicator of community association strength) for each subject. Differences in coclassification and structural connectivity (indexed by streamline density) were assessed via the Network Based Statistics Toolbox.ResultsAUD had higher fractional anisotropy (FA) values throughout the major WM tracts, but also had lower FA values in WM tracts in the cerebellum and right insula (pTFCE < 0.05). Mean diffusivity was generally lower in the AUD group (pTFCE < 0.05). AUD had lower coclassification of nodes between ventral attention and default mode networks and higher coclassification between nodes of visual, default mode, and somatomotor networks. Additionally, AUD had higher fiber density between an adjacent pair of nodes within the default mode network.ConclusionsOur results indicate that emerging adulthood AUD subjects may have differential patterns of FA and distinct differences in structural connectomes compared with CON. These data suggest that such alterations in microstructure and structural connectivity may uniquely characterize early stages of AUD and/or a predisposition for development of AUD.

Project description:BACKGROUND:Diffusion-weighted imaging (DWI) has been widely used to investigate the integrity of white matter (WM; indexed by fractional anisotropy [FA]) in alcohol dependence and cigarette smoking. These disorders are highly comorbid, yet cigarette use has often not been adequately controlled in neuroimaging studies of alcohol-dependent populations. In addition, information on WM deficits in currently drinking, nontreatment-seeking (NTS) individuals with alcohol dependence is limited. Therefore, the aim of this work was to investigate WM microstructural integrity in alcohol use disorder by comparing matched samples of cigarette smoking NTS and social drinkers (SD). METHODS:Thirty-eight smoking NTS and 19 smoking SD subjects underwent DWI as well as structural magnetic resonance imaging. After an in-house preprocessing of the DWI data, FA images were analyzed with tract-based spatial statistics (TBSS). FA obtained from the TBSS skeleton was tested for correlation with recent alcohol consumption. RESULTS:Smoking NTS had lower FA relative to smoking SD, predominantly in the left hemisphere (p < 0.05, family-wise error rate corrected across FA skeleton). Across the full sample, FA and number of drinks per week were negatively related (? = -0.348, p = 0.008). Qualitative analyses of the structural connections through compromised WM as identified by TBSS showed differential connectivity of gray matter in NTS compared to SD subjects of left frontal, temporal, and parietal regions. CONCLUSIONS:NTS subjects had lower WM FA than SD, indicating compromised WM integrity in the NTS population. The inverse relationship of entire WM skeleton FA with self-reported alcohol consumption supports previous evidence of a continuum of detrimental effects of alcohol consumption on WM. These results provide additional evidence that alcohol dependence is associated with reduced WM integrity in currently drinking NTS alcohol-dependent individuals, after controlling for the key variable of cigarette smoking.

Project description:Neighborhood disadvantage and community violence are common in poor, urban communities and are risk factors for emotional dysfunction. Emotional processes are supported by neural circuitry that includes the prefrontal cortex (PFC), hippocampus, amygdala, and hypothalamus. These brain regions are connected by white matter pathways that include the cingulum bundle, uncinate fasciculus, stria terminalis, and fornix. Emotional function varies with the microstructure of these white matter pathways. However, it is not clear whether the microstructure of these pathways varies with risk factors for emotional dysfunction (e.g., neighborhood disadvantage and violence exposure). Therefore, determining the relationships between neighborhood disadvantage, violence exposure, and white matter microstructure may offer insight into the neural mechanisms by which adverse life experiences alter developing neural systems. The current study investigated the association that exposure to neighborhood disadvantage and violence have with the quantitative anisotropy (QA), a measure of the amount of directional water diffusion, of the cingulum bundle, uncinate fasciculus, stria terminalis, and fornix. Neighborhood disadvantage (Mage = 11.20) and violence exposure (MW1age = 11.20; MW2age = 13.05; MW3age = 16.20; MW4age = 19.25) were assessed during adolescence and participants returned for magnetic resonance imaging as young adults (N = 303; Mage = 20.25, SD = 1.55), during which diffusion weighted brain images were collected. The QA of the cingulum bundle, uncinate fasciculus, and stria terminalis/fornix varied negatively with neighborhood disadvantage such that the QA of these white matter tracts decreased as neighborhood disadvantage increased. Violence exposure was not related to QA in any tract (i.e., cingulum bundle, uncinate fasciculus, and stria terminalis/fornix) after correction for multiple comparisons. These results suggest that an adolescent's neighborhood may play an important role in the microstructure (i.e., QA) of white matter pathways that connect brain regions that support emotional function.

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The impact of levamisole and alcohol on white matter microstructure in adult chronic cocaine users.

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