scholarly journals An Initial Investigation of Disrupted Intracortical Myelin as a Novel Brain Marker of Alcohol Use Disorder

2020 ◽  
Author(s):  
Vanessa Morris ◽  
Luciano Minuzzi ◽  
Nicholas Bock ◽  
James MacKillop ◽  
Michael Amlung
Keyword(s):  
Sex Differences ◽  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Gray Matter ◽  
Alcohol Use Disorder ◽  
A Priori ◽  
Anterior Cingulate ◽  
Posterior Cingulate ◽  
Cohen’S D ◽  
Cohen's D

Abstract: Although disruption of cortical gray matter and white matter tracts are well-established markers of alcohol use disorder (AUD), this is the first study to examine the specific role of intracortical myelin (ICM; i.e., highly myelinated gray matter in deeper cortical layers) in AUD. The current study used a 3T MRI sequence optimized for high intracortical contrast to examine patterns of ICM-related MRI signal in 30 individuals with AUD and 33 healthy social drinkers. Secondary aims included exploring continuous associations with alcohol problem severity and examining sex differences. Surface-based analytic techniques were used to quantify ICM-related MRI signal for a priori region of interest analyses (20 bilateral regions) and exploratory vertex-wise analyses (using Cohen’s d). Although the distribution of ICM-related signal was generally comparable between groups, the AUD group exhibited significantly (p<.05) greater ICM-related MRI signal in precuneus, ventromedial prefrontal cortex, posterior cingulate, middle anterior cingulate, middle/posterior insula, dorsolateral prefrontal cortex, and posterior cingulate, among other regions (Cohen’s d = .50-.75, indicating medium magnitude effects). Significant positive correlations between ICM signal and AUD severity were found in several frontal, parietal, cingulate, and temporal regions (rs .25-.34). No sex differences in ICM were observed. These findings provide initial proof-of-concept for examining ICM in relation to AUD. Understanding the pathophysiological mechanisms of these associations (e.g., neuroinflammation) and the clinical relevance of ICM is warranted.

Extrastriatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder and Individuals at High Risk

2022 ◽  
pp. 1-10
Author(s):  
Gianna Spitta ◽  
Tobias Gleich ◽  
Kristin Zacharias ◽  
Oisin Butler ◽  
Ralph Buchert ◽  
...  
Keyword(s):  
High Risk ◽  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Protective Factor ◽  
Region Of Interest ◽  
Anterior Cingulate ◽  
Dopamine D2 ◽  
Positron Emission ◽  
Significant Difference ◽  
Meta Analyses

<b><i>Introduction:</i></b> Reduced striatal dopamine D2/3 receptor availability in alcohol use disorder (AUD) has been demonstrated in recent clinical studies and meta-analyses. However, only a limited number of studies investigated extrastriatal D2/3 availability in AUD or in at-risk populations. In line with a dimensional understanding of addiction, extrastriatal dopaminergic neuroadaptations have been suggested to be relevant from a pathobiological perspective. <b><i>Methods:</i></b> We investigated D2/3 receptor availability via <sup>18</sup>F-fallypride positron emission tomography applying a region of interest (ROI) approach. We selected ROIs for the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC). Our sample included 19 healthy controls (low risk [LR]), 19 individuals at high risk (HR) to develop addiction, and 20 recently detoxified AUD patients. <b><i>Results:</i></b> We found significantly higher D2/3 receptor availability of HR compared to AUD in the left and right rostral ACC (rACC), as well as in the left ventrolateral PFC (vlPFC). We did not observe a significant difference between AUD and LR. After corrections for multiple comparisons none of the ROIs reached significance throughout the group comparison. The D2/3 receptor availability in the left rACC was inversely correlated with symptom severity assessed with the Alcohol Dependency Scale. <b><i>Discussion:</i></b> To our knowledge, the present work is the first study investigating extrastriatal D2/3 receptor availabilities in individuals at HR and patients with AUD. The observation that D2/3 receptor availabilities are highest in HR might suggest that their pathobiology differs from subjects with AUD. Future studies are necessary to clarify the intraindividual course of this biomarker over different disease stages and its possible role as a risk or protective factor.

scholarly journals Prefrontal cortex eQTLs/mQTLs enriched in genetic variants associated with alcohol use disorder and other diseases

Epigenomics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 789-800
Author(s):  
Honghuang Lin ◽  
Fan Wang ◽  
Andrew J Rosato ◽  
Lindsay A Farrer ◽  
David C Henderson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Alcohol Use ◽  
Genetic Variants ◽  
Alcohol Use Disorder ◽  
Genome Wide Association Study ◽  
Disease Risk ◽  
Genome Wide ◽  
Morphine Addiction ◽  
Methylation Patterns ◽  
Methylation Quantitative Trait Loci

Aim: This study aimed to investigate the function of genome-wide association study (GWAS)-identified variants associated with alcohol use disorder (AUD)/comorbid psychiatric disorders. Materials & methods: Genome-wide genotype, transcriptome and DNA methylome data were obtained from postmortem prefrontal cortex (PFC) of 48 Caucasians (24 AUD cases/24 controls). Expression/methylation quantitative trait loci (eQTL/mQTL) were identified and their enrichment in GWAS signals for the above disorders were analyzed. Results: PFC cis-eQTLs (923 from cases+controls, 27 from cases and 98 from controls) and cis-mQTLs (9,932 from cases+controls, 264 from cases and 695 from controls) were enriched in GWAS-identified genetic variants for the above disorders. Cis-eQTLs from AUD cases were mapped to morphine addiction-related genes. Conclusion: PFC cis-eQTLs/ cis-mQTLs influence gene expression/DNA methylation patterns, thus increasing the disease risk.

scholarly journals Random Forest Classification of Alcohol Use Disorder Using fMRI Functional Connectivity, Neuropsychological Functioning, and Impulsivity Measures

2020 ◽  
Vol 10 (2) ◽  
pp. 115 ◽  
Author(s):  
Chella Kamarajan ◽  
Babak A. Ardekani ◽  
Ashwini K. Pandey ◽  
Sivan Kinreich ◽  
Gayathri Pandey ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Random Forest ◽  
Alcohol Use ◽  
Long Range ◽  
Alcohol Use Disorder ◽  
Neuropsychological Functioning ◽  
Brain Networks ◽  
Cingulate Cortex ◽  
Anterior Cingulate ◽  
Neuropsychological Performance

Individuals with alcohol use disorder (AUD) are known to manifest a variety of neurocognitive impairments that can be attributed to alterations in specific brain networks. The current study aims to identify specific features of brain connectivity, neuropsychological performance, and impulsivity traits that can classify adult males with AUD (n = 30) from healthy controls (CTL, n = 30) using the Random Forest (RF) classification method. The predictor variables were: (i) fMRI-based within-network functional connectivity (FC) of the Default Mode Network (DMN), (ii) neuropsychological scores from the Tower of London Test (TOLT), and the Visual Span Test (VST), and (iii) impulsivity factors from the Barratt Impulsiveness Scale (BIS). The RF model, with a classification accuracy of 76.67%, identified fourteen DMN connections, two neuropsychological variables (memory span and total correct scores of the forward condition of the VST), and all impulsivity factors as significantly important for classifying participants into either the AUD or CTL group. Specifically, the AUD group manifested hyperconnectivity across the bilateral anterior cingulate cortex and the prefrontal cortex as well as between the bilateral posterior cingulate cortex and the left inferior parietal lobule, while showing hypoconnectivity in long-range anterior–posterior and interhemispheric long-range connections. Individuals with AUD also showed poorer memory performance and increased impulsivity compared to CTL individuals. Furthermore, there were significant associations among FC, impulsivity, neuropsychological performance, and AUD status. These results confirm the previous findings that alterations in specific brain networks coupled with poor neuropsychological functioning and heightened impulsivity may characterize individuals with AUD, who can be efficiently identified using classification algorithms such as Random Forest.

scholarly journals Hot and cold executive functions in the brain: A prefrontal-cingular network

2021 ◽  
Author(s):  
Mohammad Ali Salehinejad ◽  
Elham Ghanavati ◽  
Mohammed Harun Ar Rashid ◽  
Michael A Nitsche
Keyword(s):  
Prefrontal Cortex ◽  
Executive Functions ◽  
Anterior Cingulate Cortex ◽  
Functional Model ◽  
Cingulate Cortex ◽  
Neuropsychiatric Disorders ◽  
Anterior Cingulate ◽  
Posterior Cingulate ◽  
Specific Focus ◽  
The Brain

Executive functions (EFs), or cognitive control, are higher-order cognitive functions needed for adaptive goal-directed behaviours and are significantly impaired in majority of neuropsychiatric disorders. Different models and approaches are proposed for describing how EFs are functionally organized in the brain. One popular and recently proposed organizing principle of EFs is the distinction between hot (i.e., reward or affective-related) vs cold (i.e., purely cognitive) domains of EFs. The prefrontal cortex is traditionally linked to EFs, but on the other hand, anterior and posterior cingulate cortices are involved in EFs as well. In this review, we first define EFs, their domains, and the appropriate methods for studying them. Second, we discuss how hot and cold EFs are linked to different areas of the prefrontal cortex. Third, we discuss the association of hot vs cold EFs with the cingulate cortex with a specific focus on anterior and posterior compartments. Finally, we propose a functional model for hot and cold EF organization in the brain with a specific focus on the fronto-cingular network. We also discuss clinical implications of hot vs cold cognition in major neuropsychiatric disorders (depression, schizophrenia, anxiety disorders, substance use disorder, attention-deficit hyperactivity disorder, and autism) and attempt to characterize their profile according to the functional dominance of hot-cold cognition. Our model proposes that the lateral prefrontal cortex, along with the dorsal anterior cingulate cortex are more relevant for cold EFs and the medial-orbital prefrontal cortex along with the ventral anterior cingulate cortex, and posterior cingulate cortex are more closely involved in hot EFs. This functional distinction, however, is not absolute and depends on several factors including task features, context, and the extent to which the measured function relies on cognition and emotion or both.

scholarly journals Predicting the Amputation Risk for Patients with Diabetic Foot Ulceration – A Bayesian Decision Support Tool

2020 ◽  
Author(s):  
Jens Hüsers ◽  
Guido Hafer ◽  
Jan Heggemann ◽  
Stefan Wiemeyer ◽  
Swen Malte John ◽  
...  
Keyword(s):  
Decision Support ◽  
Diabetic Foot ◽  
Prediction Models ◽  
A Priori ◽  
Decision Support Tool ◽  
Major Amputation ◽  
Statistical Prediction ◽  
Support Tool ◽  
Cohen’S D ◽  
Cohen's D

Abstract Background: Diabetes mellitus is a major global health issue with a growing prevalence. In this context, the number of diabetic complications is also on the rise, such as diabetic foot ulcers (DFU), which are closely linked to the risk of lower extremity amputation (LEA). Statistical prediction tools may support clinicians to initiate early tertiary LEA prevention for DFU patients. Thus, we designed Bayesian prediction models, as they produce transparent decision rules, quantify uncertainty intuitively and acknowledge prior available scientific knowledge.Method: A logistic regression using observational collected according to the standardised PEDIS classification was utilised to compute the six-month amputation risk of DFU patients for two types of LEA: 1.) any-amputation and 2.) major-amputation. Being able to incorporate information which is available before the analysis, the Bayesian models were fitted following a twofold strategy. First, the designed prediction models waive the available information and, second, we incorporated the a priori available scientific knowledge into our models. Then, we evaluated each model with respect to the effect of the predictors and validity of the models. Next, we compared the performance of both models with respect to the incorporation of prior knowledge.Results: This study included 237 patients. The mean age was 65.9 (SD 12.3), and 83.5 per cent were male. Concerning the outcome, 31.6% underwent any- and 12.2% underwent a major-amputation procedure. The risk factors of perfusion, ulcer extent and depth revealed an impact on the outcomes, whereas the infection status and sensation did not. The major-amputation model using prior information outperformed the uninformed counterpart (AUC 0.765 vs AUC 0.790, Cohen’s d 2.21). In contrast, the models predicting any-amputation performed similarly (0.793 vs 0.790, Cohen’s d 0.22).Conclusions: Both of the Bayesian amputation risk models showed acceptable prognostic values, and the major-amputation model benefitted from incorporating a priori information from a previous study. Thus, PEDIS serves as a valid foundation for a clinical decision support tool for the prediction of the amputation risk in DFU patients. Furthermore, we demonstrated the use of the available prior scientific information within a Bayesian framework to establish chains of knowledge.

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