• Energy Research
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The zebrafish is increasingly well utilized in alcohol research, particularly in modeling human fetal alcohol spectrum disorders (FASD). FASD results from alcohol reaching the developing fetus intra utero, a completely preventable yet prevalent and devastating life-long disorder. The hope with animal models, including the zebrafish, is to discover the mechanisms underlying this disease, which may aid treatment and diagnosis. In the past, we developed an embryonic alcohol exposure regimen that is aimed at mimicking the milder, and most prevalent, forms of FASD in zebrafish. We have found numerous lasting alterations in behavior, neurochemistry, neuronal markers and glial cell phenotypes in this zebrafish FASD model. Using the same model (2 h long bath immersion of 24 h post-fertilization old zebrafish eggs into 1% vol/vol ethanol), here we conduct a proof of concept analysis of voltage-gated cation channels, investigating potential embryonic alcohol induced changes in L-, T- and N- type Ca++ and the SCN1A Na+ channels using Western blot followed by immunohistochemical analysis of the same channels in the pallium and cerebellum of the zebrafish brain. We report significant reduction of expression in all four channel proteins using both methods. We conclude that reduced voltage-gated cation channel expression induced by short and low dose exposure to alcohol during embryonic development of zebrafish may contribute to the previously demonstrated lasting behavioral and neurobiological changes.

Abstract The age- and time-dependent effects of binge drinking on adolescent brain development have not been well characterized even though binge drinking is a health crisis among adolescents. The impact of binge drinking on gray matter volume (GMV) development was examined using 5 waves of longitudinal data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study. Binge drinkers (n = 166) were compared with non-binge drinkers (n = 82 after matching on potential confounders). Number of binge drinking episodes in the past year was linked to decreased GMVs in bilateral Desikan–Killiany cortical parcellations (26 of 34 with P < 0.05/34) with the strongest effects observed in frontal regions. Interactions of binge drinking episodes and baseline age demonstrated stronger effects in younger participants. Statistical models sensitive to number of binge episodes and their temporal proximity to brain volumes provided the best fits. Consistent with prior research, results of this study highlight the negative effects of binge drinking on the developing brain. Our results present novel findings that cortical GMV decreases were greater in closer proximity to binge drinking episodes in a dose–response manner. This relation suggests a causal effect and raises the possibility that normal growth trajectories may be reinstated with alcohol abstinence.

Abstract Study Objectives Adolescence is characterized by significant brain development, accompanied by changes in sleep timing and architecture. It also is a period of profound psychosocial changes, including the initiation of alcohol use; however, it is unknown how alcohol use affects sleep architecture in the context of adolescent development. We tracked developmental changes in polysomnographic (PSG) and electroencephalographic (EEG) sleep measures and their relationship with emergent alcohol use in adolescents considering confounding effects (e.g. cannabis use). Methods Adolescents (n = 94, 43% female, age: 12–21 years) in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study had annual laboratory PSG recordings across 4-years. Participants were no/low drinkers at baseline. Results Linear mixed effect models showed developmental changes in sleep macrostructure and EEG, including a decrease in slow wave sleep and slow wave (delta) EEG activity with advancing age. Emergent moderate/heavy alcohol use across three follow-up years was associated with a decline in percentage rapid eye movement (REM) sleep over time, a longer sleep onset latency (SOL) and shorter total sleep time (TST) in older adolescents, and lower non-REM delta and theta power in males. Conclusions These longitudinal data show substantial developmental changes in sleep architecture. Emergent alcohol use during this period was associated with altered sleep continuity, architecture, and EEG measures, with some effects dependent on age and sex. These effects, in part, could be attributed to the effects of alcohol on underlying brain maturation processes involved in sleep–wake regulation.

Alcohol is one of the most widely used substances. Alcohol use accounts for 5.1% of the global disease burden, contributes substantially to societal and economic costs, and leads to approximately 3 million global deaths yearly. Alcohol use disorder (AUD) includes various drinking behavior patterns that lead to short-term or long-lasting effects on health. Ethanol, the main psychoactive molecule acting in alcoholic beverages, directly impacts the GABAergic system, contributing to GABAergic dysregulations that vary depending on the intensity and duration of alcohol consumption. A small number of interventions have been developed that target the GABAergic system, but there are promising future therapeutic avenues to explore. This review provides an overview of the impact of alcohol on the GABAergic system, the current interventions available for AUD that target the GABAergic system, and the novel interventions being explored that in the future could be included among first-line therapies for the treatment of AUD.

AbstractWith the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Approximately 10% of congenital heart diseases (CHDs) include Tetralogy of Fallot (TOF). Fortunately, due to advanced surgical techniques, most patients survive until adulthood. However, these patients require frequent monitoring for postoperative complications leading to heart hemodynamic alterations. Turbulent kinetic energy (TKE), as derived from 4D-flow magnetic resonance imaging (4D-flow MRI), has been used to characterize abnormal heart hemodynamics in CHD. Hence, this study aimed to assess the difference in TKE between patients with repaired TOF (rTOF) and healthy volunteers. A total of 35 subjects, 17 rTOF patients and 18 controls, underwent standard-of-care cardiac MRI and research 4D-flow MRI using a clinical 3T scanner. Heart chambers and great vessels were segmented using 3D angiograms derived from 4D-flow MRI. The TKE was quantified within segmented volumes. TKE was compared to standard cardiac MRI metrics. Controls demonstrated higher TKE in the left atria and left ventricle. However, patients demonstrated higher TKE in the right atria, right ventricle (p < 0.05), and pulmonary artery. Lastly, no correlation was observed between TKE and standard clinical measurements. TKE can be a key indicator of the abnormal hemodynamics present in patients with rTOF and can assist future interventions and help monitor long-term outcomes.

AbstractBackground and AimsBinge drinking contributes to the immense public health burden associated with alcohol use, especially among younger drinkers. Little is known about the underlying neurobiology of changes in this behavior over time. This preliminary study aimed to identify neurobiological markers of binge drinking behavior change during emerging adulthood.DesignObservational prospective investigation of neurobiological predictors of binge drinking behavior.SettingCommunities surrounding a large, public university in the northeastern United States.ParticipantsA total of 42 emerging adults (48% female), approximately half meeting criteria for an alcohol use disorder.MeasurementsPast month binge drinking, the dependent variable, was assessed at two time‐points (T1, T2) via self‐report. Ten indices of resting‐state functional connectivity within the central executive network (CEN), a brain network involved in executive function, were collected at T1 and specified as independent variables in cross‐sectional and prospective Poisson models. All models controlled for age, sex, and alcohol use disorder status.FindingsThe cross‐sectional model yielded five significant associations between CEN connectivity and binge drinking incidence. Connections anchored primarily in the anterior CEN exhibited negative associations with binge drinking incidence (P = 0.001, 0.004, 0.011), and connections stemming from the right posterior parietal cortex exhibited positive associations with binge drinking incidence (P = 0.041, 0.045). In prospective models, stronger frontoparietal connectivity between the right dorsolateral prefrontal cortex and left posterior parietal cortex predicted greater increases in binge drinking incidence over time (P = 0.003).ConclusionsThere is an association between central executive network connectivity and heavy drinking, as well as evidence that functional pathways within the central executive network may contribute to changes in problematic drinking behaviors.

AbstractBackgroundPrenatal alcohol exposure (PAE) is associated with smaller regional and global brain volumes. In rats, gestational choline supplementation mitigates adverse developmental effects of ethanol exposure. Our recent randomized, double‐blind, placebo‐controlled maternal choline supplementation trial showed improved somatic and functional outcomes in infants at 6.5 and 12 months postpartum. Here, we examined whether maternal choline supplementation protected the newborn brain from PAE‐related volume reductions and, if so, whether these volume changes were associated with improved infant recognition memory.MethodsFifty‐two infants born to heavy‐drinking women who had participated in a choline supplementation trial during pregnancy underwent structural magnetic resonance imaging with a multi‐echo FLASH protocol on a 3T Siemens Allegra MRI (median age = 2.8 weeks postpartum). Subcortical regions were manually segmented. Recognition memory was assessed at 12 months on the Fagan Test of Infant Intelligence (FTII). We examined the effects of choline on regional brain volumes, whether choline‐related volume increases were associated with higher FTII scores, and the degree to which the regional volume increases mediated the effects of choline on the FTII.ResultsUsable MRI data were acquired in 50 infants (choline: n = 27; placebo: n = 23). Normalized volumes were larger in six of 12 regions in the choline than placebo arm (t ≥ 2.05, p ≤ 0.05) and were correlated with the degree of maternal choline adherence (β ≥ 0.28, p ≤ 0.04). Larger right putamen and corpus callosum were related to higher FTII scores (r = 0.36, p = 0.02) with a trend toward partial mediation of the choline effect on recognition memory.ConclusionsHigh‐dose choline supplementation during pregnancy mitigated PAE‐related regional volume reductions, with larger volumes associated with improved 12‐month recognition memory. These results provide the first evidence that choline may be neuroprotective against PAE‐related brain structural deficits in humans.