Longitudinal alcohol-related brain changes in older adults: The Sydney Memory and Ageing Study.

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

Early onset adolescent binge drinking is associated with reduced white matter integrity in post-9/11 adult veterans.

Adolescence represents a critical period of neural development during which binge drinking (BD) is prevalent. Though prior work has shown that white matter (WM) integrity is susceptible to damage from excessive alcohol intake in adults, the effect of early adolescent BD on WM health in adulthood remains unknown. Veterans with a history of BD onset before age 15 [n = 49; mean age = 31.8 years; early-onset adolescent binge drinkers (EBD)] and after age 15 [n = 290; mean age = 32.2 years; late-onset adolescent binge drinkers (LBD)] were studied with diffusion tensor imaging. Group differences in fractional anisotropy (FA; movement of water molecules along the WM) and mean diffusivity (MD; average movement of water molecules) were examined as indices of WM integrity using FreeSurfer and FMRIB Software Library (FSL) processing streams. Lower FA and higher MD are thought to represent degradations in WM integrity. A reference group (RG) of social drinkers with no history of BD (n = 31) was used to provide comparative normative data. We observed widespread decreased FA and increased MD in EBDs, compared to LBDs, as well as decreased FA in the pars triangularis, lateral orbitofrontal cortex, superior frontal cortex, isthmus cingulate, and genu and splenium of the corpus callosum EBDs also had lower WM integrity compared to the RG. Adults who initiated BD during early adolescence demonstrated decreased FA and increased MD throughout the frontostriatal circuits that mediate inhibitory control and thus may result in impulsive behavior and a predisposition for developing alcohol use disorder during adulthood.

Cognitive Challenges Are Better in Distinguishing Binge From Nonbinge Drinkers: An Exploratory Deep-Learning Study of fMRI Data of Multiple Behavioral Tasks and Resting State.

BACKGROUND: Studies have identified imaging markers of binge drinking. Functional connectivity during both task challenges and resting state was shown to distinguish binge and nonbinge drinkers. However, no studies have compared the efficacy of task and resting data in the classification. HYPOTHESIS: Task outperforms resting-state functional magnetic resonance imaging (fMRI) data in the differentiation of binge and nonbinge drinkers. We tested the hypothesis via multiple deep learning algorithms. STUDY TYPE: Cross-sectional; retrospective. POPULATION: A total of 149 binge (107 men) and 151 demographically matched, nonbinge (92 men) drinkers curated from the Human Connectome Project, with 80% randomly selected for model development and 20% for validation/test. FIELD STRENGTH/SEQUENCE: A 3 T; fMRI with a blood oxygen level-dependent (BOLD) gradient-echo echo-planar sequence. ASSESSMENT: FMRI data of resting state and seven behavioral tasks were acquired. Graph convolutional network (GCN), long short-term memory, convolutional, and recurrent neural network models were built to distinguish bingers and nonbingers using connectivity matrices of 8, 116, and 268 regions of interest (ROI). Nodal metrics including betweenness centrality, degree centrality, clustering coefficient, efficiency, local efficiency, and shortest path length were calculated from the GCN model. STATISTICAL TESTS: Model performance was quantified by the area under the curve (AUC) in receiver operating characteristic analysis. A P value < 0.05 was considered statistically significant. RESULTS: Task outperformed resting data in classification by approximately 8% by AUC in the test set. Across models and ROI sets, the gambling, motor, language and working memory tasks, each with AUC of 0.614, 0.612, 0.605, and 0.603, performed better than resting data (AUC = 0.548). Models with 116 ROIs (AUC = 0.602) consistently outperformed those with 8 ROIs (AUC = 0.569). Task data performed best with GCN (AUC = 0.619). Nodal metrics of left supplementary motor area and right cuneus showed significant group main effect across tasks. CONCLUSION: Neural responses to cognitive challenges relative to resting state better characterize binge drinking. The performance of different network models may depend on behavioral tasks and the number of ROIs. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Effects of binge drinking during adolescence and emerging adulthood on the brain: A systematic review of neuroimaging studies.

Binge drinking (BD) is a common pattern of alcohol consumption which is generating great concern because of its deleterious consequences. We selected 33 neuroimaging studies of healthy young binge drinkers (BDs) by following PRISMA guidelines. This review provides a comprehensive overview of the relationship between BD and neurocognitive anomalies reported across magnetic resonance studies. Moreover, this work is the first in which results of relatively new imaging techniques, such as resting-state functional connectivity (RS-FC) and neurite orientation dispersion and density imaging (NODDI), have been reviewed using a systematic procedure. We established strict inclusion criteria in order to isolate the various potential effects of BD on the adolescent brain. Two authors independently evaluated the methodological quality, assessing different aspects related to sample size, and statistical correction methods, which are of particular importance in neuroimaging studies. BD is associated with structural and functional anomalies in several cortical and subcortical brain regions intimately involved in the control and regulation of impulsive or risky behaviours, as well as in the processing of reinforcing stimuli.

"It's a beer!": Brain functional hyperconnectivity during processing of alcohol-related images in young binge drinkers.

Alcohol attentional bias has been pointed as a major marker of alcohol misuse. Recent evidence has revealed that brain functional connectivity (FC) may be a valuable index of the brain networks' integrity in young binge drinkers (BDs). However, there is no study to date examining the FC networks linked to the processing of alcohol-related images in this population. The present study aimed to explore the FC signatures underlying alcohol attention bias in young BDs. Thus, electroencephalographic (EEG) activity was recorded in 54 college students (55.5% females; 27 non/low-drinkers and 27 BDs) while performing a visual alcohol cue-reactivity task. We evaluated whole-brain FC profiles during the processing of alcoholic and non-alcoholic cues, as well as their potential relationship with craving and severity of alcohol use. Results showed that, at the behavioural level, BDs rated alcohol-related images as more pleasant/attractive than non/low-drinkers. Furthermore, at the electrophysiological level, BDs exhibited increased beta-band FC-particularly in the fronto-parieto-occipital network-when processing alcoholic cues. Conversely, they displayed reduced theta-band FC relatively to non/low-drinkers for non-alcoholic images. These hyper-/hypo-connectivity patterns were associated with higher alcohol craving levels. Findings are congruent with previous neurofunctional studies reporting an attentional bias towards alcohol-related information in BDs. These results may have important clinical implications as this neural reactivity to alcoholic cues may contribute to the maintenance and/or escalation of the drinking pattern. Finally, the present study constitutes the first evidence showing that FC networks may be a sensitive indicator to alcohol attentional bias in BDs.

Impact of binge drinking during college on resting state functional connectivity.

AIM: The current study examined the longitudinal effects of standard binge drinking (4+/5+ drinks for females/males in 2 hours) and extreme binge drinking (8+/10+ drinks for females/males in 2 hours) on resting-state functional connectivity. METHOD: 119 college students (61 males) were recruited in groups of distinct bingeing patterns at baseline: non-bingeing controls, standard and extreme bingers. Resting-state scans were first obtained when participants were freshmen/sophomores and again approximately two years later. Associations between longitudinal bingeing (reported during this two-year gap) and network connectivity were examined. Network connectivity was calculated by aggregating all edges affiliated with the same network (an edge is a functional connection between two brain regions). The relationship between longitudinal bingeing and connectivity edges was also studied using connectome-based predictive modeling (CPM). RESULTS: Greater standard bingeing was negatively associated with change in connectivity between Default Mode Network and Ventral Attention Network (DMN-VAN; False Discovery Rate corrected), controlling for initial binge groups, longitudinal network changes, motions, scanner, SES, sex, and age. The correlations between change in DMN-VAN connectivity and change in cognitive performance (Stroop, Digit Span, Letter Fluency, and Trail Making) were also tested, but the results were not significant. Lastly, CPM failed to identify a generalizable predictive model of longitudinal bingeing from change in connectivity edges. CONCLUSIONS: Binge drinking is associated with abnormality in networks implicated in attention and self-focused processes, which, in turn, have been implicated in rumination, craving, and relapse. More extensive alterations in functional connectivity might be observed with heavier or longer binge drinking pattern.

Age of onset of adolescent binge drinking is differentially associated with cortical thickness in post-9/11 adult Veterans.

BACKGROUND: Adolescence is a critical period for neural development and has been associated with high rates of alcohol abuse. This research examined potential long-term brain and behavioral effects of early versus late-onset adolescent binge drinking in an adult sample of post-9/11 Veterans. METHODS: We compared cortical thickness measures in Veterans with a history of binge drinking that began before the age of 15 (n = 50; mean age = 32.1 years) to those with a history of binge drinking with onset after the age of 15 (n = 300; mean age = 32.1 years). Data processing was conducted with FreeSurfer. A targeted neuropsychological battery (Digit Span test, Delis-Kaplan Executive Function System Color-Word Interference Test, California Verbal Learning Test-II) was used to examine the relationships between cortical thickness and attention, memory, and inhibition. A reference group of social drinkers with no history of early binge drinking (n = 31) was used to provide normative data. RESULTS: Early-onset adolescent binge drinkers (EBD) had greater cortical thickness in several regions than late-onset adolescent binge drinkers (LBD); both binge-drinking groups had greater cortical thickness than the reference group. There was a stronger negative association between cortical thickness and age in EBDs than LBDs in the (i) lateral orbitofrontal cortex, (ii) supramarginal gyrus, (iii) paracentral lobule, and (iv) anterior caudal cingulate. Poorer performance on the attention and inhibition tasks in the EBDs was also associated with thicker cortices. CONCLUSIONS: This study demonstrates greater cortical thickness across frontoparietal regions in adults who began binge drinking in early versus late adolescence. A stronger negative association between cortical thickness and age in the EBDs suggests that early-onset adolescent binge drinking may be associated with accelerated cortical thinning. Thicker cortex in these regions, which are known to mediate inhibitory control, may increase impulsive behavior and contribute to the risk of alcohol addiction.

Acute electrical, autonomic and structural effects of binge drinking: Insights into the 'holiday heart syndrome'.

BACKGROUND: Binge drinking is a common atrial fibrillation (AF) trigger, however the mechanisms are poorly understood. OBJECTIVE: To investigate the effects of alcohol intoxication and hangover with rhythm monitoring and cardiac MRI. METHODS: Patients underwent serial cardiac MRI pre- and post-binge with continuous Holter monitoring. Time periods analyzed: baseline (24 h pre-binge), consumption, hangover (0- 24 h post-consumption) and post-hangover (24-48 h post-consumption). RESULTS: 50 patients (age 49 ± 15 years, 40% paroxysmal AF) completed the study (intake 8.4 ± 3.1 standard drinks). Mean heart rate increased from 72 ± 10 to 80 ± 13 beats per minute (bpm) during consumption (p < 0.001). The hangover period was characterised by higher daily atrial ectopic count (50, IQR 10-132 vs baseline 43, IQR 10-113; p = 0.04) and reduced heart rate variability (SDNN 55 ms, IQR 40-65 versus 62 ms, IQR 51-66; p = 0.007). There was evidence of heightened parasympathetic activity post-hangover with heart rate slowing (mean HR 54 ± 6 bpm; p = 0.03) and increased activity in the High frequency band when separating the complex heart rate variability waveform into its component rhythms (291 ms2, 97-538 versus baseline 237 ms2, IQR 104-332; p = 0.04). Three patients developed AF 11, 29 and 34 h post-binge. Cardiac MRI (2.7 ± 0.7 days post-binge) demonstrated a decrease in left atrial (LA) emptying fraction (57.9 ± 8.5 to 53.5 ± 6.7%; p = 0.003) but no change in LA volume, left ventricular ejection fraction or markers of ventricular inflammation. CONCLUSION: Binge drinking is associated with sympathetic activation followed by a 'rebound' parasympathetic response and atrial mechanical dysfunction which may explain the propensity and temporal association between binge drinking and AF.

Drinking and responses to antidrinking messages among young adults: An fMRI study.

Young adults consume most of their alcohol by binge drinking, and more than one-third report binge drinking in the past month. Some will transition out of excessive drinking, while others will maintain or increase alcohol use into adulthood. Public health campaigns depicting negative consequences of drinking have shown some efficacy at reducing this behavior. However, substance use in dependent individuals is governed in part by automatic or habitual responses to drug cues rather than the consequences. This study used functional magnetic resonance imaging to measure neural responses to drinking cues and drinking cues paired with antidrinking messages among young adults who binge drink (N = 30). This study also explored responses to smoking cues and antismoking messages. Neural responses were also compared between drinking/smoking and neutral cues. Self-reported drinking and smoking were collected at baseline, postscan, and 1 month. Results indicate that activity in the ventral striatum-implicated in reward processing-was lower for drinking cues paired with antidrinking messages than drinking cues. This difference was less pronounced in young adults who reported greater baseline past month drinking quantity. Past month drinking quantity decreased from baseline to 1 month. Further, young adults who showed higher activity during antidrinking messages in the medial prefrontal cortex-implicated in processing message self-relevance- reported a greater decrease in past month drinking frequency from baseline to 1 month. Findings may help to identify young adults who are at risk for continued heavy drinking in adulthood and inform interventions aimed to reduce drinking and reward in young adults.

Jacobian Mapping Reveals Converging Brain Substrates of Disruption and Repair in Response to Ethanol Exposure and Abstinence in 2 Strains of Rats.

BACKGROUND: In a previous study using Jacobian mapping to evaluate the morphological effects on the brain of binge (4-day) intragastric ethanol (EtOH) on wild-type Wistar rats, we reported reversible thalamic shrinkage and lateral ventricular enlargement, but persistent superior and inferior colliculi shrinkage in response to binge EtOH treatment. METHODS: Herein, we used similar voxel-based comparisons of Magnetic Resonance Images collected in EtOH-exposed relative to control animals to test the hypothesis that regardless of the intoxication protocol or the rat strain, the hippocampi, thalami, and colliculi would be affected. RESULTS: Two experiments [binge (4-day) intragastric EtOH in Fisher 344 rats and chronic (1-month) vaporized EtOH in Wistar rats] showed similarly affected brain regions including retrosplenial and cingulate cortices, dorsal hippocampi, central and ventroposterior thalami, superior and inferior colliculi, periaqueductal gray, and corpus callosum. While most of these regions showed significant recovery, volumes of the colliculi and periaqueductal gray continued to show response to each proximal EtOH exposure but at diminished levels with repeated cycles. CONCLUSIONS: Given the high metabolic rate of these enduringly affected regions, the current findings suggest that EtOH per se may affect cellular respiration leading to brain volume deficits. Further, responsivity greatly diminished likely reflecting neuroadaptation to repeated alcohol exposure. In summary, this unbiased, in vivo-based approach demonstrating convergent brain systems responsive to 2 EtOH exposure protocols in 2 rat strains highlights regions that warrant further investigation in both animal models of alcoholism and in humans with alcohol use disorder.

Alcohol effects on globus pallidus connectivity: Role of impulsivity and binge drinking.

Despite the harm caused by binge drinking, the neural mechanisms leading to risky and disinhibited intoxication-related behaviors are not well understood. Evidence suggests that the globus pallidus externus (GPe), a substructure within the basal ganglia, participates in inhibitory control processes, as examined in stop-signaling tasks. In fact, studies in rodents have revealed that alcohol can change GPe activity by decreasing neuronal firing rates, suggesting that the GPe may have a central role in explaining impulsive behaviors and failures of inhibition that occur during binge drinking. In this study, twenty-five healthy volunteers underwent intravenous alcohol infusion to achieve a blood alcohol level of 0.08 g/dl, which is equivalent to a binge drinking episode. A resting state functional magnetic resonance imaging scan was collected prior to the infusion and at binge-level exposure. Functional connectivity analysis was used to investigate the association between alcohol-induced changes in GPe connectivity, drinking behaviors, and impulsivity traits. We found that individuals with greater number of drinks or heavy drinking days in the recent past had greater alcohol-induced deficits in GPe connectivity, particularly to the striatum. Our data also indicated an association between impulsivity and alcohol-induced deficits in GPe-frontal/precentral connectivity. Moreover, alcohol induced changes in GPe-amygdala circuitry suggested greater vulnerabilities to stress-related drinking in some individuals. Taken together, these findings suggest that alcohol may interact with impulsive personality traits and drinking patterns to drive alterations in GPe circuitry associated with behavioral inhibition, possibly indicating a neural mechanism by which binge drinking could lead to impulsive behaviors.

Prospective Associations between BOLD Markers of Response Inhibition and the Transition to Frequent Binge Drinking.

BACKGROUND: Altered brain activation during response inhibition has been linked to a greater risk for alcohol and other substance use behaviors in late adolescence. However, the ability of neural markers of response inhibition, acquired during adolescence, to temporally predict the transition from less frequent and lower quantity alcohol use to high-risk, frequent (≥ weekly) binge drinking behavior remains unclear. METHODS: Adolescents (N = 29; 9 females) were selected from a larger ongoing longitudinal study to include those who transitioned to at least weekly binge drinking (≥5/4 alcoholic drinks for males/females per occasion) over a 15-year follow-up period. Prior to the onset of weekly binge drinking (mean age = 18.0), participants underwent a functional MRI including a go/no-go task. Whole-brain activation from the no-go correct rejection versus no-go false alarm contrast was used to predict time to transition to frequent binge drinking. RESULTS: Less no-go correct rejection versus no-go false alarm activation in a cluster including the precentral gyri, insula, and inferior frontal gyri predicted a more rapid transition into frequent binge drinking (voxel-wise alpha < 0.001, cluster-wise alpha < 0.05, cluster threshold ≥ 18 voxels). CONCLUSIONS: Results from this study are supported by literature suggesting that frontoinsular involvement is important for successful inhibition and cognitive control. Altered brain activation during response inhibition may thus represent neural antecedents of impulse regulation difficulties related to alcohol consumption. The magnitude of this activation provides temporal information that may be used to inform and optimize timing of interventions aimed at preventing the escalation and transition to problematic drinking for youth who have already begun to engage in drinking behaviors.

Associations between nucleus accumbens structural connectivity, brain function, and initiation of binge drinking.

Adolescent alcohol use is associated with increased risk for alcohol use disorders later in life; therefore, identifying biomarkers for initiation of heavy alcohol use, such as individual differences in the development of white-matter microstructure, may inform prevention strategies that improve public health. This prospective cohort study included 40 adolescents, ages 14 and 15, without substantial history of alcohol or drug use at baseline. Fractional anisotropy (FA), an index of white-matter microstructure, was assessed in pathways connecting the nucleus accumbens (NAcc) to the rest of the brain using diffusion tensor imaging. Path analyses were conducted voxel-wise within these pathways to examine direct effects of premorbid FA on number of months between baseline assessment and the onset of binge drinking and indirect effects mediated by NAcc activation during decision making assessed using functional magnetic resonance imaging. Adolescents with lower premorbid accumbofrontal FA began binge drinking sooner, an effect which was mediated by greater NAcc activation during decision making involving greater levels of risk and reward (P < .05 corrected). An additional direct effect of FA on duration to onset of binge drinking was observed in white matter near the ventral pallidum, as adolescents with lower premorbid FA in this region began binge drinking sooner (P < .05 corrected). Findings suggest that delayed maturation of prefrontal white matter is associated with less top-down control over striatal sensitivity to reward. These factors, along with individual differences in white matter proximal to ventral pallidum, may represent premorbid risk factors for earlier initiation of heavy alcohol use.

Binge drinking is associated with altered resting state functional connectivity of reward-salience and top down control networks.

Binge drinking is characterized by bouts of high-intensity alcohol intake and is associated with an array of health-related harms. Even though the transition from occasional impulsive to addictive alcohol use is not well understood, neurobiological models of addiction suggest that repeated cycles of intoxication and withdrawal contribute to the development of addiction in part through dysregulation of neurofunctional networks. Research on the neural sequelae associated with binge drinking is scant but resting state functional connectivity (RSFC) studies of alcohol use disorders (AUD) indicate that the development and maintenance of long-term excessive drinking may be mediated by network-level disruptions. The present study examined RSFC in young adult binge (BD) and light (LD) drinkers with seeds representing the networks subserving reward (the nucleus accumbens and caudate nucleus), salience (anterior cingulate cortex, ACC), and executive control (inferior frontal cortex, IFC). BDs exhibited enhanced connectivity between the striatal reward areas and the orbitofrontal cortex and the ACC, which is consistent with AUD studies and may be indicative of alcohol-motivated appetitive behaviors. Conversely, BDs demonstrated lower connectivity between the IFC and hippocampus which was associated with higher craving. This may indicate impaired ability to suppress unwanted thoughts and a failure to employ memory of the harmful consequences of heavy drinking in prospective plans and intentions. The observed greater connectivity of the reward/salience network and the lower prefrontal-hippocampal connectivity were associated with hazardous drinking levels indicating that dysregulation of neurofunctional networks may underlie binge drinking patterns.

Functional and structural connectivity of the executive control network in college binge drinkers.

Binge Drinking (BD) is a pattern of excessive alcohol consumption highly prevalent among college students, and has been associated with structural and functional alterations of brain networks. Recent advances in the resting-state connectivity analysis have boosted the research of the network-level connectivity disturbances associated with many psychiatric and neurological disorders, including addiction. Accordingly, atypical functional connectivity patterns in resting-state networks such as the Executive Control Network (ECN) have been found in substance users and alcohol-dependent individuals. In this study, we assessed for the first time the ECN functional and structural connectivity in a group of 34 college students, 20 (10 women) binge drinkers (BDs) in comparison with a group of 14 (8 women) alcohol abstinent controls (AACs). Overall, our findings documented increased resting-state functional connectivity (rsFC) in the BDs left middle frontal cortex of the left ECN in comparison to the AACs, while no structural connectivity differences were observed between groups. Pearson correlations revealed a positive association between the left middle frontal gyrus rsFC and the frequency of BD episodes per month, in the BD group. These findings suggest that maintaining a pattern of acute and intermittent alcohol consumption during important stages of brain development, as the transition from adolescence to adulthood, is associated with impaired ECN rsFC despite no group differences being yet noticed in the ECN structural connectivity.

Associations Between Drinking and Cortical Thickness in Younger Adult Drinkers: Findings From the Human Connectome Project.

BACKGROUND: Previous neuroimaging studies examining relations between alcohol misuse and cortical thickness have revealed that increased drinking quantity and alcohol-related problems are associated with thinner cortex. Although conflicting regional effects are often observed, associations are generally localized to frontal regions (e.g., dorsolateral prefrontal cortex [DLPFC], inferior frontal gyrus [IFG], and anterior cingulate cortex). Inconsistent findings may be attributed to methodological differences, modest sample sizes, and limited consideration of sex differences. METHODS: This study examined neuroanatomical correlates of drinking quantity and heavy episodic drinking in a large sample of younger adults (N = 706; Mage  = 28.8; 51% female) using magnetic resonance imaging data from the Human Connectome Project. Exploratory analyses examined neuroanatomical correlates of executive function (flanker task) and working memory (list sorting). RESULTS: Hierarchical linear regression models (controlling for age, sex, education, income, smoking, drug use, twin status, and intracranial volume) revealed significant inverse associations between drinks in past week and frequency of heavy drinking and cortical thickness in a majority of regions examined. The largest effect sizes were found for frontal regions (DLPFC, IFG, and the precentral gyrus). Follow-up regression models revealed that the left DLPFC was uniquely associated with both drinking variables. Sex differences were also observed, with significant effects largely specific to men. CONCLUSIONS: This study adds to the understanding of brain correlates of alcohol use in a large, gender-balanced sample of younger adults. Although the cross-sectional methodology precludes causal inferences, these findings provide a foundation for rigorous hypothesis testing in future longitudinal investigations.

Adolescent binge drinking disrupts normal trajectories of brain functional organization and personality maturation.

Adolescent binge drinking has been associated with higher risks for the development of many health problems throughout the lifespan. Adolescents undergo multiple changes that involve the co-development processes of brain, personality and behavior; therefore, certain behavior, such as alcohol consumption, can have disruptive effects on both brain development and personality maturation. However, these effects remain unclear due to the scarcity of longitudinal studies. In the current study, we used multivariate approaches to explore discriminative features in brain functional architecture, personality traits, and genetic variants in 19-year-old individuals (n = 212). Taking advantage of a longitudinal design, we selected features that were more drastically altered in drinkers with an earlier onset of binge drinking. With the selected features, we trained a hierarchical model of support vector machines using a training sample (n = 139). Using an independent sample (n = 73), we tested the model and achieved a classification accuracy of 71.2%. We demonstrated longitudinally that after the onset of binge drinking the developmental trajectory of improvement in impulsivity slowed down. This study identified the disrupting effects of adolescent binge drinking on the developmental trajectories of both brain and personality.

Altered frontostriatal white matter microstructure is associated with familial alcoholism and future binge drinking in adolescence.

Adolescence is a time of significant neurobiological development, including changes in white matter microstructure. Familial alcoholism and adolescent binge-drinking have both been associated with altered white matter microstructure; however, the temporal nature of these effects, and their interaction, is unclear. Using diffusion-weighted imaging and voxel-wise multilevel modeling, the effects of familial alcoholism and future binge-drinking on white matter microstructural development were assessed in 45 adolescents, who went on to binge-drink (but were alcohol-naive at baseline), and 68 adolescents, who remained largely alcohol-naive, all with varying degrees of familial alcoholism. Both future binge-drinking and familial alcoholism were associated with altered frontostriatal white matter microstructure early in adolescence, prior to alcohol use. While several binge-drinking-related effects persisted throughout adolescence (in the posterior limb of the internal capsule, superior corona radiata, and cerebellar peduncles), the association between familial alcoholism and altered white matter microstructure dissipated across adolescence in all regions. There were no white matter regions identified where future binge-drinking or familial alcoholism were significantly associated with emergent or exacerbated alterations in white matter microstructure. Altogether, these findings suggest that alterations in frontostiatal white matter microstructure, some of which are associated with familial alcoholism, may be used to predict which adolescents are more likely to go on and engage in alcohol use. Meanwhile, a reduction in family history-related associations with altered white matter microstructure by late-adolescence is encouraging for future prevention work targeted at at-risk youth.

Risk profiles for heavy drinking in adolescence: differential effects of gender.

Abnormalities across different domains of neuropsychological functioning may constitute a risk factor for heavy drinking during adolescence and for developing alcohol use disorders later in life. However, the exact nature of such multi-domain risk profiles is unclear, and it is further unclear whether these risk profiles differ between genders. We combined longitudinal and cross-sectional analyses on the large IMAGEN sample (N ≈ 1000) to predict heavy drinking at age 19 from gray matter volume as well as from psychosocial data at age 14 and 19-for males and females separately. Heavy drinking was associated with reduced gray matter volume in 19-year-olds' bilateral ACC, MPFC, thalamus, middle, medial and superior OFC as well as left amygdala and anterior insula and right inferior OFC. Notably, this lower gray matter volume associated with heavy drinking was stronger in females than in males. In both genders, we observed that impulsivity and facets of novelty seeking at the age of 14 and 19, as well as hopelessness at the age of 14, are risk factors for heavy drinking at the age of 19. Stressful life events with internal (but not external) locus of control were associated with heavy drinking only at age 19. Personality and stress assessment in adolescents may help to better target counseling and prevention programs. This might reduce heavy drinking in adolescents and hence reduce the risk of early brain atrophy, especially in females. In turn, this could additionally reduce the risk of developing alcohol use disorders later in adulthood.

Binge drinking is associated with attenuated frontal and parietal activation during successful response inhibition in fearful context.

Binge drinking is associated with increased impulsivity and altered emotional processing. This study investigated, in a group of university students who differed in their level of binge drinking, whether the ability to inhibit a pre-potent response and to delay gratification is disrupted in the presence of emotional context. We further tested whether functional connectivity within intrinsic resting-state networks was associated with alcohol use. Higher incidence of binge drinking was associated with enhanced activation of the lateral occipital cortex, angular gyrus, the left frontal pole during successful response inhibition irrespective of emotional context. This observation suggests a compensatory mechanism. However, higher binge drinking attenuated frontal and parietal activation during successful response inhibition within a fearful context, indicating the selective emotional facilitation of inhibitory control. Similarly, higher binge drinking was associated with attenuated frontopolar activation when choosing a delayed reward over an immediate reward within the fearful, relative to the neutral, context. Resting-state functional data analysis revealed that binge drinking decreased coupling between the right supramarginal gyrus and Ventral Attention Network, indicating alcohol-associated disruption of functional connectivity within brain substrates directing attention. Together, our results suggest that binge drinking makes response inhibition more effortful, yet emotional (more arousing) contexts may mitigate this; disrupted functional connectivity between regions underlying adaptive attentional control, is a likely mechanism underlying these response inhibition effects associated with binge drinking.