Influence of alcohol use and family history of alcoholism on neural response to alcohol cues in college drinkers.

BACKGROUND: Heavy drinkers show altered functional magnetic resonance imaging (fMRI) response to alcohol cues. Little is known about alcohol cue reactivity among college age drinkers, who show the greatest rates of alcohol use disorders. Family history of alcoholism (family history positive [FHP]) is a risk factor for problematic drinking, but the impact on alcohol cue reactivity is unclear. We investigated the influence of heavy drinking and family history of alcoholism on alcohol cue-related fMRI response among college students. METHODS: Participants were 19 family history negative (FHN) light drinkers, 11 FHP light drinkers, 25 FHN heavy drinkers, and 10 FHP heavy drinkers, aged 18 to 21. During fMRI scanning, participants viewed alcohol images, nonalcohol beverage images, and degraded control images, with each beverage image presented twice. We characterized blood oxygen level-dependent (BOLD) contrast for alcohol versus nonalcohol images and examined BOLD response to repeated alcohol images to understand exposure effects. RESULTS: Heavy drinkers exhibited greater BOLD response than light drinkers in posterior visual association regions, anterior cingulate, medial frontal cortex, hippocampus, amygdala, and dorsal striatum, and hyperactivation to repeated alcohol images in temporo-parietal, frontal, and insular regions (clusters > 8,127 µl, p < 0.05). FHP individuals showed increased activation to repeated alcohol images in temporo-parietal regions, fusiform, and hippocampus. There were no interactions between family history and drinking group. CONCLUSIONS: Our results parallel findings of hyperactivation to alcohol cues among heavy drinkers in regions subserving visual attention, memory, motivation, and habit. Heavy drinkers demonstrated heightened activation to repeated alcohol images, which could influence continued drinking. Family history of alcoholism was associated with greater response to repeated alcohol images in regions underlying visual attention, recognition, and encoding, which could suggest aspects of alcohol cue reactivity that are independent of personal drinking. Heavy drinking and family history of alcoholism may have differential impacts on neural circuitry involved in cue reactivity.

Relationships between drinking quantity and frequency and behavioral and hippocampal BOLD responses during working memory performance involving allocentric spatial navigation in college students.

BACKGROUND: Quantity and frequency of drinking may be used to effectively quantify the severity of alcohol-use. Drinking-severity has been related to neurocognitive impairments in such domains as spatial working memory (SWM). Youth drinking has been associated with altered neurofunctional underpinnings of SWM. The current study examined the relationship between drinking-severity and SWM processing. METHODS: One-hundred-and-seventy college drinkers reported the maximum number of drinks in a 24 -h period in the last six-months (quantity) and average number of drinking weeks in the last six-months (frequency). All participants performed a virtual Morris Water Task during fMRI which included trials where the target platform was visible or hidden. RESULTS: Greater quantity was associated with reduced SWM-related activity in the dorsolateral prefrontal cortex (F(1, 167) = 4.15, p = .04). Greater frequency was associated with reduced SWM-related activity in the hippocampus (F(1, 167) = 4.34, p = 0.039). Greater quantity was associated with longer search times (r = 0.21, p = .005) and greater platforms found (r = 0.19, p = .01) in VISIBLE trials. We did not find a relationship between drinking quantity or frequency and gender on SWM-related activity, although men found more platforms in both HIDDEN (F(1, 168) = 11.7, p = 0.0008) and VISIBLE (F(1, 168) = 23.0, p < .0001) trials compared to women. CONCLUSIONS: Altered SWM-related hippocampal function relating to alcohol use in young adults raises questions regarding the impact on young adult health and the nature of the findings. Future studies should examine whether these differences may lead to cognitive deficits later in life.

Longitudinal Effects of Alcohol Consumption on the Hippocampus and Parahippocampus in College Students.

BACKGROUND: The hazardous effects of alcohol consumption on both the hippocampus and memory have been well established. However, the longitudinal effects of ethanol on the developing brain and related consequences on memory are not well explored. Given the above, we investigated the longitudinal effects of college drinking on hippocampal volume in emerging college adults. METHODS: Data were derived from the longitudinal Brain and Alcohol Research with College Students study. A subset of 146 freshmen (mean age at baseline = 18.5 years) underwent brain magnetic resonance imaging scans at baseline and 24 months later. Four drinking-related measures derived from monthly surveys were reduced to a single alcohol use index using principal component analysis. Gray matter volumetric change (GMV-c) data were derived using a longitudinal pipeline. Voxelwise hippocampal/para-hippocampal GMV-c associations with the drinking index were derived using a multiple regression framework within SPM12. Supplementary associations were assessed between GMV-c and memory scores computed from the California Verbal Learning Test-II (assessed at the end of the study), and between GMV-c and total alcohol-induced memory blackouts. RESULTS: Larger alcohol use index was associated with an accelerated GMV decline in the hippocampus/para-hippocampus. Also, larger hippocampal volume decline was associated with poorer memory performance and more memory blackouts. CONCLUSIONS: Our study extends prior cross-sectional literature by showing that a heavier drinking burden while in college is associated with greater hippocampal GMV decline that is in turn associated with poorer memory scores, all of which could ultimately have a significant impact on student success.

Relationship between fMRI response during a nonverbal memory task and marijuana use in college students.

Marijuana (MJ) is widely used among college students, with peak use between ages 18-22. Research suggests memory dysfunction in adolescent and young adult MJ users, but the neural correlates are unclear. We examined functional magnetic resonance imaging (fMRI) response during a memory task among college students with varying degrees of MJ involvement. Participants were 64 college students, ages 18-20, who performed a visual encoding and recognition task during fMRI. MJ use was ascertained for 3 months prior to scanning; 27 individuals reported past 3-month MJ use, and 33 individuals did not. fMRI response was modeled during encoding based on whether targets were subsequently recognized (correct encoding), and during recognition based on target identification (hits). fMRI response in left and right inferior frontal gyrus (IFG) and hippocampal regions of interest was examined between MJ users and controls. There were no group differences between MJ users and controls on fMRI response during encoding, although single sample t-tests revealed that MJ users failed to activate the hippocampus. During recognition, MJ users showed less fMRI response than controls in right hippocampus (Cohen's d = 0.55), left hippocampus (Cohen's d = 0.67) and left IFG (Cohen's d = 0.61). Heavier MJ involvement was associated with lower fMRI response in left hippocampus and left IFG. This study provides evidence of MJ-related prefrontal and hippocampal dysfunction during recognition memory in college students. These findings may contribute to our previously identified decrements in academic performance in college MJ users and could have substantial implications for academic and occupational functioning.

Heavy Drinking in College Students Is Associated with Accelerated Gray Matter Volumetric Decline over a 2 Year Period.

Background: Heavy and/or harmful alcohol use while in college is a perennial and significant public health issue. Despite the plethora of cross-sectional research suggesting deleterious effects of alcohol on the brain, there is a lack of literature investigating the longitudinal effects of alcohol consumption on the adolescent brain. We aim to probe the longitudinal effects of college drinking on gray matter change in students during this crucial neurodevelopmental period. Methods: Data were derived from the longitudinal Brain and Alcohol Research in College Students (BARCS) study of whom a subset underwent brain MRI scans at two time points 24 months apart. Students were young adults with a mean age at baseline of about 18.5 years. Based on drinking metrics assessed at both baseline and followup, subjects were classified as sustained abstainers/light drinkers (N = 45) or sustained heavy drinkers (N = 84) based on criteria established in prior literature. Gray matter volumetric change (GMV-c) maps were derived using the longitudinal DARTEL pipeline as implemented in SPM12. GMV-c maps were then subjected to a 1-sample and 2-sample t-test in SPM12 to determine within- and between-group GMV-c differences in drinking groups. Supplementary between-group differences were also computed at baseline only. Results: Within-group analysis revealed significant decline in GMV in both groups across the 2 year followup period. However, tissue loss in the sustained heavy drinking group was more significant, larger per region, and more widespread across regions compared to abstainers/light drinkers. Between-group analysis confirmed the above and showed a greater rate of GMV-c in the heavy drinking group in several brain regions encompassing inferior/medial frontal gyrus, parahippocampus, and anterior cingulate. Supplementary analyses suggest that some of the frontal differences existed at baseline and progressively worsened. Conclusion: Sustained heavy drinking while in college was associated with accelerated GMV decline in brain regions involved with executive functioning, emotional regulation, and memory, which are critical to everyday life functioning. Areas of significant GMV decreases also overlapped largely with brain reward and stress systems implicated in addictive behavior.

Effects of drinking patterns on prospective memory performance in college students.

OBJECTIVE: Traditional college students are at a critical juncture in the development of prospective memory (PM). Their brains are vulnerable to the effects of alcohol. METHOD: There were 123 third and fourth year college students, 19-23 years old, who completed the Self-Rating Effects of Alcohol (SREA), Modified Timeline Follow-back (TFLB), Brief Young Adult Alcohol Consequences Scale (BYAACS), and Alcohol Effects Questionnaire (AEQ) once per month on a secure online database, as reported elsewhere (Dager et al., 2013). Data from the 6 months immediately before memory testing were averaged. In a single testing session participants were administered the Mini International Neuropsychiatric Interview-Diagnostic and Statistical Manual for Mental Disorders-Fourth Edition-Text Revision (MINI-DSM-IV-TR), measures of PM (event-based and time-based), and retrospective memory (RM). Based on the average score of six consecutive monthly responses to the SREA, TLFB, and AEQ, students were classified as nondrinkers, light drinkers, or heavy drinkers (as defined previously; Dager et al., 2013). Alcohol-induced amnesia (blackout) was measured with the BYAACS. RESULTS: We found a relationship between these alcohol use classifications and time-based PM, such that participants who were classified as heavier drinkers were more likely to forget to perform the time-based PM task. We also found that self-reported alcohol-induced amnesia (blackouts) during the month immediately preceding memory testing was associated with lower performance on the event-based PM task. Participants' ability to recall the RM tasks suggested the PM items were successfully encoded even when they were not carried out, and we observed no relationship between alcohol use and RM performance. CONCLUSION: Heavy alcohol use in college students may be related to impairments in PM. (PsycINFO Database Record

Longitudinal influence of alcohol and marijuana use on academic performance in college students.

BACKGROUND: Alcohol and marijuana are the two most abused substances in US colleges. However, research on the combined influence (cross sectional or longitudinal) of these substances on academic performance is currently scant. METHODS: Data were derived from the longitudinal 2-year Brain and Alcohol Research in College Students (BARCS) study including 1142 freshman students who completed monthly marijuana use and alcohol consumption surveys. Subjects were classified into data-driven groups based on their alcohol and marijuana consumption. A linear mixed-model (LMM) was employed using this grouping factor to predict grade point average (GPA), adjusted for a variety of socio-demographic and clinical factors. RESULTS: Three data-driven clusters emerged: 1) No/low users of both, 2) medium-high alcohol/no-low marijuana, and 3) medium-high users of both substances. Individual cluster derivations between consecutive semesters remained stable. No significant interaction between clusters and semester (time) was noted. Post-hoc analysis suggest that at the outset, compared to sober peers, students using moderate to high levels of alcohol and low marijuana demonstrate lower GPAs, but this difference becomes non-significant over time. In contrast, students consuming both substances at moderate-to-high levels score significantly lower at both the outset and across the 2-year investigation period. Our follow-up analysis also indicate that when students curtailed their substance use over time they had significantly higher academic GPA compared to those who remained stable in their substance use patterns over the two year period. CONCLUSIONS: Overall, our study validates and extends the current literature by providing important implications of concurrent alcohol and marijuana use on academic achievement in college.

Composite impulsivity-related domains in college students.

Impulsivity is a complex, multidimensional construct with prior theoretically and empirically derived characterizations of impulsivity-related behaviors varying considerably among studies. We assessed college students (N = 440) longitudinally with five impulsivity-related self-reported assessments and two computerized behavioral measures. Using a combination of exploratory and confirmatory factor analysis (CFA), we derived then validated several composite impulsivity-related domains (CIRDs). These factors replicated, in large part, findings from a previous study conducted by our group in an independent sample that used a similar analytical approach. The four CIRDs derived in current study are: 'Impulsive action', 'Approach/Appetite Motivation', 'Impulsivity/Compulsivity' and 'Experience and thrill seeking/Fearlessness'. Subsequent psychometric analyses found these CIRDs were relatively stable over the two-year period. Moreover, multiple regression analysis found that CIRD profiles associated with clinical and behavioral characteristics including anxiety, depression, attention deficit hyperactivity disorder and substance use symptomology. Overall, our data suggest that empirically-derived CIRDs have potential for organizing previous impulsivity-related constructs into a more naturalistic framework where distinct constructs are often expressed together in the same individuals. This framework might facilitate future research of neuropsychiatric disorder risk and etiology.

A Preliminary Prospective Study of an Escalation in 'Maximum Daily Drinks', Fronto-Parietal Circuitry and Impulsivity-Related Domains in Young Adult Drinkers.

Excessive alcohol use in young adults is associated with greater impulsivity and neurobiological alterations in executive control systems. The maximum number of drinks consumed during drinking occasions ('MaxDrinks') represents a phenotype linked to vulnerability of alcohol use disorders, and an increase, or 'escalation', in MaxDrinks may be indicative of greater risk for problematic drinking. Thirty-six young adult drinkers performed a Go/No-Go task during fMRI, completed impulsivity-related assessments, and provided monthly reports of alcohol use during a 12-month follow-up period. Participants were characterized by MaxDrinks at baseline and after follow-up, identifying 18 escalating drinkers and 18 constant drinkers. Independent component analysis was used to investigate functional brain networks associated with response inhibition, and relationships with principal component analysis derived impulsivity-related domains were examined. Greater baseline MaxDrinks was associated with an average reduction in the engagement of a right-lateralized fronto-parietal functional network, while an escalation in MaxDrinks was associated with a greater difference in fronto-parietal engagement between successful inhibitions and error trials. Escalating drinkers displayed greater impulsivity/compulsivity-related domain scores that were positively associated with fronto-parietal network engagement and change in MaxDrinks during follow-up. In young adults, an escalating MaxDrinks trajectory was prospectively associated with altered fronto-parietal control mechanisms and greater impulsivity/compulsivity scores. Continued longitudinal studies of MaxDrinks trajectories, functional network activity, and impulsivity/compulsivity-related features may lend further insight into an intermediate phenotype vulnerable for alcohol use and addictive disorders.

fMRI response during figural memory task performance in college drinkers.

RATIONALE: Eighteen- to twenty-five-year-olds show the highest rates of alcohol use disorders (AUD) and heavy drinking, which may have critical neurocognitive implications. Regions subserving memory may be particularly susceptible to alcohol-related impairments. OBJECTIVE: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine the neural correlates of visual encoding and recognition among heavy-drinking college students. We predicted that heavy drinkers would show worse memory performance, increased frontal/parietal activation, and decreased hippocampal response during encoding. METHODS: Participants were 23 heavy drinkers and 33 demographically matched light drinkers, aged 18-20, characterized using quantity/frequency of drinking and AUD diagnosis. Participants performed a figural encoding and recognition task during fMRI. BOLD response during encoding was modeled based on whether each stimulus was subsequently recognized or forgotten (i.e., correct vs. incorrect encoding). RESULTS: There were no group differences in behavioral performance. Compared to light drinkers, heavy drinkers showed (1) greater BOLD response during correct encoding in the right hippocampus/medial temporal, right dorsolateral prefrontal, left inferior frontal, and bilateral posterior parietal cortices; (2) less left inferior frontal activation and greater bilateral precuneus deactivation during incorrect encoding; and (3) less bilateral insula response during correct recognition (clusters >10,233 µl, p < 0.05 whole brain). CONCLUSIONS: This is the first investigation of the neural substrates of figural memory among heavy-drinking older adolescents. Heavy drinkers demonstrated compensatory hyperactivation of memory-related areas during correct encoding, greater deactivation of default mode regions during incorrect encoding, and reduced recognition-related response. Results could suggest use of different encoding and recognition strategies among heavy drinkers.

Functional magnetic resonance imaging (fMRI) response to alcohol pictures predicts subsequent transition to heavy drinking in college students.

BACKGROUND AND AIMS: Young adults show the highest rates of escalating drinking, yet the neural risk mechanisms remain unclear. Heavy drinkers show variant functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to alcohol cues, which may presage increasing drinking. In this longitudinal study, we ascertained whether BOLD response to alcohol pictures predicted subsequent heavy drinking among college students. METHODS: Participants were 43 18-21-year-olds in the United States who underwent BOLD scanning and completed monthly substance use surveys over the following year. Participants were categorized according to baseline and follow-up drinking into 13 continuously moderate drinkers, 16 continuously heavy drinkers and 14 transitioners who drank moderately at baseline but heavily by follow-up. During fMRI scanning at baseline, participants viewed alcohol and matched non-alcohol beverage images. RESULTS: We observed group differences in alcohol cue-elicited BOLD response in bilateral caudate, orbitofrontal cortex, medial frontal cortex/anterior cingulate and left insula (clusters > 2619 ml, voxelwise F(2,40) > 3.23, P < 0.05, whole-brain corrected P < 0.05), where transitioners hyperactivated compared with moderate and heavy drinkers (all Tukey P < 0.05). Exploratory factor analysis revealed a single brain network differentiating those who subsequently increased drinking. Exploratory regressions showed that, compared with other risk factors (e.g., alcoholism family history, impulsivity), BOLD response best predicted escalating drinking amount and alcohol-related problems. CONCLUSIONS: Neural response to pictures of alcohol is substantially enhanced among United States college students who subsequently escalate drinking. Greater cue-reactivity is associated with larger increases in drinking and alcohol-related problems, regardless of other baseline factors. Thus, neural cue-reactivity could uniquely facilitate identifying individuals at greatest risk for future problematic drinking.

A person-centered approach to understanding negative reinforcement drinking among first year college students.

The current study used a person-centered approach (i.e. latent profile analysis) to identify distinct types of college student drinkers based on the predictions of motivational, social learning, and stress and coping theories of maladaptive drinking. A large sample (N=844; 53% female) of first-year undergraduates from two institutions, public and private, who reported consuming one or more drinks in the last three months completed measures of depressive and anxiety symptoms, positive alcohol-outcome expectancies, negative life events, social support, drinking motives, drinking level and drinking-related problems. Latent profile analysis revealed a small subgroup of individuals (n=81, 9%) who conformed to the anticipated high-risk profile; specifically, this group demonstrated high levels of negative affect, coping motives, drinks per week, and drinking-related problems. However, additional groups emerged that showed patterns inconsistent with the proposed vulnerability profile (e.g., high negative affect, positive expectancies, and negative life events, but relatively low drinking levels). Findings from our person-centered approach showing the presence of groups both consistent and inconsistent with the predictions of motivational, social learning, and stress and coping theories highlight the need to identify and target certain college students for prevention and intervention of negative affect-related drinking.

Influence of alcohol use on neural response to Go/No-Go task in college drinkers.

Impaired inhibition of prepotent motor response may represent an important risk factor for alcoholism. Alcohol use may also increase impulsive behavior, including impaired response inhibition. Little is known about the brain function underlying response inhibition among college-age drinkers based on their drinking patterns, despite college-age drinkers demonstrating high rates of alcohol-use disorders. Our major objective was to compare behavior and associated brain activity measured with fMRI during a response-inhibition task in matched heavy- and light-alcohol-drinking college students. Participants were light (N=36) and heavy (N=56) drinkers, aged 18-20 years. We characterized blood oxygen level-dependent (BOLD) responses, while participants performed an fMRI Go/No-Go task to quantify inhibitory behavior and brain activity. Behaviorally, group performance differences were observed for Go correct-hit and No-Go false-alarm reaction times with increased reaction times in heavy compared with light drinkers. During fMRI No-Go correct rejections, light drinkers exhibited greater BOLD response than did heavy drinkers in left supplementary motor area (SMA), bilateral parietal lobule, right hippocampus, bilateral middle frontal gyrus, left superior temporal gyrus, and cingulate gyrus/anterior cingulate cortex (Brodmann area 24). Group differences in Go/No-Go-related regional activations correlated with alcohol- and impulsivity-related measures. These findings suggest that heavy alcohol drinkers may have dysfunction in brain regions underlying attention and response inhibition, leading to diminished abilities to suppress prepotent responding. The extent to which these tendencies relate to impulsive decision-making and behaviors in real-life settings and may guide intervention development warrants additional investigation.