Carmen Pulido

Adolescent Binge Drinking Linked to Abnormal Spatial Working Memory Brain Activation: Differential Gender Effects

BACKGROUND Binge drinking is prevalent during adolescence, and its effect on neurocognitive development is of concern. In adult and adolescent populations, heavy substance use has been associated with decrements in cognitive functioning, particularly on tasks of spatial working memory (SWM). Characterizing the gender-specific influences of heavy episodic drinking on SWM may help elucidate the early functional consequences of drinking on adolescent brain functioning. METHODS Forty binge drinkers (13 females, 27 males) and 55 controls (24 females, 31 males), aged 16 to 19 years, completed neuropsychological testing, substance use interviews, and an SWM task during functional magnetic resonance imaging. RESULTS Significant binge drinking status × gender interactions were found (p < 0.05) in 8 brain regions spanning bilateral frontal, anterior cingulate, temporal, and cerebellar cortices. In all regions, female binge drinkers showed less SWM activation than female controls, while male bingers exhibited greater SWM response than male controls. For female binge drinkers, less activation was associated with poorer sustained attention and working memory performances (p < 0.025). For male binge drinkers, greater activation was linked to better spatial performance (p < 0.025). CONCLUSION Binge drinking during adolescence is associated with gender-specific differences in frontal, temporal, and cerebellar brain activation during an SWM task, which in turn relate to cognitive performance. Activation correlates with neuropsychological performance, strengthening the argument that blood oxygen level-dependent activation is affected by alcohol use and is an important indicator of behavioral functioning. Females may be more vulnerable to the neurotoxic effects of heavy alcohol use during adolescence, while males may be more resilient to the deleterious effects of binge drinking. Future longitudinal research will examine the significance of SWM brain activation as an early neurocognitive marker of alcohol impact to the brain on future behaviors, such as driving safety, academic performance, and neuropsychological performance.

Neural activation during inhibition predicts initiation of substance use in adolescence.

BACKGROUND Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement. METHODS Thirty eight adolescents from local area middle schools, ages 12-14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n=21), or as healthy controls (CON; n=17). RESULTS At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p<.01, each cluster ≥32 contiguous voxels). CONCLUSIONS These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use.

Binge drinking differentially affects adolescent male and female brain morphometry

RationaleAdolescent binge drinking is concerning, as important neurodevelopments occur during this stage. Previous research suggests that binge drinking may disrupt typical brain development, and females may be particularly vulnerable.ObjectivesWe used magnetic resonance imaging (MRI) to examine cortical thickness in adolescent females and males with and without histories of binge drinking.MethodsParticipants (N = 59) were 16–19-year-old adolescents recruited from local schools. Recent binge drinkers (n = 29, 48% female) were matched to non-drinkers (n = 30, 50% female) on age, gender, pubertal development, and familial alcoholism. Participants completed a neuropsychological battery and MRI session. Cortical surfaces were reconstructed with FreeSurfer.ResultsBinge × gender interactions (p < .05) were seen for cortical thickness in four left frontal regions: frontal pole, pars orbitalis, medial orbital frontal, and rostral anterior cingulate. For all interactions, female bingers had thicker cortices than female controls, while male bingers had thinner cortices than male controls. Thicker left frontal cortices corresponded with poorer visuospatial, inhibition, and attention performances for female bingers (r = −0.69 to 0.50, p < 0.05) and worse attention for male bingers (r = −0.69, p = 0.005).ConclusionsAdolescent females with recent binge drinking showed ~8% thicker cortices in left frontal regions than demographically similar female non-drinkers, which was linked to worse visuospatial, inhibition, and attention performances. In contrast, adolescent binge-drinking males showed ~7% thinner cortices in these areas than non-drinking males. These cross-sectional data suggest either different gray matter risk factors for males as for females toward developing heavy drinking, or differential adverse sequelae.

Frontoparietal connectivity in substance-naive youth with and without a family history of alcoholism.

Frontoparietal connections underlie key executive cognitive functions. Abnormalities in the frontoparietal network have been observed in chronic alcoholics and associated with alcohol-related cognitive deficits. It remains unclear whether neurobiological differences in frontoparietal circuitry exist in substance-naïve youth who are at-risk for alcohol use disorders. This study used functional connectivity magnetic resonance imaging and diffusion tensor imaging to examine frontoparietal connectivity and underlying white matter microstructure in 20 substance-naïve youth with a family history of alcohol dependence and 20 well-matched controls without familial substance use disorders. Youth with a family history of alcohol dependence showed significantly less functional connectivity between posterior parietal and dorsolateral prefrontal seed regions (ps<.05), as compared to family history negative controls; however, they did not show differences in white matter architecture within tracts subserving frontoparietal circuitry (ps>.34). Substance-naïve youth with a family history of alcohol dependence show less frontoparietal functional connectivity in the absence of white matter microstructural abnormalities as compared to youth with no familial risk. This may suggest a potential neurobiological marker for the development of substance use disorders.

Alcohol cue reactivity task development.

BACKGROUND The physiological and cognitive reactions provoked by alcohol cues, as compared to non-alcohol cues, can predict future drinking. Alcohol cue reactivity tasks have been developed; however, most were created for use with alcohol use disordered individuals and utilize limited or only partially standardized stimuli. This project systematically created an alcohol cue reactivity task for studies with non-drinkers, using well-characterized stimuli. OBJECTIVES We comprehensively standardized 60 alcohol and 60 non-alcohol beverage pictures using ratings from young non-drinkers (N=82) on affective and perceptual features. RESULTS A statistical matching approach yielded 26 matched alcohol-non-alcohol picture pairs matched on valence, arousal, image complexity, brightness, and hue. The task was piloted and further refined to 22 picture pairs. An 8-minute, 32-second event-related task was created using a random stimulus function for optimized condition timing and systematic presentation of the images. CONCLUSIONS The long-term objectives of this project are to utilize this task with non-drinking youth to investigate how reactivity to alcohol stimuli may predict alcohol use initiation and escalation, to help identify the role of exposure to alcohol stimuli on the subsequent development of alcohol-related problems.

Heavy drinking relates to positive valence ratings of alcohol cues

A positive family history of alcohol use disorders (FH) is a robust predictor of personal alcohol abuse and dependence. Exposure to problem‐drinking models is one mechanism through which family history influences alcohol‐related cognitions and drinking patterns. Similarly, exposure to alcohol advertisements is associated with alcohol involvement and the relationship between affective response to alcohol cues and drinking behavior has not been well established. In addition, the collective contribution that FH, exposure to different types of problem‐drinking models (e.g. parents, peers) and personal alcohol use have on appraisal of alcohol‐related stimuli has not been evaluated with a large sample. We investigated the independent effects of FH, exposure to problem‐drinking models and personal alcohol use on valence ratings of alcohol pictures in a college sample. College students (n = 227) completed measures of personal drinking and substance use, exposure to problem‐drinking models, FH and ratings on affective valence of 60 alcohol pictures. Greater exposure to non‐familial problem‐drinkers predicted greater drinking among college students (β = 0.17, P < 0.01). However, personal drinking was the only predictor of valence ratings of alcohol pictures (β = −0.53, P < 0.001). Personal drinking level predicted valence ratings of alcohol cues over and above FH, exposure to problem‐drinking models and demographic characteristics. This suggests that positive affective responses to alcohol pictures are more a function of personal experience (i.e. repeated heavy alcohol use) than vicarious learning.

Changes in alcohol-related brain networks across the first year of college: A prospective pilot study using fMRI effective connectivity mapping

The upsurge in alcohol use that often occurs during the first year of college has been convincingly linked to a number of negative psychosocial consequences and may negatively affect brain development. In this longitudinal functional magnetic resonance imaging (fMRI) pilot study, we examined changes in neural responses to alcohol cues across the first year of college in a normative sample of late adolescents. Participants (N=11) were scanned three times across their first year of college (summer, first semester, second semester), while completing a go/no-go task in which images of alcoholic and non-alcoholic beverages were the response cues. A state-of-the-art effective connectivity mapping technique was used to capture spatiotemporal relations among brain regions of interest (ROIs) at the level of the group and the individual. Effective connections among ROIs implicated in cognitive control were greatest at the second assessment (when negative consequences of alcohol use increased), and effective connections among ROIs implicated in emotion processing were lower (and response times were slower) when participants were instructed to respond to alcohol cues compared to non-alcohol cues. These preliminary findings demonstrate the value of a prospective effective connectivity approach for understanding adolescent changes in alcohol-related neural processes.

Adolescent heavy drinkers' amplified brain responses to alcohol cues decrease over one month of abstinence

INTRODUCTION Heavy drinking during adolescence is associated with increased reactivity to alcohol related stimuli and to differential neural development. Alcohol cue reactivity has been widely studied among adults with alcohol use disorders, but little is known about the neural substrates of cue reactivity in adolescent drinkers. The current study aimed to identify changes in blood-oxygen level dependent (BOLD) signal during a cue reactivity task pre- and post-monitored abstinence from alcohol. METHOD Demographically matched adolescents (16.0-18.9 years, 54% female) with histories of heavy episodic drinking (HD; n=22) and light or non-drinking control teens (CON; n=16) were recruited to participate in a month-long study. All participants completed a functional Magnetic Resonance Imaging (fMRI) scan with an alcohol cue reactivity task and substance use assessments at baseline and after 28 days of monitored abstinence from alcohol and drugs (i.e., urine toxicology testing every 48-72 h). Repeated-measure analysis of variance (ANOVA) examined main effects of group, time, and group×time interactions on BOLD signal response in regions of interest defined by functional differences at baseline. RESULTS The HD group exhibited greater (p<.01) BOLD activation than CON to alcohol cues relative to neutral cues in all regions of interest (ROIs; bilateral striatum/globus pallidus, left anterior cingulate, bilateral cerebellum, and parahippocampal gyrus extending to the thalamus/substantia nigra) across time points. Group×time effects showed that HD exhibited greater BOLD activation to alcohol cues than CON at baseline in left anterior cingulate cortex and in the right cerebellar region, but these decreased to non-significance after one month of monitored abstinence. CONCLUSIONS In all ROIs examined, HD exhibited greater BOLD response than CON to alcohol relative to neutral beverage picture cues at baseline, indicating heightened cue reactivity to alcohol cues in heavy drinking adolescents prior to the onset of any alcohol use diagnosis. Across the majority of these brain regions, differences in BOLD response were no longer apparent following a month of abstinence, suggesting a decrease in alcohol cue reactivity among adolescent non-dependent heavy drinkers as a consequence of abstaining from alcohol. These results highlight the malleability of adolescent brain function despite no formal intervention targeting cue reactivity. Increased understanding of the neural underpinnings of cue reactivity could have implications for prevention and intervention strategies in adolescent heavy alcohol users.