Lindsay M. Squeglia, Ph.D. - US grants

DESCRIPTION (provided by applicant): Rationale: Substantial numbers of adolescents engage in moderate to heavy levels of alcohol consumption. Specifically, 44% of 12th graders have used alcohol in past month, and 26% have engaged in a binge drinking episode in the past two weeks (Johnston et al., 2008). Identifying the influence of adolescent alcohol use on brain functioning is important, as decrements incurred during ongoing neuromaturation could have lasting effects on cognitive functioning and future educational and occupational options. Visual working memory (VWM) is an essential component of information processing and executive functioning, and is therefore a useful probe for examining neural abnormalities associated with heavy adolescent drinking. Design: The aims of this investigation are: (1) to prospectively examine brain response to a VWM task in adolescents who transition into heavy drinking (n = 22) versus youth who remain non-users (n = 22) using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), and (2) examine if these neural abnormalities are associated with neuropsychological functioning. The proposed study uses data collected as part ofthe Sponsor's longitudinal study (fMRI and Cognition in Youth at Risk for Alcoholism, ROI AAI3419, 6/10/07-3/31/12), using data from 12-16 year-olds imaged prior to the onset of drinking as well as follow-up data collected after half transitioned to heavy drinking. Analyses employ Analysis of Functional Neuroimaging (AFNI) tools and conduct a group x time ANOVA on a priori specified regions of interest (right postcentral/inferior parietal, right middle frontal, bilateral medial frontal, and middle occipital regions) to see if youth who initiate heavy drinking show a change in activation pattern, as compared to youth who remain non-drinkers. Regions that show divergent activation in initiators of heavy drinking will be followed by examining correspondence to performance on neuropsychological measures of VWM and attention among the heavy drinkers (n = 22) in regression analyses. PUBLIC HEALTH RELEVANCE: This investigation will help clarify the effects of alcohol use on brain functioning during adolescence, and aid in understanding whether deficits in VWM result from alcohol involvement. Deficits in VWM could interfere with tasks requiring higher-order executive functioning. The long-term goals of this line of work are to (1) disseminate any findings through adolescent drinking prevention materials and public service campaigns, and (2) inform intervention and psychoeducational programs on how to optimally intervene with youth engaging in heavy drinking, considering brain response and neurocognitive patterns linked to adolescent alcohol use.

DESCRIPTION (provided by applicant): Neuroimaging studies have shown that extensive cortical maturation (e.g., reductions in gray matter cortical thickness) occurs during adolescence, which correspond to more efficient and mature brain functioning. These ongoing maturational processes parallel significant increases in adolescent risk taking, particularly binge drinking (i.e., >4 drinks for females, >5 drinks for males on one occasion), with almost 25% of high school seniors reporting binge drinking in the past 2 weeks [34]. Binge drinking is of great public health concern as it increases an adolescent's likelihood of engaging in other risky behaviors like drunk driving, riding with an impaired driver, violence, unsafe sex, and other substance use [40]. Proclivity to engage in risk taking behaviors such as binge drinking during adolescence appears to have a large neurobiological component, but the link between brain functioning and risky binge drinking has not been clearly defined. Emerging evidence suggests that abnormalities in alcohol-naive adolescents' brain response might contribute to future substance use [41, 63], particularly reaction to tasks of working memory [7, 20, 68]. Understanding the neurological contribution to the initiation or substance use will help disentangle predisposing risk factors from insults incurred due to binge drinking and will help determine appropriate prevention and intervention techniques for adolescents. Therefore, the aim of this investigation is to prospectively examine brain structure using: (1) cortical thickness indices and (2) brain response to a working memory task using fMRI in a sizable longitudinal sample of adolescents (N>120), first studied before they have ever drank alcohol, to see if brain structure and function predispose adolescents to future heavy drinking. This research will clarify the effects of brain structure and functioning on initiating heavy drinking during adolescence, using advanced multimodal imaging techniques, and will identifying neural risk markers to target prevention and intervention efforts.