This proposal is in response to an RFA to evaluate the feasibility of conducting longitudinal assessments of the impact of alcohol exposure on adolescent brain development. Alcohol abuse among children and adolescents at a time when their brains continue to develop is a significant health risk, and the deleterious chronic effects on a developing nervous system are underappreciated. The proposed studies bring together sensitive, safe and noninvasive approaches to characterize brain neurophysiology and structural integrity during normal adolescence and to estimate the effect of alcohol abuse on the developing brain. Unique to this proposal are the use of classical sleep physiology and evoked EEG delta activity as probes of the developing nervous system and their integration with assessment of brain macro- and micro-structural integrity. Elucidation of the insidious central nervous system effects of alcohol abuse among adolescents will lead to better understanding of alcohol neurotoxicity may provide demonstrable evidence to influence adolescent behavior and may provide insights into compensatory and rehabilitative strategies for treating impaired cognitive, emotional and regulatory behavioral development. The proposal has four specific aims:
Aim 1. Establish two small, ethically balanced samples from large cohorts of boys and girls, to demonstrate the capacity to evaluate alcohol and other substance use in these cohorts, and follow each for one year. The first will consist of 20 non-drinking 6th graders. The second will consist of 10 non-drinking and 10 drinking 9th graders.
Aim 2. By comparing within and between cohorts, evaluate how advancing age and pubertal hormonal development are correlated with functional brain measures of delta activity, N550 amplitude, frontalization of delta and N550 amplitude, and cognition and emotion.
Aim 3. By comparing within and between cohorts, evaluate how advancing age and pubertal hormonal development are correlated with structural brain measures of cortical regional gray matter volume, white matter integrity, hippocampal volume, and corpus callosum size.
Aim 4. By comparing drinking with non-drinking children in the older cohort, determine the effect sizes of the measured influence of alcohol exposure on our various measures of brain development in mid-adolescence. ? ? ?
