Alcohol, Sleep and Brain Development

描述（由申请人提供）：本提案是对RFA的回应，旨在评估对酒精暴露对青少年大脑发育的影响进行纵向评估的可行性。儿童和青少年在大脑继续发育的时候酗酒是一个重大的健康风险，对发育中的神经系统的有害慢性影响被低估了。拟议的研究汇集了敏感，安全和非侵入性的方法来表征正常青春期的大脑神经生理学和结构完整性，并估计酒精滥用对发育中的大脑的影响。该提案的独特之处在于使用经典睡眠生理学和诱发的EEG Delta活动作为发育中神经系统的探针，并将其与大脑宏观和微观结构完整性的评估相结合。阐明酒精滥用对青少年中枢神经系统的潜在影响将有助于更好地了解酒精的神经毒性，可能会提供明显的证据来影响青少年的行为，并可能为治疗认知、情感和调节行为发育受损的补偿和康复策略提供见解。该提案有四个具体目标：目标1。从男孩和女孩的大队列中建立两个小的，道德平衡的样本，以证明评估这些队列中酒精和其他物质使用的能力，并对每个样本进行一年的随访。第一组将由20名不喝酒的六年级学生组成。第二组将由10名不喝酒和10名喝酒的9年级学生组成。目标2.通过在队列内和队列之间进行比较，评估年龄增长和青春期激素发育如何与δ活动，N550振幅，δ和N550振幅的额叶化以及认知和情感的功能性大脑测量相关。目标3。通过队列内和队列间的比较，评估年龄增长和青春期激素发育如何与皮质区域灰质体积、白色物质完整性、海马体积和胼胝体大小等脑结构测量值相关。目标4。通过比较饮酒与不饮酒的儿童在年龄较大的队列中，确定酒精暴露对我们在青春期中期大脑发育的各种测量的影响的效应大小。

DESCRIPTION (provided by applicant): 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.