Alcohol, Sleep and Brain Development

描述（由申请人提供）：本提案是对一项RFA的回应，该RFA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。儿童和青少年在他们的大脑还在发育的时候滥用酒精是一个重大的健康风险，而且对发育中的神经系统的有害慢性影响还没有得到重视。拟议的研究将敏感、安全和非侵入性的方法结合在一起，以表征正常青春期的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。这一建议的独特之处在于使用经典睡眠生理学和诱发脑电图δ活动作为发育中的神经系统的探针，并将它们与大脑宏观和微观结构完整性的评估结合起来。阐明青少年酒精滥用对中枢神经系统的潜在影响将有助于更好地了解酒精神经毒性，这可能为影响青少年行为提供可证明的证据，并可能为治疗认知、情绪和调节行为发育受损的代偿和康复策略提供见解。该提议有四个具体目标：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，以证明有能力评估这些队列中酒精和其他物质的使用情况，并对每个样本进行一年的随访。第一组由20名不喝酒的六年级学生组成。第二组将由10名不饮酒和10名饮酒的九年级学生组成。目标2。通过队列内部和队列之间的比较，评估年龄增长和青春期激素发育与脑功能测量的delta活动、N550振幅、delta和N550振幅的额化以及认知和情绪之间的关系。目标3。通过队列内部和队列之间的比较，评估年龄增长和青春期激素发育与大脑皮层区域灰质体积、白质完整性、海马体积和胼胝体大小的结构测量之间的关系。目标4。通过比较年龄较大的饮酒儿童和不饮酒儿童，确定酒精暴露对青春期中期大脑发育的各种测量影响的效应大小。

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.