Sleep homeostasis and neural circuitry of risky behavior in adolescents

描述（由申请人提供）：冲动行为、寻求刺激和冒险是青少年的特征，导致这一群体饮酒的发生率很高。酒精是青少年中最常用的物质，近四分之三的高中毕业生报告在他们的一生中使用酒精，大约四分之一的人报告在过去两周内酗酒。在同一时期，额叶“控制”系统和皮层下“奖励”系统的神经变化都在发生，但成熟的速度不同；这些系统之间的不平衡被认为是青少年典型危险行为的基础。然而，青春期也与昼夜节律和睡眠稳态的显著变化有关。在非快速眼动睡眠（NREM sleep）开始后，慢波脑电图活动（SWA）的初始积累（睡眠的基本驱动力的代表）减少，并且在整个晚上，青少年的衰减速度明显慢于年幼的儿童。这种与年龄相关的SWA下降在性成熟之前就开始了，在11岁到16岁之间，SWA损失了大约60%。这些影响在额叶脑区最为明显。此外，青少年开始睡眠的时间晚于内稳态睡眠驱动的高峰，从而改变了SWA的恢复功能。在这个敏感的发育时期，这些睡眠变化是如何与神经变化相互作用的，这一问题尚未得到研究。我们认为，减少SWA会导致额叶控制系统的不完全恢复，从而导致皮质下奖励系统的去抑制，从而导致行为冲动的增加。本研究将评估30名15-17岁的成年（Tanner阶段5）青少年男女（15人/组）在SWA剥夺前后的行为冲动和大脑功能。脑功能测量将包括在冲动控制和奖励预期以及静息状态连接期间的激活。在整个研究过程中，总睡眠时间将保持不变，在不唤醒受试者的情况下，声学音调将用于减少SWA活动，从而避免标准睡眠剥夺范式的总睡眠损失/SWA损失混淆。本研究的目的是：1)评估基线额侧SWA能力、冲动性和脑功能之间的关系；2)评估选择性SWA剥夺对被试冲动和脑功能的影响。鉴于已知的冲动行为的性别差异，另一个探索性目标是开始评估SWA剥夺对男孩和女孩行为冲动的影响是否不同。这里提出的工作是理解SWA个体差异与冲动行为特征之间关系的关键第一步，冲动行为特征被认为是导致高风险饮酒的原因

DESCRIPTION (provided by applicant): Impulsive behavior, sensation-seeking and risk-taking are hallmarks of adolescence, contributing to a high incidence of drinking in this group. Alcohol is the most commonly used substance among adolescents, with nearly three-quarters of high school seniors reporting alcohol use in their lifetime and approximately one- quarter reporting binge drinking in the past two weeks. During this same period, neural alterations in both the frontal "control" system and subcortical "reward" system are taking place, but are maturing at different rates; an imbalance between these systems has been proposed to underlie adolescent-typical risky behavior. However, adolescence is also associated with significant changes in circadian rhythms and sleep homeostasis. The initial accumulation of slow-wave EEG activity (SWA) after NREM sleep onset (a proxy for the basic drive for sleep) is reduced, and the rate of decay across the night is significantly slower in adolescents than in younger children. This age-related decline in SWA begins prior to sexual maturation, with a loss of approximately 60% of SWA between the ages of 11 and 16. These effects are most evident in frontal EEG regions. Moreover, adolescents initiate sleep later than the peak of homeostatic sleep drive and hence, alter the recovery function of SWA. The issue of how these sleep changes may interact with neural alterations occurring during this sensitive developmental period has not been investigated. We propose that reduced SWA leads to incomplete recovery of the frontal control system, leading to a disinhibition of the subcortical reward system and resulting in increased behavioral impulsivity. This study will assess behavioral impulsivity and brain functioning before and after SWA deprivation in 30 mature (Tanner stage 5) adolescent males and females (15/group) 15-17 years of age. Brain functional measures will include activation during impulse control and reward anticipation as well as resting-state connectivity. Total sleep time will be held constant throughout the study, and acoustic tones will be used to decrease SWA activity without waking subjects, thus avoiding the total sleep loss/SWA loss confound of standard sleep deprivation paradigms. The aims of this study are to: 1) evaluate the relationship between baseline frontal SWA power, impulsivity and brain function; and 2) assess the effect of selective SWA deprivation on impulsivity and brain function within-subjects. Given the known sex differences in impulsive behavior, an additional exploratory aim is to begin to assess whether SWA deprivation affects behavioral impulsivity differently in boys and girls. The work proposed here is a critical first step to understanding the relationship between individual differences in SWA and the impulsive behavioral profile believed to contribute to risky drinking in adolescents. An understanding of this relationship could lead to interventions to enhance SWA or normalize its time course to reduce impulsivity, thereby decreasing risk of heavy drinking in the age range. Given the potential harmful impact of alcohol exposure on the developing brain, this could have major implications for public health.