Sleep homeostasis and neural circuitry of risky behavior in adolescents

青少年的睡眠稳态和危险行为的神经回路

• 批准号: 8880081
• 负责人: Mary M Heitzeg
• 金额: $ 10.18万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8880081
• 关键词: 17 year old; Acoustics; Adolescence; Adolescent; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohol or Other Drugs use; Alcohols; Behavior; Behavioral; Brain; Child; Circadian Rhythms; Corpus striatum structure; Data; Development; Disinhibition; Drug usage; Electroencephalography; Esthesia; Female; Health; Heavy Drinking; Homeostasis; Impulsive Behavior; Impulsivity; Incentives; Incidence; Individual Differences; Intervention; Lead; Male Adolescents; Measures; Mediating; Mediator of activation protein; Proxy; Public Health; Recovery; Recovery of Function; Regulation; Reporting; Rest; Rewards; Risk; Risk Behaviors; Risk-Taking; Sex Characteristics; Sexual Maturation; Sleep; Sleep Deprivation; Staging; Synapses; System; Systems Development; Time; Work; age related; alcohol exposure; analog; base; binge drinking; boys; deprivation; drinking; girls; high risk; high risk drinking; innovation; neural circuit; neural correlate; relating to nervous system; response; sleep onset; sleep regulation; trait; twelfth grade

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.

描述（由申请人提供）：冲动的行为，寻求刺激和冒险是青春期的标志，导致这一群体的饮酒率很高。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典型的冒险行为的基础。然而，青春期也与昼夜节律和睡眠稳态的显著变化有关。NREM睡眠开始后慢波EEG活动（SWA）的初始积累（睡眠基本驱动力的代理）减少，青少年夜间的衰减速度明显慢于年幼的儿童。这种与年龄相关的SWA下降开始于性成熟之前，在11至16岁之间损失约60%的SWA。这些影响在额叶EEG区域中最为明显。此外，青少年启动睡眠晚于稳态睡眠驱动的高峰，因此，改变SWA的恢复功能。这些睡眠变化如何与在这个敏感的发育时期发生的神经改变相互作用的问题尚未被研究。我们建议，减少SWA导致额叶控制系统的不完全恢复，导致皮层下奖励系统的去抑制，并导致行为冲动性增加。本研究将评估30名15-17岁的成年（坦纳5期）青少年男性和女性（15名/组）在SWA剥夺前后的行为冲动和脑功能。大脑功能测量将包括冲动控制和奖励预期期间的激活以及休息状态连接。在整个研究期间，总睡眠时间将保持恒定，并且将使用声学音调来减少SWA活动而不唤醒受试者，从而避免标准睡眠剥夺范例的总睡眠损失/SWA损失混淆。本研究的目的是：1）评估基线额叶SWA功率，冲动和脑功能之间的关系; 2）评估选择性SWA剥夺对冲动和脑功能的影响。考虑到冲动行为的性别差异，另一个探索性的目标是开始评估SWA剥夺是否会影响男孩和女孩的行为冲动性。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，这些行为特征被认为是导致危险饮酒的原因。 青少年。了解这种关系可能会导致干预措施，以提高SWA或使其时间过程正常化，以减少冲动，从而降低该年龄段大量饮酒的风险。鉴于酒精暴露对发育中的大脑的潜在有害影响，这可能对公共卫生产生重大影响。