Sleep homeostasis and neural circuitry of risky behavior in adolescents

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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.