Sex, puberty, and the timing of sleep EEG measured adolescent brain maturation

Abstract

The steep adolescent decline in the slow wave (delta, 1-4 Hz) electroencephalogram (EEG) of nonrapid eye movement (NREM) sleep is a dramatic maturational change in brain electrophysiology thought to be driven by cortical synaptic pruning. A perennial question is whether this change in brain electrophysiology is related to sexual maturation. Applying Gompertz growth models to longitudinal data spanning ages 9-18 y, we found that the timing of the delta decline was significantly (P < 0.0001) linked to timing of pubertal maturation. This timing relation remained significant when sex differences in the timing of the delta decline were statistically controlled. Sex differences and the relation to the timing of puberty jointly explained 67% of the between-subject variance in the timing of the delta decline. These data provide a demonstration of a temporal relation between puberty and an electrophysiological marker of adolescent brain development. They can guide research into whether the neuroendocrine events of puberty are mechanistically linked to cortical maturation or whether, instead, the two maturational processes are parallel but independent programs of human ontogenesis. n an ongoing longitudinal study of adolescent sleep EEG, we identified the age range 12-16.5 y as a critical period of late brain maturation (1). Centrally recorded slow wave (delta, 1-4 Hz) EEG power in nonrapid eye movement (NREM) sleep declines by >60% in this 4.5-y range. We (2) and others (3,4) have proposed that the decline in delta power reflects the cortical synaptic pruning discovered by Huttenlocher (5). The decline in delta power also bears importantly on the physiology of sleep regulation because NREM slow wave EEG seems to reflect a recuperative process (6, 7); it increases with prior waking duration and declines across the night.A recurrent question is whether the dramatic changes in sleep electrophysiology during adolescence are related to the concurrent physical changes of puberty. Previous studies have found lower levels of visually scored slow wave sleep (8) or delta power (3) in more sexually mature subjects, but these studies did not control for age. In 2006, we analyzed the data then available from our longitudinal study to examine sleep EEG changes in relation to both age and pubertal maturation (9). We reported a strong relation between the rate of the delta decline and the rate of progression through the Tanner stages of pubertal maturation. However, both rates were strongly related to age. When age was statistically controlled, the relation between delta power and Tanner stage became nonsignificant.Our 2006 article included data only from ages 9-11 and 12-14 y and evaluated the rate of delta decline but not its timing. We are now able to analyze the timing of the relation between the decline in NREM delta EEG power and pubertal maturation in an expanded longitudinal dataset, which now includes ages 9-18 y. These analyses show a highly significant relation between the timing of the delta decline and the timing of pubert...

The Relationship Between Estrogen and the Decline in Delta Power During Adolescence

“…A potential role for an adrenal-derived hormone in the decline in delta power during adolescence was suggested by Campbell et al based on the strong association between the age of most rapid delta decline and the age of most rapid increase in pubic hair in girls. 8 Note that while the same association was observed in the boys in that study, pubic hair develops in boys in response to both testicular and adrenal-derived androgens, whereas in girls with normally-timed puberty, pubic hair typically reflects adrenarche. Furthermore, whereas DHEAS has been shown to act centrally in animal models, 35 in humans, DHEAS in peripheral blood does not easily penetrate the blood brain barrier.…”

“…In studies that included both physician-determined Tanner staging of puberty and PSG sleep studies at 6-month intervals, Campbell et al found that the age of most rapid delta decline was in fact related to the age of most rapid pubertal maturation, favoring a causal role for sex steroids. 8 Further, men with congenital GnRH deficiency who fail to undergo puberty have more SWS than age-matched controls and demonstrate a decrease in SWS after treatment with testosterone, 9,10 providing further support for the hypothesis that sex steroids may modulate sleep staging and depth.…”

The journey through the world of adolescent sleep

“…Additional data from the same subjects (Campbell et al, 2012) showed that although the rate of the delta decline was not associated with the rate of pubertal maturation, the timing of both maturational processes was related -a highly significant relation between the age of most rapid pubertal maturation and the age of most rapid delta decline has been observed. It was also demonstrated that this timing relationship was independent of sex differences, i.e., the earlier delta power decline in girls compared to boys (Campbell et al, 2012). The authors suggest that the timing of cortical synaptic pruning, considered as the most possible cause of delta decline, is strongly related to the timing of puberty.…”

Out of synch with society

“…The steep decline in slow-wave sleep at around the time of puberty is considered a milestone in physiological brain maturation [48]. This is a critical window during which DSPD symptoms can emerge, which could be taken as circumstantial theory that changes in sleep homeostatic factors, and their differential emergence during puberty, may also play a role in the disorder's pathophysiology [49].…”