Abstract Introduction We examined the impact of acute sleep restriction and circadian misalignment on reaction times in adolescents. Methods Adolescents (n=38, 21 girls) aged 14.1-18.0 years completed a 14-day protocol. On days 1-7, participants slept at home on individualized 10-h sleep/dark schedules. On days 8-14, they lived in the laboratory. On day 8, Dim Light Melatonin Onset (DLMO) was measured. On Days 9-13, sleep opportunity was restricted to 8.5h (n=9), 7h (n=12), or 5.5h (n=8). A fourth group was not sleep restricted a had a 10-h sleep opportunity (control; n=9). On days 11-13, sleep/dark gradually shifted earlier with morning bright light to advance circadian rhythms. Final DLMO was measured on day 14. Participants completed simple reaction time tasks on days 5 (baseline), 11 (after 2 sleep restriction (SR) nights = post-SR), and 13 (after 2 shifted sleep/dark nights = post-shift). Testing began 2.5h, 5.5h, 8.5h, and 11.5h after wake. Daily difference from baseline scores for post-SR lapses, median reaction time (MedRT), mean 1/RT (responses/sec), fastest 10% RT (F10), and slowest 10% 1/RT (S10) were compared between sleep opportunity groups. Final temperature minimum (Tmin) was estimated post-hoc (Final DLMO+7h). Tmin 2-4h before wake defined an aligned subgroup (N=16) and Tmin after wake defined a misaligned subgroup (N=10). Post-SR scores (day 11) were subtracted from post-shift scores (day 13) at corresponding times relative to wake. Aligned and misaligned subgroups were compared to determine the of impact circadian misalignment. Results Lapses [F(3,34)=3.8,p=.02] and MedRT [F(3,34=3.3,p=.03] increased from baseline in a SR-dose-dependent manner. Lapses and MedRT increased more with 7hSR (lapsesΔ=19.4±9.1; MedRTΔ=80.7±51.4 msec) and 5.5hSR (lapsesΔ=25.8±18.6; MedRTΔ=99.5±74.6 msec) compared to Control (lapsesΔ=5.4±4.8; MedRTΔ=20.8±21.7 msec). Mean 1/RT, F10, and S10 showed similar trends (p’s≤0.1). MedRT slowed [t(24)=2.24,p=0.04] and response rate decreased (Mean 1/RT: t(24)=2.06,p=.05; S10: t(24)=2.16,p=.04) in the misaligned compared to the aligned group 2.5h after wake. Conclusion Attention decrements occurred when sleep was restricted to 5.5h or 7h, the latter being a typical sleep opportunity for high school students. Circadian misalignment also contributed to decrements in morning attention, which has major implications for safety during the school commute and academics. Support (if any) R01 HL146772 (Crowley)
Many adolescents fall asleep too late to obtain sufficient sleep on school nights. Bright morning light can advance circadian rhythms, facilitating earlier sleep times and longer sleep. We are testing whether these interventions can improve executive functions in late and short-sleeping adolescents attending high school. So far, 32 healthy adolescents (14.6-17.9 years; 16 female) completed a four-week study, in which they were randomly assigned to a control (n=17) or intervention (n=15) group. Following two weeks of usual home sleep, participants lived in the lab for a weekend. On Friday night, a 9-h sleep opportunity ended at average school-day wake. On Saturday (09:00, 10:00, or 12:30) participants completed five measures from the Delis-Kaplan Executive Function System (D-KEFS), a paper-and-pencil neuropsychological battery that assesses components of executive function. During the subsequent two weeks, intervention participants were assigned earlier school-night bedtimes; 1-h and 2-h advance during weeks three and four, respectively. During the intervening weekend, intervention participants received 2.5h intermittent bright light from light boxes (~6000lux) on both mornings in the laboratory to advance circadian rhythms. The control group was not given instruction about bedtimes and did not receive morning bright light. The D-KEFS was repeated during the Saturday of a final lab weekend at the same time as before. Time-by-group interactions from repeated measures ANOVAs are reported. Color Word inhibition performance improved in the intervention group, but not in the control group, F(1, 30)=5.05, p=.03. Design Fluency scores increased in both groups, but more in the intervention group, F(1, 31)=4.68, p=.04. Circadian phase advanced 50 mins, sleep onset advanced 89 mins, and total sleep time increased 68 mins in the intervention group, but remained unchanged in the control group (see companion abstract by Crowley et al). Two weeks of advancing circadian rhythms and bedtimes (making them earlier) and increasing sleep duration in adolescents produced better executive functioning performance in the domains of inhibition and visual creativity. These data have implications for academic performance and healthy decision making in adolescents. R01HL105395 (S.J.C.)
To produce a compromise circadian phase position for permanent night shift work in which the sleepiest circadian time is delayed out of the night work period and into the first half of the day sleep period. This is predicted to improve night shift alertness and performance while permitting adequate late night sleep on days off. Between-subjects. Home and laboratory. 24 healthy subjects. Subjects underwent 3 simulated night shifts, 2 days off, and 4 more night shifts. Experimental subjects received five, 15 minute bright light pulses from light boxes during night shifts, wore dark sunglasses when outside, slept in dark bedrooms at scheduled times after night shifts and on days off, and received outdoor afternoon light exposure (the "light brake"). Control subjects remained in normal room light during night shifts, wore lighter sunglasses, and had unrestricted sleep and outdoor light exposure. The final dim light melatonin onset (DLMO) of the experimental group was ~04:30, close to our target compromise phase position, and significantly later than the control group at ~00:30. Experimental subjects performed better than controls, and slept for nearly all of the allotted time in bed. By the last night shift, they performed almost as well during the night as during daytime baseline. Controls demonstrated pronounced performance impairments late in the night shifts, and exhibited large individual differences in sleep duration. Relatively inexpensive and feasible interventions can produce adaptation to night shift work while still allowing adequate nighttime sleep on days off.
The timing of the circadian clock, circadian period and chronotype varies among individuals. To date, not much is known about how these parameters vary over time in an individual. We performed an analysis of the following five common circadian clock and chronotype measures: 1) the dim light melatonin onset (DLMO, a measure of circadian phase), 2) phase angle of entrainment (the phase the circadian clock assumes within the 24-h day, measured here as the interval between DLMO and bedtime/dark onset), 3) free-running circadian period (tau) from an ultradian forced desynchrony protocol (tau influences circadian phase and phase angle of entrainment), 4) mid-sleep on work-free days (MSF from the Munich ChronoType Questionnaire; MCTQ) and 5) the score from the Morningness–Eveningness Questionnaire (MEQ). The first three are objective physiological measures, and the last two are measures of chronotype obtained from questionnaires. These data were collected from 18 individuals (10 men, eight women, ages 21–44 years) who participated in two studies with identical protocols for the first 10 days. We show how much these circadian rhythm and chronotype measures changed from the first to the second study. The time between the two studies ranged from 9 months to almost 3 years, depending on the individual. Since the full experiment required living in the laboratory for 14 days, participants were unemployed, had part-time jobs or were freelance workers with flexible hours. Thus, they did not have many constraints on their sleep schedules before the studies. The DLMO was measured on the first night in the lab, after free-sleeping at home and also after sleeping in the lab on fixed 8-h sleep schedules (loosely tailored to their sleep times before entering the laboratory) for four nights. Graphs with lines of unity (when the value from the first study is identical to the value from the second study) showed how much each variable changed from the first to the second study. The DLMO did not change more than 2 h from the first to the second study, except for two participants whose sleep schedules changed the most between studies, a change in sleep times of 3 h. Phase angle did not change by more than 2 h regardless of changes in the sleep schedule. Circadian period did not change more than 0.2 h, except for one participant. MSF did not change more than 1 h, except for two participants. MEQ did not change more than 10 points and the categories (e.g. M-type) did not change. Pearson's correlations for the DLMO between the first and second studies increased after participants slept in the lab on their individually timed fixed 8-h sleep schedules for four nights. A longer time between the two studies did not increase the difference between any of the variables from the first to the second study. This analysis shows that the circadian clock and chronotype measures were fairly reproducible, even after many months between the two studies.
Abstract Introduction Previous work shows an association between afternoon bright light exposure and early circadian phase in adults (Van der Maren et al, 2018; Wilson et al, 2018). Our phase response curve (PRC) to bright light in adolescents also suggests a novel phase advancing region in the afternoon (Crowley & Eastman, 2017). Here, we examined phase shifts in response to bright light timed in the afternoon. Methods So far, 30 older adolescents (15F) aged 18.3-20.9 years completed a 13-day protocol during the academic year. On days 1-7 (baseline), participants kept a 9-h individualized sleep schedule at home and then lived in the lab on days 8-13. On day 8, baseline Dim Light Melatonin Onset (DLMO) was measured. After one night (day 9) on their individualized 9-h sleep schedules, sleep/dark advanced by 1h each day on days 10-12. The afternoon bright light (ABL) group (n=18) received 3h of bright intermittent light (four 45-min bright light exposures (8512±795 lux) alternated with 15-min room light exposures (43±24 lux)) in the afternoon on 3 days (days 10-12). Day 10 bright light began 5h after baseline wake time, with the goal of timing bright light 4-7h before baseline DLMO. Subsequent exposures were advanced by 1h daily. The room light (RL) group completed the same protocol, except they remained in room light throughout. Final DLMO was assessed on day 13. Results Both the RL and ABL group displayed a phase advance (0.8±0.6; 0.9±0.6, respectively), but groups did not differ [t(27)=0.13, p=0.90]. Post-hoc analysis revealed that participants whose day 10 light exposure ended within the target afternoon phase advancing region (4-7h before baseline DLMO) advanced more (1.0±0.2, n=13) than individuals whose day 10 bright light ended closer in time to baseline DLMO (0.4±0.1, n=5) [t(16)=2.11, p=0.05]. Conclusion Gradually shifting sleep/dark earlier over 3 days advanced circadian phase by ~1h, and the administration of afternoon bright light did not significantly increase the magnitude of this advance. Afternoon bright light timing, however, may have been too late in some adolescents. Ambient light history and sleep quality will be examined as other potential causes for the insignificant difference. Support (if any) R01HL151512 (Crowley)
Disturbed sleep and on‐the‐job sleepiness are widespread problems among night shift workers. The pineal hormone melatonin may prove to be a useful treatment because it has both sleep‐promoting and circadian phase‐shifting effects. This study was designed to isolate melatonin’s sleep‐promoting effects, and to determine whether melatonin could improve daytime sleep and thus improve night time alertness and performance during the night shift. The study utilized a placebo‐controlled, double‐blind, cross‐over design. Subjects ( n =21, mean age=27.0 ± 5.0 years) participated in two 6‐day laboratory sessions. Each session included one adaptation night, two baseline nights, two consecutive 8‐h night shifts followed by 8‐h daytime sleep episodes and one recovery night. Subjects took 1.8 mg sustained‐release melatonin 0.5 h before the two daytime sleep episodes during one session, and placebo before the daytime sleep episodes during the other session. Sleep was recorded using polysomnography. Sleepiness, performance, and mood during the night shifts were evaluated using the multiple sleep latency test (MSLT) and a computerized neurobehavioral testing battery. Melatonin prevented the decrease in sleep time during daytime sleep relative to baseline, but only on the first day of melatonin administration. Melatonin increased sleep time more in subjects who demonstrated difficulty in sleeping during the day. Melatonin had no effect on alertness on the MSLT, or performance and mood during the night shift. There were no hangover effects from melatonin administration. These findings suggest that although melatonin can help night workers obtain more sleep during the day, they are still likely to face difficulties working at night because of circadian rhythm misalignment. The possibility of tolerance to the sleep‐promoting effects of melatonin across more than 1 day needs further investigation.
The rationale for the treatment of sleep disorders by scheduled exposure to bright light in seasonal affective disorder, jet lag, shift work, delayed sleep phase syndrome, and the elderly is, in part, based on a conceptual framework developed by nonclinical circadian rhythm researchers working with humans and other species. Some of the behavioral and physiological data that contributed to these concepts are reviewed, and some pitfalls related to their application to bright light treatment of sleep disorders are discussed. In humans and other mammals the daily light-dark (LD) cycle is a major synchronizer responsible for entrainment of circadian rhythms to the 24-h day, and phase response curves (PRCs) to light have been obtained. In humans, phase delays can be induced by light exposure scheduled before the minimum of the endogenous circadian rhythm of core body temperature (CBT), whereas phase advances are induced when light exposure is scheduled after the minimum of CBT. Since in healthy young subjects the minimum of CBT is located approximately 1 to 2 h before the habitual time of awakening, the most sensitive phase of the PRC to light coincides with sleep, and the timing of the monophasic sleep-wake cycle itself is a major determinant of light input to the pacemaker. The effects of light are mediated by the retinohypothalamic tract, and excitatory amino acids play a key role in the transduction of light information to the suprachiasmatic nuclei. LD cycles have direct "masking" effects on many variables, including sleep, which complicates the assessment of endogenous circadian phase and the interpretation of the effects of light treatment on sleep disorders. In some rodents motor activity has been shown to affect circadian phase, but in humans the evidence for such a feedback of activity on the pacemaker is still preliminary. The endogenous circadian pacemaker is a major determinant of sleep propensity and sleep structure; these, however, are also strongly influenced by the prior history of sleep and wakefulness. In healthy young subjects, light exposure schedules that do not curtail sleep but induce moderate shifts of endogenous circadian phase have been shown to influence the timing of sleep and wakefulness without markedly affecting sleep structure.
Advanced and delayed sleep phase disorders, and the hypersomnia that can accompany winter depression, have been treated successfully by appropriately timed artificial bright light exposure. Under entrainment to the 24-h day-night cycle, the sleep-wake pattern may assume various phase relationships to the circadian pacemaker, as indexed, for example, by abnormally long or short intervals between the onset of melatonin production or the core body temperature minimum and wake-up time. Advanced and delayed sleep phase syndromes and non-24-h sleep-wake syndrome have been variously ascribed to abnormal intrinsic circadian periodicity, deficiency of the entrainment mechanism, or—most simply—patterns of daily light exposure insufficient for adequate phase resetting. The timing of sleep is influenced by underlying circadian phase, but psychosocial constraints also play a major role. Exposure to light early or late in the subjective night has been used therapeutically to produce corrective phase delays or advances, respectively, in both the sleep pattern and circadian rhythms. Supplemental light exposure in fall and winter can reduce the hypersomnia of winter depression, although the therapeutic effect may be less dependent on timing.
'/%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h10080v5040H0z'/%3e%3cpath stroke='%23fff' stroke-width='.6' d='m0 0 6 3m0-3L0 3' clip-path='url(%23b)' transform='scale(840)'/%3e%3cpath stroke='%23e4002b' stroke-width='.4' d='m0 0 6 3m0-3L0 3' clip-path='url(%23c)' transform='scale(840)'/%3e%3cpath stroke='%23fff' stroke-width='840' d='M2520 0v2520M0 1260h5040'/%3e%3cpath stroke='%23e4002b' stroke-width='504' d='M2520 0v2520M0 1260h5040'/%3e%3cg fill='%23fff'%3e%3cuse xlink:href='%23d' x='2520' y='3780'/%3e%3cuse xlink:href='%23a' x='7560' y='4200'/%3e%3cuse xlink:href='%23a' x='6300' y='2205'/%3e%3cuse xlink:href='%23a' x='7560' y='840'/%3e%3cuse xlink:href='%23a' x='8680' y='1869'/%3e%3cuse xlink:href='%23e' x='8064' y='2730'/%3e%3c/g%3e%3c/svg%3e)
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
