https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(99)01376-8.pdf

Impact of sleep debt on metabolic and endocrine function

OBJECTIVES: To inform the debate over whether human sleep can be chronically reduced without consequences, we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation. DESIGN: The chronic sleep restriction experiment involved randomization to one of three sleep doses (4 h, 6 h, or 8 h time in bed per night), which were maintained for 14 consecutive days. The total sleep deprivation experiment involved 3 nights without sleep (0 h time in bed). Each study also involved 3 baseline (pre-deprivation) days and 3 recovery days. SETTING: Both experiments were conducted under standardized laboratory conditions with continuous behavioral, physiological and medical monitoring. PARTICIPANTS: A total of n = 48 healthy adults (ages 21-38) participated in the experiments. INTERVENTIONS: Noctumal sleep periods were restricted to 8 h, 6 h or 4 h per day for 14 days, or to 0 h for 3 days. All other sleep was prohibited. RESULTS: Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days resulted in significant cumulative, dose-dependent deficits in cognitive performance on all tasks. Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days, and did not significantly differentiate the 6 h and 4 h conditions. Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis--displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights. Comparison of chronic sleep restriction to total sleep deprivation showed that the latter resulted in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost. A statistical model revealed that, regardless of the mode of sleep deprivation, lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h (s.e. 0.73 h). CONCLUSIONS: Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation, it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults. Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits, which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign. Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses, but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions. This suggests that sleep debt is perhaps best understood as resulting in additional wakefulness that has a neurobiological "cost" which accumulates over time.

/pdf/the-cumulative-cost-of-additional-wakefulness-dose-response-3yfrcni48x.pdf

The Cumulative Cost of Additional Wakefulness: Dose-Response Effects on Neurobehavioral Functions and Sleep Physiology From Chronic Sleep Restriction and Total Sleep Deprivation

To determine whether a cumulative sleep debt (in a range commonly experienced) would result in cumulative changes in measures of waking neurobehavioral alertness, 16 healthy young adults had their sleep restricted 33% below habitual sleep duration, to an average 4.98 hours per night [standard deviation (SD) = 0.57] for seven consecutive nights. Subjects slept in the laboratory, and sleep and waking were monitored by staff and actigraphy. Three times each day (1000, 1600, and 2200 hours) subjects were assessed for subjective sleepiness (SSS) and mood (POMS) and were evaluated on a brief performance battery that included psychomotor vigilance (PVT), probed memory (PRM), and serial-addition testing, Once each day they completed a series of visual analog scales (VAS) and reported sleepiness and somatic and cognitive/emotional problems. Sleep restriction resulted in statistically robust cumulative effects on waking functions. SSS ratings, subscale scores for fatigue, confusion, tension, and total mood disturbance from the POMS and VAS ratings of mental exhaustion and stress were evaluated across days of restricted sleep (p = 0.009 to p = 0.0001). PVT performance parameters, including the frequency and duration of lapses, were also significantly increased by restriction (p = 0.018 to p = 0.0001). Significant time-of-day effects were evident in SSS and PVT data, but time-of-day did not interact with the effects of sleep restriction across days. The temporal profiles of cumulative changes in neurobehavioral measures of alertness as a function of sleep restriction were generally consistent. Subjective changes tended to precede performance changes by 1 day, but overall changes in both classes of measure were greatest during the first 2 days (P1, P2) and last 2 days (P6, P7) of sleep restriction. Data from subsets of subjects also showed: 1) that significant decreases in the MSLT occurred during sleep restriction, 2) that the elevated sleepiness and performance deficits continued beyond day 7 of restriction, and 3) that recovery from these deficits appeared to require two full nights of sleep. The cumulative increase in performance lapses across days of sleep restriction correlated closely with MSLT results (r = -0.95) from an earlier comparable experiment by Carskadon and Dement (1). These findings suggest that cumulative nocturnal sleep debt had a dynamic and escalating analog in cumulative daytime sleepiness and that asymptotic or steady-state sleepiness was not achieved in response to sleep restriction.

/pdf/cumulative-sleepiness-mood-disturbance-and-psychomotor-3dmt6gtthk.pdf

Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4-5 hours per night

Daytime performance changes were examined during chronic sleep restriction or augmentation and following subsequent recovery sleep. Sixty-six normal volunteers spent either 3 (n = 18), 5 (n= 16), 7 (n = 16), or 9 h (n = 16) daily time in bed (TIB) for 7 days (restriction/augmentation) followed by 3 days with 8 h daily TIB (recovery). In the 3-h group, speed (mean and fastest 10% of responses) on the psychomotor vigilance task (PVT) declined, and PVT lapses (reaction times greater than 500 ms) increased steadily across the 7 days of sleep restriction. In the 7- and 5-h groups speed initially declined, then appeared to stabilize at a reduced level; lapses were increased only in the 5-h group. In the 9-h group, speed and lapses remained at baseline levels. During recovery, PVT speed in the 7- and 5-h groups (and lapses in the 5-h group) remained at the stable, but reduced levels seen during the last days of the experimental phase, with no evidence of recovery. Speed and lapses in the 3-h group recovered rapidly following the first night of recovery sleep; however, recovery was incomplete with speed and lapses stabilizing at a level comparable with the 7- and 5-h groups. Performance in the 9-h group remained at baseline levels during the recovery phase. These results suggest that the brain adapts to chronic sleep restriction. In mild to moderate sleep restriction this adaptation is sufficient to stabilize performance, although at a reduced level. These adaptive changes are hypothesized to restrict brain operational capacity and to persist for several days after normal sleep duration is restored, delaying recovery.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2869.2003.00337.x

Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study

Adequate sleep is essential for general healthy functioning. This paper reviews recent research on the effects of chronic sleep restriction on neurobehavioral and physiological functioning and discusses implications for health and lifestyle. Restricting sleep below an individual's optimal time in bed (TIB) can cause a range of neurobehavioral deficits, including lapses of attention, slowed working memory, reduced cognitive throughput, depressed mood, and perseveration of thought. Neurobehavioral deficits accumulate across days of partial sleep loss to levels equivalent to those found after 1 to 3 nights of total sleep loss. Recent experiments reveal that following days of chronic restriction of sleep duration below 7 hours per night, significant daytime cognitive dysfunction accumulates to levels comparable to that found after severe acute total sleep deprivation. Additionally, individual variability in neurobehavioral responses to sleep restriction appears to be stable, suggesting a traitlike (possibly genetic) differential vulnerability or compensatory changes in the neurobiological systems involved in cognition. A causal role for reduced sleep duration in adverse health outcomes remains unclear, but laboratory studies of healthy adults subjected to sleep restriction have found adverse effects on endocrine functions, metabolic and inflammatory responses, suggesting that sleep restriction produces physiological consequences that may be unhealthy.

Citation:
Banks S; Dinges DF. Behavioral and physiological consequences of sleep restriction. J Clin Sleep Med 2007;3(5):519-528.

/pdf/behavioral-and-physiological-consequences-of-sleep-4kripq40g7.pdf

Behavioral and physiological consequences of sleep restriction

Long-term gradual sleep reduction effects were investigated on 4 young adult collegiate couples. The battery of assessment tools included a sleep log, Stanford Sleepiness Scale, Profile of Mood States, Feeling Tone Checklist, a measure of circadian oral temperature, Williams Word Memory test, Digit Span test, Wilkinson Auditory Vigilance task, Wilkinson Addition task, Minnesota Multiphasic Personality Inventory, Rapid Alternation task, psychiatric and medical examinations, and a subjective effects questionnnaire. It was concluded that 6–8 months of gradual sleep restriction, down to 4.5–5.5 hrs per night, does not result in behavioral effects measurable by the instruments used. Subjective fatigue appears to be the limiting factor in determining tolerability of gradual sleep restriction. At the end of an additional 12-month follow-up period, total sleep time was still 1–2.5 hrs below baseline, but measures of well-being had returned to baseline levels.

Performance and mood during and after gradual sleep reduction.

To determine: 1) the minimum amounts of sleep subjects would tolerate, 2) the changes in EEG sleep measures, and 3) whether subjects would revert to baseline sleep after study termination, 4 couples gradually reduced their sleep. Three couples reduced their TST in 30-min steps from a baseline of 8 hrs and one couple from a baseline of 6.5 hrs. Subjective estimates of sleep time, sleep quality, and mood were collected daily. Home EEG sleep recordings were obtained 3 nights a week.



Two of the 8-hr sleepers reduced their sleep to 5.5 hrs, 2 to 5.0 hrs, and 2 reached 4.5 hrs. These 6 subjects continued sleeping 1 to 2.5 hrs below baseline amounts a year after reduction terminated. The 6.5-hr baseline couple reached 5.0 hrs and returned to 6.5 hrs TST during follow-up.



Stages W, 2, and REM decreased significantly in absolute amounts. Percentage of stages W and 2 also decreased significantly. REM percent remained constant. Stage 3 was constant while stage 4 increased in both absolute and relative amounts. REM cycle length remained constant. Stage 4 rebound on 7-hr nights was not observed during times of greatest sleep reduction. Occurrences of stage REM within 10 min of stage 1 onset were observed in 2 subjects when their TST was below 6.5 hrs.



Our results are consistent with other studies of shortened sleep, indicating that TST is the major determinant of sleep-stage characteristics.

J K Friedmann

Papers

Performance and mood during and after gradual sleep reduction.

Sleep During and After Gradual Sleep Reduction