Sleep Onset. Nighttime Drop in Body Temperature: A Physiological Trigger for Sleep Onset?

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1 Sleep, 20(7): American Sleep Disorders Association and Sleep Research Society Sleep Onset Nighttime Drop in Body Temperature: A Physiological Trigger for Sleep Onset? Patricia J. Murphy and Scott S. Campbell Laboratory of Human Chronobiology, Department of Psychiatry, Cornell University Medical College, White Plains, New York, U,S,A, Summary: Relationships between changes in the slope of the body temperature (BT) and the initiation of sleep were examined in 44 subjects ranging from 19 to 82 years of age, Following an adaptation night, subjects remained in the laboratory for a baseline night and 72 hours in temporal and social isolation, with strictly limited behavioral options ("disentrainment") during which continuous electroencephalograph (EEG) and BT were recorded. Polysomnographic sleep variables (e.g. sleep onset, percentage of each sleep stage) were determined for nighttime sleep periods at baseline and during the disentrainment period. Periods of the BT curve surrounding these sleep bouts were examined for minute to minute changes, and the time at which the maximum rate of decline (MROD) in temperature occurred was compared with the time of sleep onset (SO) and sleep quality parameters. On the baseline night, the MROD occurred, on average, 60 minutes prior to SO. During disentrainment, the MROD occurred, on average, 44 minutes prior to SO. The proximity of MROD to SO did not affect subsequent sleep quality on the baseline night, but during disentrainment, there were significant correlations between the interval from MROD to sleep onset and the amount of slow-wave sleep (SWS) obtained during the sleep bout. There were no significant age differences on variables related to MROD on baseline night, but the timing of both MROD and SO were significantly advanced in older, relative to younger, subjects during the disentrainment period. t is suggested that a rapid decline in core body temperature increases the likelihood of sleep initiation and may facilitate an entry into the deeper stages of sleep. Key Words: Core body temperature-sleep-disentrainment-aging. n healthy young adults, most nighttime sleep episodes occur between 6 hours before and 2 hours after the body temperature (BT) minimum (1,2). While the association between the timing of major sleep episodes and the circadian rhythm of body temperature is well documented, less is known about the nature of the relationship between the initiation of sleep and body temperature. On one hand, it has long been maintained that the changes in activity (e,g. posture) associated with going to bed and the subsequent reduction in metabolism associated with falling asleep result in a decline in BT (3,4). ndeed, this view is supported by considerable objective data (5-7). Yet, few studies have examined BT changes in the interval prior to sleep onset in an effort to determine whether temperature changes may provide a physiological signal that the brain is ready for sleep. Accepted for publication May Address correspondence and requests for reprints to Patricia J. Murphy, Ph.D., The New York Hospital-Cornell Medical Center, 21 Bloomingdale Rd., White Plains, NY 10605, U.S.A. 505 n an earlier study (8) we explored this possibility using a group of elderly subjects whose bedtimes and waketimes were not circumscribed, thus permitting an assessment of the natural relationship between BT and sleep onset (SO). n that study, we found that eight of 10 subjects showed a maximum rate of decline (MROD) in BT prior to their decision to retire (i.e. verbally informing staff that they were "going to bed") and the subsequent initiation of sleep (i.e. polysomnographically defined SO), with an average interval between MROD and SO of 65 minutes. Because those subjects were older and sleep-disturbed, there may be some question as to the generalizability of the findings. The current investigation sought to replicate our previous study in a group of young and old non-sleep-disturbed subjects. n addition, we wished to examine the consistency of the relationship between MROD and sleep initiation without the influence of time cues or social factors in an environment with minimal levels of activity. Thus, the current study was undertaken while subjects lived in temporal and social isolation.

2 506 P. 1. MURPHY AND S. S. CAMPBELL DSENTRANMENT EXPERMENTAL DESGN : ;j ;;:;;;:ad<ip'wion:;::j; 1:,;1 /:: 1:i;1i4SeHnl(;H:+ls;iij.tr!$.ro:erit: :{:;:;:;':;:; ;;;, ';;<,S;; n M., "., ' "'.",,:,.,".,-, iii', ::.' '..< "'.,< :.i '.",,; "..;: o,' '.,vi, \:,";',,<::'.;:., :::.'.,v FG. 1. Schematic of the "disentrainment" experimental protocol. Subjects spent one adaptation night in the laboratory, followed immediately by one baseline night. An electrode montage was placed on the subject by 2200 hours on the baseline night, after which time he or she was aljowed to engage in leisure activities within the laboratory until bedtime. From 0800 hours the following morning, and for the next 72 hours, the subject was in temporal and social isolation and was instructed as follows: "Do not structure your day by eating and sleeping at regular intervals; rather, eat and sleep whenever inclined to do so". Behavioral options were strictly limited in order to facilitate expression of sleep behavior. Procedures METHODS Forty-four subjects (mean age, 41.5 ± 19.1 years, range years; 21 males, 23 females) participated in the study. For some analyses (where noted) a subset of young (n = 17; mean age = 22.9 ± 2.9 years, all <30 years) and old (n = 13; mean age = 67.6 ± 6.1 years, all >60 years) subjects was used. Potential subjects received a physical examination and psychiatric screening [mini-mental status examination (9) and 24-item Hamilton depression rating scale (10) for all subjects, plus geriatric depression scale (11) for old subjects] to exclude from participation those with active, serious medical problems or a current or past history of psychiatric disorder. Minor, controlled medical problems such as mild hypertension or mild arthritis were not grounds for exclusion from the study. On the first night in the laboratory, all subjects over age 60 were screened for sleep pathology including periodic limb movements (PLM) and sleep apnea. A PLM index <5lhour and an apnea index < 1Olhour were necessary for inclusion in the study. n addition, all subjects completed a daily sleep log for 2 weeks prior to study participation. n this log they noted bedtime and waketime each night, the approximate time and duration of awakenings, as well as any daytime naps, and provided a subjective estimate of each night's sleep quality. Only subjects who reported regular, normal sleep patterns (e.g. slept between 6 and 9 hours per night) were included in the study. As shown in Fig. 1, the experimental period con- sisted of an adaptation night and a baseline night, followed immediately by three consecutive days and nights in a "disentrained" environment (12,13). During this time, subjects lived individually in studio apartments isolated from all cues to time of day. Throughout disentrainment, subjects were encouraged to eat and sleep whenever they felt inclined to do so; they were specifically instructed not to try to overcome bouts of sleepiness, but rather to respond to such feelings by taking a nap or major sleep episode. Compliance with these instructions was further encouraged by severely restricting behavioral options during the disentrainment period. Subjects had only a deck of cards, a jigsaw puzzle, and very limited reading material. They were permitted only minimal exercise (e.g. stretching) and were discouraged, both prior to participation and during their time in disentrainment, from doing any physical activity that might keep them awake. This protocol was designed to maximally "unmask" sleep propensity, specifically, to exlude social and temporal constraints that may exert a strong influence on the natural expression of the endogenous sleep system. One important requirement of the disentrainment protocol is that subjects are maintained in a relatively sedentary environment. Consequently, activity levels during disentrainment were consistently low, and most subjects were sitting on the couch or laying in bed a majority of the time. Showers were not permitted during the disentrainment period, and subjects usually wore pajamalike, comfortable clothing throughout the entire 72 hours. n addition, subjects were continuously monitored, thereby ensuring no activities other than those explicitly permitted by the protocol (playing solitaire, working on a jigsaw puzzle). llumination in the isolation suite was provided by desk and floor lamps and did not exceed 100 lux. On the night following adaptation, subjects reported to the laboratory between 2000 hours and 2100 hours (baseline night). Within 30 minutes of their arrival, they inserted indwelling rectal thermistors (Yellow Springs Series 4400, VWR Scientific Products, Cleveland, OH) attached to ambulatory recording devices. Body core temperature was recorded continuously, in 1 minute epochs, throughout the baseline night and the disentrainment period, except for during brief periods for personal hygiene. Electrode placement for polysomnography (electroencephalogram (EEG) sites F3, C3, P3, F4, C4, and P4 referenced to linked mastoids; cross-referenced electrooculogram (EOG) sites; submental electromyogram (EMG) sites) was completed by 2200 hours. As with temperature, EEG, EOG, and EMG were recorded throughout the entire study. These data were acquired using a Biosentry telemetry system (Biosentry, Torrance, CA) that permitted complete free-

3 DROP N BODY TEMPERATURE PROR TO SLEEP 507 dom of movement around the isolation suite. The continuous collection of telemetric data also allowed subjects to sleep anywhere in the isolation suite at any time, without having to plug in a cable to start a sleep recording. Following electrode placement, subjects retired to their isolation suites. That night's sleep, and all subsequent sleep episodes, were initiated and terminated at the subjects' discretion. Electrographic data were transmitted from the telemetry device to an Oxford nstruments 847 Sleep Analyzing Computer for on-line waveform display and storage to optical disk for subsequent scoring and analysis. Recordings from the baseline night throughout the entire 72 hours of disentrainment were scored by trained scorers in 30-second epochs according to standard criteria (14). Sleep onset was defined as the first epoch of stages 2, 3,4, or rapid eye movement (REM) sleep. Data analysis Temperature data sets for the baseline night were generated for each subject. These temperature sets included data from the time of insertion of the rectal thermistor until 0800 hours the following morning. Additional data sets were also generated for the dis entrainment period. Each subject's 72-hour disentrainment period was examined for sleep bouts that met two criteria: 1) they were initiated (i.e. SO occurred) between 2200 and 0600 hours, and 2) they were at least 4 hours in length, with < 1 hour of intervening wake time. A temperature set was then generated that included the 4 hours prior to initiation of each of these sleep bouts, the duration of the sleep bout, and at least 2 hours following the sleep bout. Although of interest (15), results from temperature changes prior to daytime sleep episodes during disentrainment (i.e. initiated outside the hour window) were excluded for the following reasons: 1) examination of all sleep bouts during disentrainment revealed that the average length of sleep periods was 4: 31 (SD 3:09) and that 83% of all sleep bouts 2:4 hours in length were initiated between 2200 and 0600 hours (i.e. only 17% were initiated between 0600 and 2200 hours); 2) there were no baseline data collected during the daytime prior to the disentrainment period that would permit comparison with daytime data from the time-free environment; and 3) altering the criteria to include shorter daytime sleep episodes (i.e. naps) would change the focus of the current paper, as the temperature pattern during the daytime hours, prior to nap sleep, is markedly different from the course of temperature during the nighttime hours prior to nocturnal sleep episodes. Application of the criteria stated above would permit direct comparison with our earlier study (8) \\ 0... '" ;:l,,.., f-<..., \ 37.00,.- \ '- '" 0.. ::;: '" f-< l \ \ -.." * E; ""Z "'c 0...,...,'" $ z:s: C') ",Z CLOCK TME (hr) _c t1..., -'" FG. 2. Sample temperature plot and rate of change curve. These data depict a raw rectal temperature data set (solid line) across an approximately 12-hour period. Temperature data sets for each subject comprised the period from 2 hours prior to sleep onset (SO) through the entire sleep period and 4 hours following termination of the sleep period. The raw data were fitted with a ninth-order polynomial curve. The minute to minute rate of change of the polynomial curve fit was calculated and then superimposed (dotted line) on the raw temperature data. The maximum rate of decline in the rate of change curve (MROD) was determined (denoted by *) and compared with the time at which SO (first epoch of stage 2) occurred (denoted by 6.). This procedure was completed for each baseline night sleep period and for sleep bouts during the disentrainment period that were initiated between 2200 and 0600 hours and were of at least 4 hours' duration with less than hour of intervening wakefulness. Both the baseline and dis entrainment temperature data sets were smoothed using a ninth-order polynomial curve fit. This type of curve fit was chosen because such a procedure does not involve restrictive assumptions about the nature of the data, because polynomial regression reliably accounts for more of the variance in a given data set, and because using this procedure allowed for a closer fit to transient changes in temperature (16). A rate-of-change curve (degrees/ minute) was then generated for each data set to determine the magnitude by which body temperature declined (or increased) from minute to minute. A sample temperature plot, with the corresponding rate-ofchange curve, is shown in Fig. 2. From each rate-of-change curve, the time at which BT declined at its maximum rate could be ascertained. The time at which this MROD occurred was then compared with the time of SO for the corresponding sleep period to determine the MROD to sleep onset interval (Fig. 2). A series of correlation coefficients was generated to examine relationships between MROD, SO, various sleep parameters, and the temperature minimum (Tmin) in closest proximity to each sleep bout. To determine if there were differences between the young and old subjects in sleep quality, or in the relationship between BT and sleep timing, one-way analyses of variance (ANOVAs) for age were performed for the

4 508 P. J. MURPHY AND S. S. CAMPBELL... en 20 u f fo ::J 15 en... 0 "i 10 '" Z SLEEP ONSET T o o L o MROD RELATVE TO SLEEP ONSET (HOURLY NTERVALS) FG. 3. Distribution, in hourly intervals, of timing of the maximum rate of decline (MROD) in body temperature (BT) relative to sleep onset (SO) for sleep baseline night sleep periods. baseline night and disentrainment sleep periods. n addition, to investigate potential differences between the baseline night sleep periods and sleep bouts during disentrainment, paired t tests were performed. RESULTS Baseline night all subjects A verage SO time for all subjects on the baseline night was 2430 hours (SD = 54 minutes). Average MROD time was 2330 hours (SD = 72 minutes). Thus, the average difference between MROD and SO was 60 minutes (SD = 78 minutes). The average nadir of temperature (obtained from the ninth-order polynomial fit) was 0354 hours (SD = 126 minutes) and occurred, on average, 264 minutes (SD = 138 minutes) after MROD. Figure 3 shows the distribution of the timing of MROD relative to SO for each hourly interval for the baseline night sleep periods. The MROD occurred prior to SO in 89% (39/44) of subjects (X2(l) = 13.68, P < 0.001); for 77% (30/39) of those subjects, MROD occurred within the 2 hours prior to sleep onset (X2(2) = lo.74, P < 0.01). f only those subjects whose MROD occurred prior to sleep are considered (i.e. excluding the five subjects whose MROD occurred after SO), the average interval from MROD to SO was 75 minutes (SD = 73 minutes). To examine the relationship between the timing of MROD relative to SO and subsequent sleep quality, the MROD to sleep onset interval for each subject was correlated with the following measures of sleep quality: percentage of wakefulness after sleep onset (WASO) throughout the sleep period, WASO in the first hour, percentage of stages 3 and 4 sleep [slow- wave sleep (SWS)] throughout the sleep period, SWS in the first hour after SO, and the number of awakenings in the sleep period. For the group as a whole, the MROD to sleep interval was not significantly correlated with any of these measures of sleep quality on the baseline night. Further, there was not a reiationship between the timing of MROD and the BT minimum. Baseline night, young versus old subjects There were 17 young subjects «30 years) and 13 old subjects (>60 years) from whom baseline night data were analyzed. Average SO time was 2430 hours (SD = 48 minutes) for young versus 2412 hours (SD = 60 minutes) for old subjects (ns). The MROD occurred at 2330 hours (SD = 72 minutes) for the young group and at 2324 hours (SD = 66 minutes) for the old group (ns). Thus, MROD occurred 60 minutes (SD = 67 minutes) prior to SO in young subjects and 47 minutes (SD = 79 minutes) prior to SO in old subjects (ns). The average Tmin occurred at 0400 hours (SD = 114 minutes) for the young group and at 0254 hours (SD = 108 minutes) for the old group (ns). The time from MROD to Tmin was 270 minutes (SD = 132 minutes) and 210 minutes (SD = 120 minutes) for the young and old groups, respectively (ns). Of the five subjects whose MROD occurred after SO, two were from the young and three were from the old group (ns). When these subjects were not considered, the interval from MROD to SO was 64 minutes (SD = 52 minutes) and 52 minutes (SD = 67 minutes) for the young and old subjects, respectively (ns). To determine whether the timing of MROD differentially influenced sleep quality and to assess whether the age groups differed in sleep quality, one-way ANOV As were performed to compare young and old subjects on the following variables: WASO and SWS in the first hour after SO, amount of WASO and SWS throughout the night, and number of awakenings throughout the night. Although group differences were not significant for MROD time, SO time, Tmin time, MROD to SO interval, or MROD to Tmin interval, significantly lower sleep quality was observed in old subjects. Old subjects had more WASO in the first hour after SO [F(l,28) = 8.85, p < 0.01], which resulted in less SWS in the first hour of sleep [F(l,28) = 8.98, P < 0.01]. n addition, old subjects had more WASO throughout the night [F(1,28) = 23.51, p < 0.001]. The number of awakenings did not differ between young and old subjects. Disentrainment period, all subjects For the disentrainment period, 65 sleep bouts that met the criteria stated above were obtained. Average

5 DROP N BODY TEMPERATURE PROR TO SLEEP 509 <Jl U -=> '" ;:J 15 <Jl 0 '" 10 => '" ::E ;:J Z SLEEP ONSET T MROD RELATVE TO SLEEP ONSET (HOURLY NTERVALS) FG_ 4_ Distribution, in hourly intervals, of timing of the maximum rate of decline (MROD) in body temperature (BT) relative to sleep onset (SO) for sleep periods during the 72-hour disentrainment period. onset time for nighttime sleep episodes recorded during disentrainment was 2455 hours (SD = 148 minutes), which was not significantly different from the mean SO time on the baseline night. Corresponding MRODs occurred, on average, at 2411 hours (SD = 148 minutes). Thus, the average difference between MROD and SO was 44 minutes (SD = 64 minutes) when subjects were in a disentrained environment. For the group as a whole, the MROD time was significantly later during disentrainment than at baseline (t = -2.7, P < 0.05), and the interval from MROD to SO was significantly shorter than on the baseline night (t = 7.77, P < 0.001). When only subjects whose MROD occurred prior to SO were considered, the average time from MROD to SO was 76 minutes (SD = 45 minutes). The average time of the temperature nadir associated with these sleep bouts was 0518 hours (SD = 130 minutes), which was 307 minutes (SD = 128 minutes) after MROD. The time of Tmin was significantly later during disentrainment than at baseline (t = -2.4, P < 0.05), but because MROD was also later, the proximity of MROD to Tmin was not significantly different from baseline. Figure 4 shows the distribution of MRODs relative to SO for each hourly interval for disentrainment period sleep bouts. The MROD occurred prior to SO in 74% (48/65) of the sleep bouts (X2(1) = 6.89, P < 0.01) and within the 2 hours prior to SO in 79% (38/ 48) of those subjects (X2(1) = 7.70, P < 0.01). Figure 4 also demonstrates the consolidation of the MROD to SO intervals during disentrainment, as well as the decrease in variability of this interval. That is, of subjects whose MROD occurred prior to SO, all fell asleep within the 3 hours after their MROD. As with baseline sleep periods, the relationship between the MROD to SO interval and measures of sleep quality were examined for these sleep episodes. During disentrainment, there was a significant negative correlation (r = -0.24) between the proximity of MROD to SO and the amount of SWS obtained throughout the night. When only those subjects whose MROD occurred prior to SO were considered, the relationship between the proximity of MROD to SO and SWS throughout the sleep period was stronger (r = -0.34). n addition, significant correlations between the proximity of MROD to SO and SWS in the first hour of sleep (r = -0.30), as well as the amount of WASO throughout the sleep period (r = 0.28), were observed. These results indicate that subjects with a shorter interval between MROD and SO spent less time awake within the sleep bout and obtained more SWS in the first hour of sleep and throughout the night. Disentrainment period, young versus old subjects When the sample was subdivided into young and old groups, there were 26 sleep bouts obtained from 13 young subjects and 14 sleep bouts obtained from nine old subjects. Four young and four old subjects had no sleep bouts that met the criteria. n every case, these eight subjects contributed no sleep bouts during disentrainment because the sleep bouts that occurred between 2200 and 0600 hours were <4 hours in length, rather than because sleep bouts that met the duration criterion were initiated outside of the hour window. Average SO time for the young group was 0122 hours (SD = 128 minutes) versus 2322 hours (SD = 166 minutes) for the old group [F(1,38) = 6.44, p < 0.05]. Average MROD time was 2446 hours (SD = 142 minutes) for the young group and 2247 hours (SD = 156 minutes) for the old group [F(1,38) = 5.06, p < 0.05]. The average interval between MROD and SO was 36 minutes (SD = 62 minutes) in young subjects and 35 minutes (SD = 66 minutes) in old subjects (ns). The temperature nadir occurred at 0525 hours (SD = 118 minutes) for the young group and at 0506 hours (SD = 140 minutes) for the old group (ns). The amount of time from MROD to the temperature nadir averaged 279 minutes (SD = 117 minutes) and 379 minutes (SD = 143 minutes) for the young and old groups, respectively. Although the time of Tmin did not differ between age groups, the MROD was earlier in the old relative to the young group; thus, the interval from MROD to Tmin was significantly different between age groups [F(1,38) = 8.06, p < 0.01]. Of the 13 sleep bouts that were initiated prior to MROD, nine were contributed by young subjects and four were contributed by old subjects (ns). When these 13 sleep bouts were not con-

6 510 P. J. MURPHY AND S. S. CAMPBELL sidered, the average time from MROD to SO was 54 minutes (SD = 65 minutes) and 50 minutes (SD = 62 minutes) for the young and old subjects, respectively (ns). As with the baseline night, one-way ANOVAs across age groups were performed for variables related to sleep quality. n contrast to the baseline night, during these disentrainment sleep bouts, there were no significant differences between age groups on any sleep quality measures with the exception that the amount of W ASO in the 1 st hour of the sleep bout was greater for old subjects [F(l,38) = 4.57, P < 0.05]. However, the old subjects had significantly less WASO throughout the night during the disentrainment sleep periods compared to their baseline night sleep (t = 2.88, P < 0.05). While the time of SO for sleep periods initiated between 2200 and 0600 hours was advanced during disentrainment for old subjects, it was delayed for young subjects relative to baseline SO times. The withingroup changes in SO time from baseline to disentrainment were not significant for either age group, even though the disentrainment MROD and SO times were significantly later for the young group compared to the old group, as stated above. DSCUSSON These data indicate that BT shows a maximum rate of decline, on average, 60 minutes before the initiation of major nighttime sleep episodes. This relationship held even when subjects were isolated from time cues and had no behavioral, social, or experimental constraints restricting sleep initiation (i.e. sleep onset). These results, using both young and old non sleepdisturbed subjects, support and extend those previously reported for a group of sleep-disturbed elderly individuals, and they strongly suggest that a rapid decline in BT may act as the brain's signal that one is physiologically ready for sleep. Nearly 90% of all subjects studied exhibited their maximum rate of decline in BT within a few hours prior to falling asleep. Nevertheless, it is clear that the putative signal provided by a precipitous drop in BT may be overridden by motivation or homeostatic factors since there were sleep episodes that were initiated before the occurrence of MROD. The results from this study merely note that the occurrence of MROD greatly increases the likelihood of the occurrence of SO within approximately 60 minutes, without the implication that SO must occur within a few hours of MROD. n this regard, there were no apparent or systematic differences between sleep episodes that were initiated before the occurrence of MROD and the majority that occurred shortly after MROD. No variables that were examined, including gender, age, time of Tmin, proxmity of MROD to Tmin, or sleep quality parameters distinguished between sleep episodes that were initiated before versus after MROD. There was a trend for sleep episodes that were initiated prior to the occurrence of MROD to start at an earlier clock time than the group average and for MROD to occur at a later clock time than the group average. n several of these cases, a secondary drop in BT that was not at the maximum rate, but nonetheless a rapid and steep temperature decline, preceded SO. lt may be argued that any such relationship between BT and sleep observed under entrained conditions is confounded by social and temporal cues. However, in the current experiment, when time and social cues were eliminated, the amount of time between MROD and SO decreased. We interpret this finding as demonstration of a "tighter" relationship between MROD and sleep initiation, suggesting that subjects were more likely to "respond" to their MROD by going to sleep when other behavioral responses were limited. Given that the electrode montage was placed on the subjects 2-3 hours prior to SO on the baseline night, the drop in BT that produced the MROD, as well as the relationship between MROD and SO, could have been as artefact of the behavior of sitting in a chair and the general period of relaxation that accompanied the hookup procedure. Yet, the fact that the relationship between the drop in BT and subsequent SO held while subjects were in the disentrained environment, when a hookup prior to SO was not necessary, argues against this notion. Additionally, the strict limitations on behavior and activity during the disentrainment period and the minimal activity required prior to sleeping (i.e. subjects did not need to change into pajamas or brush their teeth and were generally already laying in their beds for long periods prior to SO) decrease the likelihood that the MROD prior to sleep initiation was the result of a change in activity levels. Nevertheless, the effects of activity on BT are considerable, and the present results cannot rule out the possibility that activity changes in the hours prior to SO were associated with the MROD. Experiments that analyze activity levels are needed to confirm the present findings. Although there was not a strong relationship between how soon after the MROD subjects fell asleep and subsequent sleep quality in this study, there were statistically significant correlations between proximity of MROD to SO and 1) the amount of SWS (i.e. more) during both the first hour after SO and throughout the night, and 2) the amount of WASO (i.e. less) throughout the sleep episode for the disentrainment sleep periods. As stated above, the average time from MROD to SO was significantly shorter in the disentrained condition compared to the baseline, entrained conditions. Taken together, these results suggest that responding

7 DROP N BODY TEMPERATURE PROR TO SLEEP 511 to one's MROD signal may facilitate a more rapid entry into the deeper stages of sleep. However, it should be emphasized that these correlations were not robust, explaining only 8-12% of the variance in the data. Further evidence that responding to one's MROD may provide some benefit for subsequent sleep relates to the advance of old subjects' MROD and SO times during disentrainment. Old subjects' MRODs occurred nearly an hour earlier when in temporal isolation than in entrained conditions, and these subjects fell asleep earlier than on their baseline nights. nterestingly, there was a significant decrease in W ASO throughout the sleep period for the old subjects when in disentrainment, and the differences in sleep quality between young and old subjects that were observed on the baseline night all but disappeared. These results suggest that although the advance in MROD and SO times from baseline to disentrainment was not statistically significant for these subjects, the shorter interval between MROD and SO may have contributed to a reduction in WASO in the disentrainment sleep periods. n practical terms, this may mean that if older individuals were to initiate nighttime sleep at an earlier clock time, the quality of their nighttime sleep might improve. One might expect that old subjects' SO times would be earlier than 2200 hours, and the time window criterion used for these analyses (i.e hours) might constitute a source of bias against inclusion of old subjects' nighttime sleep episodes. However, even though the SO time was at 2230 hours and the MROD time was at 2247 hours for the old group, there were not a significant number of sleep bouts "missed" by the use of the time window criterion. n fact, during disentrainment, only five of 177 sleep periods of >4 hours in length were initiated between 1800 and 2200 hours, and only three of those were in old subjects. Of all sleep periods, regardless of duration, only 17 began in the interval from 1800 to 2200 hours. The potential bias that might have been a problem if old subjects were going to bed outside the time window used for these analyses was, therefore, not a problem. n summary, SO during the nighttime hours is facilitated by a precipitous drop in BT. n a manner similar to the increased likelihood of sleep termination on the rising portion of the temperature curve, sleep initiation is more likely to occur shortly after temperature declines most rapidly. The relevance of this drop in BT for the entirety of the subsequent sleep period is not clear, but the amount of SWS obtained immediately following SO, as well as the amount of WASO throughout the sleep period, may be influenced by the response to MROD. One corollary to the current findings is that introducing a rapid and steep decline in BT might facilitate SO. For example, inducing a rapid decline in BT in an individual with SO insomnia, with, for example, an appropriately timed hot bath or administration of exogenous melatonin, might decrease SO latency. Whether there is a corresponding change in temperature, or perhaps another type of change in temperature prior to daytime naps, is also of interest. We are currently examining the possibility that changes in the slope of the BT rhythm during the daytime nap phase are related to the initiation of naps, as well as the quality of the nap sleep. Acknowledgements: This research was supported by grants ROl AGl2112, ROl MH45067, K02 MH01099, P02 MH49762, and a grant from the Tolly Vinik Trust, CUMC. The authors would like to thank Catharine Boothroyd and Tom Stauble for assistance with data processing and the technicial staff of the Laboratory of Human Chronobiology. REFERENCES 1. Czeisler CA, Weitzman ED, Moore-Ede M, Zimmerman J, Knauer R. Human sleep: its duration and organization depend on its circadian phase. Science 1980;210: Zulley J, Wever R, Aschoff J. The dependence of onset and duration of sleep on the circadian rhythm of rectal temperature. Pfiugers Arch 1981;391: Fraser G, Trinder J, Colrain 1M, Montgomery. Effect of sleep and circadian cycle on sleep period energy expenditure. J Appl Physiol 1989;66(2): Kleitman N, Doktorsky A. The effect of the position of the body and of sleep on rectal temperature in man. Am J Physiol 1933; 104: Barrett J, Lack L, Morris M. The sleep-evoked decrease of body temperature. 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