Enhanced sleep restores cAMP levels in clock neurons expressing tau. . Locomotor activity was measured in 1-minute bins and sleep was defined as periods. Fig 1. Citation: Slocumb ME, Regalado JM, Yoshizawa M, Neely GG, Masek P, Gibbs AG, et al. () Enhanced Sleep Is an Evolutionarily. 1. J Psychopharmacol. Feb;31(2) doi: Signs of enhanced sleep and sleep-associated memory processing following the.
Sleep 1. Enhanced
Two-tailed significance levels were set at 0. Unlike in previous studies—and due to the fact that the manipulations forced the skin temperature to slowly cycle only within a very subtle range of 0. Manipulation of the proximal part of the thermosuit accounted for Likewise, the independently manipulated temperature of the distal part of the thermosuit accounted for Table 1 shows the average temperatures during the warmest and coolest levels of the manipulations separately for each of the three groups.
In general, subjects showed less wakefulness and more sleep with increasing temperature of the thermosuit, especially in the proximal region. In order to obtain a first model-free description we therefore focused on the proximal thermosuit temperature T suit-prox threshold above which sleep was most promoted. Individual T suit-prox temperature values were determined for each night, such that the proportion of wake during the time spent above that temperature differed maximally from the proportion of wake during the time spent below it.
There were no significant differences between the average thresholds of young adults Because the effects of distal manipulations were less pronounced relative to the effects of proximal manipulation, a determination of thresholds and corresponding wake and sleep-stage proportions for distal temperature was difficult due to strong masking effects of simultaneous proximal temperature changes.
The descriptive data in Table 2 suggest that not only a reduction in wakefulness occurred but also that a deepening of sleep was induced by the warmer thermosuit temperatures.
This was tested using logistic regression analyses as described later. The percentage values represent the time spent in wake and sleep stages relative to the time spent below left column or above right column the proximal thermosuit temperature threshold that was determined for each individual night in each subject, such that the proportion of wake during the time spent above that temperature differed maximally from the proportion of wake during the time spent below it see example in Fig.
In order to evaluate in detail the effect of temperature manipulation on the probability of occurrence of sleep stages, logistic regression was applied. Odds ratios were translated into cumulative probability distribution plots for these stages throughout the night to provide a graphical representation of the regression-model-predicted sleep stage distribution during the periods of minimal T suit The data in Fig.
Distal skin warming enhanced REM sleep and suppressed S1 in the young adults and the elderly people without sleep complaints. In contrast, it suppressed REM sleep and marginally enhanced S1 in elderly insomniacs. Its effects on the other sleep stages were less uniform over the age groups. Distal skin warming suppressed S2 in young adults, enhanced S2 in elderly people without sleep complaints, and did not affect S2 in elderly insomniacs.
In both groups of elderly, but not in young adults, distal skin warming suppressed Wake. Moreover, distal skin warming strongly enhanced SWS in elderly insomniacs, but not in young and elderly participants without sleep complaints.
Graphical representation of the main effects logistic regression results. The stacked areas visualize the cumulative proportion of each sleep stage occurring over the whole night in case of the cool versus warm thermosuit temperatures for young adults top panels , elderly without sleep complaints middle panels and insomniac elderly bottom panels.
Effects of proximal warming versus cooling [ T suit prox at their minimal level of Graphical representation of the results of the logistic regression analyses that included main effects, time of night modulation and manipulation by time of night interactions. Stacked areas represent the model-predicted cumulative proportion of each sleep stage occurring at each time of the night in case of cool [minimal proximal and distal T suit both Odds ratio OR , confidence interval CI and significance P for the occurrence of each sleep state are given per C modulation of the temperature of the thermosuit T suit prox and T suit dist warming the distal and proximal skin areas.
A supplementary file contains a Table 4 which provides models including changes over time and interactions effects of T suit by time.
Two questions of relevance to the utility of an ultimate home-applicable system for sleep optimization by skin-temperature control are whether a certain temperature level is equally effective from the beginning to the end of the night and whether this is of the same magnitude in young subjects, elderly without sleep complaints and elderly insomniacs.
Within each group, we evaluated how the time of night modulated sleep-stage probabilities and their sensitivity to temperature manipulations. Therefore, we added non-linear time and time by temperature interaction terms to the logistic regression models. The parameter estimates and a more detailed description of their meaning are available in a supplementary file.
They are also visualized in Fig. Some temperature by time of night interaction effects on sleep-stage probabilities can be highlighted as having practical relevance.
First, the net effect of distal and proximal temperature by time of night interactions indicates that skin warming enhances SWS most effectively in the beginning of the night in young and elderly subjects without sleep complaints.
In contrast, SWS enhancement by skin warming commenced only after about one and a half hour of sleep in elderly insomniacs, and continued throughout the night. Second, in both elderly subject without sleep complaints and elderly insomniacs, the net wake-suppressing effect of skin warming increased towards the end of the night, when its sleep-preserving effect was very marked and consequently prevented early morning awakening.
EEG power spectra averaged over all artifact-free 30 s epochs scored as NREM sleep throughout the night from FpzCz left panels and PzOz right panels for young adults upper panels , elderly without sleep complaints middle panels and insomniac elderly lower panels.
Black bars represent power changes induced by manipulation of the proximal part of the thermosuit. Gray bars represent power changes induced by manipulation of the distal part of the thermosuit. Proximal warming also enhanced the parieto-occipital expression of the sleep-related 0. Parieto-occipital, distal warming suppressed the sleep-related 0.
As compared to the elderly people without sleep complaints, the overall EEG power spectra of elderly insomniacs Fig. The effects of temperature manipulation on the power spectra of the insomniac elderly were more restricted. Other than some minor spectral changes, only the enhancement of the sleep-related parieto-occipital slow wave sleep-related 0. To summarize the strongest effects of proximal warming: Moreover, it enhanced the higher sleep spindle frequency bin 14—15 Hz in young adults and elderly without sleep complaints, but rather suppressed it in elderly insomniacs.
Proximal warming also suppressed the wake-related higher frequencies in young adults and elderly without sleep complaints, but somewhat enhanced it fronto-central only in elderly insomniacs.
To summarize the strongest effects of distal warming: It suppressed the alpha range 8—12 Hz and induced some increase in the beta range 15—23 Hz. Only in elderly without sleep complaints and only on PzOz, it suppressed the slow oscillation, delta and lower theta ranges 0. The results of the present study have demonstrated for the first time that sleep depth is strongly affected by direct mild manipulation of skin temperature within the thermoneutral zone that normally occurs during everyday life under comfortable sleeping conditions.
Of note, core body temperature remained unchanged and could thus not have mediated any of the effects. After demonstrating the effect of skin temperature manipulations in young adults, the robustness of the effects was verified in elderly with, and without, sleep complaints, in whom both thermosensitive and thermoregulatory capacities are changed Van Someren et al. In young and older subjects without sleep complaints, proximal warming resulted in deeper sleep and suppressed wakefulness, whereas distal skin warming enhanced REM sleep and suppressed light sleep see Fig.
Elderly insomniacs responded somewhat differently, in that proximal warming enhanced slow wave sleep and REM sleep, whereas distal warming enhanced slow wave sleep and suppressed REM sleep Fig.
The fraction of SWS Table 2 reported here may seem high for elderly and insomniacs and could result from the fact that we limited the allowed sleep time to 6 h 5.
The even higher fraction of SWS in the skin warming condition suggests that this procedure can raise the amount SWS to a level not habitually seen in elderly people. Most importantly, the results show that mild skin temperature manipulations can be chosen such as to significantly reduce early morning awakening and enhance deeper sleep stages Fig. Early morning awakening and a lack of deep sleep are typical findings even in elderly people who do not have sleep complaints.
Elderly participants showed such a pronounced sensitivity to skin temperature manipulations, that the induction of a relatively small 0. In addition, subtle skin warming significantly restored the age-related decrease in SWS—often considered the most physiologically restorative stage of sleep.
The induction of a 0. An important question to be evaluated in further studies is whether the mild skin warming procedure would be equally effective if it was applied continuously during the whole night instead of intermittently as in the present study. This was verified in one published study Raymann et al.
We also ensured that the skin temperatures induced in our present protocol did not drop below normal proximal and distal skin temperatures measured using ambulatory equipment van Marken Lichtenbelt et al.
Our present manipulations never induced the mean distal skin temperature to drop below Similarly, the mean proximal skin temperature measured in bed at home was Warming studies over the whole nocturnal period are warranted to verify that the sleep-enhancing effect and sleep-depth-enhancing effect of mild skin warming can indeed be sustained.
Future research should also be designed in a way that is more suitable to evaluate temperature effects on REM sleep; mainly for reasons of logistics our protocol finished at 6: In the present study, skin temperature was manipulated within a narrow 0. Of note, the sleep-enhancing effects of slight warming cannot simply be attributed to changes in comfort, since we previously demonstrated that the upper limit of the manipulated range is in fact perceived as slightly less comfortable Raymann et al.
We do not expect that elevating ambient temperature instead of directly manipulating the proximal and distal skin, would lead to any comparable sleep improvements, because elevated air temperatures may be experienced as uncomfortable. It thus appears of utmost importance to limit the manipulations to the proximal and distal skin area, i. The finding that skin temperature modulates sleep depth may provide a possible explanation for the sleep improvement that previous researchers found to occur following passive body heating Horne and Reid, ; Horne and Shackell, ; Bunnell et al.
The increase in core body temperature induced by passive body heating activates heat loss mechanisms including increased skin blood flow, resulting in increased skin temperature. The results of the study indicate that performance is significantly worse on free recall of the list of nouns when sleep deprived an average of 2. In terms of brain regions activated, the left prefrontal cortex , premotor cortex , and temporal lobes were found to be activated during the task in the rested state and discrete regions of the prefrontal cortex were even more activated during the task in the sleep deprived state.
As well, the bilateral parietal lobe , left middle frontal gyrus , and right interior frontal gyrus were found to be activated for those sleep deprived. The implication of these findings are that the brain can initially compensate for the effects of sleep deprivation while maintaining partially intact performance, which declines with an increasing time-on-task.
This initial compensation may be found in the bilateral regions of both frontal and parietal lobes and the activation of the prefrontal cortex is significantly correlated with sleepiness. Cerebral activation during performance on three cognitive tasks verbal learning, arithmetic, and divided attention were compared after both normal sleep and 35 hours of total sleep deprivation TSD in a study by Drummond and Brown.
Use of fMRI measured these differences in the brain. In the verbal learning task, fMRI indicated the regions involved in both verbal learning and memorization. The results found that both TSD and a normal night of sleep showed a significant response in the prefrontal cortex and following TSD displayed a response of additional areas which included other prefrontal areas, bilateral inferior parietal lobule and superior parietal lobes.
Increases in sleepiness also correlated with activation of two ventral prefrontal regions and a correlation between a greater activation in bilateral parietal lobes which include language areas and lower levels of impairment on free recall were also found following TSD.
In the arithmetic task normal sleep showed the expected activation in the bilateral prefrontal and parietal working memory regions but following TSD only showed activation in the left superior parietal lobe and the left premotor cortex in response, with no new areas to compensate as was found in verbal learning.
Increased sleepiness was also correlated with activation in a ventral prefrontal region, but only one region. The divided attention task combined both verbal learning and the arithmetic task. The implication of this finding is that additional brain regions activated after both verbal learning and divided attention tasks following TSD represent a cerebral compensatory response to lacking sleep.
For example, there is a decline in response of the left temporal lobes during both tasks which is involved in different learning tasks during a rested state but involvement of the left inferior parietal lobe in short-term verbal memory storage following TSD suggests that this region might compensate. No new areas for the arithmetic task may suggest that it relies heavily on working memory so compensation is not possible, in comparison to tasks such as verbal learning which rely less on working memory.
Slow wave sleep occurs during stages 3 and 4 of the sleep process. SPW-Rs are the most synchronous neuronal patterns in the mammalian brain. Neurons within SPW-R are sequentially organized and many of the fast sequences are related to the order of neuronal firing during the pre-sleep experience of the animal. For example, when the rat explores a maze, place cell sequences in the different arms of the maze are replayed either in a forward as during the experience itself or reverse order but compressed in time several fold.
SPW-R are temporally linked to both sleep spindles and slow oscillations of the neocortex. SPW-R is therefore the most prominent physiological biomarker of episodic i. Researchers used rats in order to investigate the effects of novel tactile objects on the long-term evolution of the major rodent forebrain loops essential in species-specific behaviours, including such structures as the hippocampus , putamen , neocortex and the thalamus.
At some point four novel tactile objects were placed in the four corners of the rat's cage. They were all very different from one another and they were there for a total of one hour. The brain activity during this hour was used as a baseline or template to compare. Data analysis implied that the neural assemblies during SWS correlated significantly more with templates than during waking hours or REM sleep. As well, these post-learning, post-SWS reverberations lasted 48 hours, much longer than the duration of novel object learning one hour , indicating long term potentiation.
Another difference noticed was the highest correlation peaks in SWS corresponded with the lowest rate of neuron firing in the forebrain, opposite that of REM sleep and waking where rate of firing is the highest. It is hypothesized that this is due to interference from other incoming stimuli during waking periods.
In SWS there is no incoming stimuli so the novel experience can be replayed, without interruption. A study by Peigneux et al. This study was done to prove that the same hippocampal areas are activated in humans during route learning in a virtual town, and are reactivated during subsequent slow wave sleep SWS.
The finding noted that the amount of hippocampal activation during slow-wave sleep positively correlated to the improvement on the virtual tour task the following day, which indicates that hippocampal activity during sleep correlates with the improvement in memory performance.
These findings prove that learning-dependent modulation in hippocampal activity while sleeping shows processing of the previously learned episodic and spatial memory traces. This modulation of the hippocampus leads to plastic changes in the brain and ultimately an improvement in performance. The results of this study showed that spatial memory traces are processed in humans while they are in NREM sleep.
It showed a reaction of the hippocampal formation during SWS, after a declarative spatial memory task. Experimenters also found, that in humans, there is experience dependent modulations of activity during NREM sleep in the hippocampal regions, but not during REM sleep after learning. The evidence from this study was substantial to its hypothesis that the information learned while awake, is altered, and strengthened while humans are sleeping.
In this study, two groups of participants took part in a two night counterbalanced study. Two tasks were learned by all participants between The declarative task was a paired-associate word list of 40 German semantically related word pairs. The non-declarative task was a mirror-tracing task. Physostigmine is an acetylcholinesterase inhibitor ; it is a drug that inhibits the breakdown of the inhibitory neurotransmitter Acetylcholine , thereby allowing it to remain active longer in the synapses.
The sleep group was put to bed while the other group stayed awake. Testing of both tasks took place at 2: Results showed that the increased ACh negatively affected recall memory declarative task , in the sleep condition compared to participants given the placebo. Conversely, neither speed nor accuracy declined in the non-declarative mirror task when participants were given physostigmine, and neither task performance was affected in the wake groups when physotigmine was administered.
This suggests that the purpose of ACh suppression during SWS allows for hippocampus —dependent declarative memory consolidation; high levels of ACh during SWS blocks memory replay on a hippocampal level. Sleep spindles are short and intense bursts of neurons firing in sync, occurring in the thalamo-cortical networks. These peak late in the night and are defining characteristics of stage two sleep. Sleep spindles are thought to aid in information consolidating during sleep and have been shown to increase after training on a motor task.
A study, using 49 rats indicated the increase of sleep spindles during slow-wave sleep following learning. It gave evidence to the increase of spindle frequency during non-REM sleep following paired associate of motor-skill learning tasks.
Using an EEG , sleep spindles were detected and showed to be present only during slow-wave sleep. Beginning with a preliminary study, rats underwent six hours of monitored sleep, after a period of learning. Results showed that during the first hour following learning, there was the most evident effect on learning-modulated sleep spindle density.
However, this increase in spindle density was not dependent on the training condition. In other words, there was an increase in spindles regardless of how the rats were trained. EEG patterns showed a significant difference in the density of sleep spindles compared to the density of a control group of rats, who did not undergo any training before their sleep spindles were measured.
This effect of increased spindle density only lasted for the first hour into sleep following training, and then disappeared within the second hour into sleep. In a study by Fischer and Born, ,  previous knowledge of monetary reward and post-training sleep are proven to be significant predictors of overall finger sequence tapping performance.
Subjects were presented with two different finger sequence tasks that would have to be replicated at a later time. The subjects were told that there would be a reward offered for improvement upon a specific finger tapping sequence task. A control group was not given any knowledge of a reward. The subjects were separated further by allowing a sleep period between initial training and final testing for one group while another group faced a wake retention interval. It was concluded that the group that received both information about reward as well as being able to sleep displayed the highest increase in performance on both finger tapping sequences.
Knowledge of reward without sleep and sleep without knowledge of reward were both significant contributors to improved performance. In all cases sleep was determined to have an advantageous effect on overall performance when compared to groups that underwent a twelve-hour wake retention period. Non-declarative memory is memory gained from previous experiences that is unconsciously applied to everyday scenarios.
Non-declarative memory is essential for the performance of learned skills and habits, for example, running or cooking a favourite meal. There are three types of non-declarative memories: Extracellular signal-related kinases, also known as classical MAP kinase , are a group of protein kinases located in neurons. These proteins are activated or deactivated by phosphorylation adding of a phosphate group using ATP , in response to neurotransmitters and growth factors.
A study tested four groups of rats in the Morris Water Maze, two groups in the spatial task hidden platform and two groups in the non-spatial task visible platform. The effects of six hours of total sleep deprivation TSD were assessed for the experimental group one spatial group, one non-spatial group in both tasks. Six hours after the TSD period or sleep period for controls , the groups of rats were trained on either task then tested 24 hours later.
In addition, the levels of total ERK phosphorylation ERK 1 and ERK 2 , protein phosphate 1 PP1 , and MAPK phosphatase 2 latter two both involved in dephosphorylation were assessed by decapitating four other groups of mice, two sleep deprived and two non-sleep deprived , and removing their hippocampuses after the six hours of TSD, or two hours after TSD eight hours total.
Results showed that TSD did not impair learning of the spatial task, but it did impair memory. With regards to the non-spatial task, learning again was no different in the TSD; however, memory in the TSD group was actually slightly better, although not quite significantly. TSD did not affect proteins in the cortex which indicates that the decreases in ERK levels were due to impaired signal transduction in the hippocampus.
REM sleep is known for its vivid creations and similarity to the bioelectric outputs of a waking person. This stage of sleep is characterized by muscle atonia, fast but low voltage EEG and, as the name suggests, rapid eye movement. It is difficult to attribute memory gains to a single stage of sleep when it may be the entire sleep cycle that is responsible for memory consolidation. Recent research conducted by Datta et al. It was found that not only were the P waves increased during post-training sleep but also the density of the waves.
These findings may imply that P waves during REM sleep may help to activate critical forebrain and cortical structures dealing with memory consolidation. In a Hennevin et al. The rats in the experiment were trained to run a maze in search of a food reward. One group of rats was given non-awakening MRF electrical stimulations after each of their maze trials compared to a control group which did not receive any electrical stimulation.
It was noticed that the stimulated rats performed significantly better in respect to error reduction. These findings imply that dynamic memory processes occur both during training as well as during post-training sleep. Another study by Hennevin et al. The interesting part of the experiment is that fear responding to the noise measured in the amygdala was observed when the noise was presented during REM sleep.
This was compared to a group of pseudo-conditioned rats who did not display the same amygdalar activation during post-training sleep. This would suggest that neural responding to previously salient stimuli is maintained even during REM sleep. There is no shortage of research conducted on the effects that REM sleep has on the working brain but consistency in the findings is what plagues recent research. There is no guarantee as to what functions REM sleep may perform for our bodies and brains but modern research is always expanding and assimilating new ideas to further our understanding of such processes.
In animals, the appearance of ponto-geniculo-occipital waves PGO waves is related to that of the bioelectric outputs of rapid eye movements. Although these phasic waves are observed in many portions of the animal brain, they are most noticeable in the pons, lateral geniculate bodies, and the occipital cortex.
This would add to the theory that activation in these areas is similar to PGO wave activation in animals. The Sleep Disorders Questionnaire. Creation and multivariate structure of SDQ.
Electroencephalogr Clin Neurophysiol Influence of proximity to sleep. Sleep - DE, JA, et al. PMID - Marken 6 The effect of postural changes on body temperature and heat balance - Tikuisis - 5 The effect of afternoon body heating on body temperature and slow wave sleep.
Psychophysiology - Jordan, Montgomery, et al. Show Context Citation Context The Pittsburgh Sleep Quality Index: Sleep - DJ - Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans - DJ. Trends Neurosci - McGinty, Szymusiak - Sleep - DJ. Sleep ;27 - JD, MH. Behav Res and Ther - KL. The rhythms of human sleep propensity and core body temperature - LC, Lushington - Zarcone VP Jr, et al.
Night-time sleep EEG changes following body heating in a warm bath. Hypothalamic neuronal responses to peripheral and deep-body temperatures - JA, KE. Passive body heating and sleep: The effect of postural changes on body temperature and heat balance - Tikuisis - The effect of afternoon body heating on body temperature and slow wave sleep.
Acta Psychiatr Neurol - Magnussen. Luboshitzky R, Lavie P:
Sleep and memory
1). After sleeping for one night at home subjects returned for a second night, with the temperature manipulation sequences inversed compared. Promotes optimal sleep and stress management. 30 capsules. Item# Retail Price: $ Your Price: $ Save 25%. Select Multi-Unit Discount, 1 . leukin l-enhanced sleep. Am. J. Physiol. (Regulatory Inte- grative Comp. Physiol. 19): RR, The effects of human interleukin 1.