We propose that during sleep, the central nervous system and ANS communicate bidirectionally and that the neural dynamics of the REM brain combine with increased parasympathetic activity to create an optimized internal environment, specific to REM sleep, that promotes creative associative memory processing. Using functional magnetic resonance imaging, Lane et al. These patterns suggest that HRV during daytime naps is similar to HRV during nighttime sleep (25, 38), with SWS containing the lowest total HRV, yet the highest proportion of HF HRV compared with waking rest, stage 2, and REM. Subjects were read the instructions aloud and were given four practice problems to ensure understanding of the task. Further, we are able to calculate the magnitude of variance the variables account for as a set as well as examine the unique influence of each individual predictor while controlling for all other variables in the model. (2011) 108:15438–43. For the Primed condition, the set of sleep variables in model 1 accounted for 46% of the variance in postnap performance [adjusted (Adj) R2 = 0.46, F(3, 13) = 5.47, P = 0.012; Fig. One possible influence that has received little attention in the sleep and memory literature is the autonomic nervous system (ANS). Biomedical communities and journals need to standardize nomenclature of gene products to enhance accuracy in scientific and public communication. Ten of the analogy answers served as primes for the answers to the RAT items administered in the primed condition during the PM session. Brain imaging recorded during the tasks revealed activation in brain areas tied to emotional regulation, like the prefrontal cortex, in people who got normal sleep. While deep NREM sleep is about the body, REM sleep is about the brain. This analysis revealed a significant effect of condition [F(3,33) = 6.66, P = 0.001, ηp2 = 0.38]. Other experimental techniques, such as intracranial recordings in humans to assess electrophysiological events like pontine-geniculate-occipital waves during REM sleep (53), may be necessary to reveal relationships between complex performance outcomes and underlying neural mechanisms. In the current study, we repeated this experimental design to investigate the relative contributions of sleep and HRV during sleep to these memory benefits. Prior studies have established that parasympathetic/vagal activity is associated with the high-frequency component of HRV [HF HRV; 0.15–0.40 Hz (23)]. This analysis revealed a significant effect of group [F(3,51) = 6.57, P = 0.001, ηp2= 0.28]. Eighty-one healthy, nonsmoking participants (age = 21.79 ± 3.29 y, 31 females) with no personal history of neurological, psychological, or other chronic illness provided informed consent, which was approved by the University of California, Riverside Human Research Review Board. Again, similar to the Primed condition, greater HF HRV during REM was associated with better performance. Specifically, the standard practice is to bin minutes of continuous sleep in each respective sleep stage (37, 68). When the tumor is successfully treated, normal alertness is restored. We used a MANOVA to compare performance (proportion correct at test) between Nap and QW groups in all three RAT conditions: Novel, Primed, and Repeated. 12. During the different sleep and alertness states, the researchers monitored the neural activity, blood vessel dilation, electromyography activity and whisker and body movements of the mice. Excessive daytime sleepiness microsleep Brief shifts in brain activity to the pattern normally recorded during sleep. You can change your choices at any time by visiting Your Privacy Controls. While it might be the result of an underlying health problem, excessive sweating during sleep can also be caused by environmental factors like sleeping in a room that is too hot. Specifically, subjects may have SWS or REM sleep in their nap, allowing us to include them in the behavioral analyses; however, 5 min of undisturbed sleep in each sleep stage is not as common in daytime naps and confines the total sample considerably. Missing and ectopic beats were corrected via cubic spline interpolation. In rats, pairing vagal nerve stimulation with auditory stimuli has been shown to reorganize neural circuits (17) and strengthen neural response to speech sounds in the auditory cortex (18). Specifically, sleep alone (SWS minutes, REM minutes, and sleep spindles) significantly predicted improvement (model 1: Adj R2 = 0.46, P = 0.01), but sleep plus HF HRV predicted a greater amount of behavioral change (model 2: Adj R2 = 0.73, P = 0.001). Instead, HF HRV during REM was a predictor (β = 0.54, P = 0.02). Here, we examined whether changes in cardiac ANS activity (HRV) during a daytime nap were related to performance on two memory conditions (Primed and Repeated) and a nonmemory control condition on the Remote Associates Test. REM is a deep stage of sleep with intense brain activity in the forebrain and midbrain. Similar to the full sample, analyses revealed a 90-min nap with both NREM and REM sleep boosted performance in the Primed condition [F(1,35) = 16.08, P < 0.001, ηp2= 0.31] above QW. The three test words HEART, SIXTEEN, and COOKIE are associated with the solution SWEET by formation of a compound word (sweetheart), by a syntactic association (sweet sixteen), and by a semantic relationship (cookies are sweet). Prior studies have established that parasympathetic/vagal activity is associated with the high-frequency component of HRV [HF HRV; 0.15–0.40 Hz (23)]. Our model 1 result is consistent with previous literature implicating sleep spindles as a marker of explicit memory consolidation (39). Due to the restrictions of HRV calculations (SI Materials and Methods), we could only conduct regressions on a subset of subjects (17 nappers). Incorrectly detected R-peaks were manually edited. Adapted from ref. Ten problems were exactly the same as the AM baseline RAT problems (Repeated condition), 10 problems had the same answers as 10 (out of 30) of the AM analogies (Primed condition), and 10 problems were completely novel (Novel condition). Epochs of stage 1 and wake after sleep onset were not analyzed, because these periods have not been previously reported to contribute to memory consolidation. doi: 10.1073/pnas.1112503108 Sleep and HRV parameters during the nap are reported in Tables S1 and S2. Although the evidence is still limited, a growing body of research suggests music may have beneficial effects for diseases such as Parkinson’s. Peripheral activity has been purported to affect memory consolidation via vagal afferent nerve fibers, which communicate information about ANS excitation and arousal via projections to the brainstem, which then project to memory-related areas, including the amygdala complex, hippocampus, and prefrontal cortex (PFC) (11). For the analysis of RR and frequency-domain HRV measures during different sleep stages, consecutive, artifact-free, 5-min windows of undisturbed sleep (i.e., free from stage transitions) were selected across the nap. However, the role of ANS in sleep-dependent memory consolidation has never been examined. As such, 49% of stage 2, 76% of SWS, and 66% of REM epochs were used for the current analyses. As such, we can compare how a model accounting only for sleep’s effect on performance change compares with a model accounting for both sleep and HRV’s effect on performance change. During REM sleep, the dilation was even larger than during non-REM sleep. This article is a PNAS Direct Submission. However, model 2 suggests HF HRV may be an even better predictor of explicit memory improvement, implicating previously unidentified avenues of research into how autonomic fluctuations interact with known markers of sleep-dependent plasticity. (4), sleep and quiet wake both contributed to increased performance in the Repeated condition. For the Novel condition, sleep variables did not significantly predict performance in model 1 [F(3,13) = 0.89, P = 0.47]. Specifically, during REM sleep, the PFC shows increased neural activity compared with other sleep stages (65). The current results complement the neurovisceral integration model (12, 14), which posits that constant dialogue between cardiac and central brain structures (e.g., PFC, amygdala), via vagal afferents, modulates cognitive and emotional processing (14, 35). To enable Verizon Media and our partners to process your personal data select 'I agree', or select 'Manage settings' for more information and to manage your choices. Behavioral performance on the RAT: Percent change. The subject is required to find a fourth word that serves as an associative link between these three words. Fast and slow spindles during the sleep slow oscillation: Disparate coalescence and engagement in memory processing, Hemodynamic cerebral correlates of sleep spindles during human non-rapid eye movement sleep, Topographic distribution of sleep spindles in young healthy subjects, Proceedings of the National Academy of Sciences, Earth, Atmospheric, and Planetary Sciences, www.pnas.org/lookup/suppl/doi:10.1073/pnas.1518202113/-/DCSupplemental, Autonomic activity during sleep predicts memory consolidation in humans, Science & Culture: At the nexus of music and medicine, some see disease treatments, Opinion: Standardizing gene product nomenclature—a call to action, Journal Club: Study reveals evolutionary origins of fold-switching protein, Transplantation of sperm-producing stem cells. Interplay between spontaneous and induced brain activity during human non-rapid eye movement sleep. The neuromodulator profile of REM sleep reveals a powerful boost in acetylcholine, combined with a diminished role of norepinephrine and serotonin (55). 1). Edited by Thomas D. Albright, The Salk Institute for Biological Studies, La Jolla, CA, and approved May 6, 2016 (received for review September 12, 2015). Sleep is an essential bodily function that everyone needs. Lines denote bidirectional connections, and arrows denote monodirectional projections. We calculated two performance measures for the task: (i) proportion correct = number of correct RAT items in each subcategory (Baseline, Novel, Repeated, Primed)/total number of items in that subcategory, and (ii) performance change = proportion correct PM − proportion correct AM/AM * 100. RVLM, rostral ventrolateral medulla. In contrast, without sleep, subjects may have had difficulty in breaking with the associations set up by the analogies task, and thus showed decreased ability to use the primed words in the subsequent creativity task. For each problem, the subject has to combine or relate the three words drawn from mutually remote associative clusters (e.g., COOKIES, SIXTEEN, HEART: ______). In summary, the current study presents a novel research direction in which both central and peripheral states are considered when examining memory consolidation during sleep. Another explanation that lends itself to the current data is that increased REM sleep was associated with increased forgetting, and therefore worse memory, in the Primed condition. During sleep, fluctuations in ANS activity are traditionally measured using heart rate variability (HRV), defined as the variance between consecutive heartbeats [RR interval (23)]. Proc Natl Acad Sci USA. For individuals with REM sleep behavior disorder, paralysis does not occur during the REM stage. Our study suggests that REM sleep, a period of high acetylcholine (but low norepinephrine) and vagal activity, may be a brain state optimally positioned to enhance plasticity. High-pass filters were set at 0.3 Hz, and low-pass filters were set at 35 Hz for EEG and EOG electrodes. Additionally, we varied which set of 10 problems in each group of 30 would be assigned to Novel, Repeated, and Primed conditions. One theory of sleep as restorative states that the chemicals in the brain, _____, are replenished during REM sleep. Central nervous system memory-related areas and autonomic control of the heart. In this view, HRV may be a proxy measure of the level of these ongoing plasticity processes. For example, minutes spent in slow wave sleep (SWS) and the number of sleep spindles [transient neural events in nonrapid eye movement (NREM) sleep, 12–15 Hz] in a posttraining sleep period correlate with the magnitude of explicit memory improvement [e.g., conscious, episodic memories (2, 3)]. Using regression analyses, we compared the proportion of variance in performance associated with traditionally reported sleep features (model 1) vs. sleep features and HRV during sleep (model 2). Subjects were given no time limit for the analogies, and were required to provide one answer for each analogy. One way to test this hypothesis would be to manipulate the timing of the nap to modulate the duration of REM sleep experimentally (e.g., early morning naps vs. late afternoon naps) and compare performance across these different nap conditions. Thank you for your interest in spreading the word on PNAS. designed research; L.N.W., E.A.M., and K.A.D. No significant correlations were revealed between HF HRV in the Quiet Wake condition and performance [Novel: Pearson correlation coefficient (r) = −0.17, P = 0.48; Primed: r = −0.28, P = 0.23; Repeated: r = 0.006, P = 0.98]. The brain starts to eat itself after chronic sleep deprivation Sleep loss in mice sends the brain’s immune cells into overdrive. Interestingly, here and in the study by Cai et al. This leap away from existing associations has been hypothesized to require changes to memory that involve the disintegration of existing schemas to ignite new and useful combinations (54). We tested two different types of memory conditions adopted from Cai et al. We hypothesize that the decreased Primed performance may be related to an inability in the QW group to disengage from the associations that were set up by the analogies task, which impaired their ability to generate new associations to the primed words in the RAT task. Find out more about how we use your information in our Privacy Policy and Cookie Policy. Thus, when the arousal threshold is highest (i.e., sleep is “deepest”), the EEG shows slow-wave sleep … In the QW group (n = 21), subjects were attached to electroencephalographic electrodes and watched a nature videotape lasting 50 min while lying in bed. In contrast, decreased resting HF HRV is associated with poor cognitive function and maladaptive emotional processing (14, 26). Additionally, there was higher normalized HF HRV during stage 2 compared with REM (P = 0.045), but not compared with prenap wake (P = 0.10). Asterisks represent significance at P < 0.05. Commonly referred to as sleep hyperhidrosis, this type of sleep disorder causes repeated disruption of normal sleep cycles. We and our partners will store and/or access information on your device through the use of cookies and similar technologies, to display personalised ads and content, for ad and content measurement, audience insights and product development. It is characterized by dreaming and the absence of motor function with the exception of the eye muscles and the diaphragm. For 11 nap subjects, we were unable to detect an RR interval and were unable to perform HRV analyses for these subjects, so they were excluded. We used a hierarchical regression approach and entered the sleep variables (SWS minutes, REM minutes, and number of sleep spindles; mean-centered) into the regression first, allowing these three variables to account for variance in performance change before entering in the HRV variables (HF HRV during SWS and REM; mean-centered). Sleep spindles in NREM sleep were detected with an automated spindle detector that used both MATLAB routines and BrainVision Analyzer software (70). Nap sleep staging is reported in Tables S1 and S2. Here, we present the first evidence, to our knowledge, that the ANS plays a significant and substantial role in associative memory consolidation during sleep. Subjects were required to provide an answer for all of the analogies and were not given a time limit. This allows us to dream quietly and safely throughout the night. Next, we used a multivariate ANOVA (MANOVA) with group (Nap and QW) as the independent variable; performance (proportion correct at PM) in Novel, Primed, and Repeated conditions as dependent variables; and baseline performance as a covariate. (4) tested three groups, Quiet Wake, NREM nap, and NREM + REM nap, on three RAT conditions. For the regression analyses, only those subjects who were represented on all five variables (SWS minutes, REM minutes, number of sleep spindles, and HF HRV during SWS and REM) were entered into the models (n = 17). Other neurotransmitters that shape sleep and wakefulness include acetylcholine, histamine, adrenaline, cortisol, and serotonin. As a consequence, on average, of the 10 analogy items used as primes, fewer than two were discarded due to this restriction across the subjects (mean = 8.75, SD = 1.1). Subjects were given this problem as an example of the ways in which the fourth word could be linked to the other three, but were informed that the correct answer could be connected to the other three words in many ways. Excessive sleepiness is the feeling of being especially tired or drowsy during the day. [19] Importantly, animal studies have shown that stimulating the vagus nerve leads to a release of plasticity-related neuromodulators in the brain, including acetylcholine and norepinephrine (63). ↵1L.N.W. These 90 items were further parsed into three distinct groups with 30 problems each. We first compared baseline scores between groups, but found a nonsignificant difference [t(54) = 1.76, P = 0.08]. In the current study, REM sleep may have facilitated subjects’ ability to break the schematic relationship between words presented as analogies and enhanced their ability to use the analogy answers in a new and useful way to complete the unrelated RAT problems. They were given a total time of 2 h in bed to sleep. 6 Follow-up of … To retain more statistical power, future studies should explore these relationships in a nocturnal sleep paradigm. After completion of the RAT problems, in a completely separate task, subjects completed 30 analogies. On average, a 90-min nap will typically comprise about 15–20 min of REM sleep (5, 48, 49). Shapeshifting designs could have wide-ranging pharmaceutical and biomedical applications in coming years. 2). Some subjects had atypically long durations of REM sleep. Minutes in rapid eye movement (REM) sleep, on the other hand, are associated with improvements in implicit memory [e.g., unconscious, priming, procedural skills (4, 5)]. For both the Primed and Repeated conditions, model 2 (sleep + HRV) predicted performance significantly better (73% and 58% of variance explained, respectively) compared with model 1 (sleep only, 46% and 26% of variance explained, respectively). It is thought that excessive EMG activity in RBD reflects dysfunction of the brainstem structures responsible for muscle atonia during REM sleep. To ensure similar performance profiles as the full sample, we tested performance differences in this partial sample. We also analyzed 5 min of prenap wakefulness (Wake). contributed new reagents/analytic tools; L.N.W., N.C., and E.A.M. In the Novel condition, neither problems nor answers were seen before test. Using a regression framework, we examined the amount of performance change (computed as proportion correct PM − proportion correct AM/proportion correct AM * 100; Table 2 and SI Materials and Methods) in each condition accounted for by the sleep predictors in model 1, as well as the sleep and HRV predictors in model 2. Next, we used a MANOVA on group (Nap and QW) and performance (proportion correct at PM) in Novel, Primed, and Repeated conditions, again controlling for baseline performance. However, model 2 (sleep and HRV variables) significantly increased the variance explained to 58% [Adj R2 = 0.58, F(5,11) = 5.47, P = 0.009]. Now a new study shows that getting only half a night’s sleep – as many medical workers and military personnel often do – hijacks the brain… This split provided three versions of the task within each group of 30 RAT problems, which resulted in a total of nine different versions of the RAT. Sleep has been shown to facilitate the transformation of recent experiences into stable, long-term memories (i.e., consolidation), and specific electrophysiological sleep features have been implicated in this process (1). Here, sleep spindles were no longer a significant contributor (β = 0.24, P = 0.24). The Huynh–Feldt correction was applied when sphericity assumptions were violated. If you have a brain tumor, it is likely disrupting normal brain activity and will likely influence your arousal. CRISPR-Cas9 gene editing can improve the effectiveness of spermatogonial stem cell transplantation in mice and livestock, a study finds. Mice move their whiskers during rapid eye movement (REM) sleep instead of moving their eyes, and also sleep with their eyelids open. Their actigraph percentages of ECG epochs for the HRV analysis another underlying health condition HRV has associated! To prevent automated spam submissions corrections were used for all of the AM session Desseilles. 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