REM sleep in naps differentially relates to memory consolidation in typical preschoolers and children with Down syndrome Goffredina Spanòa,b,1, Rebecca L. Gómeza,c, Bianca I. Demaraa, Mary Altd, Stephen L. Cowena,e, and Jamie O. Edgina,c,f,1 aDepartment of Psychology, University of Arizona, Tucson, AZ 85721; bWellcome Centre for Human Neuroimaging, Institute of Neurology, University College London, London WC1N 3AR, United Kingdom; cCognitive Science Program, University of Arizona, Tucson, AZ 85719; dSpeech, Language, and Hearing Sciences, University of Arizona, Tucson, AZ 85721; eEvelyn F. McKnight Brain Institute, University of Arizona, Tucson, AZ 85724; and fSonoran University Center for Excellence in Developmental Disabilities, Tucson, AZ 85721 Edited by Terrence J. Sejnowski, Salk Institute for Biological Studies, La Jolla, CA, and approved September 24, 2018 (received for review July 4, 2018) Sleep is recognized as a physiological state associated with wave) sleep orchestrates hippocampal–neocortical dialogue and learning, with studies showing that knowledge acquisition im- information transfer (19, 20). Recent work sheds new light on proves with naps. Little work has examined sleep-dependent the importance of REM sleep as well (16, 21, 22), with NREM learning in people with developmental disorders, for whom sleep and REM potentially working in concert to facilitate learning. quality is often impaired. We examined the effect of natural, in- DS provides an interesting condition to examine the effects of home naps on word learning in typical young children and children sleep disturbance due to well-replicated REM disruptions in the with Down syndrome (DS). Despite similar immediate memory context of broader sleep impairments, including sleep apnea (23). retention, naps benefitted memory performance in typical children We investigated word learning across naps and periods of wake- but hindered performance in children with DS, who retained less fulness in preschoolers with and without DS. Our aims were: (i)to when tested after a nap, but were more accurate after a wake examine how preschoolers with DS learn after naps compared with interval. These effects of napping persisted 24 h later in both TD children and (ii) to relate sleep parameters to learning outcomes. groups, even after an intervening overnight period of sleep. To measure learning, we assessed retention of new words (auditory During naps in typical children, memory retention for object- COGNITIVE SCIENCES labels for novel visual stimuli) across different intervals, with one in- PSYCHOLOGICAL AND label associations correlated positively with percent of time in terval containing a nap. Each child was tested on novel word learning rapid eye movement (REM) sleep. However, in children with DS, a in three counterbalanced, within-subject conditions: (i) 5-min delay, population with reduced REM, learning was impaired, but only ii iii A after the nap. This finding shows that a nap can increase memory ( ) wake, and ( ) sleep (Fig. 1 ). In the 5-min delay condition, loss in a subpopulation, highlighting that naps are not universally childrenreceivedtherecognitiontest5minafterthetrainingphase, beneficial. Further, in healthy preschooler’s naps, processes in REM whereas in the wake and sleep conditions, children were tested after sleep may benefit learning. 4 h as well as 24 h later to examine long-term retention. Sleep physiology was assessed with nap polysomnography (PSG). naps | sleep | memory | development | Down syndrome Results Behavioral analyses were conducted in 25 children with DS [52% n our productivity-driven society, the benefits of sleep for our female; mean (SD) age = 54.16 (9.49) mo] and 24 TD children long-term health and new learning are often ignored. The capacity I [54% female; mean age = 33.38 (5.05) mo]. Groups were of a full night’s sleep or short naps to improve learning has been observed in healthy adults (1–3), infants, and preschoolers (4–6). While considerable evidence indicates that sleep promotes active Significance memory consolidation (7), theories also suggest that sleep facilitates memory stabilization by reducing the impact of overactive synapses This paper demonstrates that typical children have enhanced through synaptic downscaling (8). Studies investigating the rela- learning of new words across sleep periods (naps) which is tionship between napping and memory consolidation have focused linked to the amount of time in rapid eye movement (REM) primarily on healthy groups, raising the question of whether naps are sleep and shows sleep-dependent learning losses in an atypi- always beneficial across populations. Indeed, napping’s universal cally developing group of children with REM deficits (e.g., utility is a current debate. The potential for cognitive benefits Down syndrome). The work yields both medical and theoretical i through naps is an open question as the neural processes involved in impacts by ( ) highlighting a modifiable mechanism of in- sleep and memory formation can differ throughout healthy devel- tellectual disability in Down syndrome that has not been de- ii opment and in individuals with developmental disorders (9–11). scribed before and ( ) emphasizing the important role of REM ’ In this study, we assessed whether children with Down syn- sleep in children s learning. drome (DS, trisomy 21), a condition associated with sleep dis- Author contributions: G.S., R.L.G., and J.O.E. designed research; G.S. and B.I.D. performed orders, receive the same benefits from daytime naps as typically research; M.A. and S.L.C. contributed new reagents/analytic tools; G.S. and J.O.E. analyzed developing (TD) children (4, 6). DS is the most common genetic data; and G.S. and J.O.E. wrote the paper. form of intellectual disability (12) that carries a unique cognitive The authors declare no conflict of interest. profile characterized by cognitive deficits, language difficulties This article is a PNAS Direct Submission. (13), and hippocampal-dependent memory deficits (14, 15). Published under the PNAS license. Despite decades of research characterizing the cognitive profile Data deposition: The data reported in this paper have been deposited in Open Science of DS, the role of disturbed sleep in cognitive deficits is largely Framework and can be accessed using the following website https://osf.io/tuab9/. unexplored in this population. 1To whom correspondence may be addressed. Email: [email protected] or jedgin@email. What physiological processes allow the sleep experienced arizona.edu. while napping to be beneficial? Both rapid eye movement This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. (REM) and non-REM (NREM) stages of sleep contribute to the 1073/pnas.1811488115/-/DCSupplemental. consolidation of nascent material (7, 16–18). NREM 3 (N3, slow www.pnas.org/cgi/doi/10.1073/pnas.1811488115 PNAS Latest Articles | 1of6 Downloaded by guest on September 25, 2021 Fig. 1. Protocol design and behavioral results. (A) Protocol design and object-label association task. Each child was tested with an object-label pairing task in three counterbalanced, within-subject conditions separated by 1–2 wk: (i) immediate, (ii) wake, and (iii) sleep. Every condition included two phases: training and test. During the training phase, children were exposed to three novel object-label mappings and three novel unlabeled distractors, trained to a set criterion (four out of six correct trials, 66.7%). Both 4- and 24-h tests included six trials. (B) Training: Number of repetitions required to meet criterion in children with DS (in blue) and TD toddlers (in red). (C) Test: Retention performance on the object–word association task across immediate, wake, and sleep conditions. *We found a group × condition type interaction at the 4-h and 24-h delays (see Results and SI Appendix). equivalent on basic cognitive scales and background factors (SI SI Appendix, Table S4 shows the correlations between sleep Appendix, Table S1). Despite equivalent retention at 5 min (Fig. architecture and retention in both groups at 4 and 24 h. The 1B and SI Appendix, Table S2; P = 0.39, alpha Holm–Bonferroni groups did differ in the correlation between % REM and re- adjusted for six comparisons), groups differed across the wake tention at 4 h in the nap condition (z = −2.57, P = 0.01, P ad- and nap conditions at 4 h [Fig. 1C; significant group × condition justed = 0.04), but no other tests of the differences of correlation interaction, F(1, 47) = 74.68, P < 0.001, P adjusted = 0.006]. The were significant at 4 h (Fig. 3). In other exploratory analysis, we DS group retained less than the TD group when tested after found that sleep spindle density, wake after sleep onset, and sleep (P < 0.001; d = 2.57, P adjusted = 0.006), but were more oxygen level (SaO2) did not relate to word recognition after accurate in the wake condition (P < 0.001; d = −1.28, P ad- sleep in either group. justed = 0.006). While the TD group demonstrated a benefit from the nap (P < 0.001, P adjusted = 0.006), children with DS Discussion were significantly more accurate after wake than following a nap In this study, we trained children to learn novel words across (P < 0.001, P adjusted = 0.006), with the same pattern of sig- intervals containing a nap and wake. Using measures of sleep nificance 24 h later (SI Appendix, Table S2). physiology collected in their home environment, we investigated While exploratory analyses showed total nap time and sleep how sleep quality, architecture, and quantitative EEG power onset latency did not differ across the groups (SI Appendix, Table during the nap related to retention. First, we found that naps S3), children with DS spent significantly less time in REM sleep function differently across different populations. Specifically, (P = 0.01, Holm–Bonferroni adjusted for four comparisons, P = while naps were beneficial for long-term retention in TD children, 0.04), consistent with the past literature.