Overnight Memory Consolidation Research Articles

O013 Sleep and overnight emotional memory in older adults with depression: A high-density EEG investigation

Abstract Older adults with depression have a high incidence of sleep disturbance which is posited to be mechanistically involved in maladaptive overnight emotional memory consolidation. In older adults (≥ 50 years) with and without depression, we aimed to compare group differences in overnight emotional memory and rapid eye movement (REM) and non-rapid eye movement (NREM) (N2 and N3) sleep disturbance. Secondly, we investigated the relationship between emotional memory consolidation, self-report emotional valence and arousal perception, and sleep disturbance. Participants underwent overnight PSG with high-density EEG. An emotional memory image task with concurrent subjective emotional arousal and valence rating was completed before and after sleep. REM sleep disturbance was measured by REM sleep duration, global REM gamma and alpha activity and REM EEG arousal index. NREM sleep disturbance was measured by NREM sleep duration, global NREM delta, alpha and sigma power, and NREM EEG arousal index. T-tests and non-parametric tests were used for group comparisons. Linear regressions were used to assess relationships between sleep disturbance and emotional memory. Twenty-two older adults (Depression: n = 12, Control: n = 10) with a mean age of 63.7 ± 6.5 years completed the study. Older adults with depression demonstrated differences in overnight perception of emotional valence and arousal for negative information, suggesting sleep may be involved in emotion perception. Global delta power in NREM was reduced in older adults with depression, suggestive of homeostatic alterations. However, no robust associations between overnight memory consolidation, emotional valence or arousal and REM or NREM sleep disturbance were observed.

0056 Overnight Memory Consolidation in Adolescents: Effects of Change in DLMO Phase After Sleep Restriction

0056 Overnight Memory Consolidation in Adolescents: Effects of Change in DLMO Phase After Sleep Restriction

Reduced slow‐wave sleep is associated with greater tau accumulation and reduced cortical thickness in the temporal lobe

AbstractBackgroundSlow wave sleep (SWS) plays an important role in overnight memory consolidation and promotes overnight clearance of amyloid‐β and tau proteins. Reduced SWS has been associated with higher amyloid burden in CSF in preclinical stages of Alzheimer’s disease (AD). However, little is known about the relationship between SWS, tau burden and neurodegeneration in cognitively unimpaired (CU) adults. Thus, we investigated the relationships between slow‐wave sleep, regional tau PET (18F‐flortaucipir; FTP‐PET) and temporal lobe cortical thickness in cognitively unimpaired adults at risk of AD.MethodsThis study included 39 CU adults from the Harvard Aging Brain Study (mean age 74.6 years, 61.5% females) who underwent at‐home polysomnography (PSG; Compumedics Somte), tau PET (FTP‐PET, amyloid PET (PIB‐PET) and MRI (Table 1). We used separate multivariate linear regressions to assess associations between the percentage of slow‐wave sleep (SWS) and tau PET signal in the following ROIs: entorhinal cortex, inferior temporal cortex, and a temporal composite comprised of entorhinal, inferior temporal, middle temporal and fusiform cortices. Primary analyses were adjusted for age and sex. Secondary analyses also adjusted for global amyloid (PiB‐PET) burden. Lastly, we investigated the relationship between SWS and cortical thickness in the same ROIs, assessed using FreeSurfer v6.0.ResultsLower percentage of SWS was associated with greater tau burden in entorhinal (p = 0.036), inferior temporal (p = 0.011), and temporal composite ROIs (p = 0.005). Associations between reduced SWS and greater FTP‐PET signal in the inferior temporal cortex and temporal composite ROI remained after controlling for PiB‐PET (p = 0.028; p = 0.017, respectively; Table 2). Additionally, lower SWS was associated with reduced cortical thickness in the entorhinal (p = 0.031), inferior temporal (p = 0.023) and temporal composite ROIs (p = 0.002) (Table 3).ConclusionsLower SWS in CU adults was associated with higher tau burden in regions of the temporal lobe that are commonly sites of early tau accumulation. These effects were independent of amyloid burden, suggesting disrupted sleep may lead to increased tau accumulation via an amyloid‐independent pathway. Importantly, lower SWS was also associated with reduced cortical thickness in temporal regions, suggesting that disrupted sleep may be tied to early AD‐related neuronal loss in the temporal lobe.

SLEEP MICROARCHITECTURE IN MILD COGNITIVE IMPAIRMENT: A HIGH‐DENSITY EEG STUDY

AbstractBackgroundSleep disturbance and sleep disorders are potential risk factors for dementia. Adults with mild cognitive impairment (MCI) are at increased risk of developing dementia and many report disturbed sleep. Altered sleep neurophysiology including deficits in sleep spindles and slow wave activity (SWA) during NREM sleep have been reported in MCI, though studies are sparse. These NREM EEG oscillations are crucial for overnight memory consolidation and optimal daytime functioning. Abnormal EEG activity during sleep in MCI may adversely impact sleep‐dependent memory processes and cognitive trajectory. This study is the first to examine sleep microarchitecture using high‐density EEG technology in MCI.MethodOlder adults with multi‐domain MCI (n = 19, mean age 68.5 years) and cognitively‐intact controls (n = 22, 69 years) had 256‐channel high‐density EEG recordings during overnight polysomnography and resting wakefulness. Declarative (word paired associates) and procedural (finger tapping) memory tasks were administered before and after sleep. Neuropsychological testing and brain MRI scans were also performed. After artefact processing, spectral analysis was performed for high‐density EEG recordings. Topographical power maps were calculated for standard frequency ranges for NREM sleep (N2 and N3 (slow wave sleep)). Maps were compared between groups using normalized power (z‐scores computed for each subject).ResultThe MCI group had worse declarative (% retention, MCI vs Controls: 84.2 ± 16.6 vs. 94.5 ± 7.8, p = 0.024) and procedural (% early improvement: 92.9 ± 11.0 vs. 103.0 ± 12.0%, p = 0.017) overnight memory consolidation than the controls. Topographic analysis of high‐density EEG data revealed a regional increase in SWA (1‐4.5Hz) EEG power during N3 in a cluster of 18 electrodes overlying the centroparietal cortex in the MCI group (cluster mean t‐value = 3.11, p = 0.0036, uncorrected) and a regional reduction in SWA in the left frontal (5 channels, t = ‐3.75, p<0.001) and right temporal areas (5 channels, t = ‐3.46, p = 0.001), Figure 1.ConclusionOvernight memory consolidation was impaired in this MCI population. Regional differences in SWA during deep sleep were present in distinct brain regions and may indicate pathology. Future analysis exploring associations between EEG abnormalities with underlying brain structures may provide mechanistic insights into the impact of altered sleep neurophysiology on cognitive outcomes in MCI.

Associations between self-reported sleep, overnight memory consolidation, and emotion perception: A large-scale online study in the general population.

Experimental studies suggest that short or disrupted sleep impairs memory consolidation, mood, and perception of emotional stimuli. However, studies have chiefly relied on laboratory-based study designs and small sample sizes. The aim of this fully online and pre-registered study was to investigate the association between sleep and overnight memory consolidation, emotion perception, and affect in a large, self-selected UK sample. A total of 1646 participants (473 completed) took part in an online study, where they completed a declarative (word-pairs) memory task, emotion perception task (valence ratings of images), and rated their affect within 2 h of bed-time. The following morning, participants reported on their state affect, sleep for the previous night, completed a cued recall task for the previously presented word-pairs, rated the valence of previously viewed images, and completed a surprise recognition task. Demographic data and habitual sleep quality and duration (sleep traits) were also recorded. Habitual sleep traits were associated with immediate recall for the word-pairs task, while self-reported sleep parameters for the specific night were not associated with overnight memory consolidation. Neither habitual sleep traits, nor nightly sleep parameters were associated with unpleasantness ratings to negative stimuli or overnight habituation. Habitual poor sleep was associated with less positive and more negative affect, and morning affect was predicted by the specific night's sleep. This study suggests that overnight emotional processing and declarative memory may not be associated with self-reported sleep across individuals. More work is needed to understand how findings from laboratory-based studies extrapolate to real-world samples and contexts.

33 Associations Between Long-Term Forgetting and Slow Wave Activity in Autosomal-Dominant Alzheimer’s Disease: Findings from the Colombia-Boston (COLBOS) Biomarker Study

Objective:Sleep contributes to memory retention and recall. Alzheimer’s disease (AD) patients experience decreased slow wave activity (SWA) during sleep. This decrease in SWA is associated with impaired memory consolidation (Lee et al., 2020). Long-term forgetting (LTF) over days or weeks has been linked to memory consolidation deficits and has been suggested as an early marker of AD that could be useful for identifying at-risk individuals for preclinical AD trials (Weston et al., 2018). Here, we examined associations between LTF and SWA in a sample of Presenilin-1 (PSEN1) E280A mutation carriers with autosomal dominant Alzheimer’s disease and non-carrier family members. Carriers of this mutation usually develop dementia in their forties (Fuller et al., 2019).Participants and Methods:Fourteen cognitively unimpaired PSEN1-E280A mutation carriers and sixteen age-matched non-carriers (mean age: 34.2 years) from the Colombia-Boston (COLBOS) biomarker study were included. Participants completed an overnight polysomnogram (PSG) and memory testing (NEUROPSI Word List) at 3-time points: 1) the night before PSG: immediate recall (Day1-ImmRecall) and a 20-minute delayed recall (Day1-DelayedRecall), 2) recall the following day (Day2-recall), and 3) recall one week later (Day7-recall). SWA was measured as the ratio 0. 6-1Hz/0.6-4Hz in frontopolar and frontotemporal regions and was calculated for sleep stages N2+N3 (slow wave sleep) based on an automated staging algorithm. Each participant’s LTF was calculated as the percent retention between Day 1 immediate recall and Day 7 recall (Butler, 2009). Mann-Whitney U tests were used to compare differences in recall, SWA, and LTF between groups. Spearman’s correlation was used to examine the associations between memory recall at different time points and SWA, as well as between LTF and SWA.Results:On Day 1, carriers had lower performance in immediate recall (p=0.02), compared to non-carriers, but there were no group differences in the 20-minute delayed recall. Carriers also recalled fewer words on Day 2 (p=0.03) and Day 7 (p=0.009) and had greater LTF (p=0.03). There were no group differences in SWA. In our overall sample, worse performance on word list delayed recall on Day 1, Day 2, and Day 7 was associated with less SWA across both frontotemporal (Day1: p=0.04, Day2: p=0.02, Day7: p=0.02) and frontopolar (all Ps<0.01) regions. In carriers, only worse performance on Day 1 delayed recall was associated with lower SWA in the frontopolar region (r= 0.535; p=0.049). Memory recall on other days was not associated with SWA in any brain regions. Additionally, greater LTF was associated with less SWA across both frontopolar (r= 0.507; p=0.005) and frontotemporal regions (r= 0.463 p= 0.01).Conclusions:Preliminary findings suggest that long-term forgetting is associated with less slow- wave activity in preclinical autosomal dominant Alzheimer’s disease. These results also suggest that SWA may be related to pre-sleep learning and subsequent overnight memory consolidation processes. LTF testing may be useful in selecting individuals for preclinical AD trials. Future research on the impact of slow wave activity on LTF may be useful in identifying ways to enhance short- and long-term memory consolidation in individuals at greater risk for dementia.

Memory ability and retention performance relate differentially to sleep depth and spindle type

Temporal interactions between non-rapid eye movement (NREM) sleep rhythms especially the coupling between cortical slow oscillations (SO, ∼1Hz) and thalamic spindles (∼12Hz) have been proposed to contribute to multi-regional interactions crucial for memory processing and cognitive ability. We investigated relationships between NREM sleep depth, sleep spindles and SO-spindle coupling regarding memory ability and memory consolidation in healthy humans. Findings underscore the functional relevance of spindle dynamics (slow versus fast), SO-phase, and most importantly NREM sleep depth for cognitive processing. Cross-frequency coupling analyses demonstrated stronger precise temporal coordination of slow spindles to SO down-state in N2 for subjects with higher general memory ability. A GLM model underscored this relationship, and furthermore that fast spindle properties were predictive of overnight memory consolidation. Our results suggest cognitive fingerprints dependent on conjoint fine-tuned SO-spindle temporal coupling, spindle properties, and brain sleep state.

Human REM sleep recalibrates neural activity in support of memory formation.

The proposed mechanisms of sleep-dependent memory consolidation involve the overnight regulation of neural activity at both synaptic and whole-network levels. Now, there is a lack of in vivo data in humans elucidating if, and how, sleep and its varied stages balance neural activity, and if such recalibration benefits memory. We combined electrophysiology with in vivo two-photon calcium imaging in rodents as well as intracranial and scalp electroencephalography (EEG) in humans to reveal a key role for non-oscillatory brain activity during rapid eye movement (REM) sleep to mediate sleep-dependent recalibration of neural population dynamics. The extent of this REM sleep recalibration predicted the success of overnight memory consolidation, expressly the modulation of hippocampal-neocortical activity, favoring remembering rather than forgetting. The findings describe a non-oscillatory mechanism how human REM sleep modulates neural population activity to enhance long-term memory.

Psilocybin intoxication did not affect daytime or sleep-related declarative memory consolidation in a small sample exploratory analysis

Psilocybin is investigated as a fast-acting antidepressant used in conjunction with psychotherapy. Intact cognitive functions, including memory, are one of the basic conditions of effective psychedelic-assisted therapy. While cognitive and memory processing is attenuated on various domains during psilocybin intoxication, the effect of psilocybin on the consolidation of memories learned outside of acute intoxication is not known. Thus the main aim of the current study was to test the effects of psilocybin on (A) memory consolidation of previously learned material just after the psilocybin session and (B) on overnight memory consolidation the night just after the psilocybin session. 20 healthy volunteers (10 M/10F) were enrolled in a placebo-controlled, double-blind, cross-over design. Effects on declarative memory consolidation in condition (A) The Groton Maze Learning Task and Rey Auditory Verbal Learning Test were used, and for (B) the Pair Associative Learning Test was used. We did not find psilocybin to improve memory consolidation. At the same time, we did not find psilocybin to negatively affect memory consolidation in any of the tests used. This evidence adds to the safety profile for the use of psilocybin.

Slow oscillation-spindle cross-frequency coupling predicts overnight declarative memory consolidation in older adults.

Cross-frequency coupling (CFC) between brain oscillations during non-rapid-eye-movement (NREM) sleep (e.g. slow oscillations [SO] and spindles) may be a neural mechanism of overnight memory consolidation. Declines in CFC across the lifespan might accompany coinciding memory problems with ageing. However, there are few reports of CFC changes during sleep after learning in older adults, controlling for baseline effects. Our objective was to examine NREM CFC in healthy older adults, with an emphasis on spindle activity and SOs from frontal electroencephalogram (EEG), during a learning night after a declarative learning task, as compared to a baseline night without learning. Twenty-five older adults (M [SD] age = 69.12 [5.53]years; 64% female) completed a two-night study, with a pre- and post-sleep word-pair associates task completed on the second night. SO-spindle coupling strength and a measure of coupling phase distance from the SO up-state were both examined for between-night differences and associations with memory consolidation. Coupling strength and phase distance from the up-state peak were both stable between nights. Change in coupling strength between nights was not associated with memory consolidation, but a shift in coupling phase towards (vs. away from) the up-state peak after learning predicted better memory consolidation. Also, an exploratory interaction model suggested that associations between coupling phase closer to the up-state peak and memory consolidation may be moderated by higher (vs. lower) coupling strength. This study supports a role for NREM CFC in sleep-related memory consolidation in older adults.

O005 Overnight consolidation of spatial navigation memories is impaired in Mild Cognitive Impairment and is associated with loss of sleep spindles and hippocampal subfield volumes

Abstract Introduction Allocentric spatial navigation (SN) is considered a measure for conversion from mild cognitive impairment (MCI) to Alzheimer’s disease. NREM sleep slow waves and spindles, and hippocampal volume (HV) are impaired in MCI, however their relationship with SN overnight memory consolidation (OMC) is unknown. This study aimed to examine: 1) SN OMC in MCI, and, 2) associations between SN OMC and NREM oscillations and HV. Methods Cognitively-intact (n=25), non-amnestic MCI (naMCI, n=22) and amnestic-MCI (aMCI, n=10) older adults completed neuropsychological assessment, neuroimaging, overnight routine and high-density EEG polysomnography (hdEEG subset; controls=17, MCI=8). Slow oscillations, slow wave activity, slow and fast spindle density and power were computed. OMC% was calculated by: ([post-sleep error score/pre-sleep error score]*100) from a familiar and novel (allocentric) location. Right CA1, dentate gyrus (DG) and entorhinal cortex were computed using ASHS software. Results MCI performed worse on familiar location-OMC% compared to controls (Cohens d= -.67, p= .016). aMCI performed worse on allocentric-OMC% compared to controls (omega2= .09, p= .032). Reduced spindles were associated with worse allocentric-OMC% in aMCI (frontal-slow spindles [rho= -.782 p= .008], parietal-fast spindles [rho= -.576, p= .082]). Using hdEEG, widespread fast spindle and allocentric-OMC% associations were indicated in MCI. Reduced right HV (DG [r= -.453, p= .023], CA1 [r= -.426, p= .068]) was related to worse allocentric-OMC% in MCI. Discussion In MCI, SN OMC is impaired, with worse consolidation associated with spindle and right HV loss. Future studies should examine whether SN OMC and spindles capture conversion to Alzheimer’s disease in ‘at-risk’ older adults.

Sleep Biomarkers Help Predict the Development of Alzheimer Disease.

Middle-aged or older adults who self-report sleep-wake disorders are at an increased risk for incident dementia, mild cognitive impairment, and Alzheimer disease. Dementia in people with mild cognitive impairment and Alzheimer disease who complain of sleep-wake disorders progress faster than those without sleep-wake disorders. Removal of amyloid-beta and tau tangles occurs preferentially in non-rapid eye movement 3 sleep and fragmented or insufficient sleep may lead to accumulation of these neurotoxins even in preclinical stages. Selective atrophy in the medial temporal lobe on brain MRI has been shown to predict impaired coupling of slow oscillations and sleep spindles. Impaired slow wave-spindle coupling has been shown to correlate with impaired overnight memory consolidation. Whereas, a decrease in the amplitude of 0.6 to 1 Hz slow wave activity predicts higher cortical Aβ burden on amyloid PET scans. Overexpression of the wake-promoting neurotransmitter orexin may predispose patients with mild cognitive impairment and Alzheimer disease to increased wakefulness, decreasing time they need to clear from the brain the neurotoxic accumulation of amyloid-beta and especially tau. More research exploring these relationships is needed and continuing.

P143 Sleep-dependent declarative memory consolidation and NREM sleep EEG oscillations in older adults with obstructive sleep apnea

Abstract Objectives To compare overnight declarative memory consolidation and NREM sleep EEG oscillations in older adults with OSA to an age-matched control group, and to assess the quantitative sleep EEG features as correlates of memory consolidation. Methods 46 participants (24 without OSA and 22 patients with OSA) were recruited. Participants completed a word-paired associates declarative memory task before and after an 8-hour sleep opportunity with full polysomnography. Power spectral analysis was performed on all-night EEG recorded at frontal and central electrode sites. We calculated slow wave activity (slow oscillations absolute power 0.25–1 Hz; and delta EEG power (0.5–4.5 Hz) in NREM sleep. Slow spindle density (11–13 Hz, events p/min) and fast spindle density (13–16 Hz, events p/min) in stage N2 was derived using an automated spindle detection algorithm. Results Patients with OSA showed no significant differences in overnight memory recall and recognition compared to individuals without OSA. The OSA group showed reduced slow spindle density at the central region and fast spindle density at the frontal region relative to controls. No differences were observed in SWA. Within group correlations showed slow and fast spindle density were correlated to percent recognition in the control group. Conclusion Older adults with OSA had deficits in slow and fast sleep spindles compared to controls. OSA patients showed preserved sleep-dependent declarative memory consolidation despite sleep fragmentation and intermittent hypoxemia. Sleep spindles were positively correlated with overnight memory consolidation in controls but not OSA patients. Targeted interventions to boost spindles may enhance memory consolidation in older adults.

Dysfunctional Overnight Memory Consolidation in Patients with Schizophrenia in Comparison to Healthy Controls: Disturbed Slow-Wave Sleep as Contributing Factor?

Introduction: Memory deficiency has been shown in schizophrenia patients, but results on the role of sleep parameters in overnight consolidation of associative verbal memory are still missing. Therefore, the aim of our study was to elucidate underlying processes of impaired sleep-related consolidation of associative word pairs in schizophrenia including standard sleep parameters as well as sleep spindle counts and spectral analysis. Methods: Eighteen stably medicated schizophrenia patients and 24 healthy age-matched controls performed an associative declarative memory task before and after polysomnographic recordings. Part of the participants expected verbal associative memory testing in the morning, while the others did not. Furthermore, participants filled in self-rating questionnaires of schizophrenia-typical experiences (Eppendorf Schizophrenia Inventory [ESI] and Psychotic Symptom Rating Scale). Results: Schizophrenia patients performed worse in verbal declarative memory in the evening as well as in overnight consolidation (morning compared to evening performance). While duration of slow-wave sleep was nearly comparable between groups, schizophrenia patients showed lower sleep spindle count, reduced delta power during slow-wave sleep, and reduced spindle power during the slow oscillation (SO) up-state. In healthy but not in schizophrenia patients, a linear relationship between overnight memory consolidation and slow-wave sleep duration as well as delta power was evident. No significant effect with respect to the expectation of memory retrieval was evident in our data. Additionally, we observed a negative linear relationship between total number of sleep spindles and ESI score in healthy participants. Discussion/Conclusion: As expected, schizophrenia patients showed deficient overnight verbal declarative memory consolidation as compared to healthy controls. Reduced sleep spindles, delta power, and spindle power during the SO up-state may link sleep and memory deficiency in schizophrenia. Additionally, the absence of a linear relationship between sleep-related memory consolidation and slow-wave sleep as well as delta power suggests further functional impairments in schizophrenia. Note that this conclusion is based on observational data. Future studies should investigate if stimulation of delta waves during sleep could improve memory performance and thereby quality of life in schizophrenia.

Offline Bi-Frontal Anodal Transcranial Direct Current Stimulation Decreases Total Sleep Time Without Disturbing Overnight Memory Consolidation

A proposed replay of memory traces between the hippocampus and frontal cortical brain areas during sleep is of high relevance for overnight memory consolidation. Recently, we demonstrated that bi-frontal anodal transcranial direct current stimulation (tDCS) prior to sleep increases waking EEG gamma power and decreases total sleep time during the night. It is unclear whether this effect on cortical excitability has an influence on overnight memory consolidation. We hypothesized that bi-frontal evening tDCS interferes with overnight memory consolidation with a polarity specific impairment following anodal tDCS. Nineteen healthy participants underwent a within-subject, repeated-measures protocol in the sleep laboratory with bi-frontal tDCS applied prior to sleep according to the experimental protocol (anodal, cathodal, sham stimulation). Memory tasks for declarative and procedural memory were assessed prior to tDCS and on the following morning. No deterioration of overnight memory consolidation following evening offline bi-frontal tDCS could be detected. The application of tDCS can be considered safe regarding overnight memory consolidation and represents a promising treatment approach in conditions of decreased vigilance and arousal.

Modulating overnight memory consolidation by acoustic stimulation during slow-wave sleep: a systematic review and meta-analysis.

The low-frequency high-amplitude oscillations of slow-wave sleep (SWS) are considered to promote the consolidation of episodic memory. Previous research suggests that sleep slow waves can be entrained and enhanced by presenting short acoustic stimuli to the up-states of endogenous waves. Several studies have investigated the effects of these increases in slow-wave activity on overnight memory consolidation, with inconsistent results. The aim of this meta-analysis was to evaluate the accumulated evidence connecting acoustic stimulation during sleep to episodic memory consolidation. A systematic literature search was conducted in October 2020 using PubMed, Web of Science, and PsycInfo. The main study inclusion criteria were the application of acoustic slow wave enhancement in healthy participants and an assessment of pre- and post-sleep episodic memory performance. Effect sizes were pooled using a random-effects model. A total of 10 primary studies with 11 experiments and 177 participants were included. Results showed a combined effect size (Hedges' g) of 0.25 (p = 0.07). Subgroup models based on young adults (n = 8), phase-locked stimulation approaches (n = 8), and their combination (n = 6) showed combined effect sizes of 0.31 (p = 0.051), 0.36 (p = 0.047), and 0.44 (p = 0.01), respectively. There was no indication of publication bias or bias in individual studies. Acoustic enhancement of SWS tends to increase the overnight consolidation of episodic memory but effects remain small and-with the exception of subgroup models-at trend levels. Currently, the evidence is not sufficient to recommend the use of commercially available devices.

Susceptibility to auditory closed-loop stimulation of sleep slow oscillations changes with age.

Study ObjectivesCortical slow oscillations (SOs) and thalamocortical sleep spindles hallmark slow wave sleep and facilitate memory consolidation, both of which are reduced with age. Experiments utilizing auditory closed-loop stimulation to enhance these oscillations showed great potential in young and older subjects. However, the magnitude of responses has yet to be compared between these age groups. We examined the possibility of enhancing SOs and performance on different memory tasks in a healthy middle-aged population using this stimulation and contrast effects to younger adults.MethodsIn a within-subject design, 17 subjects (55.7 ± 1.0 years) received auditory stimulation in synchrony with SO up-states, which was compared to a no-stimulation sham condition. Overnight memory consolidation was assessed for declarative word-pairs and procedural finger-tapping skill. Post-sleep encoding capabilities were tested with a picture recognition task. Electrophysiological effects of stimulation were compared to a previous younger cohort (n = 11, 24.2 ± 0.9 years).ResultsOvernight retention and post-sleep encoding performance of the older cohort revealed no beneficial effect of stimulation, which contrasts with the enhancing effect the same stimulation protocol had in our younger cohort. Auditory stimulation prolonged endogenous SO trains and induced sleep spindles phase-locked to SO up-states in the older population. However, responses were markedly reduced compared to younger subjects. Additionally, the temporal dynamics of stimulation effects on SOs and spindles differed between age groups.ConclusionsOur findings suggest that the susceptibility to auditory stimulation during sleep drastically changes with age and reveal the difficulties of translating a functional protocol from younger to older populations.

0548 Overnight Memory Consolidation in Insomnia versus Normal and Experimentally Disrupted Sleep

Abstract Introduction Healthy sleep is assumed to play an important role in the consolidation of newly acquired memories. Evidence suggest that periods of sleep after learning facilitates memory consolidation relative to wakefulness. Insomnia is associated with cognitive impairment but few studies have assessed overnight memory consolidation. We compared overnight consolidation in people with insomnia to a group of good sleepers who were randomised to either a normal night of sleep (uninterrupted sleep, US) or one night of sleep continuity disruption via forced awakenings (FA). Methods 51 good sleepers (37 female; mean age: 24 years, SD: 3.63), randomised to either one night of US (n=24) or one night of FA (n=27), were compared to 27 participants meeting criteria for insomnia disorder (23 female; mean age: 53 years, SD: 8.34) who were assessed at baseline as part of a randomised controlled trial of digital cognitive-behavioural therapy. Overnight memory consolidation (difference in correctly recalled word pairs between evening and morning recall) was assessed using the same word-pair task and protocol in the two lab-based studies. Results Overnight memory consolidation was significantly lower in the insomnia (mean: 5.4, SD: 5.8, p=0.001) and the FA (mean: 6.7, SD: 4.1, p<0.001) group compared to the US group (mean: 11.6, SD: 5.3). However, when adjusted for age only the FA group, but not the insomnia group, showed significantly lower memory performance than the US group. Conclusion While our findings suggest that overnight memory consolidation is impaired in insomnia relative to normal sleep we cannot rule out an age-related explanation given the difference in ages between the study samples. Future work will assess whether overnight consolidation improves following cognitive behavioural therapy. Support The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC) and the Dr Mortimer and Theresa Sackler Foundation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

Multisession transcranial direct current stimulation facilitates verbal learning and memory consolidation in young and older adults

This study investigated effects of multisession transcranial direct-current stimulation on learning and maintenance of novel memory content and scrutinised effects of baseline cognitive status and the role of multi-session tDCS on overnight memory consolidation. In a prospective, randomized, double-blind, parallel-group, sham-tDCS controlled design, 101 healthy young and older adults completed a five-day verbal associative learning paradigm while receiving multisession tDCS to the task-relevant left prefrontal cortex. In older adults, active multisession tDCS enhanced recall performance after each daily training session. Effects were maintained the next morning and during follow-up assessments (one week; three months). In young adults, multisession tDCS significantly increased long-term recall. Unlike previous findings in the motor domain, beneficial effects of multisession tDCS on cognitive learning and memory were notexclusively due to enhanced memory consolidation. Positive stimulation effects were primarily found in participants with lower baseline learning ability, suggesting that multisession tDCS may counteract memory impairment in health and disease.

One night of sleep continuity disruption engenders impairment in overnight memory consolidation and vigilance but not emotion perception or regulation: results from a randomised, lab-based experimental study

One night of sleep continuity disruption engenders impairment in overnight memory consolidation and vigilance but not emotion perception or regulation: results from a randomised, lab-based experimental study