Paired-associate Word Research Articles

Bypassing Striatal Learning Mechanisms Using Delayed Feedback to Circumvent Learning Deficits in Traumatic Brain Injury.

Feedback facilitates learning by guiding and modifying behaviors through an action-outcome contingency. As the majority of existing studies have focused on the immediate presentation of feedback, the impact of delayed feedback on learning is understudied. Prior work demonstrated that learning from immediate and delayed feedback employed distinct brain regions in healthy individuals, and compared to healthy individuals, individuals with traumatic brain injury (TBI) are impaired in learning from immediate feedback. The goal of the current investigation was to assess the effects of delayed vs immediate feedback on learning in individuals with TBI and examine brain networks associated with delayed and immediate feedback processing. Nonprofit research organization. Twenty-eight individuals with moderate-to-severe TBI. Participants completed a paired-associate word learning task while undergoing magnetic resonance imaging. During the task, feedback was presented either immediately, after a delay, or not at all (control condition). Learning performance accuracy, confidence ratings, post-task questionnaire, and blood oxygen level-dependent signal. Behavioral data showed that delayed feedback resulted in better learning performance than immediate feedback and no feedback. In addition, participants reported higher confidence in their performance during delayed feedback trials. During delayed vs immediate feedback processing, greater activation was observed in the superior parietal and angular gyrus. Activation in these areas has been previously associated with successful retrieval and greater memory confidence. The observed results might be explained by delayed feedback processing circumventing the striatal dopaminergic regions responsible for learning from immediate feedback that are impaired in TBI. In addition, delayed feedback evokes less of an affective reaction than immediate feedback, which likely benefited memory performance. Indeed, compared to delayed feedback, positive or negative immediate feedback was more likely to be rated as rewarding or punishing, respectively. The findings have significant implications for TBI rehabilitation and suggest that delaying feedback during rehabilitation might recruit brain regions that lead to better functional outcomes.

A visual paired associate learning (vPAL) paradigm to study memory consolidation during sleep.

Sleep improves the consolidation and long-term stability of newly formed memories and associations. Most research on human declarative memory and its consolidation during sleep uses word-pair associations requiring exhaustive learning. In the present study, we present the visual paired association learning (vPAL) paradigm, in which participants learn new associations between images of celebrities and animals. The vPAL is based on a one-shot exposure that resembles learning in natural conditions. We tested if vPAL can reveal a role for sleep in memory consolidation by assessing the specificity of memory recognition, and the cued recall performance, before and after sleep. We found that a daytime nap improved the stability of recognition memory and discrimination abilities compared to identical intervals of wakefulness. By contrast, cued recall of associations did not exhibit significant sleep-dependent effects. High-density electroencephalography during naps further revealed an association between sleep spindle density and stability of recognition memory. Thus, the vPAL paradigm opens new avenues for future research on sleep and memory consolidation across ages and heterogeneous populations in health and disease.

Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SO, and the time delay between SO and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

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.

Vigilant attention mediates the association between resting EEG alpha oscillations and word learning ability

Individuals exhibit considerable variability in their capacity to learn and retain new information, including novel vocabulary. Prior research has established the importance of vigilance and electroencephalogram (EEG) alpha rhythm in the learning process. However, the interplay between vigilant attention, EEG alpha oscillations, and an individual's word learning ability (WLA) remains elusive. To address this knowledge gap, here we conducted two experiments with a total of 140 young and middle-aged adults who underwent resting EEG recordings prior to completing a paired-associate word learning task and a psychomotor vigilance test (PVT). The results of both experiments consistently revealed significant positive correlations between WLA and resting EEG alpha oscillations in the occipital and frontal regions. Furthermore, the association between resting EEG alpha oscillations and WLA was mediated by vigilant attention, as measured by the PVT. These findings provide compelling evidence supporting the crucial role of vigilant attention in linking EEG alpha oscillations to an individual's learning ability.

The function of REM and NREM sleep on memory distortion and consolidation

During rapid eye movement (REM) sleep, newly consolidated memories can be distorted to adjust the existing memory base in memory integration. However, only a few studies have demonstrated the role of REM sleep in memory distortion. The present study aims to clarify the role of REM sleep in the facilitation of memory distortion, that is, hindsight bias, compared to non-rapid eye movement (NREM) sleep and wake states. The split-night paradigm was used to segregate REM and NREM sleep. The hypotheses are (1) hindsight bias—memory distortion—is more substantial during REM-rich sleep (late-night sleep) than during NREM-rich sleep (early-night sleep); (2) memory stabilization is more substantial during NREM-rich sleep (early-night sleep) than during REM-rich sleep (late-night sleep); and (3) memory distortion takes longer time than memory stabilization. The results of the hindsight bias test show that more memory distortions were observed after the REM condition in comparison to the NREM condition. Contrary to the hindsight bias, the correct response in the word-pair association test was observed more in the NREM than in the REM condition. The difference in the hindsight bias index between the REM and NREM conditions was identified only one week later. Comparatively, the difference in correct responses in the word-pair association task between the conditions appeared three hours later and one week later. The present study found that (1) memory distortion occurs more during REM-rich sleep than during NREM-rich sleep, while memory stabilization occurs more during NREM-rich sleep than during REM-rich sleep. Moreover, (2) the newly encoded memory could be stabilized immediately after encoding, but memory distortion occurs over several days. These results suggest that the roles of NREM and REM sleep in memory processes could be different.

ALFF response interaction with learning during feedback in individuals with multiple sclerosis.

Amplitude of low-frequency fluctuations (ALFF) is defined as changes of BOLD signal during resting state (RS) brain activity. Previous studies identified differences in RS activation between healthy and multiple sclerosis (MS) participants. However, no research has investigated the relationship between ALFF and learning in MS. We thus examine this here. Twenty-five MS and nineteen healthy participants performed a paired-associate word learning task where participants were presented with extrinsic or intrinsic performance feedback. Compared to healthy participants, MS participants showed higher local brain activation in the right thalamus. We also observed a positive correlation in the MS group between ALFF and extrinsic feedback within the left inferior frontal gyrus, and within the left superior temporal gyrus in association with intrinsic feedback. Healthy participants showed a positive correlation in the right fusiform gyrus between ALFF and extrinsic feedback. Findings suggest that while MS participants do not show a feedback learning impairment compared to the healthy participants, ALFF differences might suggest a general maladaptive pattern of task unrelated thalamic activation and adaptive activation in frontal and temporal regions. Results indicate that ALFF can be successfully used at capturing pathophysiological changes in local brain activation in MS in association with learning through feedback.

Emotional Distraction in E-learning Environment: Effect on Declarative Memory and Exploration of Physiological Marker

One of the advantage of e-learning method is the flexibility of embedding audio-visual materials, however whether this goal-irrelevant stimuli would distract the users instead and hinder their performance is generally unknown. The present study aimed to investigate the effects of emotional distraction (ED) on the declarative memory performance. The study was conducted using the within-subject experiment on 38 students aged 18-21 years (20 males). Declarative memory was measured using a Word-Pair Association (WPA) task. ED is given using the International Affective Pictures System (IAPS) and International Affective Digitized Sounds (IADS) grouped based on their valence (neutral, positive, and negative). Measurement of physiological responses was done by measuring Galvanic Skin Responses (GSR), and Electroencephalography (EEG) with Frontal Alpha Asymmetry (FAA) index. Result: significant difference on the WPA score of which Positive is lower than Neutral condition (p = 0.011), but only on the group which the positive block were presented first. From the GSR data, significant main effect of the order of experimental block regardless of the ED valence (p < 0.001; F = 16.045), the first block elicits significantly higher GSR amplitude compared to second (p < 0.001; t = 4.94) and third (p = 0.001; t = 3.90). Meanwhile, the FAA index showed no significant difference (p = 0.654; F = 0.433).

Development of a Word Paired-Associates Task for Longitudinal Assessment of Memory Overnight

"Development of a Word Paired-Associates Task for Longitudinal Assessment of Memory Overnight." Multivariate Behavioral Research, ahead-of-print(ahead-of-print), pp. 1–2

Transfer of Test-Enhanced Learning.

Memory for paired-associate words is facilitated by interim testing relative to restudy. According to the mediator effectiveness hypothesis, the benefit of retrieval practice is a consequence of the activation of a mediator word linking the cue and target. Evidence for the activation of cue-related mediators stems from the finding that mediators are more effective at prompting recall of target words than are words not associated with the original cue, a pattern that is larger following testing than restudy. The benefit of testing for the unstudied cues at the final test is referred to as transfer of test-enhanced learning. One goal of the current study was to examine whether the activation of mediators leads to the recall of targets indirectly via the original cues in a process known as backward chaining. We indexed backward chaining with the probability of incorrectly recalling a trial-specific original cue in place of a target. The second goal was to explore whether testing would yield a transfer effect for cues associated with target words. In four experiments, following an initial study of weakly related word pairs (e.g., Mother-CHILD), participants either restudied the pairs or attempted to recall the target given the original cue (e.g., Mother). On a final cued-recall test, participants were presented with unstudied cues that were related to either the original cue (semantic mediators, e.g., Father) or the target (target-related cues, e.g., Baby). The type of new cue presented on the final test was varied either between subjects (Experiment 1) or mixed within a list (Experiments 2, 3, and 4). Mixing mediators and target-related cues reduced the transfer of test-enhanced learning and increased the likelihood of recalling the original cues when shown a mediator. These results challenge the assumptions of the mediator effectiveness hypothesis.

Asymmetric Weights and Retrieval Practice in an Autoassociative Neural Network Model of Paired-Associate Learning.

Rizzuto and Kahana (2001) applied an autoassociative Hopfield network to a paired-associate word learning experiment in which (1) participants studied word pairs (e.g., ABSENCE-HOLLOW), (2) were tested in one direction (ABSENCE-?) on a first test, and (3) were tested in the same direction again or in the reverse direction (?-HOLLOW) on a second test. The model contained a correlation parameter to capture the dependence between forward versus backward learning between the two words of a word pair, revealing correlation values close to 1.0 for all participants, consistent with neural network models that use the same weight for communication in both directions between nodes. We addressed several limitations of the model simulations and proposed two new models incorporating retrieval practice learning (e.g., the effect of the first test on the second) that fit the accuracy data more effectively, revealing substantially lower correlation values (average of .45 across participants, with zero correlation for some participants). In addition, we analyzed recall latencies, finding that second test recall was faster in the same direction after a correct first test. Only a model with stochastic retrieval practice learning predicted this effect. In conclusion, recall accuracy and recall latency suggest asymmetric learning, particularly in light of retrieval practice effects.

Neural correlates of extrinsic and intrinsic outcome processing during learning in individuals with TBI: a pilot investigation.

Outcome processing, the ability to learn from feedback, is an important component of adaptive behavior and rehabilitation. Evidence from healthy adults implicates the striatum and dopamine in outcome processing. Animal research shows that damage to dopaminergic pathways in the brain can lead to a disruption of dopamine tone and transmission. Such evidence thus suggests that persons with TBI experience deficits in outcome processing. However, no research has directly investigated outcome processing and associated neural mechanisms in TBI. Here, we examine outcome processing in individuals with TBI during learning. Given that TBI negatively impacts striatal and dopaminergic systems, we hypothesize that individuals with TBI exhibit deficits in learning from outcomes. To test this hypothesis, individuals with moderate-to-severe TBI and healthy adults were presented with a declarative paired-associate word learning task. Outcomes indicating performance accuracy were presented immediately during task performance and in the form of either monetary or performance-based feedback. Two types of feedback provided the opportunity to test whether extrinsic and intrinsic motivational aspects of outcome presentation play a role during learning and outcome processing. Our results show that individuals with TBI exhibited impaired learning from feedback compared to healthy participants. Additionally, individuals with TBI exhibited increased activation in the striatum during outcome processing. The results of this study suggest that outcome processing and learning from immediate outcomes is impaired in individuals with TBI and might be related to inefficient use of neural resources during task performance as reflected by increased activation of the striatum.

Facilitation effect of incidental environmental context on the computer screen for paired-associate learning.

Three experiments, in which a total of 198 undergraduates engaged, investigate whether the incidental environmental context on the computer screen influences paired-associate learning. Experiment 1 compared the learning of foreign- and native-language words between a constant context condition, where the stimulus and response pairs were presented twice on the same 5-s video background context, and a varied context condition, where the pairs were presented twice on different video contexts. Repetition in the same context resulted in better learning than in different contexts, evaluated with a paper-and-pencil test. Experiment 2 investigated learning of paired-associate foreign and native words in the same video contexts, or photograph contexts, or on a neutral grey background. Both the video and the photograph contexts equally facilitated the paired-associate learning compared with the grey background. Experiment 3 investigated whether the incidental environmental context similarly facilitated face-name paired-associate learning. We added a new condition of spot illustrations, and a second testing 1 day later. The repetition of face-name pairs within the same complex incidental environmental context on the computer screen (either video or photograph background) facilitated the paired-associate learning. There was no significant difference in learning performance between video and photograph background contexts, which were significantly better than grey or spot-illustration backgrounds which did not differ from each other. The retention interval did not interact with the effect of the background. The present results show that repetition within the same video or photograph context, covering the entire background of the video screen on which each item pair was superimposed, facilitates paired-associate learning.

Impact of menstrual cycle phase and oral contraceptives on sleep and overnight memory consolidation.

Sleep spindles benefit declarative memory consolidation and are considered to be a biological marker for general cognitive abilities. However, the impact of sexual hormones and hormonal oral contraceptives (OCs) on these relationships are less clear. Thus, we here investigated the influence of endogenous progesterone levels of naturally cycling women and women using OCs on nocturnal sleep and overnight memory consolidation. Nineteen healthy women using OCs (MAge = 21.4, SD = 2.1 years) were compared to 43 healthy women with a natural menstrual cycle (follicular phase: n = 16, MAge = 21.4, SD = 3.1 years; luteal phase: n = 27, MAge = 22.5, SD = 3.6 years). Sleep spindle density and salivary progesterone were measured during an adaptation and an experimental night. A word pair association task preceding the experimental night followed by two recalls (pre‐sleep and post‐sleep) was performed to test declarative memory performance. We found that memory performance improved overnight in all women. Interestingly, women using OCs (characterized by a low endogenous progesterone level but with very potent synthetic progestins) and naturally cycling women during the luteal phase (characterized by a high endogenous progesterone level) had a higher fast sleep spindle density compared to naturally cycling women during the follicular phase (characterized by a low endogenous progesterone level). Furthermore, we observed a positive correlation between endogenous progesterone level and fast spindle density in women during the luteal phase. Results suggest that the use of OCs and the menstrual cycle phase affects sleep spindles and therefore should be considered in further studies investigating sleep spindles and cognitive performance.

Metacognitive preserved generation strategy benefits for both younger and elderly participants with schizophrenia.

Cognitive memory and introspection disturbances are considered core features of schizophrenia. Moreover, it remains unclear whether or not participants with schizophrenia are more cognitively impaired with ageing than healthy participants. The aims of this study were to use a metacognitive approach to determine whether elderly participants with schizophrenia are able to improve their memory performance using a specific generation strategy and to evaluate the memory benefits for them using this strategy. 20 younger and 20 older participants with schizophrenia and their comparison participants matched for age, gender and education learned paired associates words with either reading or generation, rated judgment of learning (JOL) and performed cued recall. Participants with schizophrenia recalled fewer words than healthy comparison participants, but they benefited more from generation, and this difference was stable with ageing. Their JOL magnitude was lower than that of healthy comparison participants, but JOL accuracy was not affected by either age or the pathology. In spite of their memory deficit, elderly and younger participants with schizophrenia benefited remarkably from the memory generation strategy. This result gives some cause for optimism as to the possibility for participants with schizophrenia to reduce memory impairment if learning conditions lead them to encode deeply.

Better Phonological Short-Term Memory Is Linked to Improved Cortical Memory Representations for Word Forms and Better Word Learning.

Language learning relies on both short-term and long-term memory. Phonological short-term memory (pSTM) is thought to play an important role in the learning of novel word forms. However, language learners may differ in their ability to maintain word representations in pSTM during interfering auditory input. We used magnetoencephalography (MEG) to investigate how pSTM capacity in better and poorer pSTM groups is linked to language learning and the maintenance of pseudowords in pSTM. In particular, MEG was recorded while participants maintained pseudowords in pSTM by covert speech rehearsal, and while these brain representations were probed by presenting auditory pseudowords with first or third syllables matching or mismatching the rehearsed item. A control condition included identical stimuli but no rehearsal. Differences in response strength between matching and mismatching syllables were interpreted as the phonological mapping negativity (PMN). While PMN for the first syllable was found in both groups, it was observed for the third syllable only in the group with better pSTM. This suggests that individuals with better pSTM maintained representations of trisyllabic pseudowords more accurately during interference than individuals with poorer pSTM. Importantly, the group with better pSTM learned words faster in a paired-associate word learning task, linking the PMN findings to language learning.

0094 The Effect of Zolpidem on Sleep-Dependent Declarative Memory Consolidation

Abstract Introduction Sleep plays a critical role in memory consolidation. At the same time, about 20% of population in the U.S. suffer from sleep disorders or deprivation, and about 16% of them reported using sleep aids (CDC, 2015). However, the effect of sleep aids on sleep-dependent memory consolidation remains unclear. Previous studies have observed an improvement in sleep-dependent declarative memory consolidation with zolpidem over a daytime nap (Mednick et al., 2013). The current study investigates the effect of zolpidem on declarative memory consolidation over a night of sleep and over 24 hours. Methods This study employed a double-blind, placebo-controlled, within-subject design, in which every subject (N=26, 12 females) experienced both zolpidem and placebo. All subjects were healthy, college-aged adults without sleep disorder. A 32-channel electroencephalogram cap was used to record brain activity during sleep. Word paired-associates task was used to evaluate memory performance. Participants reported to the laboratory in the evening, performed word paired-associates task (test1), then ingested either zolpidem or placebo before sleep. They were tested on the task in the following morning (test2) as well as in the following evening (test3). Paired-sample t-tests for retrieval difference scores between placebo and zolpidem conditions were conducted. Results Participants showed similar baseline performance on the word paired-associates task (test 1, p=0.45). Zolpidem condition showed higher memory retention compared to placebo 24hr after drug ingestion (test3-test1, t₂ 5=2.09, p<0.05). The improvement in performance for zolpidem condition occurred across the following day (test3-test2, t₂ 5=2.22, p<0.05), as no difference was observed between conditions after sleep (test2-test1, t₂ 5=0.34, p=0.74) Conclusion Consistent with previous studies, participants showed better memory performance after taking zolpidem compared to placebo. However, the current study showed that the improvement in memory occurred across a day of wakefulness after nighttime drug ingestion, while other studies observed improvements shortly after sleep, indicating a potential delayed benefit of zolpidem on memory consolidation. Support This work was supported by the Office of Naval Research grant N00014-14-1-0513

0093 Topographical Analysis of Sleep Spindles and Their Coordination with Slow Oscillations

Abstract Introduction Brain oscillations found during sleep are hypothesized to mediate sleep-dependent memory consolidation, by coordinating cortical-subcortical activity and enabling synaptic plasticity. In particular, sleep spindles (10-16Hz) density and coordination with slow oscillations (SOs, 0.5–1.5 Hz) have been shown to correlate with memory performance post-sleep. In this study, we characterize how spindles are organized on the electrode manifold, and their relation to SO topography. Methods We conducted a sleep-memory study where subjects learned word-pair associations in the morning and were tested in the evening and the next morning. Polysomnography was collected during the night. We detected sleep spindles at each electrode independently and study their basic biophysical properties (density, amplitude, frequency, duration) in light sleep (stage 2, S2) and deep sleep (slow wave sleep, SWS) separately, including their co-occurrence with SOs. We categorize spindles that are co-detected across electrodes within a short time window and study how properties change across groups. Results We find a gradual increase in average spindle frequency in the frontal-occipital axis, but no bimodality in frequency distribution. Furthermore, spindles paired to SOs (a minority in both stages) are shorter than non-paired spindles. We find that coordination between spindles and SO troughs is frequency but not amplitude selective; and differs between the two sleep stages. In S2, slow spindles precede SOs in frontal electrodes and fast spindles follow SOs in centro-posterior electrodes. Our clusters of spindle topography include a Frontal and a Posterior cluster. These clusters mirror the commonly considered slow-frontal and fast-posterior spindles, but contain less than half of all S2 spindles. Clustering identifies sub-types of spindle-SO complexes whose density is linked to memory performance. Conclusion Our study shows that specific sub-types of sleep oscillations, defined by their topography, support the coordination between spindles and SOs which could mediate cortical-subcortical dialogue during sleep. Support This work was supported by NIH grant (R01 AG046646) to Sara C. Mednick

Hippocampal and medial prefrontal cortical volume is associated with overnight declarative memory consolidation independent of specific sleep oscillations.

The current study was designed to further clarify the influence of brain morphology, sleep oscillatory activity and age on memory consolidation. Specifically, we hypothesized, that a smaller volume of hippocampus, parahippocampal and medial prefrontal cortex negatively impacts declarative, but not procedural, memory consolidation. Explorative analyses were conducted to demonstrate whether a decrease in slow-wave activity negatively impacts declarative memory consolidation, and whether these factors mediate age effects on memory consolidation. Thirty-eight healthy participants underwent an acquisition session in the evening and a retrieval session in the morning after night-time sleep with polysomnographic monitoring. Declarative memory was assessed with the paired-associate word list task, while procedural memory was tested using the mirror-tracing task. All participants underwent high-resolution magnetic resonance imaging. Participants with smaller hippocampal, parahippocampal and medial prefrontal cortex volumes displayed a reduced overnight declarative, but not procedural memory consolidation. Mediation analyses showed significant age effects on overnight declarative memory consolidation, but no significant mediation effects of brain morphology on this association. Further mediation analyses showed that the effects of age and brain morphology on overnight declarative memory consolidation were not mediated by polysomnographic variables or sleep electroencephalogram spectral power variables. Thus, the results suggest that the association between age, specific brain area volume and overnight memory consolidation is highly relevant, but does not necessarily depend on slow-wave sleep as previously conceptualized.

The effect of zolpidem on memory consolidation over a night of sleep.

Nonrapid eye movement sleep boosts hippocampus-dependent, long-term memory formation more so than wake. Studies have pointed to several electrophysiological events that likely play a role in this process, including thalamocortical sleep spindles (12-15 Hz). However, interventional studies that directly probe the causal role of spindles in consolidation are scarce. Previous studies have used zolpidem, a GABA-A agonist, to increase sleep spindles during a daytime nap and promote hippocampal-dependent episodic memory. The current study investigated the effect of zolpidem on nighttime sleep and overnight improvement of episodic memories. We used a double-blind, placebo-controlled within-subject design to test the a priori hypothesis that zolpidem would lead to increased memory performance on a word-paired associates task by boosting spindle activity. We also explored the impact of zolpidem across a range of other spectral sleep features, including slow oscillations (0-1 Hz), delta (1-4 Hz), theta (4-8 Hz), sigma (12-15 Hz), as well as spindle-SO coupling. We showed greater memory improvement after a night of sleep with zolpidem, compared to placebo, replicating a prior nap study. Additionally, zolpidem increased sigma power, decreased theta and delta power, and altered the phase angle of spindle-SO coupling, compared to placebo. Spindle density, theta power, and spindle-SO coupling were associated with next-day memory performance. These results are consistent with the hypothesis that sleep, specifically the timing and amount of sleep spindles, plays a causal role in the long-term formation of episodic memories. Furthermore, our results emphasize the role of nonrapid eye movement theta activity in human memory consolidation.