Axonal injury, sleep disturbances, and memory following traumatic brain injury.

OBJECTIVES: Traumatic brain injury (TBI) is associated with sleep deficits, but it is not clear why some report sleep disturbances and others do not. The objective of this study was to assess the associations between axonal injury, sleep, and memory in chronic and acute TBI. METHODS: Data were acquired from two independent datasets which included 156 older adult veterans (69.8 years) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with prior moderate-to-severe TBIs and 90 (69.2 years) controls and 374 (39.6 years) from Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) with a recent mild TBI (mTBI) and 87 controls (39.6 years), all who completed an MRI, memory assessment, and sleep questionnaire. RESULTS: Older adults with a prior TBI had a significant association between axonal injury and sleep disturbances [ß = 9.52, 95% CI (4.1, 14.9), p = 0.01]. Axonal injury predicted changes in memory over 1-year in TBI [ß = -8.72, 95% CI (-18, -2.7), p = 0.03]. We externally validated those findings in TRACK-TBI where axonal injury within 2 weeks after mTBI was significantly associated with higher sleep disturbances in the TBI group at 2 weeks[ß = -7.2, 95% CI (-14, -0.50), p = 0.04], 6 months [ß = -16, 95% CI (-24, -7.6), p ≤ 0.01], and 12 months post-injury [ß = -11, 95% CI (-19, -0.85), p = 0.03]. These associations were not significant in controls. INTERPRETATIONS: Axonal injury, specifically to the left anterior internal capsule is robustly associated with sleep disturbances in multiple TBI populations. Early assessment of axonal injury following mTBI could identify those at risk for persistent sleep disturbances following injury.

Can stimulants make you smarter, despite stealing your sleep?

Nonmedical use of psychostimulants for cognitive enhancement is widespread and growing in neurotypical individuals, despite mixed scientific evidence of their effectiveness. Sleep benefits cognition, yet the interaction between stimulants, sleep, and cognition in neurotypical adults has received little attention. We propose that one effect of psychostimulants, namely decreased sleep, may play an important and unconsidered role in the effect of stimulants on cognition. We discuss the role of sleep in cognition, the alerting effects of stimulants in the context of sleep loss, and the conflicting findings of stimulants for complex cognitive processes. Finally, we hypothesize that sleep may be one unconsidered factor in the mythology of stimulants as cognitive enhancers and propose a methodological approach to systematically assess this relation.

The Influence of Emergency Call Volume on Occupational Workload and Sleep Quality in Urban Firefighters.

OBJECTIVE: The aim of the study is to determine the impact of emergency call volume on exertion, autonomic activity, and sleep among urban structural firefighters. METHODS: Thirty-four firefighters wore a wrist-based monitor to track sleep and autonomic parameters and rated their level of perceived exertion (Borg Rating of Perceived Exertion) and subjective sleepiness after a 24-hour shift. Predictive variables included total run time and total run time after 11:59 PM. RESULTS: Total run time and sleep duration accounted for Borg Rating of Perceived Exertion and subjective sleepiness, while total run time and total run time after 11:59 PM accounted for sleep durations on-duty. CONCLUSIONS: The current results suggest that emergency call volume is associated with indicators of exertion and sleep. As such, call volume tracking is an important consideration for departments to ensure personnel readiness and wellness and provide a method of tracking the occupational demands experienced by firefighters on-duty.

Deep rest: An integrative model of how contemplative practices combat stress and enhance the body's restorative capacity.

Engaging in contemplative practice like meditation, yoga, and prayer, is beneficial for psychological and physical well-being. Recent research has identified several underlying psychological and biological pathways that explain these benefits. However, there is not yet consensus on the underlying overlapping physiological mechanisms of contemplative practice benefits. In this article, we integrate divergent scientific literatures on contemplative practice interventions, stress science, and mitochondrial biology, presenting a unified biopsychosocial model of how contemplative practices reduce stress and promote physical health. We argue that engaging in contemplative practice facilitates a restorative state termed "deep rest," largely through safety signaling, during which energetic resources are directed toward cellular optimization and away from energy-demanding stress states. Our model thus presents a framework for how contemplative practices enhance positive psychological and physiological functioning by optimizing cellular energy consumption. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The effect of extended shift work on autonomic function in occupational settings: A systematic review and meta-analysis.

OBJECTIVE: To examine the effect of 24-h shift work on autonomic nervous system function via heart rate variability (HRV) methodologies. METHODS: Electronic databases (indexed in either PubMed, MEDLINE, CINAHL, SPORTDiscus, or OpenDissertations) were searched from January 1964 to March 2023. A modified Downs and Black checklist was used for assessing methodological quality and the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the quality of evidence. Study design, study population, study sample, shift work description, and assessment of HRV metrics and methods were extracted from each study. FINDINGS: A total of 58 478 study articles were identified, of which 12 articles met inclusion criteria. Sample sizes varied from eight to 60 participants, with the ratio of low- to high-frequency HRV (LF/HF) as the most common frequency-domain variable reported. Of the nine included studies that observed LF/HF, three (33.3%) demonstrated a significant increase after 24-h shift work. Moreover, of the five studies that reported HF, two (40%) noted a significant decrease after 24-h shift work. When observing risk of bias, two (16.6%) studies were low quality, five (41.7%) were moderate quality, and five (41.7%) were high quality. INTERPRETATION: There were inconsistent findings demonstrating an effect of 24-h shift work on autonomic function, with a suggested shift away from parasympathetic dominance. Discrepancies in HRV methodologies, such as the duration of recordings and hardware used for measurement, may have contributed to the disparity in findings. In addition, differences in roles and responsibilities across occupations may explain the incongruence in findings across studies.

The Role of Working Memory in Age-Related Emotional Memory Bias.

Aging is accompanied by deterioration in both working memory (WM) and long-term memory (LTM), yet whether these changes are related is not understood. Sleep plays a role in the formation of LTM in young adults, but the findings in older adults are not as clear. The types of memories we store also shift with age as young adults preserve a higher proportion of negative experiences when compared to older adults. The reason for this age-related change in emotional memory bias is also not clear; however, some studies have suggested that WM changes across aging may be an important factor. In the current study, we examined performance in WM and emotional LTM in younger and older adults. We added a daytime nap in half the subjects to examine a possible role of sleep on emotional LTM. In the morning, 93 younger (18-39) and 121 older (60-85) adults completed a WM task. Subjects also encoded neutral or negative word pairs and provided valence and arousal ratings for each pair. After half the subjects took a daytime nap, LTM was examined, and valence and arousal ratings were reassessed. Results indicate that older adults showed worse recognition for negative word pairs compared with neutral, as well as decreased negative valence ratings in the afternoon. This decrease in emotional reactivity was correlated with better LTM performance. In contrast, younger adults performed better on the negative compared to neutral word pairs, with no change in emotional reactivity and no association between emotional reactivity and LTM. In addition, WM was positively related to LTM in younger, but not in older adults. Lastly, no differences were shown across sleep, regardless of age. Our findings suggest that the emotional memory bias may be associated with the emotional saliency of the information in older adults, and with WM capacity in younger adults. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-022-00134-5.

Zolpidem Maintains Memories for Negative Emotions Across a Night of Sleep.

Zolpidem, a common medication for sleep complaints, also shows secondary, unexpected memory benefits. We previously found that zolpidem prior to a nap enhanced negative, highly arousing picture memory. As zolpidem is typically administered at night, how it affects overnight emotional memory processing is relevant. We used a double-blind, placebo-controlled, within-subject, cross-over design to investigate if zolpidem boosted negative compared to neutral picture memory. Subjects learned both pictures sets in the morning. That evening, subjects were administered zolpidem or placebo and slept in the lab. Recognition was tested that evening and the following morning. We found that zolpidem maintained negative picture memory compared to forgetting in the placebo condition. Furthermore, zolpidem increased slow-wave sleep time, decreased rapid eye movement sleep time, and increased the fast spindle range in NREM. Our results suggest that zolpidem may enhance negative memory longevity and salience. These findings raise concerns for zolpidem administration to certain clinical populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00079-1.

Sex Differences in the Association Between Poor Sleep Quality and Alcohol-Related Problems Among Heavy Drinkers With Insomnia.

Background: Alcohol Use Disorder (AUD) and insomnia are highly comorbid; at least 40% of individuals with AUD suffer from insomnia. Women are more likely to report insomnia than men and have seen a concerning rise in rates of AUD in recent years. As such, the association between AUD and insomnia could be particularly pronounced in women. However, currently little is known regarding sex differences in this association. Here we examined the degree to which relationships between alcohol use and sleep quality differ between women and men. Methods: Heavy drinking women (n = 66) and men (n = 45) completed the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and the Alcohol Use Disorders Identification Test (AUDIT) to assess alcohol use and alcohol-related problems. Hierarchical regression analyses were conducted to determine sex differences in the association between poor sleep quality and alcohol-related problems. Results: After controlling for age, global subjective stress, and depression, sex significantly moderated the positive association between poor sleep quality and alcohol-related problems. Further analyses of the simple slopes for each sex revealed that poorer sleep quality (i.e., higher scores on the PSQI) were associated with greater alcohol-related problems (i.e., higher scores on the AUDIT) in women, but not in men. Conclusion: These results suggest that in heavy drinkers with insomnia, poor sleep is more strongly associated with drinking problems in women than in men. Future research is needed to investigate potential mechanisms underlying this relationship. Specifically, it will be important to determine whether sleep problems in heavy drinking women are a cause or consequence, or both, of heavy drinking.

Autonomic central coupling during daytime sleep differs between older and younger people.

Decreased functioning in the elderly is mirrored by independent changes in central and autonomic nervous systems. Additionally, recent work suggests that the coupling of these systems may also serve an important role. In young adults, Autonomic and Central Events (ACEs), measured in the temporal coincidence of heart rate bursts (HRBs) and increased slow-wave-activity (SWA, 0.5-1 Hz) and sigma activity (12-15 Hz), followed by parasympathetic surge (RRHF) during non-rapid eye movement (NREM) sleep, predicted cognitive improvements. However, ACEs have not been examined in the elderly. Thus, the current study compared ACEs during wake and daytime sleep in older and younger adults and examined associations with working memory improvement before and after a nap. Compared to youngers, older adults showed lower amplitude of ACEs during NREM sleep, but not during wake. Furthermore, while younger adults demonstrated a parasympathetic surge after HRBs, older adults showed an earlier rise and longer maintenance of the RRHF. Taken together, our results demonstrate that autonomic-central coupling declines with age. Pathological aging implicates independent roles for decreased autonomic and central nervous system functioning, the current findings suggest that the coupling of these systems may also deserve attention.

The role of sleep for episodic memory consolidation: Stabilizing or rescuing?

Prior studies suggest a role for sleep in memory consolidation, with specific contributions from slow oscillations and sleep spindles (Rasch & Born, 2013). However, recent studies failed to replicate sleep's superiority over wake in strengthening memory against interference (Cordi & Rasch, 2021). The goal of the current study is to investigate whether sleep protects newly formed memory from unspecific interference induced by daytime experiences over 24 h, as well as to elucidate the sleep features that are involved. 56 healthy adults were randomly assigned to either the Sleep First or Wake First group. The Sleep First group encoded word pairs at night before sleep, while the Wake First group encoded word pairs in the morning before a day of wakefulness. Memory was tested 30 min, 12 h, and 24 h after encoding for both groups. The Sleep First group performed significantly better 12 h after encoding, replicating prior findings that memory is better after a period of sleep compared to wake. However, after 24 h, the two groups performed similarly. The Wake First group showed a positive correlation between overnight memory improvement and the theta and delta band power during slow wave sleep, an effect not found in the Sleep First group. These correlations suggest the possibility that after a day of waking interference, the brain recruits extra sleep resources to rescue memories from further forgetting. Our results are not consistent with prior studies showing a significant role for sleep in stabilizing memory from future interference, but they may suggest that sleep rescues memories after interference has occurred.

Links between the brain and body during sleep: implications for memory processing.

Sleep is intimately related to memory processes. The established view is that the transformation of experiences into long-term memories is linked to sleep-related CNS function. However, there is increasing evidence that the autonomic nervous system (ANS), long recognized to modulate cognition during waking, can impact memory processing during sleep. Here, we review human research that examines the role of autonomic activity and sleep in memory formation. We argue that autonomic activity during sleep may set the stage for the CNS dynamics associated with sleep and memory stability and integration. Further, we consider how the link between ANS activity and polysomnographic markers of sleep may help elucidate both healthy and pathological cognitive aging in humans.

Competitive dynamics underlie cognitive improvements during sleep.

We provide evidence that human sleep is a competitive arena in which cognitive domains vie for limited resources. Using pharmacology and effective connectivity analysis, we demonstrate that long-term memory and working memory are served by distinct offline neural mechanisms that are mutually antagonistic. Specifically, we administered zolpidem to increase central sigma activity and demonstrated targeted suppression of autonomic vagal activity. With effective connectivity, we determined the central activity has greater causal influence over autonomic activity, and the magnitude of this influence during sleep produced a behavioral trade-off between offline long-term and working memory processing. These findings suggest a sleep switch mechanism that toggles between central sigma-dependent long-term memory and autonomic vagal-dependent working memory processing.

Psychostimulants may block long-term memory formation via degraded sleep in healthy adults.

Sleep is vital for biological function and long-term memory formation, with preferential enhancement of emotionally laden content. A growing trend in healthy young adults is the non-medical use of psychostimulants, or "smart drugs", to prevent sleep and, hopefully, enhance cognition. However, the effect of these drugs on sleep-dependent memory processes are unclear. Here, in a within-subject, double-blind, placebo-controlled design, we investigated the impact of morning administration of dextroamphetamine on memory retention of negative and neutral pictures after 1) 12 h of wake, and 2) 24 h with sleep. After 12-hrs of wake, stimulants increased hit rate for neutral, but not negative, pictures, compared to placebo. No differences in memory discrimination were found. In addition, stimulants impaired nighttime sleep and significantly reduced memory for neutral pictures at 24-hrs, compared to placebo. Again, no performance differences between drug conditions were found for negative pictures. Together, these findings suggest that stimulants impairment of nighttime sleep likely leads to next day memory costs.

Age-related losses in cardiac autonomic activity during a daytime nap.

In healthy, young individuals, a reduction in cardiovascular output and a shift from sympathetic to parasympathetic (vagal) dominance is observed from wake into stages of nocturnal and daytime sleep. This cardiac autonomic profile, measured by heart rate variability (HRV), has been associated with significant benefits for cardiovascular health. Aging is associated with decreased nighttime sleep quality and lower parasympathetic activity during both sleep and resting. However, it is not known whether age-related dampening of HRV extends to daytime sleep, diminishing the cardiovascular benefits of naps in the elderly. Here, we investigated this question by comparing the autonomic activity profile between young and older healthy adults during a daytime nap and a similar period of wakefulness (quiet wake; QW). For each condition, from the electrocardiogram (ECG), we obtained beat-to-beat HRV intervals (RR), root mean square of successive differences between adjacent heart-beat-intervals (RMSSD), high-frequency (HF), low-frequency (LF) power, and total power (TP), HF normalized units (HFnu ), and the LF/HF ratio. As previously reported, young subjects showed a parasympathetic dominance during NREM, compared with REM, prenap rest, and WASO. Moreover, older, compared to younger, adults showed significantly lower vagally mediated HRV (measured by RMSSD, HF, HFnu ) during NREM. Interestingly, however, no age-related differences were detected during prenap rest or QW. Altogether, our findings suggest a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.

Autonomic Activity during a Daytime Nap Facilitates Working Memory Improvement.

Recent investigations have implicated the parasympathetic branch of the autonomic nervous system in higher-order executive functions. These actions are purported to occur through autonomic nervous system's modulation of the pFC, with parasympathetic activity during wake associated with working memory (WM) ability. Compared with wake, sleep is a period with substantially greater parasympathetic tone. Recent work has reported that sleep may also contribute to improvement in WM. Here, we examined the role of cardiac parasympathetic activity during sleep on WM improvement in healthy young adults. Participants were tested in an operation span task in the morning and evening, and during the intertest period, participants experienced either a nap or wake. We measured high-frequency heart rate variability as an index of cardiac, parasympathetic activity during both wake and sleep. Participants showed the expected boost in parasympathetic activity during nap, compared with wake. Furthermore, parasympathetic activity during sleep, but not wake, was significantly correlated with WM improvement. Together, these results indicate that the natural boost in parasympathetic activity during sleep may benefit gains in prefrontal executive function in young adults. We present a conceptual model illustrating the interaction between sleep, autonomic activity, and prefrontal brain function and highlight open research questions that will facilitate understanding of the factors that contribute to executive abilities in young adults as well as in cognitive aging.

Autonomic/central coupling benefits working memory in healthy young adults.

Working memory (WM) is an executive function that can improve with training. However, the precise mechanism for this improvement is not known. Studies have shown greater WM gains after a period of sleep than a similar period of wake, and correlations between WM improvement and slow wave activity (SWA; 0.5-1 Hz) during slow wave sleep (SWS). A different body of literature has suggested an important role for autonomic activity during wake for WM. A recent study from our group reported that the temporal coupling of Autonomic/CentralEvents (ACEs) during sleep was associated with memory consolidation. We found that heart rate bursts (HR bursts) during non-rapid eye movement (NREM) sleep are accompanied by increases in SWA and sigma (12-15 Hz) power, as well as increases in the high-frequency (HF) component of the RR interval, reflecting vagal rebound. In addition, ACEs predict long-term, episodic memory improvement. Building on these previous results, we examined whether ACEs also contribute to gains in WM. We tested 104 young adults in an operation span task (OSPAN) in the morning and evening, with either a nap (n = 53; with electroencephalography (EEG) and electrocardiography (ECG)) or wake (n = 51) between testing sessions. We identified HR bursts in the ECG and replicated the increases in SWA and sigma prior to peak of the HR burst, as well as vagal rebound after the peak. Furthermore, we showed sleep-dependent WM improvement, which was predicted by ACE activity. Using regression analyses, we discovered that significantly more variance in WM improvement could be explained with ACE variables than with overall sleep activity not time-locked with ECG. These results provide the first evidence that coordinated autonomic and central events play a significant role in sleep-related WM improvement and implicate the potential of autonomic interventions during sleep for cognitive enhancement.

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

STUDY OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The impact of psychostimulants on sustained attention over a 24-h period.

The off-label use of psychostimulants is a growing trend in healthy adults with many turning to these medications to increase alertness, attentional focus, and to help them study. However, the empirical literature on the efficacy of these medications for cognitive enhancement is controversial and the longer-term impact of these drugs on health and cognitive processing has not been thoroughly examined. Specifically, sleep supports daytime alertness, vigilance, and sustained attention, yet stimulants significantly disrupt sleep. Here, using a double-blind, placebo-controlled, crossover design, we tested the impact morning administration of psychostimulants (dextroamphetamine; DEX) had on: (1) tests of attention 75-min and 12-h after drug ingestion, (2) nighttime sleep and (3) post-sleep attention in healthy, young adults. First, we found that repeated testing led to significant decreases in performance from baseline in the placebo condition, and that DEX, compared to placebo, prevented deterioration at the 75-min test, and selectively for visual field at the 12 h and 24 h tests. We also found that stimulants, compared to placebo, benefitted attentional processing 75-min post-drug but this did not persist to the delayed test 12-h after drug administration. Additionally, morning stimulant administration resulted in robust nighttime sleep disruptions, yet post-sleep sustained attention was equivalent in the stimulant and placebo conditions, indicating that the initial boost to performance dissipated at 24 h, but the decrease was not significantly worse than placebo. Together, these results suggest that stimulant medications, commonly used off-label for cognitive enhancement may prevent deterioration of sustained attention brought on by repeated within-day testing. Additionally, these medications substantially disrupt nighttime sleep; which while coming at little cost to next-day attentional processing, may have steeper consequences for other cognitive domains.

Does working memory improvement benefit from sleep in older adults?

Working Memory (WM), is an important factor influencing many higher-order cognitive functions that decline with age. Repetitive training appears to increase WM, yet the mechanisms underlying this improvement are not understood. Sleep has been shown to benefit long-term memory formation and may also play a role in WM enhancement in young adults. However, considering age-related decline in sleep, it is uninvestigated whether sleep will facilitate WM in older adults. In the present work, we investigated the impact of a nap, quiet wakefulness (QW) and active wakefulness (AW) on within-day training on the Operation Span (OSPAN) task in older adults. Improvement in WM was found following a nap and QW, but not active wake. Furthermore, better WM was associated with shared electrophysiological features, including slow oscillation (SO, 0.5-1 Hz) power in both the nap and QW, and greater coupling between SO and sigma (12-15 Hz) in the nap. In summary, our data suggest that WM improvement in older adults occurs opportunistically during offline periods that afford enhancement in slow oscillation power, and that further benefits may come with cross-frequency coupling of neural oscillations during sleep.

Morning stimulant administration reduces sleep and overnight working memory improvement.

The goal of cognitive enhancement is to improve mental functions using interventions including cognitive training, brain stimulation and pharmacology. Indeed, psychostimulants, commonly used for cognitive enhancement purposes, while preventing sleep, have been shown to increase working memory (WM) and attention. Sleep, however, is also important for cognitive function; thus, understanding the interaction between stimulants, sleep and cognition may inform current approaches to cognitive enhancement. We used a double-blind, placebo controlled, repeated measure design to investigate the effect of morning administration of a commonly used stimulant, dextroamphetamine (DEX, 20 mg), on repeated, within-day and overnight WM performance, as well as on sleep in healthy young adults. Compared with placebo (PBO), we found no within-day benefit of DEX on WM. After sleep, DEX performed worse than PBO and the overnight improvement in performance in the PBO condition was absent in the DEX condition. Moreover, sleep quality was negatively affected by DEX administration. In summary, we found no cognitive boost from psychostimulants across a day of wake and a blockade of overnight WM increases with the stimulant, compared to PBO.