Biology subjects

Whitehurst, L. N.

Publications and source records attributed to Whitehurst, L. N..

5 recordsLinked to original sources

bioRxiv2021

The sleeping brain switches between working memory and long-term memory processing.

We provide evidence that human sleep is a competitive arena where 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 show the first evidence of a sleep switch mechanism that toggles between central sigma-dependent long-term memory and autonomic vagal-dependent working memory processing. Significant StatementSleep facilitates both long-term episodic memory consolidation and short-term working memory functioning. However, the mechanism by which the sleeping brain performs both complex feats, and which sleep features are associated with these processes remain unclear. Using a pharmacological approach, we demonstrate that long-term and working memory are served by distinct offline neural mechanisms, and that these mechanisms are mutually antagonistic. We propose a Sleep Switch model in which the brain toggles between the two memory processes via a complex interaction at the synaptic, systems, and mechanistic level, with implications for research on cognitive disturbances observed in neurodegenerative disorders such as Alzheimers and Parkinsons disease, both of which involve the decline of sleep.

neuroscience↗

bioRxiv2020

Age-related differences in Autonomic/Central Coupling during a Daytime Nap

Age-dependent functional changes are mirrored by declines in both the central the autonomic nervous systems and have been related to pathological aging. Prior studies in our group have identified a temporal coupling of Autonomic and Central Events (ACEs) during sleep using electrocardiogram to measure heart rate and electroencephalography to measure brain rhythms, with heart rate bursts (HRBs) temporally coincided with increased slow-wave-activity (SWA, 0.5-1Hz) and sigma activity (12-15Hz), followed by parasympathetic surge (RRHF) during non-rapid eye movement (NREM) sleep. ACEs predicted working memory (WM) improvement in young adults. Given that there are paralleling age-related declines in both the ANS and CNS, the current study investigated differences in ACE activity during daytime sleep in older and younger adults and their functional impact on working memory. Compared to youngers, older adults showed lower amplitude of ACEs during NREM sleep, but no age-related difference during Wake. Furthermore, while younger adults demonstrated a parasympathetic surge after HRBs, older adults showed a different pattern, with a earlier rise and maintenance of the RRHF. Finally, we examined whether ACE predicted WM in older adults. We found that older adults with good WM show stronger coupling, whereas low WM performers had less robust ACE activity. Taken together, our results demonstrated that autonomic-central coupling declines with age, with possible links to deterioration in WM function. Given that age-related deterioration in autonomic and central nervous system activity is implicated in pathological decline, the current findings may facilitate novel insights to the cognitive neuroscience of aging.

neuroscience↗

bioRxiv2020

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, pre-nap rest, and WASO. On the other hand, 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 pre-nap rest or QW. Altogether, our findings suggest a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.Impact Statement Sleep is naturally modulated by the autonomic nervous system (ANS), with greater dominance of parasympathetic over sympathetic activity during non-rapid-eye-movement (NREM) sleep. As such, sleep has been termed a “cardiovascular holiday” and has been associated with positive health outcomes. Aging, however, is linked to decreases in cardiac autonomic activity and sympathovagal imbalance. While the impact of aging on ANS activity during nocturnal sleep has received some attention, the cardiac profiles during a daytime nap, to our knowledge, have not yet been studied under the context of aging. Herein, young adults demonstrated increased parasympathetic activity during deep sleep. Older adults, however, showed less parasympathetic modulation during NREM sleep, suggesting loss of the cardiovascular holiday. Importantly, no age-related declines in parasympathetic activity were detected during wake, suggesting a sleep-specific reduction in parasympathetic modulation that is unique to NREM sleep in older adults.Competing Interest StatementThe authors have declared no competing interest.View Full Text

physiology↗

bioRxiv2020

Autonomic/Central Coupling Boosts 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 (Kuriyama et al. 2008a; Zinke, Noack, and Born 2018), with WM improvement correlated with slow wave activity (SWA; 0.5-1Hz) during slow wave sleep (SWS) (Sattari et al. 2019; Pugin et al. 2015; Ferrarelli et al. 2019). A different body of literature has suggested an important role for autonomic activity during wake for WM (Hansen et al. 2004; Mosley, Laborde, and Kavanagh 2018). A recent study from our group reported that the temporal coupling of autonomic and central events (ACEs) during sleep was associated with memory consolidation (Naji et al. 2019). We found that heart rate bursts (HR bursts) during non-rapid eye movement (NREM) sleep are accompanied by increases in SWA and sigma (12-15Hz) 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 may 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 (with electroencephalography (EEG) and electrocardiography (ECG)) or wake 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.

neuroscience↗

bioRxiv2020

Autonomic activity during a daytime nap facilitates working memory improvement

Recent investigations have implicated the parasympathetic branch of the autonomic nervous system (ANS) in higher-order executive functions. These actions are purported to occur through ANSs modulation of the prefrontal cortex, with parasympathetic activity during wake associated with working memory ability (WM). 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 (OSpan) in the morning and evening, and during the inter-test period subjects either experienced a nap or wake. We measured high frequency heart rate variability (HF HRV) 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, as well as greater WM improvement after a nap compared with an equivalent period awake. 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 has substantial benefits to 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. Significance StatementRecently, the neurovisceral integration model has implicated activity on the parasympathetic branch of the autonomic nervous system (ANS) during wake in executive functioning. Parasympathetic activity peaks during deep sleep, and sleep has been shown to facilitate executive functioning. Yet, the role of parasympathetic activity during sleep for executive functioning is not known. Herein, participants demonstrated increased parasympathetic activity during deep sleep, sleep-dependent WM improvement, and associations between performance gains and parasympathetic activity in sleep, not wake. Our conceptual model illustrates the interaction between sleep, autonomic activity, and prefrontal brain function that may contribute to executive abilities in young adults and to cognitive aging.

neuroscience↗