Biology subjects

Kent, B. A.

Publications and source records attributed to Kent, B. A..

4 recordsLinked to original sources

bioRxiv2025

The relationship between sleep, mental health, and performance on tests of pattern separation in young adults

ObjectivesYoung adults experience the highest rates of mental health disorders of any age group. Given that mental health disorders are associated with sleep disturbances and cognitive impairments, we investigated whether sleep moderates the effects on cognition. MethodsUniversity students (N=89; aged 18-30 years) remotely monitored their sleep for seven consecutive days using wrist actigraphy and sleep diaries. On day seven, participants completed cognitive testing and mental health questionnaires. Cognitive tests included the Psychomotor Vigilance Task (PVT), Cambridge Neuropsychological Test Automated Battery (CANTAB), and the Mnemonic Similarity Task (MST). CANTABs Delayed Matching to Sample (DMS) and MST are designed to tax pattern separation, a computational mechanism supporting encoding of similar experiences as distinct representations. Becks Depression Inventory and Becks Anxiety Inventory assessed mental health. ResultsEighty participants (mean age: 20.13{+/-}2.00) were included in the analyses. Most participants reported mild to severe depressive and anxiety symptoms. Depressive symptoms were correlated with wake-up time ({rho}=.35, p=.002) as well as PVT ({rho}=.26, p=.02) and DMS ({rho}=.24, p=.04) performance. Bedtime was correlated with performance on MST (r=-.29, r=.02) and DMS ({rho}=.25, p=.03), while wake-up time was correlated with performance on MST (r=- .31, p=.01) and DMS ({rho}=.28, p=.01). Sleep did not moderate the effects of mental health on cognitive performance. ConclusionCognitive tests taxing pattern separation are sensitive to depressive symptoms and sleep timing. While students face a disproportionate burden of mental health disorders compromising cognitive functioning, improving sleep quality may offer a partial, though not moderating, pathway to alleviating these cognitive impairments.

neuroscience↗

bioRxiv2025

The Effects of Acute Trazodone Administration on Sleep in Mice

Study ObjectivesTrazodone is an antidepressant with robust hypnotic effects, frequently prescribed off-label to treat insomnia. Trazodone has gained recent attention in the context of neurodegenerative diseases because sleep has been proposed as a novel target for disease-modifying therapeutics. Preclinical research in rodents examining the effects of trazodone on sleep is limited, so here we aimed to develop a translationally-focused protocol to study the sleep-promoting effects of trazodone in mice. MethodsWe investigated the effects of voluntary oral trazodone administration at doses of 0 mg/kg, 10 mg/kg, 40 mg/kg, and 60 mg/kg on sleep in C57BL/6J mice (n = 15; females = 6; age 10-13 months). Mice were dosed with trazodone for 6 consecutive nights, while being recorded with intracranially implanted 2-channel electroencephalogram (EEG) and electromyography (EMG). EEG/EMG recordings were analyzed for time spent in each vigilance state and power spectra. ResultsA single dose of trazodone, administered prior to the onset of the 12-h rest phase, dose-dependently increased non-rapid eye movement (NREM) sleep and delta power during NREM sleep, at the expense of rapid eye movement (REM) sleep. These effects on sleep persisted after six consecutive days of dosing, albeit to a lesser extent. ConclusionWe have validated a novel voluntary oral administration protocol for trazodone use in mice and have shown that trazodone effectively promotes NREM in mice. Our novel protocol will be useful for future research investigating the effects of trazodone on sleep in mouse models of disease. Statement of significanceTrazodone is an antidepressant known to increase slow wave sleep in humans. Slow wave sleep promotion is being explored as a disease-modifying therapeutic target for neurodegenerative diseases, such as Alzheimers disease. We have developed a novel translationally-focused protocol for administering trazodone to mice, which overcomes some of the challenges of using trazodone for preclinical sleep research. Using our protocol we have demonstrated for the first time that trazodone dose-dependently increases the amount of NREM sleep and delta power in mice, recapitulating the enhancement of slow wave sleep in humans treated with trazodone.

neuroscience↗

bioRxiv2024

Impact of Optogenetic Activation of the Thalamic Reticular Nucleus on Sleep Architecture in Mice

Alzheimers disease (AD) is a progressive neurodegenerative disorder affecting millions worldwide and is often accompanied by significant sleep disturbances, such as sleep fragmentation, early awakenings, decreased sleep efficiency, and insomnia. It has been suggested that the alterations in activity of the thalamic reticular nucleus (TRN) are closely associated with sleep disruptions in AD. Evidence suggests that activating neurons expressing gamma-aminobutyric acid (GABA) within the TRN may enhance sleep quality and potentially ameliorate neuropathology associated with AD. However, the precise mechanisms through which TRN influences sleep disruptions and AD pathophysiology remain poorly understood. In this study, we investigated whether activating GABAergic TRN neurons could alter sleep architecture in wild-type mice. Utilizing optogenetic stimulation, we observed that activation of these neurons did not significantly alter sleep state durations or delta wave power, a key indicator of Slow Wave Sleep (SWS). Furthermore, the application of a two-virus strategy inadvertently led to non-specific opsin expression beyond the targeted TRN area. We discuss the potential factors that contributed to these outcomes, providing directions for future investigations to better delineate the role of the TRN in sleep and AD.

neuroscience↗

bioRxiv2024

The relationship between sleep and cognitive performance on tests of pattern separation

Study objectivesSleep disturbances are considered both a risk factor and symptom of dementia. The present research aimed to identify cognitive tests in which performance is associated with objective sleep quality or quantity, focusing on cognitive tests designed to evaluate the earliest cognitive changes in dementia. MethodsWe recruited older adults (50 years of age or older) and remotely monitored their sleep patterns for 7 consecutive days using wrist actigraphy and sleep diaries. On day 7, participants completed a battery of cognitive tests, which included the Psychomotor Vigilance Task (PVT), the Prodromal Alzheimers and Mild Cognitive Impairment battery from the Cambridge Neuropsychological Test Automated Battery (CANTAB), and the Mnemonic Similarity Task (MST), designed to tax pattern separation. The participants were also assessed with the Montreal Cognitive Assessment (MoCA). ResultsThe final sample included 34 participants (mean age: 65.56, SD: 9.57). There were significant correlations between objective total sleep time and PVT and MST performance. MoCA scores were correlated with performance on CANTAB and MST. Objective total sleep time also predicted MST performance when controlling for age and gender. ConclusionsPerformance on cognitive tests designed to assess pattern separation are sensitive to older adults objective sleep duration and the early cognitive changes associated with dementia. MST should be evaluated for potential use as a clinical trial outcome measure for sleep-promoting treatments in older adults. Statement of SignificanceThere is growing emphasis on the importance of sleep as a potential therapeutic target for neurodegenerative diseases (e.g., Alzheimers disease). Identifying cognitive measures that are sensitive to both sleep and the earliest cognitive changes associated with dementia are needed for use as outcome measures in clinical trials evaluating the effectiveness of sleep-promoting interventions. Our research addresses this need by investigating the relationship between sleep patterns and performance on cognitive tests designed to assess the earliest cognitive changes in dementia. Our results suggest that cognitive tests designed to assess pattern separation are uniquely sensitive to sleep quantity in older adults.

neuroscience↗