Translational measures of the effects of insufficient sleep on cognition in the rat

Insufficient sleep is highly prevalent and associated with deficits in functional wakefulness. Thus, a need remains for pre-clinical evaluation of sleep restriction to develop countermeasures for functional deficits. The overall aim of this thesis was to evaluate translational methods to assess the cognitive consequences of sleep loss in the rat. We first compared the effects of 11-h sleep restriction induced by three novel non-invasive protocols on attention using a Simple Response Latency task (SRLT). Wakefulness was enforced by cylinder rotation following a Constant, Decreasing or ‘Weibull’ (i.e., modelled on EEG-driven sleep restriction) protocols. While all protocols resulted in sleep loss and attentional deficits, differences in sleep recovery and functional alterations were identified, with the Decreasing and Weibull methods inducing attentional deficits similar to those observed in humans. Many behavioural tasks use food as a reward in rodents, thus we next assessed the interaction of food and sleep restriction. Food-restricted rats displayed resilience in SRLT performance to the effects of 11-h sleep restriction compared to ad libitum-fed rats. By contrast, motivation for food reward value was not altered in a progressive ratio task. We then evaluated the effects of pharmacological treatments to counteract the effects of 11-h sleep restriction. The drugs showed distinct pro-vigilant profiles, with caffeine and modafinil displaying beneficial effects on SRLT performance. A non-pharmacological counter-measure (naps) was unsuccessful in alleviating functional deficits induced by sleep loss. Finally, we applied oxygen amperometry, as a surrogate of neuroimaging, and measured oxygen consumption in the nucleus accumbens during the SRLT. However, data interpretation was limited due to throughput capabilities. Overall, the data indicated the sleep restriction methodologies provide a translational platform to develop novel pro-vigilant compounds that improve sustained attention. Careful choice of methodologies (i.e., sleep restriction protocols; reward) is important when studying functional deficits induced by sleep loss in rodents

Food restriction induces functional resilience to sleep restriction in rats

Study Objectives. Sleep restriction leads to performance decrements across cognitive domains but underlying mechanisms remain largely unknown. The impact of sleep restriction on performance in rodents is often assessed using tasks in which food is the reward. Investigating how the drives of hunger and sleep interact to modulate performance may provide insights into mechanisms underlying sleep loss related performance decrements. Methods. Three experiments were conducted in male adult Wistar rats to assess: 1) Effects of food restriction on performance in the simple response latency task (SRLT) across the diurnal cycle (n=30); 2) Interaction of food restriction and sleep restriction (11-h) on SRLT performance, sleep EEG and event-related potentials (ERP) (n=10-13); 3) Effects of food restriction and sleep restriction on progressive ratio (PR) task performance to probe the reward value of food reinforcement (n=19). Results. Food restriction increased premature responding on the SRLT at the end of the light period of the diurnal cycle. Sleep restriction led to marked impairments in SRLT performance in the ad libitum-fed group, which were absent in the food-restricted group. After sleep restriction, food restricted rats displayed a higher amplitude of cue-evoked ERP components during the SRLT compared to the ad libitum group. Sleep restriction did not affect PR performance while food restriction improved performance. Conclusions. Hunger may induce a functional resilience to negative effects of sleep loss during subsequent task performance, possibly by maintaining attention to food-related cues.</p

Disturbances of sleep quality, timing and structure and their relationship with other neuropsychiatric symptoms in Alzheimer’s disease and schizophrenia: Insights from studies in patient populations and animal models

The high prevalence of sleep disturbance in neurodegenerative and psychiatric conditions is often interpreted as evidence for both sleep’s sensitivity to and causal involvement in brain pathology. Nevertheless, how and which aspects of sleep contribute to brain function remains largely unknown. This review provides a critical evaluation of clinical and animal literature describing sleep and circadian disturbances in two distinct conditions and animal models thereof: Alzheimer’s disease (AD) and schizophrenia. Its goal is to identify commonalities and distinctiveness of specific aspects of sleep disturbance and their relationship to symptoms across conditions. Despite limited standardisation, data imply that reductions in sleep continuity and alterations in sleep timing are common to AD and schizophrenia, whereas reductions in REM sleep and sleep spindle activity appear more specific to AD and schizophrenia, respectively. Putative mechanisms underlying these alterations are discussed. A standardised neuroscience based quantification of sleep and disease-independent assessment of symptoms in patients and animal models holds promise for furthering the understanding of mechanistic links between sleep and brain function in health and disease

Body-based perceptual rescaling revealed through the size-weight illusion

An embodied approach to the perception of spatial layout contends that the body is used as a 'perceptual ruler' with which individuals scale the perceived environmental layout. In support of this notion, previous research has shown that the perceived size of objects can be influenced by changes in the apparent size of hand. The size-weight illusion is a well known phenomenon, which occurs when people lift two objects of equal weight but differing sizes and perceive that the larger object feels lighter. Therefore, if apparent hand size influences perceived object size, it should also influence the object's perceived weight. In this study, we investigated this possibility by using perceived weight as a measure and found that changes in the apparent size of the hand influence objects' perceived weight

Welcome to Wonderland:the influence of the size and shape of a virtual hand on the perceived size and shape of virtual objects

The notion of body-based scaling suggests that our body and its action capabilities are used to scale the spatial layout of the environment. Here we present four studies supporting this perspective by showing that the hand acts as a metric which individuals use to scale the apparent sizes of objects in the environment. However to test this, one must be able to manipulate the size and/or dimensions of the perceiver’s hand which is difficult in the real world due to impliability of hand dimensions. To overcome this limitation, we used virtual reality to manipulate dimensions of participants’ fully-tracked, virtual hands to investigate its influence on the perceived size and shape of virtual objects. In a series of experiments, using several measures, we show that individuals’ estimations of the sizes of virtual objects differ depending on the size of their virtual hand in the direction consistent with the body-based scaling hypothesis. Additionally, we found that these effects were specific to participants’ virtual hands rather than another avatar’s hands or a salient familiar-sized object. While these studies provide support for a body-based approach to the scaling of the spatial layout, they also demonstrate the influence of virtual bodies on perception of virtual environments