The role of spindles activity in the consolidation of neutral and emotional stimuli

Literature suggests that sleep plays a role in memory consolidation, including emotional memories, but it is still argued the underlying mechanism of this process. In this regard, spindles are sleep wave components whose role has been associated with memory consolidation, although researchers still report conflicting results. This research aims to understand if sleep spindle activity has a role in memory consolidation and whether it acts differently on neutral and emotional stimuli.Literature suggests that sleep plays a role in memory consolidation, including emotional memories, but it is still argued the underlying mechanism of this process. In this regard, spindles are sleep wave components whose role has been associated with memory consolidation, although researchers still report conflicting results. This research aims to understand if sleep spindle activity has a role in memory consolidation and whether it acts differently on neutral and emotional stimuli

The contribution of sleep to cognitive function in children with epilepsy

Cognitive impairment is the major co-morbidity in childhood epilepsy, and in many cases will have a larger long-term impact than the seizures themselves. However, the mechanisms contributing to this are poorly understood, precluding targetted intervention. Sleep is crucial for intelllectual functioning. Yet sleep in children with epilepsy, and its impact on intellectual function has scarcely been studied. This thesis aims to examine the structure and regulation of sleep in children with epilepsy, and to provide direct evidence of the impact of sleep on cognitive function by correlating neurophysiological characteristics with performance on sleep dependent neuropsychological tasks administered over the same interval as the sleep recorded. To examine sleep architecture in children with epilepsy, I developed a modified system for visual sleep scoring, taking into account nocturnal seizures and interictal activity. This was validated in a pilot sample, then applied to the scoring of 52 recordings from children with epilepsy. Based on established memory consolidation tasks and open-source psycholinguistic data, I developed and piloted a memory consolidation task battery suitable for testing school-aged English-speaking children, comprising parallel versions of a visuospatial and a verbal task. With these tools, I performed a prospective, within-subject comparison of memory retention across similar length intervals with or without sleep, in order to determine the contribution of sleep to memory consolidation. I compared results from patient (n=22) and healthy control (n=21) samples, finding – contrary to expectations – that sleep benefits memory consolidation in children with epilepsy to the same degree as controls. However, the benefit of sleep showed an inverse relationship to the nocturnal interictal discharge load. I also employed quantitative EEG analysis of slow wave activity to examine sleep homeostasis in patients with epilepsy, studying a retrospective sample (n=16) who had undergone partial sleep deprivation. Sleep homeostasis was fundamentally intact in these patients, who had similar clinical characteristics to the prospective sample. Findings from this thesis provide the first direct evidence that sleep benefits intellectual functioning in children with epilepsy, particularly where its structure and regulation is intact. Sleep-related memory consolidation may represent a compensatory mechanism, perhaps accounting for the relative cognitive preservation in this cohort of children with epilepsy with a structural aetiology, despite the early onset of seizures

Sex Differences in the Transitional Period between Slow-Wave Sleep and REM Sleep: A Novel Metric for Sleep Quality and Neuropsychiatric Disorders

Sleep is an important biological process, and it is well-documented that sleep disturbances often precede neuropsychiatric disorders. Sleep has traditionally been divided into two basic stages, non-REM and REM sleep. These two stages are often considered to have distinct functions and are usually studied independently. However, an additional sleep stage, the transitional period between non-REM and REM sleep, has been described but not well investigated. While sex differences in the other stages of sleep have been documented and are deemed clinically relevant, no study has investigated sex differences in this transitional period. In the present study, this period is termed transition sleep is directly compared between male and female rats for the first time. Eight male and eight female adult rats were fitted with sleep-recording implants, and their sleep-wake activity was recorded every four days for two weeks. The results indicate that female rats spend more time in transition sleep and have a higher frequency of transition sleep episodes. Additionally, regression models of the percentage of time spent in each sleep stage revealed that the different sleep stages had larger effects on one another in the female rats compared to the males. This indicates that, for the females, the different sleep stages were more interdependent, pointing to a difference in the biological mechanisms that are involved in regulating transitions between sleep stages. These findings provide novel insight into sex differences in sleep and a new approach for investigating the link between sleep disturbances and psychiatric illness

A clinicopathological investigation of brainstem nuclei in Lewy body dementia

Introduction: Lewy Body Dementias (LBD) - Dementia with Lewy Bodies (DLB) and Parkinson’s Disease Dementia (PDD) - are clinical diagnoses based on the one-year rule and varied symptom onset. Previously, degeneration of the locus coeruleus (LC) and dorsal raphe nucleus (DRN) in LBD has been well established. However, the precise relationship between underlying neuropathology and clinical presentation remains to be determined. Methods: Immunohistochemical and image analysis techniques have been performed to examine neuronal loss and protein pathologies in the noradrenergic and serotonergic systems of 20 PD, 20 PD-MCI, 20 PDD, 20 DLB cases and 20 controls. RNAscope technology was used to decipher the role of cell-surface receptors in LBD pathophysiology. Possible associations between administration of pharmacological agents with LBD pathology and disease duration was also examined. Results: The hippocampus, thalamus and cingulate cortex - crucial components of the Papez circuit - were most affected by the proteinopathies, particularly deposition that correlated with the onset of some DLB symptomatology and non-motor symptoms. LC noradrenergic neurons were reduced in LBD compared to PD. The 5-HT2A receptor seemed to be more abundant than the α2A-adrenergic receptor (AR) and serotonin transporter (SERT) in the frontal cortex of a PD patient than a PDD or DLB patient. Conclusion: LBD phenotypes may be differentiated through their limbic involvement in the Papez circuit, where α-syn accumulation may contribute to non-motor symptoms. The behaviour of each protein type may be extremely heterogenous within each region of the noradrenergic and serotonergic systems, such that it correlates with the onset of different symptoms. There may be lower expression of receptors in LBD than PD patients, perhaps due to end-stage disease and more widespread degeneration. Hence, this study may have provided further insights into LBD pathophysiology and possibly assist clinical trials in future therapeutic interventions.Open Acces