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  • Sleep and Circadian Rhythm Disruption in Psychosis

    27 October 2017

    © 2015 John Wiley & Sons, Inc. Sleep is a complex physiological process involving the interaction of multiple neurotransmitter systems and a diverse network of both arousal and sleep-promoting brain nuclei. This chapter focuses primarily on schizophrenia and bipolar disorder. These disorders form part of a broader psychosis spectrum. Sleep and circadian rhythm disruption (SCRD) has been reported in 30-80% of patients with schizophrenia. In bipolar disorder, sleep disturbances have been shown to be triggers for manic episodes, including irregular sleep timing and reduced total sleep time. Further mechanistic evidence for a link between the circadian system and bipolar disorder comes from work on animal models. Another factor that should be considered in this context is that circadian rhythms and sleep are mechanistically different, albeit interacting, processes. A number of potential mechanisms that may account for SCRD in psychosis are summarized and discussed in more detail in the chapter.

  • A preliminary investigation of sleep quality in functional neurological disorders: Poor sleep appears common, and is associated with functional impairment.

    17 November 2017

    PURPOSE: Functional neurological disorders (FND) are disabling conditions for which there are few empirically-supported treatments. Disturbed sleep appears to be part of the FND context; however, the clinical importance of sleep disturbance (extent, characteristics and impact) remains largely unknown. We described sleep quality in two samples, and investigated the relationship between sleep and FND-related functional impairment. METHODS: We included a sample recruited online via patient charities (N=205) and a consecutive clinical sample (N=20). Participants completed validated measures of sleep quality and sleep characteristics (e.g. total sleep time, sleep efficiency), mood, and FND-related functional impairment. RESULTS: Poor sleep was common in both samples (89% in the clinical range), which was characterised by low sleep efficiency (M=65.40%) and low total sleep time (M=6.05h). In regression analysis, sleep quality was negatively associated with FND-related functional impairment, accounting for 16% of the variance and remaining significant after the introduction of mood variables. CONCLUSIONS: These preliminary analyses suggest that subjective sleep disturbance (low efficiency, short sleep) is common in FND. Sleep quality was negatively associated with the functional impairment attributed to FND, independent of depression. Therefore, sleep disturbance may be a clinically important feature of FND.

  • Individuals with clinically significant insomnia symptoms are characterised by a negative sleep-related expectancy bias: Results from a cognitive-experimental assessment.

    27 October 2017

    Cognitive models of insomnia consistently suggest that negative expectations regarding the consequences of poor sleep contribute to the maintenance of insomnia. To date, however, no research has sought to determine whether insomnia is indeed characterised by such a negative sleep-related expectancy bias, using objective cognitive assessment tasks which are more immune to response biases than questionnaire assessments. Therefore, the current study employed a reaction-time task assessing biased expectations among a group with clinically significant insomnia symptoms (n = 30) and a low insomnia symptoms group (n = 40). The task involved the presentation of scenarios describing the consequences of poor sleep, and non-sleep related activities, which could be resolved in a benign or a negative manner. The results demonstrated that the high insomnia symptoms group were disproportionately fast to resolve sleep-related scenarios in line with negative outcomes, as compared to benign outcomes, relative to the low insomnia symptoms group. The two groups did not differ in their pattern of resolving non-sleep related scenarios. This pattern of findings is entirely consistent with a sleep-specific expectancy bias operating in individuals with clinically significant insomnia symptoms, and highlights the potential of cognitive-experimental assessment tasks to objectively index patterns of biased cognition in insomnia.

  • Progression of Late-Onset Stargardt Disease.

    27 October 2017

    Purpose: Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. Methods: We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset ≥ 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. Results: Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. Conclusions: We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high.

  • Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study.

    22 November 2017

    Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were "alcohol dependent" according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.

  • Simultaneous EEG-fNIRS reveals how age and feedback affects motor imagery signatures

    27 October 2017

    Stroke frequently results in motor impairment. Motor imagery (MI), the mental practice of movements, has been suggested as a promising complement to other therapeutic approaches facilitating motor rehabilitation. Of particular potential is the combination of MI with neurofeedback (NF). However, MI NF protocols have been largely optimized only in younger healthy adults, although strokes occur more frequently in older adults. The present study examined the influence of age on the neural correlates of MI supported by electroencephalogram (EEG)-based NF and on the neural correlates of motor execution. We adopted a multimodal neuroimaging framework focusing on EEG-derived event-related desynchronization (ERD%) and oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentrations simultaneously acquired using functional near-infrared spectroscopy (fNIRS). ERD%, HbO concentration and HbR concentration were compared between younger (mean age: 24.4 years) and older healthy adults (mean age: 62.6 years). During MI, ERD% and HbR concentration were less lateralized in older adults than in younger adults. The lateralization-by-age interaction was not significant for movement execution. Moreover, EEG-based NF was related to an increase in task-specific activity when compared to the absence of feedback in both older and younger adults. Finally, significant modulation correlations were found between ERD% and hemodynamic measures despite the absence of significant amplitude correlations. Overall, the findings suggest a complex relationship between age and movement-related activity in electrophysiological and hemodynamic measures. Our results emphasize that the age of the actual end-user should be taken into account when designing neurorehabilitation protocols.

  • Lateralization patterns of covert but not overt movements change with age: An EEG neurofeedback study.

    23 November 2017

    The mental practice of movements has been suggested as a promising add-on therapy to facilitate motor recovery after stroke. In the case of mentally practised movements, electroencephalogram (EEG) can be utilized to provide feedback about an otherwise covert act. The main target group for such an intervention are elderly patients, though research so far is largely focused on young populations (<30 years). The present study therefore aimed to examine the influence of age on the neural correlates of covert movements (CMs) in a real-time EEG neurofeedback framework. CM-induced event-related desynchronization (ERD) was studied in young (mean age: 23.6 years) and elderly (mean age: 62.7 years) healthy adults. Participants performed covert and overt hand movements. CMs were based on kinesthetic motor imagery (MI) or quasi-movements (QM). Based on previous studies investigating QM in the mu frequency range (8-13Hz) QM were expected to result in more lateralized ERD% patterns and accordingly higher classification accuracies. Independent of CM strategy the elderly were characterized by a significantly reduced lateralization of ERD%, due to stronger ipsilateral ERD%, and in consequence, reduced classification accuracies. QM were generally perceived as more vivid, but no differences were evident between MI and QM in ERD% or classification accuracies. EEG feedback enhanced task-related activity independently of strategy and age. ERD% measures of overt and covert movements were strongly related in young adults, whereas in the elderly ERD% lateralization is dissociated. In summary, we did not find evidence in support of more pronounced ERD% lateralization patterns in QM. Our finding of a less lateralized activation pattern in the elderly is in accordance to previous research and with the idea that compensatory processes help to overcome neurodegenerative changes related to normal ageing. Importantly, it indicates that EEG neurofeedback studies should place more emphasis on the age of the potential end-users.