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Human motor cortical gamma activity relates to GABAergic intracortical inhibition and motor learning
Abstract Gamma activity (γ, >30 Hz) is universally demonstrated across brain regions and species. However, the physiological basis and functional role of γ sub-bands (slow-γ, mid-γ, fast-γ) have been predominantly studied in rodent hippocampus; γ activity in the human neocortex is much less well understood. We use electrophysiology, non-invasive brain stimulation and several motor tasks to examine the properties of sensorimotor γ activity sub-bands and their relationship to both local GABAergic activity and motor learning. Data from three experimental studies are presented. Experiment 1 (N = 33) comprises magnetoencephalography (MEG), transcranial magnetic stimulation (TMS), and a motor learning paradigm; experiment 2 (N = 19) uses MEG and motor learning; and experiment 3 (N = 18) uses EEG and TMS. We characterised two distinct γ sub-bands (slow-γ, mid-γ) which show a movement-related increase in activity during unilateral index finger movements and are characterised by distinct temporal-spectral-spatial profiles. Bayesian correlation analysis revealed strong evidence for a positive relationship between slow-γ (~30-60Hz) peak frequency and GABAergic intracortical inhibition (as assessed using the TMS-metric short interval intracortical inhibition). There was also moderate evidence for a relationship between the power of the movement-related mid-γ activity (60-90Hz) and motor learning. These relationships were neurochemical- and frequency-specific. These data provide new insights into the neurophysiological basis and functional roles of γ activity in human M1 and allow the development of a new theoretical framework for γ activity in the human neocortex.
Neuropathological Evidence of Reduced Amyloid Beta and Neurofibrillary Tangles in Multiple Sclerosis Cortex
Multiple sclerosis (MS) and Alzheimer's disease are neurodegenerative diseases with age‐related disability accumulation. In MS, inflammation spans decades, whereas AD is characterized by Aβ plaques and neurofibrillary tangles (NFT). Few studies explore accumulation of amyloids in MS. We examined Aβ deposition and NFT density in temporal and frontal cortices from postmortem MS (n = 75) and control (n = 66) cases. Compared with controls, MS cases showed reduced Aβ, especially in those aged <65 years, and reduced NFT, notably in cases aged >65 years. Aβ deposition predicted greater NFT density both in MS cases and controls. MS‐related factors may affect Aβ/NFT deposition and/or clearance, offering new therapeutic insights for both diseases. ANN NEUROL 2025
Process evaluation in a randomised controlled trial of DREAMS-START (dementia related manual for sleep; strategies for relatives) for sleep disturbance in people with dementia and their carers.
INTRODUCTION: DREAMS-START is a multicomponent intervention targeting sleep disturbance in people with dementia. To enhance understanding of the DREAMS-START randomised controlled trial, which showed improved sleep in the intervention compared to the control arm, we conducted a process evaluation exploring (i) DREAMS-START delivery, (ii) behaviour change mechanisms and (iii) contextual factors impacting outcomes. METHODS: Mixed-methods design. We measured intervention adherence, fidelity and additional therapeutic process measures. We interviewed a sub-sample of intervention arm family carers and facilitators delivering DREAMS-START. We analysed data thematically guided by a prespecified theory of change logic model informed by the Theoretical Domains Framework. We measured movement using an actigraph worn by the person with dementia at baseline and at four- and eight-month follow-ups to explore potential mechanisms of action. RESULTS: Attendance was good (82.8% attended ≥4/6 sessions). Mean fidelity score (95.4%; SD 0.08) and median score for all four process measures assessed (5/5; IQR 5-5) were high. We interviewed 43/188 family carers and 9/49 DREAMS-START facilitators. We identified three overarching themes aligned with our model: (i) knowledge and facilitation enable behaviour change, (ii) increasing sleep pressure and developing skills to manage sleep disturbances and (iii) Establishing a routine and sense of control. We were unable to collect sufficient data for pre-specified actigraphy analyses. CONCLUSION: Despite competing demands, carers attended DREAMS-START. It promoted behaviour change through supportive in-session reflection, increasing carer knowledge and skills. This was embedded between sessions and actions were positively reinforced as carers experienced changes. Results will inform future implementation in clinical services.
Is it time to revisit the scoring of Slow Wave (N3) Sleep?
Abstract The use of a fixed electroencephalogram (EEG) amplitude threshold of 75 µV for labelling slow waves is a subject of ongoing discussion given EEG amplitude is known to vary with age and sex. This paper investigates the impact of this amplitude threshold on age- and sex-related trends in visually-annotated SWS. Automated methods for labelling SWS using data-driven thresholds and amplitude- or frequency-based inputs are developed. Age- and sex-related trends in SWS derived from visual annotation and automated labelling are then compared across a cohort of 2,913 participants from the Sleep Heart Health Study. In the selected cohort, males exhibit an age-related decrease in visually-annotated SWS, which is preserved when using automated labelling. In contrast, females exhibit a mild age-related increase in visually-annotated and amplitude-labelled SWS, but an age-related decrease in frequency-labelled SWS. Further, using frequency-labelled SWS results in a reduction in SWS in females to a level comparable to that of males. Overall, the consistency of age-related trends in SWS in males between visual annotation and automated labelling, as well as the lack of consistency in these trends in females, is striking. Given that the 75 µV amplitude threshold was established using data acquired primarily from young males, these results suggest that observed sex-based differences in visually-annotated SWS may be artefactual rather than physiological, and a result of the 75 µV amplitude criterion. This sex-related disparity highlights the need for the AASM guidelines for scoring SWS to be reviewed and updated to provide equivalent performance for males and females.
Sleep Health and White Matter Integrity in the UK Biobank.
Many people experience impaired sleep health, yet knowledge about its neurobiological correlates is limited. As previous studies have found associations between white matter integrity and several sleep traits, white matter integrity could be causally implicated in poor sleep health. However, these studies were often limited by small sample sizes. In this study, we examine associations between multiple indices of white matter integrity and sleep health in 29,114 UK Biobank participants. Late chronotype, daytime sleepiness, insomnia symptoms and, most extensively, long sleep duration were independently associated with diffusion MRI markers of reduced white matter integrity. Previous findings showing an association between insomnia symptoms and decreased fractional anisotropy (FA) in the anterior internal capsule could not be replicated. To our knowledge, the current analysis is the first study to find an association between long sleep duration and impaired microstructural white matter integrity. Previous assumptions concerning the role of white matter integrity for insomnia are challenged.
The UK clinical eye research strategy: refreshing research priorities for clinical eye research in the UK.
OBJECTIVES: To validate and update the 2013 James Lind Alliance (JLA) Sight Loss and Vision Priority Setting Partnership (PSP)'s research priorities for Ophthalmology, as part of the UK Clinical Eye Research Strategy. METHODS: Twelve ophthalmology research themes were identified from the JLA report. They were allocated to five Clinical Study Groups of diverse stakeholders who reviewed the top 10 research priorities for each theme. Using an online survey (April 2021-February 2023), respondents were invited to complete one or more of nine subspecialty surveys. Respondents indicated which of the research questions they considered important and subsequently ranked them. RESULTS: In total, 2240 people responded to the survey (mean age, 59.3 years), from across the UK. 68.1% were female. 68.2% were patients, 22.3% healthcare professionals or vision researchers, 7.1% carers, and 2.1% were charity support workers. Highest ranked questions by subspecialty: Cataract (prevention), Cornea (improving microbial keratitis treatment), Optometric (impact of integration of ophthalmic primary and secondary care via community optometric care pathways), Refractive (factors influencing development and/or progression of refractive error), Childhood onset (improving early detection of visual disorders), Glaucoma (effective and improved treatments), Neuro-ophthalmology (improvements in prevention, diagnosis and treatment of neurodegeneration affecting vision), Retina (improving prevention, diagnosis and treatment of dry age-related macular degeneration), Uveitis (effective treatments for ocular and orbital inflammatory diseases). CONCLUSIONS: A decade after the initial PSP, the results refocus the most important research questions for each subspecialty, and prime targeted research proposals within Ophthalmology, a chronically underfunded specialty given the substantial burden of disability caused by eye disease.
Effect of the COVID-19 pandemic on diabetic retinopathy and referral levels in the English National Health Service Diabetic Eye Screening Programme.
AIMS: The aim was to determine the effect of the COVID-19 pandemic on diabetic retinopathy and referral rates in the English National Health Service (NHS) Diabetic Eye Screening Programme (DESP). METHODS: Non-patient identifiable data are submitted centrally from the 57 regional centres in the NHS DESP on a quarterly basis and analysed using STATA, comparing 01/04/2019-31/03/2020 and 01/04/2021-31/03/2022. Patient characteristics were analysed from National Diabetes Audit (NDA) data. RESULTS: There were 2,274,635 grades from the 57 centres in 2019-2020 and 2,199,623 grades in 2021-2022. The proportion of eyes with referable DR increased from 3.1% in 2019-2020 to 3.2% in the 2021-2022 NHS year (p