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  • The effects of improving sleep on mental health (OASIS): a randomised controlled trial with mediation analysis.

    22 November 2017

    BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment. Online assessments took place at weeks 0, 3, 10 (end of therapy), and 22. The primary outcome measures were for insomnia, paranoia, and hallucinatory experiences. We did intention-to-treat analyses. The trial is registered with the ISRCTN registry, number ISRCTN61272251. FINDINGS: Between March 5, 2015, and Feb 17, 2016, we randomly assigned 3755 participants to receive digital CBT for insomnia (n=1891) or usual practice (n=1864). Compared with usual practice, the sleep intervention at 10 weeks reduced insomnia (adjusted difference 4·78, 95% CI 4·29 to 5·26, Cohen's d=1·11; p<0·0001), paranoia (-2·22, -2·98 to -1·45, Cohen's d=0·19; p<0·0001), and hallucinations (-1·58, -1·98 to -1·18, Cohen's d=0·24; p<0·0001). Insomnia was a mediator of change in paranoia and hallucinations. No adverse events were reported. INTERPRETATION: To our knowledge, this is the largest randomised controlled trial of a psychological intervention for a mental health problem. It provides strong evidence that insomnia is a causal factor in the occurrence of psychotic experiences and other mental health problems. Whether the results generalise beyond a student population requires testing. The treatment of disrupted sleep might require a higher priority in mental health provision. FUNDING: Wellcome Trust.

  • Choice of reference measurements affects quantification of long diffusion time behaviour using stimulated echoes.

    20 November 2017

    PURPOSE: To demonstrate how reference data affect the quantification of the apparent diffusion coefficient (ADC) in long diffusion time measurements with diffusion-weighted stimulated echo acquisition mode (DW-STEAM) measurements, and to present a modification to avoid contribution from crusher gradients in DW-STEAM. METHODS: For DW-STEAM, reference measurements at long diffusion times have significant b0 value, because b = 0 cannot be achieved in practice as a result of the need for signal spoiling. Two strategies for acquiring reference data over a range of diffusion times were considered: constant diffusion weighting (fixed-b0 ) and constant gradient area (fixed-q0 ). Fixed-b0 and fixed-q0 were compared using signal calculations for systems with one and two diffusion coefficients, and experimentally using data from postmortem human corpus callosum samples. RESULTS: Calculations of biexponential diffusion decay show that the ADC is underestimated for reference images with b > 0, which can induce an apparent time-dependence for fixed-q0 . Restricted systems were also found to be affected. Experimentally, the exaggeration of the diffusion time-dependent effect under fixed-q0 versus fixed-b0 was in a range predicted theoretically, accounting for 62% (longitudinal) and 35% (radial) of the time dependence observed in white matter. CONCLUSIONS: Variation in the b-value of reference measurements in DW-STEAM can induce artificial diffusion time dependence in ADC, even in the absence of restriction. Magn Reson Med, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

  • White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment After Transient Ischemic Attack and Minor Stroke.

    17 November 2017

    BACKGROUND AND PURPOSE: Among screening tools for cognitive impairment in large cohorts, the Montreal Cognitive Assessment (MoCA) seems to be more sensitive to early cognitive impairment than the Mini-Mental State Examination (MMSE), particularly after transient ischemic attack or minor stroke. We reasoned that if MoCA-detected early cognitive impairment is pathologically significant, then it should be specifically associated with the presence of white matter hyperintensities (WMHs) and reduced fractional anisotropy (FA) on magnetic resonance imaging. METHODS: Consecutive eligible patients with transient ischemic attack or minor stroke (Oxford Vascular Study) underwent magnetic resonance imaging and cognitive assessment. We correlated MoCA and MMSE scores with WMH and FA, then specifically studied patients with low MoCA and normal MMSE. RESULTS: Among 400 patients, MoCA and MMSE scores were significantly correlated (all P<0.001) with WMH volumes (rMoCA=-0.336; rMMSE=-0.297) and FA (rMoCA=0.409; rMMSE=0.369) and-on voxel-wise analyses-with WMH in frontal white matter and reduced FA in almost all white matter tracts. However, only the MoCA was independently correlated with WMH volumes (r=-0.183; P<0.001), average FA values (r=0.218; P<0.001), and voxel-wise reduced FA in anterior tracts after controlling for the MMSE. In addition, patients with low MoCA but normal MMSE (n=57) had higher WMH volumes (t=3.1; P=0.002), lower average FA (t=-4.0; P<0.001), and lower voxel-wise FA in almost all white matter tracts than those with normal MoCA and MMSE (n=238). CONCLUSIONS: In patients with transient ischemic attack or minor stroke, early cognitive impairment detected with the MoCA but not with the MMSE was independently associated with white matter damage on magnetic resonance imaging, particularly reduced FA.

  • Clinical Correlates, Ethnic Differences, and Prognostic Implications of Perivascular Spaces in Transient Ischemic Attack and Ischemic Stroke.

    27 October 2017

    BACKGROUND AND PURPOSE: Perivascular spaces (PVSs) are considered markers of small vessel disease. However, their long-term prognostic implications in transient ischemic attack/ischemic stroke patients are unknown. Ethnic differences in PVS prevalence are also unknown. METHODS: Two independent prospective studies were conducted, 1 comprising predominantly whites with transient ischemic attack/ischemic stroke (OXVASC [Oxford Vascular] study) and 1 comprising predominantly Chinese with ischemic stroke (University of Hong Kong). Clinical and imaging correlates, prognostic implications for stroke and death, and ethnic differences in basal ganglia (BG) and centrum semiovale (CS) PVSs were studied with adjustment for age, sex, vascular risk factors, and scanner strength. RESULTS: Whites with transient ischemic attack/ischemic stroke (n=1028) had a higher prevalence of both BG and CS-PVSs compared with Chinese (n=974; >20 BG-PVSs: 22.4% versus 7.1%; >20 CS-PVSs: 45.8% versus 10.4%; P<0.0001). More than 20 BG or CS-PVSs were both associated with increasing age and white matter hyperintensity, although associations with BG-PVSs were stronger (all P<0.0001). During 6924 patient-years of follow-up, BG-PVSs were also independently associated with an increased risk of recurrent ischemic stroke (adjusted hazard ratio compared with <11 PVSs, 11-20 PVSs: HR, 1.15; 95% confidence interval, 0.78-1.68; >20 PVSs: HR, 1.82; 1.18-2.80; P=0.011) but not intracerebral hemorrhage (P=0.10) or all-cause mortality (P=0.16). CS-PVSs were not associated with recurrent stroke (P=0.57) or mortality (P=0.072). Prognostic associations were similar in both cohorts. CONCLUSIONS: Over and above ethnic differences in frequency of PVSs in transient ischemic attack/ischemic stroke patients, BG and CS-PVSs had similar risk factors, but although >20 BG-PVSs were associated with an increased risk of recurrent ischemic stroke, CS-PVSs were not.

  • Light and the laboratory mouse.

    17 November 2017

    Light exerts widespread effects on physiology and behaviour. As well as the widely-appreciated role of light in vision, light also plays a critical role in many non-visual responses, including regulating circadian rhythms, sleep, pupil constriction, heart rate, hormone release and learning and memory. In mammals, responses to light are all mediated via retinal photoreceptors, including the classical rods and cones involved in vision as well as the recently identified melanopsin-expressing photoreceptive retinal ganglion cells (pRGCs). Understanding the effects of light on the laboratory mouse therefore depends upon an appreciation of the physiology of these retinal photoreceptors, including their differing sens itivities to absolute light levels and wavelengths. The signals from these photoreceptors are often integrated, with different responses involving distinct retinal projections, making generalisations challenging. Furthermore, many commonly used laboratory mouse strains carry mutations that affect visual or non-visual physiology, ranging from inherited retinal degeneration to genetic differences in sleep and circadian rhythms. Here we provide an overview of the visual and non-visual systems before discussing practical considerations for the use of light for researchers and animal facility staff working with laboratory mice.

  • Oxford Subarachnoid Haemorrhage Research Group

    6 June 2017


    Our group aims to achieve a better understanding of what happens in the brains of patients who have just had a subarachnoid haemorrhage, which is a type of stroke.

  • Action, Cognition & Neurotherapeutics

    10 June 2015


    We aim to understand processes of selective attention and action, learning and memory in the human brain. Through experiments in healthy volunteers and patients with brain disorders we seek to characterize how information processing networks respond (adaptively or maladaptively) when challenged by interference. Our motivation is to develop rational neurocognitive intervention strategies to help promote recovery from conditions such as depression and brain injury.

  • pain & mind

    11 August 2016


    Beliefs shape our perception of pain. Using non-invasive magnetic resonance imaging in humans, we investigate how beliefs are generated, maintained and revised in the brain and how they influence pain perception.

  • Oxford Motor Neuron Disease Centre

    15 January 2013


    Our research is aimed at improving understanding of motor neuron diseases, principally amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), to find treatments to improve the lives of patients with these currently incurable conditions.

  • Diagnostic and Advisory Service for Neuromyelitis Optica

    15 January 2013


    Neuromyelitis optica (NMO) is a rare disease causing inflammation in the spinal cord and optic nerves. The NMO service brings together expertise in diagnostics and clinical management to improve outcomes for this often isolated group of patients.

  • Autoimmune Neurology Group

    18 June 2014


    Our group aims to characterise the immune system in patients with autoantibody-mediated diseases of the nervous system to better diagnose and understand the underlying disease processes, and provide a rational approach to immunotherapies.

  • Perioperative Medicine

    31 July 2017


    How can we make sure people are fit for surgery, improve safety in the operating theatre, and ensure better recovery after major operations?

  • Neurovascular Imaging

    15 January 2013


    We are collaborating with clinical colleagues to develop novel MRI acquisition and analysis methods that address the wide spectrum of cerebrovascular disease.

  • Neuropathology

    15 January 2013


    Neuropathology is at the interface of clinical and basic neurosciences.