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  • Antimalarial drugs and the prevalence of mental and neurological manifestations: A systematic review and meta-analysis

    20 March 2018

    Copyright: © 2017 Bitta MA et al. Background: Antimalarial drugs affect the central nervous system, but it is difficult to differentiate the effect of these drugs from that of the malaria illness. We conducted a systematic review to determine the association between anti-malarial drugs and mental and neurological impairment in humans. Methods: We systematically searched online databases, including Medline/PubMed, PsychoInfo, and Embase, for articles published up to 14th July 2016. Pooled prevalence, heterogeneity and factors associated with prevalence of mental and neurological manifestations were determined using meta-analytic techniques. Results: Of the 2,349 records identified in the initial search, 51 human studies met the eligibility criteria. The median pooled prevalence range of mental and neurological manifestations associated with antimalarial drugs ranged from 0.7% (dapsone) to 48.3% (minocycline) across all studies, while it ranged from 0.6% (pyrimethamine) to 42.7% (amodiaquine) during treatment of acute malaria, and 0.7% (primaquine/dapsone) to 55.0% (sulfadoxine) during prophylaxis. Pooled prevalence of mental and neurological manifestations across all studies was associated with an increased number of antimalarial drugs (prevalence ratio= 5.51 (95%CI, 1.05-29.04); P=0.045) in a meta-regression analysis. Headaches (15%) and dizziness (14%) were the most common mental and neurological manifestations across all studies. Of individual antimalarial drugs still on the market, mental and neurological manifestations were most common with the use of sulphadoxine (55%) for prophylaxis studies and amodiaquine (42.7%) for acute malaria studies. Mefloquine affected more domains of mental and neurological manifestations than any other antimalarial drug. Conclusions: Antimalarial drugs, particularly those used for prophylaxis, may be associated with mental and neurological manifestations, and the number of antimalarial drugs taken determines the association. Mental and neurological manifestations should be assessed following the use of antimalarial drugs.

  • Novel Intrinsic Ignition Method Measuring Local-Global Integration Characterizes Wakefulness and Deep Sleep.

    15 February 2018

    A precise definition of a brain state has proven elusive. Here, we introduce the novel local-global concept of intrinsic ignition characterizing the dynamical complexity of different brain states. Naturally occurring intrinsic ignition events reflect the capability of a given brain area to propagate neuronal activity to other regions, giving rise to different levels of integration. The ignitory capability of brain regions is computed by the elicited level of integration for each intrinsic ignition event in each brain region, averaged over all events. This intrinsic ignition method is shown to clearly distinguish human neuroimaging data of two fundamental brain states (wakefulness and deep sleep). Importantly, whole-brain computational modelling of this data shows that at the optimal working point is found where there is maximal variability of the intrinsic ignition across brain regions. Thus, combining whole brain models with intrinsic ignition can provide novel insights into underlying mechanisms of brain states.

  • The Affective Core of Emotion: Linking Pleasure, Subjective Well-Being, and Optimal Metastability in the Brain.

    2 April 2018

    Arguably, emotion is always valenced-either pleasant or unpleasant-and dependent on the pleasure system. This system serves adaptive evolutionary functions; relying on separable wanting, liking, and learning neural mechanisms mediated by mesocorticolimbic networks driving pleasure cycles with appetitive, consummatory, and satiation phases. Liking is generated in a small set of discrete hedonic hotspots and coldspots, while wanting is linked to dopamine and to larger distributed brain networks. Breakdown of the pleasure system can lead to anhedonia and other features of affective disorders. Eudaimonia and well-being are difficult to study empirically, yet whole-brain computational models could offer novel insights (e.g., routes to eudaimonia such as caregiving of infants or music) potentially linking eudaimonia to optimal metastability in the pleasure system.

  • Higher and Lower Pleasures Revisited: Evidence from Neuroscience

    1 March 2018

    © 2017 The Author(s) This paper discusses J.S. Mill’s distinction between higher and lower pleasures, and suggests that recent neuroscientific evidence counts against it.

  • Perturbation of whole-brain dynamics in silico reveals mechanistic differences between brain states.

    23 March 2018

    Human neuroimaging research has revealed that wakefulness and sleep involve very different activity patterns. Yet, it is not clear why brain states differ in their dynamical complexity, e.g. in the level of integration and segregation across brain networks over time. Here, we investigate the mechanisms underlying the dynamical stability of brain states using a novel off-line in silico perturbation protocol. We first adjust a whole-brain computational model to the basal dynamics of wakefulness and deep sleep recorded with fMRI in two independent human fMRI datasets. Then, the models of sleep and awake brain states are perturbed using two distinct multifocal protocols either promoting or disrupting synchronization in randomly selected brain areas. Once perturbation is halted, we use a novel measure, the Perturbative Integration Latency Index (PILI), to evaluate the recovery back to baseline. We find a clear distinction between models, consistently showing larger PILI in wakefulness than in deep sleep, corroborating previous experimental findings. In the models, larger recoveries are associated to a critical slowing down induced by a shift in the model's operation point, indicating that the awake brain operates further from a stable equilibrium than deep sleep. This novel approach opens up for a new level of artificial perturbative studies unconstrained by ethical limitations allowing for a deeper investigation of the dynamical properties of different brain states.

  • Harmonic Brain Modes: A Unifying Framework for Linking Space and Time in Brain Dynamics.

    20 December 2017

    A fundamental characteristic of spontaneous brain activity is coherent oscillations covering a wide range of frequencies. Interestingly, these temporal oscillations are highly correlated among spatially distributed cortical areas forming structured correlation patterns known as the resting state networks, although the brain is never truly at "rest." Here, we introduce the concept of harmonic brain modes-fundamental building blocks of complex spatiotemporal patterns of neural activity. We define these elementary harmonic brain modes as harmonic modes of structural connectivity; that is, connectome harmonics, yielding fully synchronous neural activity patterns with different frequency oscillations emerging on and constrained by the particular structure of the brain. Hence, this particular definition implicitly links the hitherto poorly understood dimensions of space and time in brain dynamics and its underlying anatomy. Further we show how harmonic brain modes can explain the relationship between neurophysiological, temporal, and network-level changes in the brain across different mental states ( wakefulness, sleep, anesthesia, psychedelic). Notably, when decoded as activation of connectome harmonics, spatial and temporal characteristics of neural activity naturally emerge from the interplay between excitation and inhibition and this critical relation fits the spatial, temporal, and neurophysiological changes associated with different mental states. Thus, the introduced framework of harmonic brain modes not only establishes a relation between the spatial structure of correlation patterns and temporal oscillations (linking space and time in brain dynamics), but also enables a new dimension of tools for understanding fundamental principles underlying brain dynamics in different states of consciousness.

  • Autoimmune causes of schizophrenia

    1 May 2013

    A proportion of patients with psychiatric disorders such as schizophrenia may have a treatable autoimmune condition underlying their symptoms. We have shown, for the first time that patients with a first episode of psychosis had antibodies against the NMDA receptor or Voltage Gated Potassium Channel.

  • Five new academic psychiatric training posts (ACFs) funded by National Institute of Health Research

    6 February 2014

    The Oxford NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) will fund 2 new academic clinical fellows (ACF) in core psychiatry and 1 new ACF run-through to child and adolescent psychiatry this year. This is in addition to 1 ACF in psychiatry funded by NIHR, and a further extra ACF post in child and adolescent psychiatry won in last year's national competition.

  • Brain injury survivors 3x more likely to die prematurely

    16 January 2014

    People who survive a traumatic brain injury are three times more likely to die prematurely than the general population, often from suicide or fatal injuries, according to a study led by Dr Seena Fazel, Wellcome Trust senior research fellow in Oxford University’s Department of Psychiatry. The study of 41 years' worth of Swedish medical records, published in JAMA Psychiatry, also found that TBI survivors were twice as likely to kill themselves (and 2.6 times as likely to die generally) before the age of 56 as unaffected siblings, who were included in the study to control for genetic factors and early upbringing. [The Guardian online, 16/01/2014, Haroon Siddique]

  • "Predicting violence in mentally disordered offenders needs considerable caution" says our Seena Fazel

    2 October 2013

    "Assessment tools used to predict how likely a psychopathic prisoner is to re-offend if freed from jail are "utterly useless" and parole boards might just as well flip a coin when deciding such risks, psychiatrists said on Tuesday. A Queen Mary University of London study found risk score tools are only around 46 percent accurate on how likely psychopathic convicts are to kill, rape or assault again. Seena Fazel, a consultant forensic psychiatrist at Britain's University of Oxford, said the reliability of the tests' predictive ability was so low that it might be best not to use them at all - and warned that at the very least, their results should only be noted by parole boards, rather than acted upon. "If you're going to use these instruments, be aware of their strengths and limitations," he said." (Reuters, 01/10/2013, Kate Kelland)

  • Oxford Medical School tops Times Higher Education World University Rankings for Clinical, Pre-Clinical and Health 2013-14

    2 October 2013

    "The 2013-2014 Times Higher Education World University Rankings' Clinical, Pre-Clinical and Health table judges world class universities across all of their core missions - teaching, research, knowledge transfer and international outlook. The ranking of the world's top 100 universities for clinical and health subjects employs 13 carefully calibrated performance indicators to provide the most comprehensive and balanced comparisons available, which are trusted by students, academics, university leaders, industry and governments."

  • Daniel Freeman on paranoia: 'At its heart is a mistaken idea of current threat'

    8 August 2016

    Professor Freeman writes for the Guardian on the paranoia spectrum and how founded perception of threat can slip into misreading intentions and excessive mistrust.

  • Blog: 'Taking part in True Colours'

    12 September 2017

    Michael Spiers shares his personal experience of bipolar and taking part in the Bipolar Disorder Research Network (BDRN) mood monitoring system True Colours, developed at the University of Oxford's Department of Psychiatry.

  • Nightmares: identifying potential causal factors

    8 August 2017

    Stephanie Rek, Bryony Sheaves and Daniel Freeman from the Department of Psychiatry have been exploring what contributes to bad dreams, and finding some surprising results.

  • Dolphin brains show signs of Alzheimer’s Disease

    24 October 2017

    A review led by Professor Simon Lovestone has found the first unambiguous signs of Alzheimer’s disease in a wild animal.

  • Dr Claire Sexton wins Vice-Chancellor’s Public Engagement with Research Award

    29 June 2017

    Dr Sexton, from the University of Oxford’s Department of Psychiatry, scoops the Early Career Researcher award for her work promoting healthy ageing in the brain.