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  • Genetic variation in GOLM1 and prefrontal cortical volume in Alzheimer's disease.

    3 November 2018

    Replications of the association between APOE-ε4 allele load and regional brain atrophy in Alzheimer's disease (AD) patients hold promise for future studies testing relationships between other disease risk gene variants and brain structure. A polymorphism, rs10868366, in the Golgi phosphoprotein 2 gene, GOLM1, was recently identified as an AD risk factor in a genome-wide association study. In a subset of the same AD cohort, we used voxel-based morphometry to test for association between the disease risk genotype and reduced regional gray matter (GM) volume in AD patients (n = 72). A mean 14% reduction in GM volume was observed in the left frontal gyrus with the higher risk GG genotype. A similar association was observed in an independent, dataset of nondemented subjects (n = 278), although with a smaller effect (1%). This replicated association with GM structural variation suggests that GOLM1 polymorphisms may be related to cognitive phenotypes. The greater effect size in AD patients also suggests that the GG genotype could be a risk factor for the expression of cognitive deficits in AD.

  • New insights into the brain involvement in patients with Crohn's disease: a voxel-based morphometry study.

    3 November 2018

    BACKGROUND: Crohn's disease (CD) is a chronic intestinal disorder characterized by overproduction of inflammatory cytokines and recurrent abdominal pain. Recently, brain morphological abnormalities in the pain matrix were found in patients with chronic pain disorders including irritable bowel syndrome. To investigate potential structural brain changes associated with CD, we used magnetic resonance imaging (MRI). Furthermore, we tested whether in patients gray matter (GM) volumes correlated with disease duration. METHODS: Eighteen CD patients in remission and 18 healthy controls underwent structural MRI. Voxel-based morphometry (VBM) is a fully automated technique allowing identification of regional differences in the amount of GM enabling an objective analysis of the whole brain between groups of subjects. VBM was used for comparisons and correlation analysis. KEY RESULTS: With respect to controls, CD patients exhibited decreased GM volumes in portion of the frontal cortex and in the anterior midcingulate cortex. Disease duration was negatively correlated with GM volumes of several brain regions including neocortical and limbic areas. CONCLUSIONS & INFERENCES: Crohn's disease is associated with brain morphological changes in cortical and subcortical structures involved in nociception, emotional, and cognitive processes. Our findings provide new insight into the brain involvement in chronic inflammatory bowel disorders.

  • Can complex visual discrimination deficits in amnesia be attributed to the medial temporal lobe? An investigation into the effects of medial temporal lobe damage on brain connectivity.

    3 November 2018

    It has been suggested that complex visual discrimination deficits in patients with medial temporal lobe (MTL) damage may be explained by damage or dysfunction beyond the MTL. We examined the resting functional networks and white matter connectivity of two amnesic patients who have consistently demonstrated discrimination impairments for complex object and/or spatial stimuli across a number of studies. Although exploratory analyses revealed some significant differences in comparison with neurologically healthy controls (more specifically in the patient with a larger MTL lesion), there were no obvious findings involving posterior occipital or posterior temporal regions, which can account entirely for their discrimination deficits. These findings converge with previous work to support the suggestion that the MTL does not subserve long-term declarative memory exclusively.

  • The organization of dorsal frontal cortex in humans and macaques.

    3 November 2018

    The human dorsal frontal cortex has been associated with the most sophisticated aspects of cognition, including those that are thought to be especially refined in humans. Here we used diffusion-weighted magnetic resonance imaging (DW-MRI) and functional MRI (fMRI) in humans and macaques to infer and compare the organization of dorsal frontal cortex in the two species. Using DW-MRI tractography-based parcellation, we identified 10 dorsal frontal regions lying between the human inferior frontal sulcus and cingulate cortex. Patterns of functional coupling between each area and the rest of the brain were then estimated with fMRI and compared with functional coupling patterns in macaques. Areas in human medial frontal cortex, including areas associated with high-level social cognitive processes such as theory of mind, showed a surprising degree of similarity in their functional coupling patterns with the frontal pole, medial prefrontal, and dorsal prefrontal convexity in the macaque. We failed to find evidence for "new" regions in human medial frontal cortex. On the lateral surface, comparison of functional coupling patterns suggested correspondences in anatomical organization distinct from those that are widely assumed. A human region sometimes referred to as lateral frontal pole more closely resembled area 46, rather than the frontal pole, of the macaque. Overall the pattern of results suggest important similarities in frontal cortex organization in humans and other primates, even in the case of regions thought to carry out uniquely human functions. The patterns of interspecies correspondences are not, however, always those that are widely assumed.

  • Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease

    3 November 2018

    In our contribution to this special issue focusing on advances in Alzheimer's disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression. © 2013 - IOS Press and the authors. All rights reserved.

  • Brain structural and functional connectivity and the progression of neuropathology in Alzheimer's disease

    3 November 2018

    In our contribution to this special issue focusing on advances in Alzheimer's disease (AD) research since the centennial, we will briefly review some of our own studies applying magnetic resonance imaging (MRI) measures of function and connectivity for characterization of genetic contributions to the neuropathology of AD and as candidate biomarkers. We review how functional MRI during both memory encoding and at rest is able to define APOE4 genotype-dependent physiological changes decades before potential development of AD and demonstrate changes distinct from those with healthy aging. More generally, imaging provides a powerful quantitative measure of phenotype for understanding associations arising from whole genome studies in AD. Structural connectivity measures derived from diffusion tensor MRI (DTI) methods offer additional markers of neuropathology arising from the secondary changes in axonal caliber and myelination that accompany decreased neuronal activity and neurodegeneration. We illustrate applications of DTI for more finely mapping neurodegenerative changes with AD in the thalamus in vivo and for defining neuropathological changes in the white matter itself. The latter efforts have highlighted how sensitivity to the neuropathology can be enhanced by using more specific DTI measures and interpreting them relative to knowledge of local white matter anatomy in the healthy brain. Together, our studies and related work are helping to establish the exciting potential of a new range of MRI methods as neuropathological measures and as biomarkers of disease progression. © 2013 The authors and IOS Press. All rights reserved.

  • Fractional anisotropy in the posterior limb of the internal capsule and prognosis in amyotrophic lateral sclerosis

    3 November 2018

    Objective: To explore the value of diffusion tensor imaging applied to those specific cerebral white matter tracts consistently involved pathologically in amyotrophic lateral sclerosis as a source of prognostic biomarkers. Design: Baseline clinical assessment and 3-T diffusion tensor imaging, repeated after approximately 6 months. Tract-based spatial statistics were used to assess voxelwise correlations of just the baseline diffusion tensor imaging indices with the progression rate (change in disability score/time interval) within the corticospinal tract and corpus callosum. Patients: The study involved 21 patients with amyotrophic lateral sclerosis and 3 patients with primary lateral sclerosis. Results: Correlation was observed between fractional anisotropy and progression rate for a region of the corticospinal tract spanning the posterior limb of the internal capsule, with a left hemisphere emphasis. Posterior limb of the internal capsule fractional anisotropy showed potential to distinguish those patients with rapid progression. Axial diffusivity significantly increased in this region in a paired t test analysis of baseline and follow-up diffusion tensor imaging, in keeping with axonal damage. No correlations were noted for the corpus callosum. Conclusions: Posterior limb of the internal capsule fractional anisotropy is a candidate prognostic marker in amyotrophic lateral sclerosis, with potential to identify incident cases with more rapid progression. ©2012 American Medical Association. All rights reserved.

  • Functional magnetic resonance imaging study reveals differences in the habituation to psychological stress in patients with Crohn's disease versus healthy controls

    3 November 2018

    In patients with Crohn's disease (CD) stress is believed to increase the incidence of disease relapse. The brain processes stressful stimuli and triggers the stress-evoked responses. Habituation to stress is an adaptive process that allows minimizing these responses. We hypothesized inadequate habituation to stress in CD patients. The aim of this study was to compare the neural habituation between CD patients and controls. Twenty CD patients and eighteen controls underwent a functional magnetic resonance imaging while performing two repeated runs of a stress-evoking task. The task elicited different neural activity between the groups across runs in (1) amygdala, hippocampus, (2) insula, putamen (3) cerebellar regions, suggesting altered habituation to stress in patients. These structures regulate the neuroendocrine and autonomic stress-evoked responses that control the proinflammatory responses. The inadequate habituation to stress that we found in patients could play a role in the relationship between stress and inflammatory exacerbations in CD. © 2012 Springer Science+Business Media, LLC.

  • Gray matter volume is associated with rate of subsequent skill learning after a long term training intervention.

    3 November 2018

    The ability to predict learning performance from brain imaging data has implications for selecting individuals for training or rehabilitation interventions. Here, we used structural MRI to test whether baseline variations in gray matter (GM) volume correlated with subsequent performance after a long-term training of a complex whole-body task. 44 naïve participants were scanned before undertaking daily juggling practice for 6weeks, following either a high intensity or a low intensity training regime. To assess performance across the training period participants' practice sessions were filmed. Greater GM volume in medial occipito-parietal areas at baseline correlated with steeper learning slopes. We also tested whether practice time or performance outcomes modulated the degree of structural brain change detected between the baseline scan and additional scans performed immediately after training and following a further 4weeks without training. Participants with better performance had higher increases in GM volume during the period following training (i.e., between scans 2 and 3) in dorsal parietal cortex and M1. When contrasting brain changes between the practice intensity groups, we did not find any straightforward effects of practice time though practice modulated the relationship between performance and GM volume change in dorsolateral prefrontal cortex. These results suggest that practice time and performance modulate the degree of structural brain change evoked by long-term training regimes.

  • Network-level reorganisation of functional connectivity following arm amputation

    3 November 2018

    © 2015 The Authors. One of the most striking demonstrations of plasticity in the adult human brain follows peripheral injury, such as amputation. In the primary sensorimotor cortex, arm amputation results in massive local remapping of the missing hands' cortical territory. However, little is known about the consequences of sensorimotor deprivation on global brain organisation. Here, we used resting-state fMRI to identify large-scale reorganisation beyond the primary sensorimotor cortex in arm amputees, compared with two-handed controls. Specifically, we characterised changes in functional connectivity between the cortical territory of the missing hand in the primary sensorimotor cortex ('missing hand cortex') and two networks of interest: the sensorimotor network, which is typically strongly associated with the hand cortex, and the default mode network (DMN), which is normally dissociated from it. Functional connectivity values between the missing hand cortex and the sensorimotor network were reduced in amputees, and connectivity was weaker in individuals amputated for longer periods. Lower levels of functional coupling between the missing hand cortex and the sensorimotor network were also associated with emerged coupling of this cortex with the DMN. Our results demonstrate that plasticity following arm amputation is not restricted to local remapping occurring within the sensorimotor homunculus of the missing hand but rather produces a cascade of cortical reorganisation at a network-level scale. These findings may provide a new framework for understanding how local deprivation following amputation could elicit complex perceptual experiences of phantom sensations, such as phantom pain.

  • Department of Psychiatry researchers join the Curiosity Carnival

    26 September 2017

    Curiosity Carnival is part of European Researchers’ Night. This is the first time that the University has taken part, and activities will be taking place across the city on 29 September.

  • Time to vote!

    20 May 2014

    Contested Elections: 12 June 2014 One member of Congregation elected by Congregation from members of the faculties in the Divisions of Mathematical, Physical and Life Sciences and of Medical Sciences

  • Clinical Lectureship Positions now open for application (Closing date: 3 June 2015)

    5 May 2015

    Applications are invited for six posts under the NIHR Integrated Academic Training Pathway. These are fixed-term, four-year posts which offer excellent opportunities to undertake high quality research within a clinically excellent environment and to undertake clinical work towards gaining a CCT.

  • From lab bench to green bench

    9 December 2015

    Dr Jessica Ash, from the Department of Psychiatry visited MP George Freeman, the life sciences minister, at the House of Commons for a week in Westminster.

  • Human trials suggest ‘rescued’ drug could be safer treatment for bipolar disorder

    9 December 2015

    A drug destined for the scrap heap has been rescued by Oxford scientists, who may have found it a new role in treating bipolar disorder.

  • Reported self-inflicted harm cases have steadily risen in UK since 2008

    9 May 2016

    The number of cases of self-harm presenting to hospitals in England has risen steadily since 2008, especially among men, reveals research co-ordinated by the Centre for Suicide Research at Oxford University Department of Psychiatry, published in the online journal BMJ Open.

  • Professor Michael Sharpe is named as Psychiatrist of the Year

    7 November 2014

    Professor Sharpe has been named as Psychiatrist of the Year at the Royal College of Psychiatrists Awards Ceremony in London

  • Self-help from the stands

    18 October 2013

    Gill Oliver probes mind and motivations of the Watford FC-supporting Oxford University Professor of Clinical Psychology

  • Simple blood test gives early warning of Alzheimer's

    8 July 2014

    BBC News online, 08/07/14, James Gallagher: Scientists have made a ‘major step forward’ in developing a blood test to predict the onset of Alzheimer's disease. Research in more than 1,000 people has identified a set of proteins in the blood which can predict the start of the dementia with 87% accuracy. The findings, published in the journal Alzheimer's & Dementia, will be used to improve trials for new dementia drugs.

  • Largest epidemiological study of epilepsy and psychiatric disorders

    22 July 2013

    In a recent Lancet paper, Seena Fazel together with Achim Wolf and Charles Newton from this department, reports that "people with epilepsy are 11 times more likely to die prematurely than the general population, and the risk appears to be substantially higher for individuals with common co-existing psychiatric illnesses." He adds: "standard psychiatric checks could help reduce the risk of premature deaths in people with epilepsy."

  • OHBA Analysis Group

    17 September 2018

    Developing new analysis tools for understanding human brain activity