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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.

  • Are spiders a problem for you?

    28 November 2017

    We are looking for healthy volunteers aged 18-60 years and fluent in English to take part in a study investigating how a single dose of the medication hydrocortisone affects attention for spiders, using simple computer tasks. Hydrocortisone is a stress hormone also naturally occurring in the body. However, we think that it may also enhance the effectiveness of psychological therapies such as Cognitive-Behaviour Therapy. The study involves four appointments of about 5 hours in total.

  • Neural mechanisms underlying decision making

    6 March 2018

    Who are we looking for? Healthy fluent English-speaking people aged 18-85 who are not pregnant. You will be asked questions about your medical history to check your suitability for an MRI scan. MRI is a method to measure brain activity that allows us to see how the brain is organised, processes information and performs skills like speech or memory. This scan is safe and does not involve any needles or injections.

  • Are you interested in how the brain works? Men needed!

    18 October 2016

    If you take part, we will ask you to: - Provide a cheek swab (to see which form of the gene you have) then, if suitable, come to the lab and: - Take a single dose of a drug or a dummy pill; - Fill in some questionnaires and give samples of saliva; - Complete tasks of mental maths, memory and reward, while in an MRI brain scanner. The study will take one afternoon (around 3.5 hours).

  • Brain Stimulation Study

    30 January 2018

    We are looking for healthy volunteers to improve our understanding of how the brain is organised and how it processes information during motor learning. Transcranial Direct Current Stimulation (TDCS) is a form of neurostimulation that uses constant, low current delivered to the brain area of interest via sensors on the scalp. Participants may experience some discomfort during TDCS. This study involves two visits to the Department of Psychiatry in Oxford. Each session will take around two hours of your time.

  • OHBA Analysis Group

    17 September 2018

    Developing new analysis tools for understanding human brain activity