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  • Language networks in anophthalmia: maintained hierarchy of processing in 'visual' cortex.

    3 November 2018

    Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary 'visual' cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across 'visual' areas. Our data do not support such a pattern of organization in anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in 'visual' cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.

  • Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE epsilon4 carriers.

    3 November 2018

    PURPOSE: To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers. MATERIALS AND METHODS: A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter. RESULTS: We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups. CONCLUSION: APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.

  • 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.

  • 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