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Luomajoki H.,ZHAW Zurich University of Applied Sciences | Moseley G.L.,University of New South Wales | Moseley G.L.,University of Oxford | Moseley G.L.,Prince of Wales Medical Research Institute
British Journal of Sports Medicine | Year: 2011

Background Voluntary lumbopelvic control is compromised in patients with back pain. Loss of proprioceptive acuity is one contributor to decreased control. Several reasons for decreased proprioceptive acuity have been proposed, but the integrity of cortical body maps has been overlooked. We investigated whether tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to lumbopelvic control in people with back pain. Methods Forty-five patients with back pain and 45 age- and sex-matched healthy controls participated in this cross-sectional study. Tactile acuity at the back was assessed using two-point discrimination (TPD) threshold in vertical and horizontal directions. Voluntary motor control was assessed using an established battery of clinical tests. Results Patients performed worse on the voluntary lumbopelvic tasks than healthy controls did (p<0.001). TPD threshold was larger in patients (mean (SD)=61(13) mm) than in healthy controls (44 (10) mm). Moreover, larger TPD threshold was positively related to worse performance on the voluntary lumbopelvic tasks (Pearson's r=0.49; p<0.001). Discussion Tactile acuity, a clear clinical signature of primary sensory cortex organisation, relates to voluntary lumbopelvic control. This relationship raises the possibility that the former contributes to the latter, in which case training tactile acuity may aid recovery and assist in achieving normal motor performance after back injury.


James C.,University of Western Sydney | Macefield V.G.,University of Western Sydney | Macefield V.G.,Prince of Wales Medical Research Institute
Autonomic Neuroscience: Basic and Clinical | Year: 2010

We tested the hypothesis that vestibular and cardiac rhythms compete to modulate muscle sympathetic nerve activity (MSNA) in human subjects. Sinusoidal galvanic vestibular stimulation was applied across the mastoid processes at each subject's cardiac frequency and at ± 0.1, ± 0.2, ± 0.3 and ± 0.6. Hz. Cyclic modulation of MSNA was weakest at this central frequency (44.8 ± 2.3%; n = 8); significantly lower than when delivered 0.1. Hz lower (57.7 ± 3.3%) or 0.1. Hz higher (56.3 ± 3.3%) than this frequency. We conclude that vestibular inputs compete with baroreceptor inputs operating at the cardiac rhythm, with vestibular modulation of MSNA being lowest when competition with the baroreceptors is highest. © 2010 Elsevier B.V.


Foley P.,Prince of Wales Medical Research Institute
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2010

Three neuropathological features attracted the attention of Alzheimer in his examination of the brain of Auguste Deter: abnormal fibrillary structures, cortical depositions now termed "plaques," and glial proliferation, whereby he noted remarkable lipid granule accumulation in the glia. These features were also recorded by Perusini and Kraepelin, but by 1930 the lipoid deposits were no longer regarded by neuropathologists with great interest. © 2010 Elsevier B.V. All rights reserved.


Pengas G.,University of Cambridge | Hodges J.R.,Prince of Wales Medical Research Institute | Watson P.,MRC Cognition and Brain science Unit | Nestor P.J.,University of Cambridge
Neurobiology of Aging | Year: 2010

Severe posterior cingulate cortex hypometabolism is a feature of incipient, sporadic Alzheimer's disease (AD). The aim was to test the hypothesis that this region is focally atrophic in very early disease by studying AD patients at the mild cognitive impairment (MCI) stage, and, if so, to determine whether the amount of atrophy was comparable to that of the hippocampus. Twenty-four patients meeting criteria for amnestic MCI, who all subsequently progressed to fulfil AD criteria, and 28 age-matched controls, were imaged with volumetric MRI. Four regions of interest were manually traced in each hemisphere: two posterior cingulate regions (BA 23 and BA 29/30), the hippocampus (as a positive control) and the anterior cingulate (as a negative control). BA 23 and BA 29/30 were both significantly atrophic and this atrophy was comparable to that found in the hippocampus, in the absence of anterior cingulate cortex (ACC) atrophy. Contrary to previous reports, there was no evidence that posterior cingulate atrophy is specifically associated with early-onset AD. The results indicate that posterior cingulate cortex atrophy is present from the earliest clinical stage of sporadic AD and that this region is as vulnerable to neurodegeneration as the hippocampus. © 2008 Elsevier Inc. All rights reserved.


Sinclair D.,Schizophrenia Research Institute | Sinclair D.,Prince of Wales Medical Research Institute | Sinclair D.,University of New South Wales | Webster M.J.,Stanley Laboratory of Brain Research | And 6 more authors.
Molecular Psychiatry | Year: 2011

The glucocorticoid receptor (GR) has a critical role in determining the brain's capacity to respond to stress, and has been implicated in the pathogenesis of psychiatric illness. We hypothesized that key changes in cortical GR occur during adolescence and young adulthood, at a time when individuals are at increased risk of developing schizophrenia, bipolar disorder and major depression. We investigated the mRNA and protein expression of GR in the dorsolateral prefrontal cortex across seven developmental time points from infancy to adulthood. GR mRNA expression, determined by microarray and quantitative real-time PCR, was lowest in neonates and peaked around young adulthood. Western blotting revealed two dynamic patterns of GRα protein expression across the lifespan, with N-terminal variants displaying differing unique patterns of abundance. GRα-A and a 67-kDa GRα isoform mirrored mRNA trends and peaked in toddlers and late in adolescence, whereas a 40-kDa isoform, very likely a GRα-D variant, peaked in neonates and decreased across the lifespan. GRα protein was localized to pyramidal neurons throughout life and most strikingly in young adulthood, but to white matter astrocytes only in neonates and infants (130 days). These results suggest that the neonatal and late adolescent periods represent critical windows of stress pathway development, and highlight the importance of white matter astrocytes and pyramidal neurons, respectively, at these stages of cortical development. Evidence of dynamic patterns of GR isoform expression and cellular localization across development strengthens the hypothesis that windows of vulnerability to stress exist across human cortical development. © 2011 Macmillan Publishers Limited All rights reserved.


Adlam A.R.,MRC Cognition and Brain science Unit | Patterson K.,MRC Cognition and Brain science Unit | Bozeat S.,MRC Cognition and Brain science Unit | Hodges J.R.,Prince of Wales Medical Research Institute
Neurocase | Year: 2010

The aims of this study were (a) to explore the utility of, and make more widely available, an updated and extended version of the Cambridge Semantic Memory test battery, and (b) to use this battery in conjunction with other tests to characterise the profile of several different forms of progressive cognitive impairment: semantic dementia (SD, n = 15), mild cognitive impairment (MCI, n = 7), established Alzheimer's disease (AD) (n = 8), all in comparison to normal controls (n = 45). The semantic battery is useful in a variety of ways for exploring the nature of semantic deficits; on its own, however, it does not provide sensitive differentiation between patients with AD and SD. An assessment including measures of episodic memory and visuospatial abilities as well as the semantic battery is recommended for good characterisation of the cognitive profiles associated with SD and AD. © 2010 Psychology Press.


Birznieks I.,Prince of Wales Medical Research Institute | Wheat H.E.,University of Melbourne | Redmond S.J.,University of New South Wales | Salo L.M.,University of Melbourne | And 2 more authors.
Journal of Physiology | Year: 2010

Torsional loads are ubiquitous during everyday dextrous manipulations. We examined how information about torque is provided to the sensorimotor control system by populations of tactile afferents. Torsional loads of different magnitudes were applied in clockwise and anticlockwise directions to a standard central site on the fingertip. Three different background levels of contact (grip) force were used. The median nerve was exposed in anaesthetized monkeys and single unit responses recorded from 66 slowly adapting type-I (SA-I) and 31 fast adapting type-I (FA-I) afferents innervating the distal segments of the fingertips. Most afferents were excited by torque but some were suppressed. Responses of the majority of both afferent types were scaled by torque magnitude applied in one or other direction, with the majority of FA-I afferent responses and about half of SA-I afferent responses scaled in both directions. Torque direction affected responses in both afferent types, but more so for the SA-I afferents. Latencies of the first spike in FA-I afferent responses depended on the parameters of the torque. We used a Parzen window classifier to assess the capacity of the SA-I and FA-I afferent populations to discriminate, concurrently and in real-time, the three stimulus parameters, namely background normal force, torque magnitude and direction. Despite the potentially confounding interactions between stimulus parameters, both the SA-I and the FA-I populations could extract torque magnitude accurately. The FA-I afferents signalled torque magnitude earlier than did the SA-I afferents, but torque direction was extracted more rapidly and more accurately by the SA-I afferent population. © 2010 The Authors. Journal compilation © 2010 The Physiological Society.


Carthery-Goulart M.T.,Federal University of ABC | Knibb J.A.,Royal Preston Hospital NHS Trust | Patterson K.,MRC Cognition and Brain science Unit | Hodges J.R.,Prince of Wales Medical Research Institute
Alzheimer Disease and Associated Disorders | Year: 2012

Background: Early progressive nonfluent aphasia (PNFA) may be difficult to differentiate from semantic dementia (SD) in a nonspecialist setting. There are descriptions of the clinical and neuropsychological profiles of patients with PNFA and SD but few systematic comparisons. METHOD: We compared the performance of groups with SD (n=27) and PNFA (n=16) with comparable ages, education, disease duration, and severity of dementia as measured by the Clinical Dementia Rating Scale on a comprehensive neuropsychological battery. Principal components analysis and intergroup comparisons were used. Results: A 5-factor solution accounted for 78.4% of the total variance with good separation of neuropsychological variables. As expected, both groups were anomic with preserved visuospatial function and mental speed. Patients with SD had lower scores on comprehension-based semantic tests and better performance on verbal working memory and phonological processing tasks. The opposite pattern was found in the PNFA group. Conclusions: Neuropsychological tests that examine verbal and nonverbal semantic associations, verbal working memory, and phonological processing are the most helpful for distinguishing between PNFA and SD. Copyright © 2012 by Lippincott Williams & Wilkins.


Alsaadi S.M.,University of Sydney | McAuley J.H.,Prince of Wales Medical Research Institute | Hush J.M.,University of Sydney | Maher C.G.,University of Sydney
European Spine Journal | Year: 2011

Low back pain (LBP) is a common health condition that is often associated with disability, psychological distress and work loss. Worldwide, billions of dollars are expended each year trying to manage LBP, often with limited success. Recently, some researchers have reported that LBP patients also report sleep disturbance as a result of their LBP. However, as most of this evidence was obtained from highly selected groups of patients or from studies with small samples, high quality data on prevalence of sleep disturbance for patients with LBP are lacking. It is also unclear whether sleep disturbance is more likely to be reported by patients with recent-onset LBP than by patients with persistent LBP. Finally, it is not known whether high pain intensity, the most relevant condition-specific variable, is associated with higher rates of reported sleep disturbance. The present study aimed to determine the prevalence of reported sleep disturbance in patients with LBP. In addition, we aimed to determine whether sleep disturbance was associated with the duration of back pain symptoms and whether pain intensity was associated with reported sleep disturbance. Data from 1,941 patients obtained from 13 studies conducted by the authors or their colleagues between 2001 and 2009 were used to determine the prevalence of sleep disturbance. Logistic regression analyses explored associations between sleep disturbance, the duration of low back symptoms and pain intensity. The estimated prevalence of sleep disturbance was 58.7% (95% CI 56.4-60.7%). Sleep disturbance was found to be dependent on pain intensity, where each increase by one point on a ten-point visual analogue scale (VAS) was associated with a 10% increase in the likelihood of reporting sleep disturbance. Our findings indicate that sleep disturbance is common in patients with LBP. In addition, we found that the intensity of back pain was only weakly associated with sleep disturbance, suggesting that other factors contribute to sleep problems for LBP patients. © 2010 Springer-Verlag.


Fonville J.M.,Imperial College London | Maheir A.D.,Prince of Wales Medical Research Institute | Coen M.,Imperial College London | Holmes E.,Imperial College London | And 2 more authors.
Analytical Chemistry | Year: 2010

Spectroscopic profiling of biological samples is an integral part of metabolically driven top-down systems biology and can be used for identifying biomarkers of toxicity and disease. However, optimal biomarker information recovery and resonance assignment still pose significant challenges in NMR-based complex mixture analysis. The reduced signal overlap as achieved when projecting twodimensional (2D) J-resolved (JRES) NMR spectra can be exploited to mitigate this problem and, here, full-resolution 1H JRES projections have been evaluated as a tool for metabolic screening and biomarker identification. We show that the recoverable information content in JRES projections is intrinsically different from that in the conventional one-dimensional (ID) and Carr - Purcell - Meiboom - Gill (CPMG) spectra, because of the combined result of reduction of the over-representation of highly split multiplet peaks and relaxation editing. Principal component and correlation analyses of full-resolution JRES spectral data demonstrated that peak alignment is necessary. The application of statistical total correlation spectroscopy (STOCSY) to JRES projections improved the identification of previously overlapped small molecule resonances in JRES 1H NMR spectra, compared to conventional ID and CPMG spectra. These approaches are demonstrated using a galactosamineinduced hepatotoxicity study in rats and show that JRES projections have a useful and complementary role to standard one-dimensional experiments in complex mixture analysis for improved biomarker identification. © 2010 American Chemical Society.

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