Publications
612 results found
Sharp D, 2017, Precision medicine in TBI: Lessons from dopaminergic treatment of cognitive impairment, 23rd World Congress of Neurology (WCN), Publisher: ELSEVIER SCIENCE BV, Pages: 1-2, ISSN: 0022-510X
Wang Y, Wu B, Lu P, et al., 2017, Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking <i>Pofut1</i>, NATURE COMMUNICATIONS, Vol: 8, ISSN: 2041-1723
- Author Web Link
- Cite
- Citations: 16
Lin C, Kayali O, Morozov EV, et al., 2017, Development of self-compacting strain-hardening cementitious composites by varying fly ash content, CONSTRUCTION AND BUILDING MATERIALS, Vol: 149, Pages: 103-110, ISSN: 0950-0618
- Author Web Link
- Cite
- Citations: 14
Ghajari M, Hellyer PJ, Sharp DJ, 2017, Predicting the location of chronic traumatic encephalopathy pathology, 2017 IRCOBI Conference, Publisher: International Research Council on Biomechanics of Injury (IRCOBI), Pages: 699-700, ISSN: 2235-3151
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to head impacts. Its distinctive neuropathologic feature is deposition of tau proteins in sulcal depths and in perivascular regions. Previous work has investigated pathological and clinical features of CTE, and here the authors report recent work on exploring the link between strain and strain rate distribution within the brain and location of CTE pathology. The authors used a high fidelity finite element (FE) model of traumatic brain injury (TBI) to test the hypothesis that strain and strain rate produced by head impacts are greatest in sulci, where neuropathology is prominently seen in CTE. The authors also analyzed diffusion tensor imaging (DTI) data from a large cohort of TBI patients to provide converging evidence from empirical neuroimaging data for the model’s prediction.
Austin TO, Matamoros AJ, Friedman JM, et al., 2017, Nanoparticle Delivery of Fidgetin siRNA as a Microtubule-based Therapy to Augment Nerve Regeneration, SCIENTIFIC REPORTS, Vol: 7, ISSN: 2045-2322
- Author Web Link
- Cite
- Citations: 19
Li LM, Violante IR, Leech R, et al., 2017, Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation
<jats:title>Abstract</jats:title><jats:p>Transcranial direct current stimulation (TDCS) has been widely used to improve cognitive function. However, current deficiencies in mechanistic understanding hinders wider applicability. To clarify its physiological effects, we acquired fMRI whilst simultaneously acquiring TDCS to the right inferior frontal gyrus (rIFG) of healthy human participants, a region involved in coordinating activity within brain networks. TDCS caused widespread modulation of network activity depending on brain state (‘rest’ or choice reaction time task) and polarity (anodal or cathodal). During task, TDCS increased salience network activation and default mode network deactivation, but had the opposite effect during ‘rest’. Furthermore, there was an interaction between brain state and TDCS polarity, with cathodal effects more pronounced during task performance and anodal effects more pronounced during ‘rest’. Overall, we show that rIFG TDCS produces brain state and polarity dependent effects within large-scale cognitive networks, in a manner that goes beyond predictions from the current literature.</jats:p>
Underwood J, Cole JH, Caan M, et al., 2017, Brain MRI changes associated with poorer cognitive function despite suppressive antiretroviral therapy, 13th International Symposium on the Neurobiology and Neuroendocrinology of Aging, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 125-125, ISSN: 0531-5565
Goverdovsky V, von Rosenberg W, Nakamura T, et al., 2017, Hearables: multimodal physiological in-ear sensing, Scientific Reports, Vol: 7, ISSN: 2045-2322
Future health systems require the means to assess and track the neural and physiological function of a user over long periods of time, and in the community. Human body responses are manifested through multiple, interacting modalities – the mechanical, electrical and chemical; yet, current physiological monitors (e.g. actigraphy, heart rate) largely lack in cross-modal ability, are inconvenient and/or stigmatizing. We address these challenges through an inconspicuous earpiece, which benefits from the relatively stable position of the ear canal with respect to vital organs. Equipped with miniature multimodal sensors, it robustly measures the brain, cardiac and respiratory functions. Comprehensive experiments validate each modality within the proposed earpiece, while its potential in wearable health monitoring is illustrated through case studies spanning these three functions. We further demonstrate how combining data from multiple sensors within such an integrated wearable device improves both the accuracy of measurements and the ability to deal with artifacts in real-world scenarios.
Feeney C, Sharp DJ, Hellyer PJ, et al., 2017, Serum IGF-I levels are associated with improved white matter recovery after TBI., Annals of Neurology, Vol: 82, Pages: 30-43, ISSN: 0364-5134
OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging (DTI) measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum IGF-I may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male; age median 30.5y; 87.2% moderate-severe; time since TBI median 16.3 months, n=4 with GHD) were scanned twice, 13.3 months (12.1-14.9) apart, and 35 healthy controls scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n=33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC), and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above vs. below the median-for-age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that GH/IGF-I system may be a potential therapeutic target following TBI. This article is protected by copyright. All rights reserved.
Chiou SY, Hellyer PJ, Sharp DJ, et al., 2017, Relationships between the integrity and function of lumbar nerve roots as assessed by diffusion tensor imaging and neurophysiology, NEURORADIOLOGY, Vol: 59, Pages: 893-903, ISSN: 0028-3940
PurposeDiffusion tensor imaging (DTI) has shown promise in the measurement of peripheral nerve integrity, although the optimal way to apply the technique for the study of lumbar spinal nerves is unclear. The aims of this study are to use an improved DTI acquisition to investigate lumbar nerve root integrity and correlate this with functional measures using neurophysiology.MethodsTwenty healthy volunteers underwent 3 T DTI of the L5/S1 area. Regions of interest were applied to L5 and S1 nerve roots, and DTI metrics (fractional anisotropy, mean, axial and radial diffusivity) were derived. Neurophysiological measures were obtained from muscles innervated by L5/S1 nerves; these included the slope of motor-evoked potential input-output curves, F-wave latency, maximal motor response, and central and peripheral motor conduction times.ResultsDTI metrics were similar between the left and right sides and between vertebral levels. Conversely, significant differences in DTI measures were seen along the course of the nerves. Regression analyses revealed that DTI metrics of the L5 nerve correlated with neurophysiological measures from the muscle innervated by it.ConclusionThe current findings suggest that DTI has the potential to be used for assessing lumbar spinal nerve integrity and that parameters derived from DTI provide quantitative information which reflects their function.
Sharp DJ, 2017, BRAIN IMAGING AFTER TBI, 30th Annual General Meeting of the British-Neuropsychiatry-Association (BNPA), Publisher: BMJ PUBLISHING GROUP, Pages: E10-E10, ISSN: 0022-3050
Booiman T, Wit FW, Maurer I, et al., 2017, High Cellular Monocyte Activation in People Living With Human Immunodeficiency Virus on Combination Antiretroviral Therapy and Lifestyle-Matched Controls Is Associated With Greater Inflammation in Cerebrospinal Fluid., Open Forum Infectious Diseases, Vol: 4, ISSN: 2328-8957
BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD). RESULTS: People living with HIV, HIV-negative individuals, and BBD had comparable percentages of classical, intermediate, and nonclassical monocytes. Expression of CD163, CD32, CD64, HLA-DR, CD38, CD40, CD86, CD91, CD11c, and CX3CR1 on monocytes did not differ between PLHIV and HIV-negative individuals, but it differed significantly from BBD. Principal component analysis revealed that 57.5% of PLHIV and 62.5% of HIV-negative individuals had a high monocyte activation profile compared with 2.9% of BBD. Cellular monocyte activation in the COBRA cohort was strongly associated with soluble markers of monocyte activation and inflammation in the CSF. CONCLUSIONS: People living with HIV and HIV-negative COBRA participants had high levels of cellular monocyte activation compared with age-matched BBD. High monocyte activation was predictive for inflammation in the CSF.
Martin-Bastida A, Ward RJ, Newbould R, et al., 2017, Brain iron chelation by deferiprone in a phase 2 randomised double-blinded placebo controlled clinical trial in Parkinson's disease, Scientific Reports, Vol: 7, ISSN: 2045-2322
Parkinson’s disease (PD) is associated with increased iron levels in the substantia nigra (SNc). This study evaluated whether the iron chelator, deferiprone, is well tolerated, able to chelate iron from various brain regions and improve PD symptomology. In a randomised double-blind, placebo controlled trial, 22 early onset PD patients, were administered deferiprone, 10 or 15 mg/kg BID or placebo, for 6 months. Patients were evaluated for PD severity, cognitive function, depression rating and quality of life. Iron concentrations were assessed in the substantia nigra (SNc), dentate and caudate nucleus, red nucleus, putamen and globus pallidus by T2* MRI at baseline and after 3 and 6 months of treatment. Deferiprone therapy was well tolerated and was associated with a reduced dentate and caudate nucleus iron content compared to placebo. Reductions in iron content of the SNc occurred in only 3 patients, with no changes being detected in the putamen or globus pallidus. Although 30 mg/kg deferiprone treated patients showed a trend for improvement in motor-UPDRS scores and quality of life, this did not reach significance. Cognitive function and mood were not adversely affected by deferiprone therapy. Such data supports more extensive clinical trials into the potential benefits of iron chelation in PD.
Renda F, Pellacani C, Strunov A, et al., 2017, The <i>Drosophila</i> orthologue of the INT6 oncoprotein regulates mitotic microtubule growth and kinetochore structure, PLOS GENETICS, Vol: 13, ISSN: 1553-7404
- Author Web Link
- Cite
- Citations: 11
Cole JH, Ritchie SJ, Bastin ME, et al., 2017, Brain age predicts mortality, Molecular Psychiatry, Vol: 23, Pages: 1385-1392, ISSN: 1476-5578
Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N = 2001), then tested in the Lothian Birth Cohort 1936 (N = 669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.
Jenkins P, De Simoni S, Bourke N, et al., 2017, Disruption to the dopaminergic system following traumatic brain injury, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
- Author Web Link
- Cite
- Citations: 1
Dautricourt S, Violante I, Mallas E-J, et al., 2017, Reduced information processing speed and event-related EEG synchronization in traumatic brain injury, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
- Author Web Link
- Cite
- Citations: 3
Gorgoraptis N, Li L, Whittington A, et al., 2017, [18F]AV-1451 positron emission tomography reveals tau pathology in long-term survivors of traumatic brain injury, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Li LM, Violante I, Zimmerman K, et al., 2017, Promoting network recovery after traumatic brain injury: exploring the targeted application of transcranial direct current stimulation, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Raffel J, Cole J, Record C, et al., 2017, Brain Age: A novel approach to quantify the impact of multiple sclerosis on the brain, Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
- Author Web Link
- Cite
- Citations: 3
Underwood J, Cole JH, Caan M, et al., 2017, Grey and white matter abnormalities in treated HIV-disease and their relationship to cognitive function., Clinical Infectious Diseases, Vol: 65, Pages: 422-432, ISSN: 1537-6591
Background: Long-term comorbidities such as cognitive impairment remain prevalent in otherwise effectively treated people-living-with-HIV. We investigate the relationship between cognitive impairment and brain structure in successfully treated patients using multi-modal neuroimaging from the Co-morBidity in Relation to AIDS (COBRA) cohort. Methods: Cognitive function, brain tissue volumes and white matter microstructure were assessed in 134 HIV-positive patients and 79 controls. All patients had suppressed plasma HIV RNA at cohort entry. In addition to comprehensive voxelwise analyses of volumetric and diffusion tensor imaging, we used an unsupervised machine learning approach to combine cognitive, diffusion and volumetric data, taking advantage of the complementary information they provide. Results: Compared to the highly comparable control group, cognitive function was impaired in four out of the six cognitive domains tested (median global T-scores: 50.8 vs. 54.2, p<0.001). Patients had lower grey but not white matter volumes, observed principally in regions where structure generally did not correlate with cognitive function. Widespread abnormalities in white matter microstructure were also seen, including reduced fractional anisotropy with increased mean and radial diffusivity. In contrast to the grey matter, these diffusion abnormalities correlated with cognitive function. Multivariate neuroimaging analysis identified a neuroimaging phenotype associated with poorer cognitive function, HIV-infection and systemic immune activation. Conclusions: Cognitive impairment, lower grey matter volume and white matter microstructural abnormalities were evident in HIV-positive individuals despite fully suppressive antiretroviral therapy. White matter abnormalities appear to be a particularly important determinant of cognitive dysfunction seen in well-treated HIV-positive individuals.
Chhabra S, Underwood J, Cole JH, et al., 2017, Clinical research cerebral MRI findings in HIV positive subjects and appropriate controls, BHIVA annual conference, Publisher: WILEY, Pages: 10-10, ISSN: 1464-2662
Whittington A, Sharp DJ, Gunn RN, 2017, An automated algorithm to quantify brain amyloid load, 28th International Symposium on Cerebral Blood Flow, Metabolism and Function / 13th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 80-80, ISSN: 0271-678X
Violante IR, Li LM, Carmichael DW, et al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance, ELIFE, Vol: 6, ISSN: 2050-084X
Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization.
Cole JH, underwood J, Caan MWA, et al., 2017, Increased brain-predicted ageing in treated HIV disease, Neurology, Vol: 88, Pages: 1349-1357, ISSN: 0028-3878
Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent “brain age” using neuroimaging and exploring whether these estimates related to HIV-status, age, cognitive performance and HIV-related clinical parameters.Methods: A large sample of virologically-suppressed HIV-positive adults (N = 162, aged 45-82 years) and highly-comparable HIV-negative controls (N = 105) were recruited as part of the COBRA collaboration. Using T1-MRI scans, a machine-learning model of healthy brain ageing was defined in an independent cohort (N = 2001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out.Results: HIV-positive individuals had greater brain-PAD score (mean ± SD = 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV-infection or other HIV-related measures.Conclusions: Increased apparent brain ageing, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain ageing related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV-infection, suggesting that HIV disease may accentuate, rather than accelerate brain ageing.
Arshad Q, Roberts RE, Ahmad H, et al., 2017, Patients with chronic dizziness following traumatic head injury typically have multiple diagnoses involving combined peripheral and central vestibular dysfunction, CLINICAL NEUROLOGY AND NEUROSURGERY, Vol: 155, Pages: 17-19, ISSN: 0303-8467
Benoit MPMH, Diaz-Valencia DJ, Asenjo AB, et al., 2017, Exploring the Mechanism of Microtubule Depolymerization by the Kinesin 13 KLP10A and it's Phosphoregulation, 58th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 428A-428A, ISSN: 0006-3495
Ghajari M, Hellyer P, Sharp D, 2017, Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology, Brain, Vol: 140, Pages: 333-343, ISSN: 0006-8950
Traumatic brain injury can lead to the neurodegenerative disease chronic traumatic encephalopathy. This condition has a clear neuropathological definition but the relationship between the initial head impact and the pattern of progressive brain pathology is poorly understood. We test the hypothesis that mechanical strain and strain rate are greatest in sulci, where neuropathology is prominently seen in chronic traumatic encephalopathy, and whether human neuroimaging observations converge with computational predictions. Three distinct types of injury were simulated. Chronic traumatic encephalopathy can occur after sporting injuries, so we studied a helmet-to-helmet impact in an American football game. In addition, we investigated an occipital head impact due to a fall from ground level and a helmeted head impact in a road traffic accident involving a motorcycle and a car. A high fidelity 3D computational model of brain injury biomechanics was developed and the contours of strain and strain rate at the grey matter–white matter boundary were mapped. Diffusion tensor imaging abnormalities in a cohort of 97 traumatic brain injury patients were also mapped at the grey matter–white matter boundary. Fifty-one healthy subjects served as controls. The computational models predicted large strain most prominent at the depths of sulci. The volume fraction of sulcal regions exceeding brain injury thresholds were significantly larger than that of gyral regions. Strain and strain rates were highest for the road traffic accident and sporting injury. Strain was greater in the sulci for all injury types, but strain rate was greater only in the road traffic and sporting injuries. Diffusion tensor imaging showed converging imaging abnormalities within sulcal regions with a significant decrease in fractional anisotropy in the patient group compared to controls within the sulci. Our results show that brain tissue deformation induced by head impact loading is greatest in sulcal
Su T, Mutsaerts HJMM, Caan MWA, et al., 2017, Cerebral blood flow and cognitive function in HI-infected men with sustained suppressed viremia on combination antiretroviral therapy, AIDS, Vol: 31, Pages: 847-856, ISSN: 0269-9370
Matamoros AJ, Wu D, Baker LA, et al., 2017, A new microtubule-based approach for augmenting nerve regeneration., Annual Joint Meeting of the American-Society-for-Cell-Biology and the European-Molecular-Biology-Organization (ASCB/EMBO), Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.