Publications
612 results found
Jamall O, Feeney C, Zaw-Linn J, et al., 2016, Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury, Clinical Endocrinology, Vol: 85, Pages: 636-644, ISSN: 1365-2265
Objectives: Traumatic brain injury (TBI) is a major cause of long-term disability with variable recovery. Preclinicalstudies suggest that vitamin D status influences recovery after TBI. However, there is no publishedclinical data on links between vitamin D status and TBI outcomes. To determine the: (i) prevalence ofvitamin D deficiency/insufficiency, and associations of vitamin D status with (ii) demographic factors andTBI severity, and with (iii) cognitive function, symptoms and quality of life, in adults after TBI.Design: Retrospective audit of patients seen between July 2009 and March 2015. Serum vitamin D (25-hydroxy-cholecalciferol) was categorised as deficient (<40nmol/L), insufficient (40-70nmol/L) or replete(>70nmol/L).Patients: 353 adults seen in tertiary hospital clinic (75.4% lighter-skinned, 74.8% male, age median 35.1y,range 26.6-48.3y), 0.3-56.5 months after TBI (74.5% moderate-severe).Measurements: Serum vitamin D concentrations; Addenbrooke’s Cognitive Examination (ACE-R), BeckDepression Inventory II (BDI-II), SF-36 Quality of Life, Pittsburgh Sleep Quality Index.Results: 46.5% of patients after TBI had vitamin D deficiency and 80.2% insufficiency/deficiency. Patientswith vitamin D deficiency had lower ACE-R scores than those vitamin D replete (mean effect size ± SEM 4.5± 2.1, P=0.034), and higher BDI-II scores than those vitamin D insufficient (4.5 ± 1.6, P=0.003), correcting forage, gender, time since TBI, TBI severity. There was no association between vitamin D status and markers ofTBI severity, sleep or quality of life.Conclusion: Vitamin D deficiency is common in patients after TBI and associated with impaired cognitivefunction and more severe depressive symptoms.
Underwood J, Cole JH, Sharp D, et al., 2016, Brain MRI changes associated with poorer cognitive function despite suppressive antiretroviral therapy, 22nd Annual Conference of the British HIV Association (BHIVA), Publisher: Wiley, Pages: 6-6, ISSN: 1464-2662
Scott GPT, Ramlackhansingh A, Edison P, et al., 2016, Amyloid pathology and axonal injury after brain trauma, Neurology, Vol: 86, Pages: 821-828, ISSN: 0028-3878
Objective: To image amyloid-β (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer’s disease.Methods: Patients 11 months to 17 years after moderate-severe TBI had 11C-Pittsburgh compound-B (PIB) PET, structural and diffusion MRI and neuropsychological examination. Healthy aged controls and AD patients had PET and structural MRI. Binding potential (BPND) images of 11C-PIB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy (FA), was estimated and correlated with 11C-PIB BPND.Results: 28 participants (9 TBI, 9 controls, 10 AD) were assessed. Increased 11C-PIB BPND was found in TBI versus controls in the posterior cingulate cortex (PCC) and cerebellum. Binding in the PCC increased with decreasing FA of associated white matter tracts, and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions, but increased in the cerebellum. Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathological features of dementia, which may relate to axonal damage produced by the injury.
Benoit MPMH, Diaz JD, Asenjo AB, et al., 2016, Exploring the Mechanisms of a Phosphorylation Induced Inhibition of Microtubule Depolymerization in the Kinesin 13 KLP10A, 60th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 462A-462A, ISSN: 0006-3495
Su T, Caan MWA, Wit FWNM, et al., 2016, White matter structure alterations in HIV-1-infected men with sustained suppression of viraemia on treatment, AIDS, Vol: 30, Pages: 311-322, ISSN: 0269-9370
Objective: Cognitive impairment is highly prevalent in HIV-1-infected (HIV+) patients, despite adequate suppression of viral replication by combination antiretroviral therapy (cART). Cerebral white matter structure alterations are often associated with cognitive impairment and have commonly been reported in the natural course of HIV infection. However, the existence of these alterations in adequately treated HIV+ patients remains unknown, as well as its possible association with cognitive impairment.Design: We used diffusion tensor imaging (DTI) to investigate whether white matter structure alterations exist in HIV+ patients with sustained suppressed viral replication on cART, and if such alterations are related to HIV-associated cognitive deficits.Methods: We compared 100 aviraemic HIV+ men on cART with 70 HIV-uninfected, otherwise comparable men. Clinical and neuropsychological assessments were performed. From DTI data, white matter fractional anisotropy and mean diffusion were calculated. Subsequently, tract-based spatial statistics (TBSS) was performed, with and without masking out white matter lesions.Results: HIV+ patients showed diffuse white matter structure alterations as compared with HIV-uninfected controls, observed as widespread decreased fractional anisotropy and an increased mean diffusion. These white matter structure alterations were associated with the number of years spent with a CD4+ cell count below 500 cells/µl, but not with HIV-associated cognitive deficits.Conclusion: Cerebral white matter structure alterations are found in middle-aged HIV+ men with sustained suppression of viraemia on cART, and may result from periods with immune deficiency when viral toxicity and host-inflammatory responses were at their peak. These white matter structure alterations were not associated with the observed subtle HIV-associated cognitive deficits.
Pangonis R, Ghajari M, Sharp DJ, 2016, Characterisation of brain tissue at high strain rates, Pages: 453-454
Baker LA, Charaffedine R, Tar MT, et al., 2016, Fidgetin-like 2, a novel microtubule regulator, can be targeted in vitro and in vivo to enhance axon regeneration, Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Kramer AH, Charaffedine R, Rourke BO, et al., 2016, Fidgetin-like 2, a microtubule severing enzyme, is a novel regulator of angiogenesis and heart regeneration., Annual Meeting of the American-Society-for-Cell-Biology (ASCB), Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Lorenz R, Monti RP, Hampshire A, et al., 2016, Towards tailoring non-invasive brain stimulation using real-time fMRI and Bayesian optimization, 6th International Workshop on Pattern Recognition in Neuroimaging (PRNI), Publisher: IEEE, Pages: 49-52, ISSN: 2330-9989
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- Citations: 1
Renda F, Pellacani C, Strunov A, et al., 2016, The <i>Drosophila</i> orthologue of the INT6 onco-protein regulates mitotic microtubule dynamics and kinetochore structure, Annual Meeting of the American-Society-for-Cell-Biology (ASCB), Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Scott G, Hellyer PJ, Ramlackhansingh AF, et al., 2015, Thalamic inflammation after brain trauma is associated with thalamo-cortical white matter damage, Journal of Neuroinflammation, Vol: 12, ISSN: 1742-2094
BackgroundTraumatic brain injury can trigger chronic neuroinflammation, which may predispose to neurodegeneration. Animal models and human pathological studies demonstrate persistent inflammation in the thalamus associated with axonal injury, but this relationship has never been shown in vivo.FindingsUsing [11C]-PK11195 positron emission tomography, a marker of microglial activation, we previously demonstrated thalamic inflammation up to 17 years after traumatic brain injury. Here, we use diffusion MRI to estimate axonal injury and show that thalamic inflammation is correlated with thalamo-cortical tract damage.ConclusionsThese findings support a link between axonal damage and persistent inflammation after brain injury.
Hampshire A, Sharp D, 2015, Inferior PFC Subregions Have Broad Cognitive Roles, TRENDS IN COGNITIVE SCIENCES, Vol: 19, Pages: 712-713, ISSN: 1364-6613
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- Citations: 8
Li LM, Leech R, Scott GT, et al., 2015, The effect of oppositional parietal transcranial direct current stimulation on lateralized brain functions, European Journal of Neuroscience, Vol: 42, Pages: 2904-2914, ISSN: 1460-9568
Cognitive functions such as numerical processing and spatial attention show varying degrees of lateralization. Transcranial direct current stimulation (tDCS) can be used to investigate how modulating cortical excitability affects performance of these tasks. This study investigated the effect of bi-parietal tDCS on numerical processing, spatial and sustained attention. It was hypothesized that tDCS would have distinct effects on these tasks because of varying lateralization (numerical processing left, spatial attention right) and that these effects are partly mediated by modulation of sustained attention. A single-blinded, crossover, sham-controlled study was performed. Eighteen healthy right-handed participants performed cognitive tasks during three sessions of oppositional parietal tDCS stimulation: sham; right anodal with left cathodal (RA/LC); and right cathodal with left anodal (RC/LA). Participants performed a number comparison task, a modified Posner task, a choice reaction task (CRT) and the rapid visual processing task (RVP). RA/LC tDCS impaired number comparison performance compared with sham, with slower responses to numerically close numbers pairs. RA/LC and RC/LA tDCS had distinct effects on CRT performance, specifically affecting vigilance level during the final block of the task. No effect of stimulation on the Posner task or RVP was found. It was demonstrated that oppositional parietal tDCS affected both numerical performance and vigilance level in a polarity-dependent manner. The effect of tDCS on numerical processing may partly be due to attentional effects. The behavioural effects of tDCS were specifically observed under high task demands, demonstrating the consequences of an interaction between stimulation type and cognitive load.
Li L, Leech R, Seemungal B, et al., 2015, A SENSE OF DIRECTION: BRAIN STIMULATION IN LATERALISED BRAIN FUNCTION, JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Vol: 86, ISSN: 0022-3050
Jenkins P, Fleminger J, De-Simoni S, et al., 2015, HOME COMPUTERISED COGNITIVE TESTING FOR TBI IS FEASIBLE AND POPULAR, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
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- Citations: 1
Gorgoraptis N, Zaw-Linn J, Feeney C, et al., 2015, THE IMPACT OF TRAUMATIC BRAIN INJURY ON PATIENT-REPORTED PHYSICAL AND MENTAL HEALTH, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
Leo L, Yu W, D'Rozario M, et al., 2015, Vertebrate Fidgetin Restrains Axonal Growth by Severing Labile Domains of Microtubules, CELL REPORTS, Vol: 12, Pages: 1723-1730, ISSN: 2211-1247
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- Citations: 44
Charafeddine RA, Makdisi J, Schairer D, et al., 2015, Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 135, Pages: 2309-2318, ISSN: 0022-202X
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- Citations: 44
Hampshire A, Sharp DJ, 2015, Contrasting network and modular perspectives on inhibitory control., Trends in Cognitive Sciences, ISSN: 1364-6613
A prominent theory proposes that the right inferior frontal cortex of the human brain houses a dedicated region for motor response inhibition. However, there is growing evidence to support the view that this inhibitory control hypothesis is incorrect. Here, we discuss evidence in favour of our alternative hypothesis, which states that response inhibition is one example of a broader class of control processes that are supported by the same set of frontoparietal networks. These domain-general networks exert control by modulating local lateral inhibition processes, which occur ubiquitously throughout the cortex. We propose that to fully understand the neural basis of behavioural control requires a more holistic approach that considers how common network mechanisms support diverse cognitive processes.
Shanahan MP, Hellyer P, Sharp DJ, et al., 2015, Cognitive flexibility through metastable neural dynamics is disrupted by damage to the structural connectome, Journal of Neuroscience, Vol: 35, Pages: 9050-9063, ISSN: 0270-6474
Current theory proposes that healthy neural dynamics operate in a metastable regime, where brain regions interact to simultaneously maximize integration and segregation. Metastability may confer important behavioral properties, such as cognitive flexibility. It is increasingly recognized that neural dynamics are constrained by the underlying structural connections between brain regions. An important challenge is, therefore, to relate structural connectivity, neural dynamics, and behavior. Traumatic brain injury (TBI) is a pre-eminent structural disconnection disorder whereby traumatic axonal injury damages large-scale connectivity, producing characteristic cognitive impairments, including slowed information processing speed and reduced cognitive flexibility, that may be a result of disrupted metastable dynamics. Therefore, TBI provides an experimental and theoretical model to examine how metastable dynamics relate to structural connectivity and cognition. Here, we use complementary empirical and computational approaches to investigate how metastability arises from the healthy structural connectome and relates to cognitive performance. We found reduced metastability in large-scale neural dynamics after TBI, measured with resting-state functional MRI. This reduction in metastability was associated with damage to the connectome, measured using diffusion MRI. Furthermore, decreased metastability was associated with reduced cognitive flexibility and information processing. A computational model, defined by empirically derived connectivity data, demonstrates how behaviorally relevant changes in neural dynamics result from structural disconnection. Our findings suggest how metastable dynamics are important for normal brain function and contingent on the structure of the human connectome.
Sharp DJ, Jenkins PO, 2015, Concussion is confusing us all., Practical Neurology, Vol: 15, Pages: 172-186, ISSN: 1474-7766
It is time to stop using the term concussion as it has no clear definition and no pathological meaning. This confusion is increasingly problematic as the management of 'concussed' individuals is a pressing concern. Historically, it has been used to describe patients briefly disabled following a head injury, with the assumption that this was due to a transient disorder of brain function without long-term sequelae. However, the symptoms of concussion are highly variable in duration, and can persist for many years with no reliable early predictors of outcome. Using vague terminology for post-traumatic problems leads to misconceptions and biases in the diagnostic process, producing uninterpretable science, poor clinical guidelines and confused policy. We propose that the term concussion should be avoided. Instead neurologists and other healthcare professionals should classify the severity of traumatic brain injury and then attempt to precisely diagnose the underlying cause of post-traumatic symptoms.
Whittington A, Iturria-Medina Y, Evans A, et al., 2015, A network-spreading model to characterize the accumulation of β-amyloid in Alzheimer's Disease, Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging, Publisher: SOC NUCLEAR MEDICINE INC, ISSN: 0161-5505
Cole JH, Leech R, Sharp DJ, 2015, Prediction of Brain Age Suggests Accelerated Atrophy after Traumatic Brain Injury, ANNALS OF NEUROLOGY, Vol: 77, Pages: 571-581, ISSN: 0364-5134
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- Citations: 261
Fagerholm ED, Hellyer PJ, Scott G, et al., 2015, Disconnection of network hubs and cognitive impairment after traumatic brain injury., Brain, Vol: 138, Pages: 1696-1709, ISSN: 0006-8950
Traumatic brain injury affects brain connectivity by producing traumatic axonal injury. This disrupts the function of large-scale networks that support cognition. The best way to describe this relationship is unclear, but one elegant approach is to view networks as graphs. Brain regions become nodes in the graph, and white matter tracts the connections. The overall effect of an injury can then be estimated by calculating graph metrics of network structure and function. Here we test which graph metrics best predict the presence of traumatic axonal injury, as well as which are most highly associated with cognitive impairment. A comprehensive range of graph metrics was calculated from structural connectivity measures for 52 patients with traumatic brain injury, 21 of whom had microbleed evidence of traumatic axonal injury, and 25 age-matched controls. White matter connections between 165 grey matter brain regions were defined using tractography, and structural connectivity matrices calculated from skeletonized diffusion tensor imaging data. This technique estimates injury at the centre of tract, but is insensitive to damage at tract edges. Graph metrics were calculated from the resulting connectivity matrices and machine-learning techniques used to select the metrics that best predicted the presence of traumatic brain injury. In addition, we used regularization and variable selection via the elastic net to predict patient behaviour on tests of information processing speed, executive function and associative memory. Support vector machines trained with graph metrics of white matter connectivity matrices from the microbleed group were able to identify patients with a history of traumatic brain injury with 93.4% accuracy, a result robust to different ways of sampling the data. Graph metrics were significantly associated with cognitive performance: information processing speed (R(2) = 0.64), executive function (R(2) = 0.56) and associative memory (R(2) = 0.25). These resul
Fagerholm ED, Lorenz R, Scott G, et al., 2015, Cascades and Cognitive State: Focused Attention Incurs Subcritical Dynamics, Journal of Neuroscience, Vol: 35, Pages: 4626-4634, ISSN: 1529-2401
Ghajari M, Sharp DJ, 2015, Computational analysis of white matter response to rear and lateral impacts, Pages: 229-230
Majewska P, Ribeiro Violante I, Lorenz R, et al., 2015, EEG characteristics of memory deficits in acute traumatic brain injury patients with post-traumatic amnesia, The Society of British Neurological Surgeons Meeting 2015
Kramer AH, Charaffedine R, O'Rourke BP, et al., 2015, Fidgetin-Like 2: At the heart of regeneration, Publisher: AMER SOC CELL BIOLOGY, ISSN: 1059-1524
Scott G, Fagerholm ED, Mutoh H, et al., 2014, Voltage imaging of waking mouse cortex reveals emergence of critical neuronal dynamics, The Journal of Neuroscience, Vol: 34, Pages: 16611-16620, ISSN: 0270-6474
Complex cognitive processes require neuronal activity to be coordinated across multiple scales, ranging from local microcircuits to cortex-wide networks. However, multiscale cortical dynamics are not well understood because few experimental approaches have provided sufficient support for hypotheses involving multiscale interactions. To address these limitations, we used, in experiments involving mice, genetically encoded voltage indicator imaging, which measures cortex-wide electrical activity at high spatiotemporal resolution. Here we show that, as mice recovered from anesthesia, scale-invariant spatiotemporal patterns of neuronal activity gradually emerge. We show for the first time that this scale-invariant activity spans four orders of magnitude in awake mice. In contrast, we found that the cortical dynamics of anesthetized mice were not scale invariant. Our results bridge empirical evidence from disparate scales and support theoretical predictions that the awake cortex operates in a dynamical regime known as criticality. The criticality hypothesis predicts that small-scale cortical dynamics are governed by the same principles as those governing larger-scale dynamics. Importantly, these scale-invariant principles also optimize certain aspects of information processing. Our results suggest that during the emergence from anesthesia, criticality arises as information processing demands increase. We expect that, as measurement tools advance toward larger scales and greater resolution, the multiscale framework offered by criticality will continue to provide quantitative predictions and insight on how neurons, microcircuits, and large-scale networks are dynamically coordinated in the brain.
Monti RP, Hellyer P, Sharp D, et al., 2014, Estimating time-varying brain connectivity networks from functional MRI time series, NEUROIMAGE, Vol: 103, Pages: 427-443, ISSN: 1053-8119
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- Citations: 114
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