142 results found
Cole JH, Jolly A, De Simoni S, et al., 2018, Spatial patterns of progressive brain volume loss after moderate-severe traumatic brain injury, Brain, ISSN: 1460-2156
Traumatic brain injury leads to significant loss of brain volume, which continues into the chronic stage. This can be sensitively measured using volumetric analysis of magnetic resonance imaging. Here we: (i) investigated longitudinal patterns of brain atrophy; (ii) tested whether atrophy is greatest in sulcal cortical regions, and (iii) showed how atrophy could be used to power intervention trials aimed at slowing neurodegeneration. In 61 moderate/severe traumatic brain injury patients (mean age = 41.55 years ± 12.77) and 32 healthy controls (mean age = 34.22 years ± 10.29), cross-sectional and longitudinal (one-year follow-up) brain structure was assessed using voxel-based morphometry on T1-weighted scans. Longitudinal brain volume changes were characterised using a novel neuroimaging analysis pipeline that generates a Jacobian determinant metric, reflecting spatial warping between baseline and follow-up scans. Jacobian determinant values were summarised regionally and compared with clinical and neuropsychological measures. Traumatic brain injury patients showed lower grey and white matter volume in multiple brain regions compared to controls at baseline. Atrophy over one year was pronounced following traumatic brain injury. Traumatic brain injury patients lost a mean (± standard deviation) of 1.55% ± 2.19 of grey matter volume per year, 1.49% ± 2.20 of white matter volume or 1.51% ± 1.60 of whole brain volume. Healthy controls lost 0.55% ± 1.13 of grey matter volume and gained 0.26% ± 1.11 of white matter volume; equating to a 0.22% ± 0.83 reduction in whole brain volume. Atrophy was greatest in white matter, where the majority (84%) of regions were affected. This effect was independent of and substantially greater than that of ageing. Increased atrophy was also seen in cortical sulci compared to gyri. There was no relationship between atrophy and time since injury or age at baseline. Atrophy rates we
Cole JH, caan M, Underwood J, et al., 2018, No evidence for accelerated ageing-related brain pathology in treated HIV: longitudinal neuroimaging results from the Comorbidity in Relation to AIDS (COBRA) project, Clinical Infectious Diseases, ISSN: 1058-4838
BackgroundDespite successful antiretroviral therapy people living with HIV (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function and cognitive impairment. This has raised concerns that PLWH may experience accelerated ageing-related brain pathology.MethodsWe performed a multi-centre longitudinal study of 134 virologically-suppressed PLWH (median age = 56.0 years) and 79 demographically-similar HIV-negative controls (median age = 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multi-modality neuroimaging (T1-weighted, T2-weighted, diffusion-MRI, resting-state functional-MRI, spectroscopy, arterial spin labelling) at baseline and after two-year follow-up. Group differences in rates of change were assessed using linear mixed effects models.Results123 PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval = 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking, alcohol use, recreational drug use, blood pressure, body-mass index or cholesterol levels.At baseline, PLWH had poorer global cognitive performance (P<0.01), lower grey matter volume (P=0.04), higher white matter hyperintensity load (P=0.02), abnormal white-matter microstructure (P<0.005) and greater ‘brain-predicted age difference’ (P=0.01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P>0.1). Cognitive performance was stable across the study period in both groups.ConclusionsOur finding indicate that when receiving successful treatment, middle-aged PLWH are not at increased risk of accelerated ageing-related brain changes or cognitive decline over two years, when compared to closely-matched HIV-negative controls.
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
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 Infect Dis, 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.
Chhabra S, Underwood J, Cole JH, et al., 2017, Clinical research cerebral MRI findings in HIV positive subjects and appropriate controls, Publisher: WILEY, Pages: 10-10, ISSN: 1464-2662
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
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.Molecular Psychiatry advance online publication, 25 April 2017; doi:10.1038/mp.2017.62.
Cole JH, Underwood J, Caan MWA, et al., 2017, Increased brain-predicted aging in treated HIV disease, NEUROLOGY, Vol: 88, Pages: 1349-1357, ISSN: 0028-3878
De Simoni S, Jenkins PO, Bourke NJ, et al., 2017, Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury., Brain
Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of ex
Feeney C, Sharp DJ, Hellyer PJ, et al., 2017, Serum Insulin-like Growth Factor-I Levels are Associated with Improved White Matter Recovery after Traumatic Brain Injury, ANNALS OF NEUROLOGY, Vol: 82, Pages: 30-43, ISSN: 0364-5134
Ghajari M, Hellyer PJ, Sharp DJ, 2017, Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology, BRAIN, Vol: 140, Pages: 333-343, ISSN: 0006-8950
Goverdovsky V, von Rosenberg W, Nakamura T, et al., 2017, Hearables: Multimodal physiological in-ear sensing., Sci Rep, Vol: 7
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.
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
Roberts RE, Ahmad H, Arshad Q, et al., 2017, Functional neuroimaging of visuo-vestibular interaction, BRAIN STRUCTURE & FUNCTION, Vol: 222, Pages: 2329-2343, ISSN: 1863-2653
Scott G, Zetterberg H, Jolly A, et al., 2017, Minocycline reduces chronic microglial activation after brain trauma but increases neurodegeneration., Brain
Survivors of a traumatic brain injury can deteriorate years later, developing brain atrophy and dementia. Traumatic brain injury triggers chronic microglial activation, but it is unclear whether this is harmful or beneficial. A successful chronic-phase treatment for traumatic brain injury might be to target microglia. In experimental models, the antibiotic minocycline inhibits microglial activation. We investigated the effect of minocycline on microglial activation and neurodegeneration using PET, MRI, and measurement of the axonal protein neurofilament light in plasma. Microglial activation was assessed using 11C-PBR28 PET. The relationships of microglial activation to measures of brain injury, and the effects of minocycline on disease progression, were assessed using structural and diffusion MRI, plasma neurofilament light, and cognitive assessment. Fifteen patients at least 6 months after a moderate-to-severe traumatic brain injury received either minocycline 100 mg orally twice daily or no drug, for 12 weeks. At baseline, 11C-PBR28 binding in patients was increased compared to controls in cerebral white matter and thalamus, and plasma neurofilament light levels were elevated. MRI measures of white matter damage were highest in areas of greater 11C-PBR28 binding. Minocycline reduced 11C-PBR28 binding (mean Δwhite matter binding = -23.30%, 95% confidence interval -40.9 to -5.64%, P = 0.018), but increased plasma neurofilament light levels. Faster rates of brain atrophy were found in patients with higher baseline neurofilament light levels. In this experimental medicine study, minocycline after traumatic brain injury reduced chronic microglial activation while increasing a marker of neurodegeneration. These findings suggest that microglial activation has a reparative effect in the chronic phase of traumatic brain injury.
Shamshiri EA, Tierney TM, Centeno M, et al., 2017, Interictal activity is an important contributor to abnormal intrinsic network connectivity in paediatric focal epilepsy, HUMAN BRAIN MAPPING, Vol: 38, Pages: 221-236, ISSN: 1065-9471
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
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
Underwood J, Cole JH, Caan M, et al., 2017, Gray and White Matter Abnormalities in Treated Human Immunodeficiency Virus Disease and Their Relationship to Cognitive Function, CLINICAL INFECTIOUS DISEASES, Vol: 65, Pages: 422-432, ISSN: 1058-4838
Violante IR, Li LM, Carmichael DW, et al., 2017, Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance., Elife, Vol: 6
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.
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
Whittington A, Sharp DJ, Gunn RN, 2017, Spatiotemporal distribution of β-amyloid in Alzheimer's disease results from heterogeneous regional carrying capacities., J Nucl Med
β-amyloid (Aβ) accumulation in the brain is one of two pathological hallmarks of Alzheimer's Disease (AD) and its spatial distribution has been studied extensively ex vivo. We apply mathematical modelling to Aβ in vivo PET imaging data in order to investigate competing theories of Aβ spread in AD. Our results provide evidence that Aβ accumulation starts in all brain regions simultaneously and that its spatiotemporal distribution is a result of heterogeneous regional carrying capacities (regional maximum possible concentration of Aβ) for the aggregated protein rather than longer term spreading from seed regions.
van Zoest RA, Underwood J, De Francesco D, et al., 2017, Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers., J Infect Dis, Vol: 217, Pages: 69-81
Background: Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. Methods: We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Results: Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. Conclusions: The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified.
Ahmad H, Arshad Q, Roberts R, et al., 2016, CHRONIC DIZZINESS POST TRAUMATIC BRAIN INJURY: A CROSS-SECTIONAL STUDY, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050
De Simoni S, Grover PJ, Jenkins PO, et al., 2016, Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia, BRAIN, Vol: 139, Pages: 3137-3150, ISSN: 0006-8950
De Simoni S, Kochaj R, Jenkins P, et al., 2016, Changes in cerebral blood flow and their relationship to cognition following traumatic brain injury, Publisher: TAYLOR & FRANCIS INC, Pages: 605-605, ISSN: 0269-9052
Dinov M, Lorenz R, Scott G, et al., 2016, Novel Modeling of Task vs. Rest Brain State Predictability Using a Dynamic Time Warping Spectrum: Comparisons and Contrasts with Other Standard Measures of Brain Dynamics, FRONTIERS IN COMPUTATIONAL NEUROSCIENCE, Vol: 10, ISSN: 1662-5188
Fagerholm ED, Scott G, Shew WL, et al., 2016, Cortical Entropy, Mutual Information and Scale-Free Dynamics in Waking Mice, CEREBRAL CORTEX, Vol: 26, Pages: 3945-3952, ISSN: 1047-3211
Feeney C, Scott G, Raffel J, et al., 2016, Kinetic analysis of the translocator protein positron emission tomography ligand [F-18]GE-180 in the human brain, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 43, Pages: 2201-2210, ISSN: 1619-7070
Jamall OA, 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: 0300-0664
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