Biology subjects

Rees, G.

Publications and source records attributed to Rees, G..

5 recordsLinked to original sources

bioRxiv2018

Stability and sensitivity of structural connectomes: effect of thresholding and filtering and demonstration in neurodegeneration

Structural connectomes derived using diffusion tractography are increasingly used to investigate white matter connectivity in neurological diseases. However inherent biases in diffusion tractography algorithms may lead to both false negatives and false positives in connectome construction. A range of graph thresholding approaches and more recently several streamline filtering algorithms have been developed to address these issues. However there is no consensus in the literature regarding the best available approach. Using a cohort of Huntingtons disease patients and healthy controls we compared the effect of several graph thresholding strategies: proportional, absolute, consensus and consistency thresholding, with and without streamline filtering, using Spherical Deconvolution Informed Filtering of tractograms (SIFT2) algorithm. We examined the effect of thresholding strategies on the stability of graph theory metrics and the sensitivity of these measures in neurodegeneration. We show that while a number of graph thresholding procedures result in stable metrics across thresholds, the detection of group differences is highly variable. We also showed that the application of streamline filtering using SIFT2 resultes in better detection of group differences and stronger clinical correlations. We therefore conclude that the application of SIFT2 streamline filtering without graph thresholding may be sufficient for structural connectome construction.

neuroscience↗

bioRxiv2018

Assessment of Functional Connectome Construction Strategies in Neurodegeneration

Connectomics can be used to investigate functional brain networks in neurodegenerative diseases including Huntingtons disease (HD). In this developing field, different connectome construction strategies have emerged in parallel. However, there is a need to understand the influences of different strategies on subsequent analyses when constructing a connectome. This study systematically compares connectome construction strategies based on their biological relevance to functional networks in neurodegeneration.\n\nWe asked which functional connectome construction strategy was best able to discriminate HD gene carriers from healthy controls, and how such a strategy affected modular organization of the network. The major factors compared were principal component-based correction versus wavelet decomposition for physiological noise correction, the type of parcellation atlas (functional, structural and multi-modal), weighted versus binarized networks, and unthresholded versus proportionally thresholded networks. We found that principal component-based correction generated the most discriminatory connectomes, while binarization and proportional thresholding did not increase discrimination between HD gene carriers and healthy controls. When a functional parcellation atlas was used, the highest discrimination rates were obtained. We observed that the group differences in modular organization of the functional connectome were greatly affected by binarization and thresholding, showing no consistent pattern of modularity.\n\nThis study suggests that functional connectome construction strategies using principal component-based correction and weighted unthresholded connectivity matrices may outperform other strategies.

neuroscience↗

bioRxiv2017

Evaluation of Metrics for Benchmarking Antimicrobial Use in the United Kingdom Dairy Industry

The issue of antimicrobial resistance is of global concern across human and animal health. In 2016 the UK government committed to new targets for reducing antimicrobial use (AMU) in livestock. However, though a number of metrics for quantifying AMU are defined in the literature, all give slightly different interpretations.\n\nThis paper reviews a selection of metrics for AMU in the dairy industry: total mg, total mg/kg, daily dose and daily course metrics. Although the focus is on their application to the dairy industry, the metrics and issues discussed are relevant across livestock sectors.\n\nIn order to be used widely, a metric should be understandable and relevant to the veterinarians and farmers who are prescribing and using antimicrobials. This means that clear methods, assumptions (and possible biases), standardised values and exceptions should be published for all metrics. Particularly relevant are assumptions around the number and weight of cattle at risk of treatment and definitions of dose rates and course lengths; incorrect assumptions can mean metrics over- or under-represent AMU.\n\nThe authors recommend that the UK dairy industry work towards UK-specific metrics using UK-specific medicine dose and course regimens as well as cattle weights in order to monitor trends nationally.

epidemiology↗

bioRxiv2017

Quantitative MRI Provides Markers Of Intra-, Inter-Regional, And Age-Related Differences In Young Adult Cortical Microstructure

Measuring the structural composition of the cortex is critical to understanding typical development, yet few investigations in humans have charted markers in vivo that are sensitive to tissue microstructural attributes. Here, we used a well-validated quantitative MR protocol to measure four parameters (R1, MT, R2*, PD*) that differ in their sensitivity to facets of the tissue microstructural environment (R1, MT: myelin, macromolecular content; R2*: paramagnetic ions, i.e., iron; PD*: free water content). Mapping these parameters across cortical regions in a young adult cohort (18-30 years, N=93) revealed expected patterns of increased macromolecular content as well as reduced tissue water content in primary and primary adjacent cortical regions. Mapping across cortical depth within regions showed decreased expression of myelin and related processes - but increased tissue water content - when progressing from the grey/white to the grey/pial boundary, in all regions. Charting developmental change in cortical microstructure, we found that parameters with the greatest sensitivity to tissue myelin (R1 & MT) showed linear increases with age across frontal and parietal cortex (change 0.5-1.0% per year). Overlap of robust age effects for both parameters emerged in left inferior frontal, right parietal and bilateral pre-central regions. Our findings afford an improved understanding of ontogeny in early adulthood and offer normative quantitative MR data for inter- and intra-cortical composition, which may be used as benchmarks in further studies.\n\nHighlights O_LIWe mapped multi-parameter maps (MPMs) across and within cortical regions\nC_LIO_LIWe charted age effects on myelin and related processes at mid-cortical depth\nC_LIO_LIInter- and intra-regional differences in MPMs emerged at primary and association cortex\nC_LIO_LIIron-sensitive R2* map foci tended to overlap MPMs sensitive to myelin (R1, MT)\nC_LIO_LIR1 and MT increased with age (0.5-1.0% per year) in frontal and parietal cortex\nC_LI

neuroscience↗

bioRxiv2017

Metacognitive impairments extend perceptual decision making weaknesses in compulsivity

Awareness of ones own abilities is of paramount importance in adaptive decision making. Psychotherapeutic theories assume such metacognitive insight is impaired in compulsivity, though this is supported by scant empirical evidence. In this study, we investigate metacognitive abilities in compulsive participants using computational models, where these enable a segregation between metacognitive and perceptual decision making impairments. We examined twenty low-compulsive and twenty high-compulsive participants, recruited from a large population-based sample, and matched for other psychiatric and cognitive dimensions. Hierarchical computational modelling of the participants metacognitive abilities on a visual global motion detection paradigm revealed that high-compulsive participants had a reduced metacognitive ability. This impairment was accompanied by a perceptual decision making deficit whereby motion-related evidence was accumulated more slowly in high compulsive participants. Our study shows that the compulsivity spectrum is associated with a reduced ability to monitor ones own performance, over and above any perceptual decision making difficulty.

neuroscience↗