Activation of innate immune cells and other compartmentalized inflammatory cells in the brains and spinal cords of people with relapsing-remitting multiple sclerosis (MS) and progressive MS has been ...well described histopathologically. However, conventional clinical MRI is largely insensitive to this inflammatory activity. The past two decades have seen the introduction of quantitative dynamic MRI scanning with contrast agents that are sensitive to the reduction in blood-brain barrier integrity associated with inflammation and to the trafficking of inflammatory myeloid cells. New MRI imaging sequences provide improved contrast for better detection of grey matter lesions. Quantitative lesion volume measures and magnetic resonance susceptibility imaging are sensitive to the activity of macrophages in the rims of white matter lesions. PET and magnetic resonance spectroscopy methods can also be used to detect contributions from innate immune activation in the brain and spinal cord. Some of these advanced research imaging methods for visualization of chronic inflammation are practical for relatively routine clinical applications. Observations made with the use of these techniques suggest ways of stratifying patients with MS to improve their care. The imaging methods also provide new tools to support the development of therapies for chronic inflammation in MS.
We developed a machine learning methodology for automatic sleep stage scoring. Our time-frequency analysis-based feature extraction is fine-tuned to capture sleep stage-specific signal features as ...described in the American Academy of Sleep Medicine manual that the human experts follow. We used ensemble learning with an ensemble of stacked sparse autoencoders for classifying the sleep stages. We used class-balanced random sampling across sleep stages for each model in the ensemble to avoid skewed performance in favor of the most represented sleep stages, and addressed the problem of misclassification errors due to class imbalance while significantly improving worst-stage classification. We used an openly available dataset from 20 healthy young adults for evaluation. We used a single channel of EEG from this dataset, which makes our method a suitable candidate for longitudinal monitoring using wearable EEG in real-world settings. Our method has both high overall accuracy (78%, range 75–80%), and high mean
F
1
-score (84%, range 82–86%) and mean accuracy across individual sleep stages (86%, range 84–88%) over all subjects. The performance of our method appears to be uncorrelated with the sleep efficiency and percentage of transitional epochs in each recording.
UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, ...with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.
UK Biobank is a large-scale prospective epidemiological study with all data accessible to researchers worldwide. It is currently in the process of bringing back 100,000 of the original participants ...for brain, heart and body MRI, carotid ultrasound and low-dose bone/fat x-ray. The brain imaging component covers 6 modalities (T1, T2 FLAIR, susceptibility weighted MRI, Resting fMRI, Task fMRI and Diffusion MRI). Raw and processed data from the first 10,000 imaged subjects has recently been released for general research access. To help convert this data into useful summary information we have developed an automated processing and QC (Quality Control) pipeline that is available for use by other researchers. In this paper we describe the pipeline in detail, following a brief overview of UK Biobank brain imaging and the acquisition protocol. We also describe several quantitative investigations carried out as part of the development of both the imaging protocol and the processing pipeline.
This paper proposes a practical approach to addressing limitations posed by using of single-channel electroencephalography (EEG) for sleep stage classification. EEG-based characterizations of sleep ...stage progression contribute the diagnosis and monitoring of the many pathologies of sleep. Several prior reports explored ways of automating the analysis of sleep EEG and of reducing the complexity of the data needed for reliable discrimination of sleep stages at lower cost in the home. However, these reports have involved recordings from electrodes placed on the cranial vertex or occiput, which are both uncomfortable and difficult to position. Previous studies of sleep stage scoring that used only frontal electrodes with a hierarchical decision tree motivated this paper, in which we have taken advantage of rectifier neural network for detecting hierarchical features and long short-term memory network for sequential data learning to optimize classification performance with single-channel recordings. After exploring alternative electrode placements, we found a comfortable configuration of a single-channel EEG on the forehead and have shown that it can be integrated with additional electrodes for simultaneous recording of the electro-oculogram. Evaluation of data from 62 people (with 494 hours sleep) demonstrated better performance of our analytical algorithm than is available from existing approaches with vertex or occipital electrode placements. Use of this recording configuration with neural network deconvolution promises to make clinically indicated home sleep studies practical.
Recent advances in connectomics have led to a synthesis of perspectives regarding the brain’s functional organization that reconciles classical concepts of localized specialization with an ...appreciation for properties that emerge from interactions across distributed functional networks. This provides a more comprehensive framework for understanding neural mechanisms of normal cognition and disease. Although fMRI has not become a routine clinical tool, research has already had important influences on clinical concepts guiding diagnosis and patient management. Here we review illustrative examples. Studies demonstrating the network plasticity possible in adults and the global consequences of even focal brain injuries or disease both have had substantial impact on modern concepts of disease evolution and expression. Applications of functional connectomics in studies of clinical populations are challenging traditional disease classifications and helping to clarify biological relationships between clinical syndromes (and thus also ways of extending indications for, or “re-purposing,” current treatments). Large datasets from prospective, longitudinal studies promise to enable the discovery and validation of functional connectomic biomarkers with the potential to identify people at high risk of disease before clinical onset, at a time when treatments may be most effective. Studies of pain and consciousness have catalyzed reconsiderations of approaches to clinical management, but also have stimulated debate about the clinical meaningfulness of differences in internal perceptual or cognitive states inferred from functional connectomics or other physiological correlates. By way of a closing summary, we offer a personal view of immediate challenges and potential opportunities for clinically relevant applications of fMRI-based functional connectomics.
Matthews and Hampshire review concepts emerging from fMRI connectomics and discuss their implications for understanding cognitive variation in health and disease. They highlight potential new applications in the clinic and outline challenges that need to be addressed to realize them.
There is strong evidence of brain-related abnormalities in COVID-19
. However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can ...reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51-81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans-with 141 days on average separating their diagnosis and the second scan-as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.
Functional neuroimaging techniques have transformed our ability to probe the neurobiological basis of behaviour and are increasingly being applied by the wider neuroscience community. However, ...concerns have recently been raised that the conclusions that are drawn from some human neuroimaging studies are either spurious or not generalizable. Problems such as low statistical power, flexibility in data analysis, software errors and a lack of direct replication apply to many fields, but perhaps particularly to functional MRI. Here, we discuss these problems, outline current and suggested best practices, and describe how we think the field should evolve to produce the most meaningful and reliable answers to neuroscientific questions.
Interest in neurofilaments has risen sharply in recent years with recognition of their potential as biomarkers of brain injury or neurodegeneration in CSF and blood. This is in the context of a ...growing appreciation for the complexity of the neurobiology of neurofilaments, new recognition of specialized roles for neurofilaments in synapses and a developing understanding of mechanisms responsible for their turnover. Here we will review the neurobiology of neurofilament proteins, describing current understanding of their structure and function, including recently discovered evidence for their roles in synapses. We will explore emerging understanding of the mechanisms of neurofilament degradation and clearance and review new methods for future elucidation of the kinetics of their turnover in humans. Primary roles of neurofilaments in the pathogenesis of human diseases will be described. With this background, we then will review critically evidence supporting use of neurofilament concentration measures as biomarkers of neuronal injury or degeneration. Finally, we will reflect on major challenges for studies of the neurobiology of intermediate filaments with specific attention to identifying what needs to be learned for more precise use and confident interpretation of neurofilament measures as biomarkers of neurodegeneration.
PDF
