Neuroscience
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Interferon-alpha (IFN-α) is an important mediator of antiviral immune responses. It is also used clinically in the treatment of hepatitis-C infection. Though effective, IFN-α-based therapies can often impair mood, motivation and cognition, which when severe can appear indistinguishable from major depression. ⋯ Acute changes in striatal microstructure additionally predicted the continued development of fatigue but not mood symptoms 4 and 8 weeks later into treatment. Our findings highlight the value of NODDI as a potential in vivo biomarker of the central effects of peripheral inflammation. We highlight the exquisite sensitivity of the striatum to IFN-α and further implicate striatal perturbation in IFN-α-induced fatigue.
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The process of neurovascular coupling ensures that increases in neuronal activity are fed by increases in cerebral blood flow. Evidence suggests that neurovascular coupling may be impaired in Multiple Sclerosis (MS) due to a combination of brain hypoperfusion, altered cerebrovascular reactivity and oxygen metabolism, and altered levels of vasoactive compounds. Here, we tested the hypothesis that neurovascular coupling is impaired in MS. ⋯ Gamma power reduction could be an indicator of GM dysfunction, possibly mediated by GABAergic changes. Altered hemodynamic responses confirm previous reports of a vascular dysfunction in MS. Despite altered neuronal and vascular responses, neurovascular coupling appears to be preserved in MS, at least within the range of damage and disability studied here.
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Huntington's disease (HD) leads to white matter (WM) degeneration that may be due to an early breakdown in axon myelination but in vivo imaging correlates of demyelination remain relatively unexplored in HD compared to other neurodegenerative diseases. This study investigated HD-related effects on a putative marker of myelin, the macromolecular proton fraction (MMPF) from quantitative magnetization transfer and on fractional anisotropy, axial and radial diffusivity from diffusion tensor MR-imaging. Microstructural differences were studied in WM pathways of the basal ganglia and motor systems known to be impaired in HD: the corpus callosum, the cortico-spinal tract, the anterior thalamic radiation, fibers between prefrontal cortex and caudate and between supplementary motor area and putamen. ⋯ Inter-individual differences in the diffusivity component correlated with patients' performance in clinical measures of the United Huntington Disease Rating Scale. In summary, HD-related reductions in MMPF suggest that myelin breakdown contributes to WM impairment in human HD and emphasize the potential of quantitative MRI metrics to inform about disease pathogenesis. Disease severity in manifest HD, however, was best captured by non-specific diffusivity metrics sensitive to multiple disease and age-related changes.
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Neuroinflammatory pathology has long been identified to contribute to the pathology of Parkinson disease. Early microstructural changes in white matter tracts might give a clue for earlier detection of PD. We investigated through diffusion MRI connectometry the structural correlates of white matter tracts of 81 patients with PD with whole blood neutrophil-to-lymphocyte ratio (NLR), controlling for age and sex. ⋯ The spin distribution function (SDF) values were used in DMRI connectometry analysis. The connectometry analyses identified white matter QA of the following fibers to be correlated with NLR score after adjustment for age and sex: bilateral cingulum, body and left crus of fornix, bilateral corticospinal tract (CST), and body and splenium of corpus callosum (CC) and superior cerebellar peduncle with decreased connectivity related to NLR (FDR = 0.04542). Keeping with emerging evidence on the role of neuroinflammation in PD pathology, these results with functional relevance to prodromal Parkinson disease, bring new insights to pivotal role of peripheral inflammation in CNS neurodegeneration.
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Our recent studies demonstrated that electrostatically stabilized very small superparamagnetic iron oxide particles (VSOPs) are promising MRI probes for detecting various pathological aspects of autoimmunity in the central nervous system (CNS). However, investigation of the precise tissue and cellular distribution of VSOP has been technically limited due to the need to use iron detection methods for VSOP visualization. Therefore, we assessed here the utility of europium (Eu)-doped VSOP as an MRI tool for in vivo investigations in the animal model experimental autoimmune encephalomyelitis (EAE), and as a tool to investigate histopathological processes in the CNS using fluorescence microscopy. ⋯ Within the choroid plexus, Eu-VSOP were associated both with monocytes/macrophages present in the plexus stroma, and associated with epithelial cells. Using Eu-VSOP, we demonstrated for the first time the involvement of the choroid plexus in relapses. Thus, Eu-VSOP have the potential to reveal various aspects of choroid plexus involvement in neuroinflammation, including monocyte recruitment from the blood and alterations of the choroid plexus epithelium.