NeuroImage. Clinical
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NeuroImage. Clinical · Jan 2020
Voxel-based analysis of gray matter relaxation rates shows different correlation patterns for cognitive impairment and physical disability in relapsing-remitting multiple sclerosis.
Regional analyses of markers of microstructural gray matter (GM) changes, including relaxation rates, have shown inconsistent correlations with physical and cognitive impairment in MS. ⋯ In relapsing-remitting MS patients, GM microstructural changes correlate diffusely with physical disability, independent of atrophy, with a preferential role of the sensorimotor cortices. Neuronal damage in the limbic system and dorsolateral prefrontal cortices correlates with cognitive dysfunction.
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NeuroImage. Clinical · Jan 2020
Involvement of the dentate nucleus in the pathophysiology of amyotrophic lateral sclerosis: A multi-center and multi-modal neuroimaging study.
Amyotrophic lateral sclerosis (ALS) is characterized primarily by motor neuron but also frontotemporal lobar degeneration. Although the cerebellum is involved in both motor and cognitive functions, little is known of its role in ALS. We targeted the dentate nucleus (DN) in the cerebellum and the associated white matter fibers tracts connecting the DN to the rest of the brain using multimodal imaging techniques to examine the cerebellar structural and functional connectivity patterns in ALS patients and hypothesized that the DN is implicated in the pathophysiology of ALS. ⋯ Impaired rsFC is likely due to the observed cerebellar peduncular WM damage given the lack of GM atrophy of the DN. This study demonstrates altered cerebellar rsFC connectivity with motor and extra-motor regions in ALS, and impaired rsFC is likely due to the observed cerebellar peduncular WM damage given the lack of GM atrophy of the DN. The correlation between the altered DN connectivity, and the behavioral data support the hypothesis that the DN plays a pathophysiological role in ALS.
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NeuroImage. Clinical · Jan 2020
"Switchboard" malfunction in motor neuron diseases: Selective pathology of thalamic nuclei in amyotrophic lateral sclerosis and primary lateral sclerosis.
The thalamus is a key cerebral hub relaying a multitude of corticoefferent and corticoafferent connections and mediating distinct extrapyramidal, sensory, cognitive and behavioural functions. While the thalamus consists of dozens of anatomically well-defined nuclei with distinctive physiological roles, existing imaging studies in motor neuron diseases typically evaluate the thalamus as a single structure. Based on the unique cortical signatures observed in ALS and PLS, we hypothesised that similarly focal thalamic involvement may be observed if the nuclei are individually evaluated. ⋯ The unique thalamic signature of PLS is in line with the distinctive clinical features of the phenotype. Our data confirm phenotype-specific patterns of thalamus involvement in motor neuron diseases with the preferential involvement of nuclei mediating motor and cognitive functions. Given the selective involvement of thalamic nuclei in ALS and PLS, future biomarker and natural history studies in MND should evaluate individual thalamic regions instead overall thalamic changes.
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NeuroImage. Clinical · Jan 2020
Multi-modal normalization of resting-state using local physiology reduces changes in functional connectivity patterns observed in mTBI patients.
Blood oxygenation level dependent (BOLD) resting-state functional magnetic resonance imaging (rs-fMRI) may serve as a sensitive marker to identify possible changes in the architecture of large-scale networks following mild traumatic brain injury (mTBI). Differences in functional connectivity (FC) measurements derived from BOLD rs-fMRI may however be confounded by changes in local cerebrovascular physiology and neurovascular coupling mechanisms, without changes in the underlying neuronally driven connectivity of networks. In this study, multi-modal neuroimaging data including BOLD rs-fMRI, baseline cerebral blood flow (CBF0) and cerebrovascular reactivity (CVR; acquired using a hypercapnic gas breathing challenge) were collected in 23 subjects with reported mTBI (14.6±14.9 months post-injury) and 27 age-matched healthy controls. ⋯ A normalization method designed to account for differences in CBF0 post-mTBI was introduced to evaluate the effects of such an approach on reported group differences in network connectivity. Inclusion of regional perfusion measurements in the computation of correlation coefficients within and across large-scale networks narrowed the differences in FC between the groups, suggesting that this approach may elucidate unique changes in connectivity post-mTBI while accounting for shared variance with CBF0. Altogether, our results provide a strong paradigm supporting the need to account for changes in physiological modulators of BOLD in order to expand our understanding of the effects of brain injury on large-scale FC of cortical networks.
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NeuroImage. Clinical · Jan 2020
Microstructural damage of white-matter tracts connecting large-scale networks is related to impaired executive profile in alcohol use disorder.
Alcohol Use Disorders (AUD) is associated with negative consequences on global functioning, likely reflecting chronic changes in brain morphology and connectivity. Previous attempts to characterize cognitive impairment in AUD addressed patients' performance in single domains, without considering their cognitive profile as a whole. While altered cognitive performance likely reflects abnormal white-matter microstructural properties, to date no study has directly addressed the relationship between a proxy of patients' cognitive profile and microstructural damage. ⋯ Within a widespread pattern of white-matter damage in patients, we found diverse types of relationship linking WM microstructure and executive performance: (i) in the whole sample, we observed a linear relationship involving MD/RD metrics within both 'superficial' white-matter systems mediating connectivity within large-scale brain networks, and deeper systems modulating their reciprocal connections; (ii) in AUD patients vs. controls, a performance-by-group interaction highlighted a MD/AD pattern involving two frontal white-matter systems, including the genu of corpus callosum and cingulum bundle, mediating structural connectivity among central executive, salience and default mode networks. Alterations of prefrontal white-matter pathways are suggestive of abnormal structural connectivity in AUD, whereby a defective interplay among large-scale networks underpins patients' executive dysfunction. These findings highlight different directions for future basic and translational research aiming to tailor novel rehabilitation strategies and assess their functional outcomes.