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Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as wel...

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Autores principales: Radetz, Angela, Mladenova, Kalina, Ciolac, Dumitru, Gonzalez-Escamilla, Gabriel, Fleischer, Vinzenz, Ellwardt, Erik, Krämer, Julia, Bittner, Stefan, Meuth, Sven G., Muthuraman, Muthuraman, Groppa, Sergiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546169/
https://www.ncbi.nlm.nih.gov/pubmed/34712236
http://dx.doi.org/10.3389/fimmu.2021.748357
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author Radetz, Angela
Mladenova, Kalina
Ciolac, Dumitru
Gonzalez-Escamilla, Gabriel
Fleischer, Vinzenz
Ellwardt, Erik
Krämer, Julia
Bittner, Stefan
Meuth, Sven G.
Muthuraman, Muthuraman
Groppa, Sergiu
author_facet Radetz, Angela
Mladenova, Kalina
Ciolac, Dumitru
Gonzalez-Escamilla, Gabriel
Fleischer, Vinzenz
Ellwardt, Erik
Krämer, Julia
Bittner, Stefan
Meuth, Sven G.
Muthuraman, Muthuraman
Groppa, Sergiu
author_sort Radetz, Angela
collection PubMed
description Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Making Test part A and B (TMT-A and TMT-B) and the Symbol Digit Modalities Test (SDMT). Patients were evaluated clinically including assessments with the Expanded Disability Status Scale. A hierarchical regression model revealed that lower neurite density index (NDI) in primary motor cortex, suggestive for axonal loss in the grey matter, predicted higher motor thresholds, i.e. reduced excitability in MS patients (p = .009, adjusted r² = 0.117). Furthermore, lower NDI was indicative of decreased cognitive-motor performance (p = .007, adjusted r² = .142 for TMT-A; p = .009, adjusted r² = .129 for TMT-B; p = .006, adjusted r² = .142 for SDMT). Motor WM tracts of patients were characterized by overlapping clusters of lowered NDI (p <.05, Cohen’s d = 0.367) and DTI-based fractional anisotropy (FA) (p <.05, Cohen’s d = 0.300), with NDI exclusively detecting a higher amount of abnormally appearing voxels. Further, orientation dispersion index of motor tracts was increased in patients compared to controls, suggesting a decreased fiber coherence (p <.05, Cohen’s d = 0.232). This study establishes a link between microstructural characteristics and excitability of neural tissue, as well as cognitive-motor performance in multiple sclerosis. We further demonstrate that the NODDI parameters neurite density index and orientation dispersion index detect a larger amount of abnormally appearing voxels in patients compared to healthy controls, as opposed to the classical DTI parameter FA. Our work outlines the potential for microstructure imaging using advanced biophysical models to forecast excitability alterations in neuroinflammation.
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spelling pubmed-85461692021-10-27 Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis Radetz, Angela Mladenova, Kalina Ciolac, Dumitru Gonzalez-Escamilla, Gabriel Fleischer, Vinzenz Ellwardt, Erik Krämer, Julia Bittner, Stefan Meuth, Sven G. Muthuraman, Muthuraman Groppa, Sergiu Front Immunol Immunology Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Making Test part A and B (TMT-A and TMT-B) and the Symbol Digit Modalities Test (SDMT). Patients were evaluated clinically including assessments with the Expanded Disability Status Scale. A hierarchical regression model revealed that lower neurite density index (NDI) in primary motor cortex, suggestive for axonal loss in the grey matter, predicted higher motor thresholds, i.e. reduced excitability in MS patients (p = .009, adjusted r² = 0.117). Furthermore, lower NDI was indicative of decreased cognitive-motor performance (p = .007, adjusted r² = .142 for TMT-A; p = .009, adjusted r² = .129 for TMT-B; p = .006, adjusted r² = .142 for SDMT). Motor WM tracts of patients were characterized by overlapping clusters of lowered NDI (p <.05, Cohen’s d = 0.367) and DTI-based fractional anisotropy (FA) (p <.05, Cohen’s d = 0.300), with NDI exclusively detecting a higher amount of abnormally appearing voxels. Further, orientation dispersion index of motor tracts was increased in patients compared to controls, suggesting a decreased fiber coherence (p <.05, Cohen’s d = 0.232). This study establishes a link between microstructural characteristics and excitability of neural tissue, as well as cognitive-motor performance in multiple sclerosis. We further demonstrate that the NODDI parameters neurite density index and orientation dispersion index detect a larger amount of abnormally appearing voxels in patients compared to healthy controls, as opposed to the classical DTI parameter FA. Our work outlines the potential for microstructure imaging using advanced biophysical models to forecast excitability alterations in neuroinflammation. Frontiers Media S.A. 2021-10-12 /pmc/articles/PMC8546169/ /pubmed/34712236 http://dx.doi.org/10.3389/fimmu.2021.748357 Text en Copyright © 2021 Radetz, Mladenova, Ciolac, Gonzalez-Escamilla, Fleischer, Ellwardt, Krämer, Bittner, Meuth, Muthuraman and Groppa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Radetz, Angela
Mladenova, Kalina
Ciolac, Dumitru
Gonzalez-Escamilla, Gabriel
Fleischer, Vinzenz
Ellwardt, Erik
Krämer, Julia
Bittner, Stefan
Meuth, Sven G.
Muthuraman, Muthuraman
Groppa, Sergiu
Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title_full Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title_fullStr Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title_full_unstemmed Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title_short Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis
title_sort linking microstructural integrity and motor cortex excitability in multiple sclerosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546169/
https://www.ncbi.nlm.nih.gov/pubmed/34712236
http://dx.doi.org/10.3389/fimmu.2021.748357
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