Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis

Frontiers in Immunology

Dumitru Ciolac¹  Julia Krämer²  Sven G. Meuth³  Gabriel Gonzalez-Escamilla⁵  Erik Ellwardt⁵  Sergiu Groppa⁵  Kalina Mladenova⁵  Vinzenz Fleischer⁵  Angela Radetz⁵  Muthuraman Muthuraman⁵  Stefan Bittner⁵ 

[1] Department of Neurology, Institute of Emergency Medicine, Chişinău, Moldova;Department of Neurology, Institute of Translational Neurology, University Hospital Münster, Münster, Germany;Department of Neurology, University Hospital Düsseldorf, Düsseldorf, Germany;Laboratory of Neurobiology and Medical Genetics, Nicolae Testemițanu State University of Medicine and Pharmacy, Chişinău, Moldova;Neuroimaging and Neurostimulation, Department of Neurology, Focus Program Translational Neuroscience (FTN), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany;

关键词: multiple sclerosis;    neurite orientation dispersion and density imaging;    NODDI;    excitability;    motor threshold;    tract-based spatial statistics;   

DOI  :  10.3389/fimmu.2021.748357

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown