Author Of 1 Presentation
P0599 - Linking microstructural integrity and motor cortex excitability in multiple sclerosis (ID 1151)
Abstract
Background
Motor skills are commonly impaired in patients with multiple sclerosis (MS) as a consequence of gray (GM) and white matter (WM) pathology and cortical excitability abnormalities.
Objectives
We hypothesized that microstructural characteristics of motor regions as assessed with the neurite orientation dispersion and density imaging (NODDI) model predict motor cortical excitability that is frequently altered in MS. Further, we evaluated pathological microstructure alterations in motor WM tracts of MS patients compared to healthy controls (HC) using NODDI in comparison to the diffusion tensor imaging (DTI) parameter fractional anisotropy (FA).
Methods
We applied advanced diffusion imaging in 50 MS patients and 49 age-matched HC. As excitability maker, we assessed resting motor thresholds using non-invasive transcranial magnetic stimulation. For quantification of microstructural integrity of the motor system, neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (IVF) and FA averaged within left primary motor cortex as the stimulation site were considered. We applied hierarchical regression modeling to evaluate the prediction of the resting motor threshold by NDI, ODI, IVF and FA in MS patients and HC. Cognitive-motor performance quantified by the Nine Hole Peg Test and Trail Making Test part A (TMT-A) and part B (TMT-B) was regressed on the diffusion parameters in a subsample of 44 MS patients. In the WM, we applied tract-based spatial statistics with the threshold-free cluster enhancement (TFCE) method within motor tracts comparing MS patients and HC. We tracked contributions of NDI and ODI to FA and evaluated if the NODDI model detects additional pathological alterations.
Results
A hierarchical regression revealed that lower NDI suggestive for axonal loss in the GM significantly predicted higher motor thresholds, i.e. reduced excitability in MS patients (F(1,48) = 7.493, p = .009). Lower NDI was indicative for decreased performance in TMT-A (F(1,42) = 8.102; p = .007) and TMT-B (F(1,42) = 7.390; p = .009). Microstructural abnormalities of the interconnected WM tracts were characterized by lowered FA, decreased NDI and increased ODI in MS (all TFCE-corrected p < .05). NDI exclusively (56%) and in overlap with FA (19%) accounted for the largest amount of differences, followed by ODI alone (9%).
Conclusions
Our work shows that lower neurite density in primary motor cortex is linked to decreased motor cortical excitability and decreased cognitive-motor performance in MS patients. Lower neurite density and higher orientation dispersion are characteristic in the WM of MS patients compared to HC. Our results suggest that these markers are more sensitive to pathological alterations than the classical DTI measure FA. This work outlines the potential of microstructure imaging using advanced biophysical models to forecast neurodegeneration and excitability alterations in neuroinflammation.