Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

Aya Ogura, Kazuya Kawabata, Hirohisa Watanabe, Shao Wei Choy, Epifanio Bagarinao, Toshiyasu Kato, Kazunori Imai, Michihito Masuda, Reiko Ohdake, Kazuhiro Hara, Ryoichi Nakamura, Naoki Atsuta, Tomohiko Nakamura, Masahisa Katsuno, Gen Sobue

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Background and purpose: To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis. Methods: We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables. Results: The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p < 0.05, familywise error-corrected), and the comparison of FCs revealed no region that was significantly different from another. Voxel-based morphometry showed cortical volume reduction in the regions, including the primary motor area. Clinical scores showed correlations with FD values in the CSTs (UMN score: rho = −0.530, p < 0.001; central motor conduction time [CMCT] in the upper limb: rho = −0.474, p = 0.008; disease duration: rho = −0.383, p = 0.007; ALS Functional Rating Scale-Revised: rho = 0.340, p = 0.018). In addition, patients whose CMCT was not calculated due to unevoked waves also showed FD reduction in the CSTs. Conclusions: Our findings suggest that FD values in the CST estimated via FBA can be potentially used in evaluating UMN impairments.

Original languageEnglish
Pages (from-to)432-440
Number of pages9
JournalEuropean Journal of Neurology
Issue number2
Publication statusPublished - 02-2022

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis'. Together they form a unique fingerprint.

Cite this