Precentral degeneration and cerebellar compensation in amyotrophic lateral sclerosis: A multimodal MRI analysis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and intractable neurodegenerative disease of human motor system characterized by progressive muscular weakness and atrophy. A considerable body of research has demonstrated significant structural and functional abnormalities of the primary motor cortex in patients with ALS. In contrast, much less attention has been paid to the abnormalities of cerebellum in this disease. Using multimodal magnetic resonance imagining data of 60 patients with ALS and 60 healthy controls, we examined changes in gray matter volume (GMV), white matter (WM) fractional anisotropy (FA), and functional connectivity (FC) in patients with ALS. Compared with healthy controls, patients with ALS showed decreased GMV in the left precentral gyrus and increased GMV in bilateral cerebellum, decreased FA in the left corticospinal tract and body of corpus callosum, and decreased FC in multiple brain regions, involving bilateral postcentral gyrus, precentral gyrus and cerebellum anterior lobe, among others. Meanwhile, we found significant intermodal correlations among GMV of left precentral gyrus, FA of altered WM tracts, and FC of left precentral gyrus, and that WM microstructural alterations seem to play important roles in mediating the relationship between GMV and FC of the precentral gyrus, as well as the relationship between GMVs of the precentral gyrus and cerebellum. These findings provided evidence for the precentral degeneration and cerebellar compensation in ALS, and the involvement of WM alterations in mediating the relationship between pathologies of the primary motor cortex and cerebellum, which may contribute to a better understanding of the pathophysiology of ALS.

Fiber-specific white matter reductions in amyotrophic lateral sclerosis

“…Our findings of significant microstructural abnormalities in the bilateral CST and the middle posterior body of the CC in ALS revealed by decreased FD are consistent with previous reports using DTI and high-angular resolution diffusion imaging (HARDI) ( Kalra et al, 2020 , Kassubek et al, 2018 , Müller et al, 2020 , Müller et al, 2016 , Qiu et al, 2019 , Trojsi et al, 2017 , Trojsi et al, 2013 ). Specifically, some HARDI studies showed a highly significant decrease of generalized FA and fiber length and density in the CST and CC ( Trojsi et al, 2017 , Trojsi et al, 2013 ).…”

“…A total of 120 right-handed subjects, including 60 patients with ALS (39 males, mean age 48.77 years old, range 26–69) and 60 healthy controls (39 males, mean age 48.15 years old, range 24–70), were included in this study. These subjects had also participated in our previous neuroimaging study ( Qiu et al, 2019 ). Briefly, all patients with ALS met the El Escorial criteria for probable or definite ALS ( Brooks et al, 2000 ) and were recruited.…”

Involvement of the dentate nucleus in the pathophysiology of amyotrophic lateral sclerosis: A multi-center and multi-modal neuroimaging study

“…Previous rs-fMRI studies in ALS have primarily reported the involvement of both motor and extra-motor brain regions i.e. the precentral gyrus, supplementary motor area, frontal, temporal, parieto-occipital areas and the cerebellum ( Mohammadi et al, 2009 , Jelsone-Swain et al, 2010 , Verstraete et al, 2010 , Agosta et al, 2011 , Agosta et al, 2013 , Douaud et al, 2011 , Luo et al, 2012 , Tedeschi et al, 2012 , Zhou et al, 2013 , Zhou et al, 2016 , Heimrath et al, 2014 , Chenji et al, 2016 , Menke et al, 2016 , Qiu et al, 2019 ). Additionally, structural MRI studies have reported grey matter (GM) alterations in cortical brain areas i.e.…”

“…The cerebellum is considered a crucial subcortical brain structure responsible for not only controlling movement, but also for maintaining higher-level cognitive functions ( Schmahmann and Sherman, 1998 , Middleton and Strick, 2000 , Strick et al, 2009 , Buckner, 2013 , Koziol et al, 2014 , Moberget and Ivry, 2019 ). The involvement of the cerebellum has been frequently studied in other neurodegenerative disorders ( Fasano et al, 2017 , Mormina et al, 2017 , Tona et al, 2017 , Bharti et al, 2019 , Qiu et al, 2019 ); however, no neuroimaging study in ALS has so far investigated, as its primary focus, the cerebellum and its connection with the rest of the brain. Thus, to address this gap in knowledge, we specifically targeted the deep brain cerebellar nuclei and in particular the dentate nucleus (DN) to investigate the structural and functional MRI alterations in the cortical and subcortical brain structures of the cerebral cortex.…”

Identification of Amyotrophic Lateral Sclerosis Based on Diffusion Tensor Imaging and Support Vector Machine

“…It is speculated that these changes may be related to the functional compensation or the reorganization of the cerebral structure in ALS (60,61). In agreement with this speculation, several compensatory phenomena, as reflected by the increased gray matter volume or the overactivation of specific brain regions (62,63), have been demonstrated in ALS.…”