Multimodal Magnetic Resonance Studies Of Patients With Amyotrophic Lateral Sclerosis

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,white matter fractional anisotropy(FA),and functional connectivity(FC)in patients with ALS.Compared with healthy controls,patients with ALS showed decreased gray matter volume in the left precentral gyrus and increased gray matter volume 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 gray matter volume of left precentral gyrus,FA of altered white matter tracts,and FC of left precentral gyrus,and that white matter microstructural alterations seem to play important roles in mediating the relationship between gray matter volume and FC of the precentral gyrus,as well as the relationship between gray matter volumes of the precentral gyrus and cerebellum.These findings provided evidence for the precentral degeneration and cerebellar compensation in ALS,and the involvement of white matter 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.In addition,we found that most of previous studies focused on the changes in certain univariate indices(such as gray matter volume,cortical thickness,FA and so on)or brain connections,fewer multimodal studies have been conducted to investigate the topological alterations of brain networks in a large cohort of patients with ALS.Therefore,we performed a multimodal MRI study to systematically characterize changes in structural and functional brain networks in patients with ALS compared with demographically matched healthy controls.Specifically,white matter network of each subject was constructed via probabilistic tractography and then compared using network based statistic and graph theoretical approaches to identify and characterize the impaired subnetwork of ALS.Subsequently,we investigated the topological alterations in functional sub-networks constructed among nodes of the subnetwork identified in the aforementioned network based statistical analysis.We firstly identified a white matter sub-network where patients with ALS were associated with increased white matter connections involving both motor and extra-motor areas.Next,compared with healthy controls,we found that the topological organizations of the white matter and functional sub-networks were altered in patients with ALS,albeit inconsistent across modalities.Specifically,patients with ALS respectively showed decreased small world index,normalized clustering coefficient and normalized characteristic path length as well as decreased nodal clustering coefficient in the identified white matter sub-network;showed increased small-world index,normalized clustering coefficient and global efficiency,as well as decreased short path length in the functional sub-network.These findings displayed a mixed picture of deterioration and improvement of the network performances,suggesting a coexistence of degenerative and compensative changes in patients with ALS,which provides new insights into understanding the pathogenies of this disorder.