Relation of sensorimotor and cognitive cerebellum functional connectivity with brain structural damage in patients with multiple sclerosis and no disability

Abstract

Background and purpose To investigate the relationship between the functional connectivity (FC) of the sensorimotor and cognitive cerebellum and measures of structural damage in patients with multiple sclerosis (MS) and no physical disability. Methods We selected 144 relapsing–remitting MS patients with an Expanded Disability Status Scale score of ≤1.5 and 98 healthy controls from the Italian Neuroimaging Network Initiative database. From multimodal 3T magnetic resonance imaging (MRI), including functional MRI at rest, we calculated lesion load, cortical thickness, and white matter, cortical gray matter, and caudate, putamen, thalamic, and cerebellar volumes. Voxel‐wise FC of the sensorimotor and cognitive cerebellum was assessed with seed‐based analysis, and multiple regression analysis was used to evaluate the relationship between FC and structural damage. Results Whole brain, white matter, caudate, putamen, and thalamic volumes were reduced in patients compared to controls, whereas cortical gray matter was not significantly different in patients versus controls. Both the sensorimotor and cognitive cerebellum showed a widespread pattern of increased and decreased FC that were negatively associated with structural measures, indicating that the lower the FC, the greater the tissue loss. Lastly, among multiple structural measures, cortical gray matter and white matter volumes were the best predictors of cerebellar FC alterations. Conclusions Increased and decreased cerebellar FC with several brain areas coexist in MS patients with no disability. Our data suggest that white matter loss hampers FC, whereas, in the absence of atrophy, cortical volume represents the framework for FC to increase.

Resting‐state functional magnetic resonance imaging reveals functional connectivity alteration in the experimental autoimmune encephalomyelitis model of multiple sclerosis

“…In MS, the cerebellum is one major site of disease pathology, leading not only to motor disability and balance deficit, but also to cognitive dysfunction 50 . Several rsfMRI studies, conducted in humans to examine the FC between different cerebellar areas and the entire brain, showed that this connectivity was altered 51–54 . Our study showed an altered connectivity between the cerebellum and the whole brain, characterized by an initial hyperconnectivity that was waning as the disease progressed.…”

“…50 Several rsfMRI studies, conducted in humans to examine the FC between different cerebellar areas and the entire brain, showed that this connectivity was altered. [51][52][53][54] Our study showed an altered connectivity between the cerebellum and the whole brain, characterized by an initial hyperconnectivity that was waning as the disease progressed. The early hyperconnectivity was also found in some humans studies, and it was interpreted as a need to recruit new regions to compensate for the deficit.…”

Male and female are not the same: a multicenter study of static and dynamic functional connectivity in relapse-remitting multiple sclerosis in China

“…We analyzed the correlation analysis between structural measures and connectivity changes and found that there was no correlation in statistics between lesion load and altered connectivity in both female and male patient cohorts. These results may indicate that the sFNC reorganization in MS patients may be caused by multiple factors, such as damage of gray matter and white matter ( 33 , 34 ). Indeed, our study found that the decreased sFNC of FPN-SMN was associated with lower BPF and GMV in RRMS males.…”

Aging, Neurodegenerative Disorders, and Cerebellum

“…A separate MRI study showed an association between reduced func-tional connectivity in the cerebellum, greater loss of cerebellar volume, and more severe lesion burden. And a loss of white matter volume reduced functional connectivity in the sensorimotor cerebellum lobes, while a loss of cortical grey matter volume was linked to increased connectivity of both sensorimotor and cognitive cerebellum tissue [146].…”

“…In patients with MS, cerebellar dysfunction starts in the early stages of the disease [146]. The walk ratio (WR) of step length/cadence serves as a speed-independent index of the neuromotor control of gait [147].…”