Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis

Abstract

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting-state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting-state fMRI, T1-weighted and T2-weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease-related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting-state fMRI, T1-weighted, T2-weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262-4275, 2016. © 2016 Wiley Periodicals, Inc.

Functional Connectivity in Multiple Sclerosis: Recent Findings and Future Directions

“…This leads to two possibilities: either (a) increases in FC have no association to task performance or (b) the “adaptiveness” of FC increases might depend on where in the brain they occur and which functional domains are classically associated with that region. While FC increases within domain-specific brain regions might improve the patient's ability to perform the task at hand [e.g., cognitively preserved patients had higher FC between the DMN-hubs, MPFC, and PCC compared to cognitively impaired patients, see ( 109 ); and patients with preserved manual function had higher FC from sensorimotor regions to the rest of the brain, see ( 39 )], it might simultaneously hamper the performance in domain-unrelated tasks [e.g., patients with upper limb motor disability had increased FC between the DMN-regions, left pallidum, and ACC compared to patients without such disability, see ( 67 ); and patients with cognitive deficits had increased FC between sensorimotor regions and the thalamus, see ( 117 )].…”

“…Likewise in the motor system, decreased connectivity between domain-specific areas leads to impairment of domain-specific behavior. Motor dysfunction in MS has been associated with reduced FC in important SMN-hubs, for example from the sensorimotor/somatosensory cortices ( 39 ) and the cerebellum ( 84 , 113 ) to the rest of the brain. Additionally, reduced motor performance co-occurred with reduced regional homogeneity in the cerebellum ( 98 ).…”

“…Moreover, lower-limb spasticity could be improved with transcranial magnetic stimulation using intermittent theta burst stimulation, which increased the integrity (assessed with graph theory) of the contralateral primary motor cortex ( 114 ). Furthermore, motor-impaired MS patients have also been distinguished from motor-preserved MS patients based on reductions of FC in the thalamus ( 115 ) and in occipital regions ( 39 , 67 ).…”

“…To study changes of connectivity of dedicated functional systems, other researchers defined seed regions by using previously identified anatomical structures, such as the basal ganglia ( 37 ), the left caudate and the left thalamus ( 38 ), or the hand-knob ( 39 ). A lesion-based strategy selected seeds as regions that showed gray matter loss ( 40 ) or those cortical regions for which tractography suggested that their structural connectivity was affected by a white matter lesion ( 41 ).…”

The Role of fMRI in the Assessment of Neuroplasticity in MS: A Systematic Review

“…MS participants in whom motor skills were preserved displayed greater FC in structurally intact visual information processing regions than MS patients in whom motor skills were impaired. By contrast, motor-impaired MS participants displayed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain [69].…”