Functional network connectivity abnormalities in multiple sclerosis: Correlations with disability and cognitive impairment

Rocca, Maria A.; Valsasina, Paola; Leavitt, Victoria M.; Rodegher, Mariaemma; Radaelli, Marta; Riccitelli, Gianna Carla; Martinelli, Vittorio; Boneschi, Filippo Martinelli; Falini, Andrea; Comı, Gıancarlo; Filippi, Massimo

doi:10.1177/1352458517699875

Cited by 112 publications

(142 citation statements)

References 32 publications

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“…In diseased patients, the insular cortex has been implicated in motor improvement after a motor stroke (Weiller et al, ) and MS relapse (Pantano et al, ). The reduction of RS FC between the thalami and caudate nuclei, cingulate cortex and cerebellum seems to have an important role in determining motor impairment in MS, in line with the results of a recent study (Rocca et al, ).…”

Section: Discussionsupporting

confidence: 88%

“…After exclusion of 8 MS and one HC due to poor image quality and/or postprocessing failure, the final cohort included 187 MS patients (136 with relapsing-remitting MS, 42 with secondary progressive MS and 9 with primary progressive MS) and 94 age-and sexmatched HC. A portion of these patients was also part of two previous investigations (Rocca et al, 2016(Rocca et al, , 2017. right and left hand).…”

Section: Subjectsmentioning

confidence: 99%

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Structural connectivity‐defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations

d’Ambrosio

Cruz

Valsasina

et al. 2017

Human Brain Mapping

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In spite of the well-known importance of thalami in multiple sclerosis (MS), only limited data on whole and subregional thalamic functional connectivity (FC) changes are available. Using diffusion tensor imaging, we performed a structural connectivity based thalamic parcellation and investigated subregional thalamic resting-state (RS) FC alterations and their relationship with clinical/cognitive measures in MS. MRI data from a reference set of healthy controls (HC) were used to parcellate the thalami into five subregions, according to their structural connectivity. For each thalamic subregion, a seed-based RS FC analysis was performed in 187 MS patients and 94 HC. Correlations between thalamic RS FC and clinical/cognitive variables were assessed. Compared to HC, MS patients showed increased intra- and inter-thalamic RS FC for almost all thalamic subregions, and increased RS FC between all thalamic subregions and the left insula. Frontal and motor thalamic subregions also showed reduced RS FC with the caudate nucleus. For the temporal thalamic subregion, we observed reduced RS FC with the ipsilateral thalamus, anterior and middle cingulate cortex, and cerebellum. Compared to cognitively preserved, cognitively impaired MS patients had higher thalamic RS FC with several temporal areas. In MS patients, lower RS FC between thalamic subregions and the caudate and cingulate cortex correlated with worse motor performance, whereas higher RS FC with the insula correlated with better motor performance. The main thalamic subregions have different RS-FC abnormalities in MS patients. Increased thalamic RS FC with the insula may have a compensatory role, whereas increased RS FC with temporal areas, observed in patients with cognitive impairment may reflect maladaptive mechanisms. Hum Brain Mapp 38:6005-6018, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionsupporting

confidence: 88%

Section: Subjectsmentioning

confidence: 99%

Structural connectivity‐defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations

d’Ambrosio

Cruz

Valsasina

et al. 2017

Human Brain Mapping

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“…Reduced connectivity of resting-state networks involving cortical regions was also observed in RRMS relative to HC,28 but was especially severe in SPMS 9. Recently, another study reported similar widespread increased and decreased functional connectivity changes in another cohort of patients with MS, whereby the level of functional connectivity, of especially cortical regions, decreased along the disease course, while DGM regions showed increased connectivity 18. This study showed earlier changes in decreased cortical connectivity than ours, which may be due to differences in the methodological approaches.…”

Section: Discussionmentioning

confidence: 76%

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

Meijer

Eijlers

Geurts

et al. 2017

J Neurol Neurosurg Psychiatry

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“…Resting-state functional magnetic resonance imaging (fMRI) is able to explore connectivity in predefined networks as for example the default mode network, the visual network, and the motor network. In MS, patients could experience either a decrease or an increase in functional connectivity [12][13][14][15][16]. In addition, resting-state fMRI might also depict network topography changes, through graph theoretical analyses.…”

Section: Introductionmentioning

confidence: 99%

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

et al. 2020

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There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. However, the role of neuromodulatory networks in multiple sclerosis (MS) has not been assessed. We applied resting-state functional connectivity and graph theory to investigate the changes in the functional connectivity within neuromodulatory networks including the serotonergic, noradrenergic, cholinergic, and dopaminergic systems in MS. Twenty-nine MS patients and twenty-four age- and gender-matched healthy controls performed clinical and cognitive assessments including the expanded disability status score, symbol digit modalities test, and Hamilton Depression rating scale. We demonstrated a diffuse reorganization of network topography (P < 0.01) in serotonergic, cholinergic, noradrenergic, and dopaminergic networks in patients with MS. Serotonergic, noradrenergic, and cholinergic network functional connectivity derangement was associated with disease duration, EDSS, and depressive symptoms (P < 0.01). Derangements in serotonergic, noradrenergic, cholinergic, and dopaminergic network impairment were associated with cognitive abilities (P < 0.01). Our results indicate that functional connectivity changes within neuromodulatory networks might be a useful tool in predicting disability burden over time, and could serve as a surrogate endpoint to assess efficacy for symptomatic treatments.

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Functional network connectivity abnormalities in multiple sclerosis: Correlations with disability and cognitive impairment

Abstract: Increased and decreased RS FC occurs in MS and contributes to a wide spectrum of clinical manifestations. RS FC reduction is related to T2 lesions. Such a paradigm is inverted for the thalamic network.

Cited by 112 publications

References 32 publications

Structural connectivity‐defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations

Structural connectivity‐defined thalamic subregions have different functional connectivity abnormalities in multiple sclerosis patients: Implications for clinical correlations

Staging of cortical and deep grey matter functional connectivity changes in multiple sclerosis

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

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