Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

Antonio Carotenuto; Heather Wilson; Beniamino Giordano; Silvia P Caminiti; Zachary Chappell; Steven C R Williams; Alexander Hammers; Eli Silber; Peter Brex; Marios Politis

doi:10.1007/s00415-020-09806-3

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

Antonio Carotenuto, Heather Wilson, Beniamino Giordano, Silvia P Caminiti, Zachary Chappell, Steven C R Williams, Alexander Hammers, Eli Silber, Peter Brex, Marios Politis

University of Naples Federico II
University of Exeter
Department of Paediatric Neurology, Neuromuscular Service, Evelina's Children Hospital, Guy's & St. Thomas' Hospital NHS Foundation Trust, London, United Kingdom; Department of Basic and Clinical Neuroscience, IoPPN, King's College London, London, United Kingdom; Randall Division of Cell and Molecular Biophysics, Muscle Signalling Section, King's College London, London, United Kingdom.

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2042-2053
Number of pages	12
Journal	Journal of Neurology
Volume	267
Issue number	7
Early online date	26 Mar 2020
DOIs	https://doi.org/10.1007/s00415-020-09806-3
Publication status	Published - 1 Jul 2020

Keywords

Functional connectivity
Graph theory
Multiple sclerosis
Neurotransmitter
Resting-state fMRI

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10.1007/s00415-020-09806-3

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title = "Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications",

abstract = "There is mounting evidence regarding the role of impairment in neuromodulatory networks for neurodegenerative diseases, such as Parkinson{\textquoteright}s and Alzheimer{\textquoteright}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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AU - Wilson, Heather

AU - Giordano, Beniamino

AU - Caminiti, Silvia P

AU - Chappell, Zachary

AU - Williams, Steven C R

AU - Hammers, Alexander

AU - Silber, Eli

AU - Brex, Peter

AU - Politis, Marios

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AB - 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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Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

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