King's College London

Research portal

Impaired connectivity within neuromodulatory networks in multiple sclerosis and clinical implications

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)2042-2053
Number of pages12
JournalJournal of Neurology
Issue number7
Early online date26 Mar 2020
Accepted/In press1 Jan 2020
E-pub ahead of print26 Mar 2020
Published1 Jul 2020

King's Authors


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.

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454