Cognitive fatigue in multiple sclerosis is associated with alterations in the functional connectivity of monoamine circuits

Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456, Dipasquale, Ottavia, Bogdan, Iulia, Carandini, Tiziana, Scott, James, Rashid, Waqar, Sabri, Osama, Hesse, Swen, Rullmann, Michael, Lopiano, Leonardo, Veronese, Mattia, Martins, Daniel and Bozzali, Marco 2021. Cognitive fatigue in multiple sclerosis is associated with alterations in the functional connectivity of monoamine circuits. Brain Communications 3 (2) , fcab023. 10.1093/braincomms/fcab023

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Abstract

Fatigue is a highly prevalent and debilitating symptom in multiple sclerosis, but currently the available treatment options have limited efficacy. The development of innovative and efficacious targeted treatments for fatigue in multiple sclerosis has been marred by the limited knowledge of the underlying mechanisms. One of the hypotheses postulates that multiple sclerosis pathology might cause reduced monoaminergic release in the central nervous system with consequences on motivation, mood and attention. Here, we applied the recently developed Receptor-Enriched Analysis of Functional Connectivity by Targets method to investigate whether patients with high and low fatigue differ in the functional connectivity (FC) of the monoamine circuits in the brain. We recruited 55 patients with multiple sclerosis, which were then classified as highly fatigued or mildly fatigued based on their scores on the cognitive sub-scale of the Modified Fatigue Impact scale. We acquired resting-state functional MRI scans and derived individual maps of connectivity associated with the distribution of the dopamine, noradrenaline and serotonin transporters as measured by positron emission tomography. We found that patients with high fatigue present decreased noradrenaline transporter (NAT)-enriched connectivity in several frontal and prefrontal areas when compared to those with lower fatigue. The NAT-enriched FC predicted negatively individual cognitive fatigue scores. Our findings support the idea that alterations in the catecholaminergic functional circuits underlie fatigue in multiple sclerosis and identify the NAT as a putative therapeutic target directed to pathophysiology.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	Oxford University Press
ISSN:	2632-1297
Date of First Compliant Deposit:	22 April 2021
Date of Acceptance:	8 January 2021
Last Modified:	05 May 2023 00:38
URI:	https://orca.cardiff.ac.uk/id/eprint/140647

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