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

Cercignani, Mara, 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 Commun, 3 (2). pp. 1-10. ISSN 2632-1297

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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
Keywords: REACT, fatigue, functional connectivity, neurotrasmitters, noradrenaline
Schools and Departments: Brighton and Sussex Medical School > Neuroscience
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 03 Jun 2021 10:11
Last Modified: 22 Oct 2021 15:37
URI: http://sro.sussex.ac.uk/id/eprint/99581

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