Cognitive Fatigue Is Associated with Altered Functional Connectivity in Interoceptive and Reward Pathways in Multiple Sclerosis.

Michelle H Chen,Helen M Genova,Bing Yao,John Deluca,Glenn R Wylie

doi:10.3390/diagnostics10110930

Michelle H Chen, Helen M Genova + Show 3 more

Open Access

https://doi.org/10.3390/diagnostics10110930

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Abstract

Cognitive fatigue is common and debilitating among persons with multiple sclerosis (pwMS). Neural mechanisms underlying fatigue are not well understood, which results in lack of adequate treatment. The current study examined cognitive fatigue-related functional connectivity among 26 pwMS and 14 demographically matched healthy controls (HCs). Participants underwent functional magnetic resonance imaging (fMRI) scanning while performing a working memory task (n-back), with two conditions: one with higher cognitive load (2-back) to induce fatigue and one with lower cognitive load (0-back) as a control condition. Task-independent residual functional connectivity was assessed, with seeds in brain regions previously implicated in cognitive fatigue (dorsolateral prefrontal cortex (DLPFC), ventromedial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), insula, and striatum). Cognitive fatigue was measured using the Visual Analogue Scale of Fatigue (VAS-F). Results indicated that as VAS-F scores increased, HCs showed increased residual functional connectivity between the striatum and the vmPFC (crucial in reward processing) during the 2-back condition compared to the 0-back condition. In contrast, pwMS displayed increased residual functional connectivity from interoceptive hubs—the insula and the dACC—to the striatum. In conclusion, pwMS showed a hyperconnectivity within the interoceptive network and disconnection within the reward circuitry when experiencing cognitive fatigue.

Highlights

Fatigue is one of the most prevalent symptoms of multiple sclerosis (MS) [1,2], an immunemediated, neurodegenerative disorder characterized with demyelination, axonal injury, and brain atrophy
The sample consisted of 26 persons with MS (pwMS) and 14 healthy controls (HCs)
The current study examined cognitive fatigue-related functional connectivity in a heterogeneous sample of pwMS compared to demographically matched task-related activations) in a heterogeneous sample of pwMS compared to demographically matched

Summary

Introduction

Fatigue is one of the most prevalent symptoms of multiple sclerosis (MS) [1,2], an immunemediated, neurodegenerative disorder characterized with demyelination, axonal injury, and brain atrophy. Fatigue is a major clinical concern among persons with MS (pwMS), as it significantly disrupts functional independence and quality of life [3]. MS Consortium registry (n = 5428) found that baseline moderate to severe fatigue was a significant predictor of decline in sustained neurologic disability and psychosocial limitations four years later [4]. Despite its high prevalence and debilitating impact on pwMS, the pathophysiology of fatigue is still not well understood, which results in limited effective treatments for fatigue in MS [5]. It is imperative to understand the mechanisms underlying fatigue, in order to develop effective treatments for fatigue and improve the lives of pwMS.

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Discussion

Conclusion