Examination of Cognitive Fatigue in Multiple Sclerosis using Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging

Helen M. Genova,Allison Binder,John DeLuca,Abhijit Das,Aparna Arjunan,Glenn Wylie,Nancy Chiaravalloti,Venkateswaran Rajagopalan,Francisco J. Esteban

doi:10.1371/journal.pone.0078811

Abstract

The present study investigated the neural correlates of cognitive fatigue in Multiple Sclerosis (MS), looking specifically at the relationship between self-reported fatigue and objective measures of cognitive fatigue. In Experiment 1, functional magnetic resonance imaging (fMRI) was used to examine where in the brain BOLD activity covaried with “state” fatigue, assessed during performance of a task designed to induce cognitive fatigue while in the scanner. In Experiment 2, diffusion tensor imaging (DTI) was used to examine where in the brain white matter damage correlated with increased “trait” fatigue in individuals with MS, assessed by the Fatigue Severity Scale (FSS) completed outside the scanning session. During the cognitively fatiguing task, the MS group had increased brain activity associated with fatigue in the caudate as compared with HCs. DTI findings revealed that reduced fractional anisotropy in the anterior internal capsule was associated with increased self-reported fatigue on the FSS. Results are discussed in terms of identifying a “fatigue-network” in MS.

Highlights

Multiple Sclerosis (MS) is a disease of the Central Nervous System characterized by chronic inflammatory demyelination and both white and grey matter pathology
This was accomplished through two experiments: the first examined the relationship between self-reported “state” fatigue and cerebral activation, while the second examined the relationship between selfreported “trait” fatigue and white matter integrity
The overall results of both experiments are consistent with the hypothesis that the striatum and its interconnections have a critical role in the subjective perception of fatigue in MS

Summary

Introduction

Multiple Sclerosis (MS) is a disease of the Central Nervous System characterized by chronic inflammatory demyelination and both white and grey matter pathology. Findings were replicated by this same group in persons with traumatic brain injury [11] These findings are consistent with the model of central or cognitive fatigue proposed by Chaudhuri & Behan [12]. The current study examines the neural correlates of self-reported “state” cognitive fatigue using fMRI (Experiment 1). Experiment 2 utilized diffusion tensor imaging (DTI) to examine the relationship between white matter integrity and cognitive ‘trait’ fatigue in a separate sample of individuals with MS. We predicted a relationship between increased subjective “trait” fatigue and damage to white matter tracts throughout the striatal-thalamic-frontal cortical system, based on the model proposed by Chaudhuri & Behan [12,16]

Methods

Results

Discussion