Kessler Foundation neuroimaging study sheds light on mechanisms of cognitive fatigue in multiple sclerosis

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The study: “Examination of cognitive fatigue in multiple sclerosis using functional magnetic resonance imaging and diffusion tensor imaging” by Helen M Genova, research scientist in neuropsychology and neuroscience research at Kessler Foundation, USA, and others sheds light on the mechanisms of underlying cognitive fatigue in patients with multiple sclerosis.

Published on 1 November 2013 in PlosOne, this is the first study to use neuroimaging to investigate aspects of cognitive fatigue, it says in a press release. The study was funded by grants from the National Multiple Sclerosis Society (USA) and Kessler Foundation. The findings of the study supports the that the part striato-thalamic-frontal cortical system plays in fatigue, suggesting a “fatigue-network” in multiple sclerosis.

The study investigated the neural correlates of cognitive fatigue in multiple sclerosis, utilising three neuroimaging approaches: functional magnetic resonance imaging (fMRI), which allows researchers to look at where in the brain activation is associated with a task or an experience; diffusion tensor imaging (DTI), which allows researchers to look at the health of the brain’s white matter and; voxel-based morphometry (VBM), which allows researchers to investigate structural changes in the brain.

These three approaches were used to examine how likely it is for an individual to report fatigue (“trait” fatigue), as well as the fatigue an individual feels in the moment (“state” fatigue). According to the press release, this is the first study to use neuroimaging to investigate these two, separable aspects of fatigue.

“We looked specifically at the relationship between individuals’ self-reported fatigue and objective measures of cognitive fatigue using state-of-the-art neuroimaging,” explains Genova. “The importance of this work lies in the fact that it demonstrates that the subjective feeling of fatigue can be related to brain activation in specific brain regions. This provides us with an objective measure of fatigue, which will have incalculable value as we begin to test interventions designed to alleviate fatigue.”

In experiment one, patients were scanned during performance of a task designed to induce cognitive fatigue. Investigators looked at the brain activation associated with state fatigue. In experiment two, DTI was used to examine where in the brain white matter damage correlated with increased trait fatigue in individuals with multiple sclerosis, as assessed by the fatigue severity scale. The findings of both the experiments support the role of a striato-thalamic-frontal cortical system in fatigue, suggesting a “fatigue-network” in multiple sclerosis.

“Identifying a network of fatigue-related brain regions could reframe the current construct of cognitive fatigue and help define the pathophysiology of this multifaceted yet elusive symptom of multiple sclerosis,” says John DeLuca, vice president of research and training at Kessler Foundation. “Replication of these findings with larger sample sizes will be an important next step.”

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