Mental Fatigue of Multiple Sclerosis Linked to Inefficient Recruitment of Neural Resources

Summary: Those with MS allocate neural resources less effectively when faced with increased cognitive task demands, and this likely results in the increased mental fatigue those with the neurodegenerative disorder experience.

Source: Kessler Foundation

Researchers at Kessler Foundation conducted a pilot study comparing the effects of mental fatigue on brain activation patterns in people with and without multiple sclerosis (MS). Their findings indicate significant differences between the two groups in their recruitment of neural resources in response to increased task demands. The article, “Neural mechanisms underlying state mental fatigue in multiple sclerosis: A pilot study,” was published in the Journal of Neurology on April 29, 2020.

This pilot study extended the Foundation’s investigation into the neural correlates of mental fatigue in MS. Mental fatigue comprises two types, state and trait, which are typically measured subjectively. The current study focused on state fatigue, which fluctuates over minutes to hours; trait fatigue is stable over longer periods, usually weeks.

The study comprised 36 participants, 19 with MS, and 17 controls. Participants underwent functional magnetic resonance imaging (fMRI) while performing the Symbol Digit Modalities Test (SDMT), a standard cognitive test modified for use with fMRI. Changes in brain activity were recorded while the SDMT was administered under two conditions: high and low cognitive loads. Neuroimaging studies were conducted at the research-dedicated Rocco Ortenzio Neuroimaging Center at Kessler Foundation.

“We found higher levels of fatigue and longer response times in the MS group,” said Dr. Chen, postdoctoral fellow in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation. “With increasing mental fatigue, the control group showed increased activation of the anterior brain regions and faster speed of response, to meet the demands of the high load condition,” added Dr. Chen. “The MS group did not show activation of these regions or an increase in processing speed, suggesting a less efficient response to the higher cognitive demands of the task.”

Ths shows a woman's head
Results of the pilot study were consistent with prior research into the functional reorganization of brain activity in response to mental fatigue. Image is in the public domain.

Results of the pilot study were consistent with prior research into the functional reorganization of brain activity in response to mental fatigue, according to Dr. Genova, assistant director of the Center for Neuropsychology and Neuroscience Research. “In the absence of effective treatment for the disabling fatigue that affects many individuals with MS, it is essential to expand our understanding of these underlying brain mechanisms. Using fMRI allows us to determine how individuals with MS differ from their peers without MS in their cerebral responses to cognitive challenges, an important first step in the development of interventions to counter mental fatigue.”

Funding: Funding sources: National Multiple Sclerosis Society (CA1069-A-7, MB-1606-08779, RG4232A1); Kessler Foundation

About this multiple sclerosis research article

Kessler Foundation
Media Contacts:
Carolann Murphy, PA – Kessler Foundation
Image Source:
The image is in the public domain.

Original Research: Closed access
“Neural mechanisms underlying state mental fatigue in multiple sclerosis: A pilot study”. by Michelle H. Chen, Glenn R. Wylie, Brian M. Sandroff et al. Journal of Neurology.


Neural mechanisms underlying state mental fatigue in multiple sclerosis: A pilot study

Neuroimaging underpinnings of state (in the moment, transient) mental fatigue in multiple sclerosis (MS) are not well understood. The current pilot study examined the effect of state mental fatigue on brain activation (measured using functional magnetic resonance imaging [fMRI]) during conditions of varying cognitive loads of rapid information processing in persons with MS relative to healthy controls. Nineteen persons with MS and 17 healthy controls underwent fMRI scanning while performing a modified version of the Symbol Digit Modalities Test, which consisted of high and low cognitive load conditions with comparable visual stimulation. State mental fatigue was assessed using the Visual Analog Scale of Fatigue before and after each run of the behavioral task. Results indicated that the healthy control group recruited significantly more anterior brain regions (superior and middle frontal gyri, insula, and superior temporal gyrus) to meet increased task demands during the high cognitive load condition as fatigue level increased (p < 0.05), which was accompanied by shorter response time. In contrast, the MS group did not recruit anterior areas to the same extent as the healthy control group as task demands and fatigue increased. Indeed, the MS group continued to activate more posterior brain regions (precuneus, lingual gyrus, and middle occipital gyrus) for the high cognitive load condition (p < 0.05) with no improvement in speed. In conclusion, persons with MS may allocate neural resources less efficiently than healthy controls when faced with increased task demands, which may result in increased mental fatigue. Results of the current pilot investigation warrant replication with a larger sample size.

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  1. do you plan to publish articles related to brain tumors and the gulf war syndrome. especially those of the gioblastomia type and is there any known correlation between geneics and these tumors as opposed to the gulf war exposure. the second part of this question is related to agent orange exposure. in a multigenerational military career family where the father was exposed to agent orange (had cancer, heart and lung plus more issues and died of those) and the family was exposed through living on military bases and item brought home from the vietnam gulf tours.. and then was exposed to the later gulf war exposures as a marine on the ground.. if this adult child has mirgrains etc. are they likely to have these issues as a second generation military person and does both exposures make it more like for them to have PTSD, TBI issues. How and where does this younger person reach out for help. Thank you.

    1. Martha Yount,

      We will definitely keep our eyes open for any research releases on these topics. We haven’t posted much on these topics recently, but there are a few older ones from Neuroscience News here that may be of interest. Gulf War Research articles and PTSD Alliance. Here are some found in PubMed: PubMed gulf war brain tumor research, Agent Orange and PTSD papers. You may want to search more in PubMed and Google Scholar for more specific terms. As for help, here are a few that may lead you to better answers: National Center for PTSD, Anxiety and Depression Association of America (PTSD resources).

      We will try to post new articles that we find pertaining to these issues. Thank you very much for your comment. These are great questions which hopefully may spark researchers that may read this to look into further as well.

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