Summary: People with multiple sclerosis (MS) appear to allocate neural resources less efficiently when cognitive demands increase, which likely contributes to the pronounced mental fatigue experienced by many with this neurodegenerative condition.
Source: Kessler Foundation
Researchers at Kessler Foundation carried out a pilot study comparing brain activation patterns under mental fatigue in individuals with multiple sclerosis (MS) and healthy controls. The results revealed notable differences in how each group recruits neural resources in response to higher cognitive load. The study, titled “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 investigation builds on ongoing efforts at Kessler Foundation to identify the neural correlates of mental fatigue in MS. Mental fatigue is commonly described in two forms: state fatigue, which fluctuates over minutes or hours, and trait fatigue, which is more stable over weeks. The present study focused on state mental fatigue, measured repeatedly during cognitive testing to capture transient changes in how participants felt and responded during the task.
Thirty-six volunteers participated in the study: 19 people diagnosed with MS and 17 healthy control subjects. All participants completed functional magnetic resonance imaging (fMRI) while performing a version of the Symbol Digit Modalities Test (SDMT) adapted for the scanner. The SDMT is a widely used measure of information processing speed and attention. In the scanner, the task presented alternating blocks of high and low cognitive load while maintaining comparable visual stimulation, allowing researchers to isolate brain activation changes related to cognitive demand. Scanning and behavioral testing were performed at the Rocco Ortenzio Neuroimaging Center, a research-dedicated facility at Kessler Foundation.
State fatigue was assessed using a Visual Analog Scale of Fatigue before and after each task run. Behavioral measures included response time and accuracy on the SDMT. Dr. Michelle H. Chen, a postdoctoral fellow at Kessler Foundation’s Center for Neuropsychology and Neuroscience Research, noted, “We found higher reported fatigue levels and longer response times in the MS group. As mental fatigue increased, healthy control participants showed greater activation in anterior brain regions and improved processing speed under the higher load condition. By contrast, the MS group did not recruit those anterior regions to the same extent, nor did they speed up, indicating a less efficient neural response to increased cognitive demands.”
Detailed neuroimaging results showed that, as state fatigue rose during high-load trials, healthy controls increased activation in anterior regions such as the superior and middle frontal gyri, insula, and superior temporal gyrus. This anterior recruitment accompanied faster response times, suggesting an adaptive neural strategy to meet higher cognitive demands. In contrast, participants with MS continued to rely more on posterior regions—including the precuneus, lingual gyrus, and middle occipital gyrus—during high-load conditions and did not demonstrate faster processing. These activation patterns suggest that people with MS may have less flexible or efficient allocation of neural resources when challenged, which could underlie their greater susceptibility to mental fatigue.
Dr. Glenn R. Wylie and Dr. Brian M. Sandroff, co-authors of the study, emphasize the clinical significance of these findings. Given the lack of universally effective treatments for disabling fatigue in MS, clarifying the brain mechanisms that contribute to mental exhaustion is critical. Functional MRI provides a window into how cerebral responses to cognitive workload differ between individuals with MS and healthy people—a necessary step toward designing targeted interventions aimed at reducing fatigue and improving cognitive functioning in MS.
Funding: This research was supported by the National Multiple Sclerosis Society (CA1069-A-7, MB-1606-08779, RG4232A1) and the Kessler Foundation.
About this multiple sclerosis research article
Source:
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.
Abstract
Neural mechanisms underlying state mental fatigue in multiple sclerosis: A pilot study
State (transient, in-the-moment) mental fatigue in multiple sclerosis remains poorly characterized at the neuroimaging level. This pilot study examined how state mental fatigue affects brain activation, measured with functional MRI, during rapid information-processing tasks that varied in cognitive load. Nineteen participants with MS and 17 healthy controls completed an fMRI-adapted Symbol Digit Modalities Test composed of alternating high and low cognitive load blocks with matched visual input. State fatigue was rated before and after each task run using a Visual Analog Scale. Healthy control participants showed increased recruitment of anterior brain regions (including superior and middle frontal gyri, insula, and superior temporal gyrus) as fatigue and task demand rose, coupled with faster response times. Participants with MS did not show the same anterior recruitment; instead, they continued to engage posterior regions (precuneus, lingual gyrus, middle occipital gyrus) under high-load conditions and did not improve processing speed. These results suggest that individuals with MS may allocate neural resources less efficiently under increased cognitive demand, potentially contributing to greater mental fatigue. Given the pilot nature of the study, replication with a larger sample is warranted.