Mental Fatigue in MS May Be Due to Poorer Brain Response to Tasks

The debilitating mental fatigue that people with multiple sclerosis (MS) can feel after a cognitively demanding task may be due to less efficient use of the brain, a pilot study that mapped brain activity during tasks suggests.

The study “Neural mechanisms underlying state mental fatigue in multiple sclerosis: a pilot study” was published in the Journal of Neurology.

Mental and physical fatigue is a prevalent MS symptom, affecting 53 to 90% of patients, and known to affect daily life, work, social interactions, and mood. In research, it is considered to come in two forms: ‘state fatigue,’ a temporary fatigue that fluctuates over minutes or hours; and  ‘trait fatigue,’ which holds stable for longer periods (weeks) and it is related with cognitive and sleep issues.

No gold standard for treating fatigue currently exists. Some non-pharmaceutical approaches have shown promise, but high quality clinical trials to validate their effectiveness are lacking. Hence, there is an urgent need to explore, and better understand, the mechanisms behind fatigue in MS.

A team led by researchers at the Kessler Foundation investigated how mental, or cognitive, fatigue affects brain function in MS patients, with a focus on ‘state fatigue.’

Mental fatigue is used to describe the mental exhaustion experienced after completing a task that demands higher thinking.

They used functional MRI (fMRI), a type of neuroimaging that allows researchers to detect which areas of the brain are active, and a cognitive task called Symbol Digit Modalities Test (SDMT). SDMT is a commonly used tool in MS research that consists in a substitution task of symbols and numbers to assess memory and processing speed.

Two SDMT test conditions were given: one with high cognitive load that requires rapid information processing of many symbols, and another of low cognitive load. Participants performed four runs of the one condition before doing four runs of the other.

Fatigue was evaluated using the Visual Analogue Scale of Fatigue (VAS-F) before and after the cognitive testing. People reported their level of mental fatigue on a scale from zero (no fatigue) to 100 (extreme fatigue) between runs. In total, they underwent five VAS-F ratings.

The study enrolled 19 MS patients (mean age, 47.37) and 17 healthy controls (mean age, 40.41), matched for age, education and sex. MS patients were relapse-free for at least four weeks.

The MS group reported significantly higher levels of fatigue, as shown by the VAS-F scores, compared with the control group. Fatigue increased in both groups with each successive cognitive test, but was significantly greater among MS patients.

“We found higher levels of fatigue and longer response times in the MS group,” Michelle Chen, PhD, the study’s first author and a postdoctoral fellow in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation, said in a press release.

Response time among MS patients was also significantly longer than among controls across test conditions, and higher fatigue scores were associated with longer response times. Test accuracy was lower among both MS and control group participants for the high cognitive load test than was accuracy under the low cognitive load condition.

fMRI results showed the brains of healthy people were significantly more active, and selectively active in particular regions, during cognitive testing compared with the MS group. Activation was mainly detected in the anterior brain regions (superior and middle frontal gyri, insula, and superior temporal gyrus) among controls.

“As mental fatigue level increased,” the researchers wrote, “the HC [healthy control] group showed more activation in more anterior brain regions … to meet increased task demands in the high cognitive load condition. This activation increase was associated with faster speed.”

In contrast, as fatigue levels rose “the MS group showed continued activation of more posterior regions (i.e., precuneus, lingual gyrus, and middle occipital gyrus) for the high cognitive load condition with no improvement in speed.”

This group difference, Chen said, suggests for MS patients “a less efficient response to the higher cognitive demands of the task.”

Lesser efficiency in the brain’s approach to a challenging mental task may lead to greater mental fatigue, the team concluded.

Larger studies are now needed to validate the findings and explore how mental fatigue impacts different MS types.

“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 mechanism,” said Helen Genova, PhD, an assistant director at the Kessler Foundation and the study’s senior author.

“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,” Genova added.