Rethinking fatigue: Feeling tired vs. being physically depleted

Brainstem. Images are from Anatomography maintained by Life Science Databases(LSDB).
Images are generated by Life Science Databases(LSDB). Creative Commons Attribution-Share Alike 2.1 jp

Fatigue affects the health and quality of life for many people, but there are few effective treatments for it, experts say.

Now new research suggests that redefining fatigue, and understanding how a brain region known as the cerebellum processes fatigue, may hold clues for better treatment.

Research by Pablo Celnik and his colleagues at Johns Hopkins University shows that performance fatigue, also known as “fatigability” – an objective measurement of a person’s ability to do a physical or cognitive task – can be different from the perception of fatigue – a person’s subjective assessment of the fatigue they feel.

Using more specific language – fatigability vs. perception of fatigue – to describe experiences of fatigue can be helpful in devising treatments, the researchers say.

Fatigue is “a very significant, common problem in patients with neurological conditions,” but “it is very poorly understood,” said Celnik, a professor and director of the physical medicine and rehabilitation department at Johns Hopkins University.

The study, published in the Journal of Neuroscience in March, only included healthy patients, but it provides important baseline information about how our brains process and prioritize fatigue, which the researchers are now building upon in the context of “long covid.”

In the study, the researchers asked participants to squeeze a small device called a force transducer between their thumb and index finger as much as possible.

Once the force that they were exerting dropped below 40 percent of their baseline, they were told to stop, and then they were asked how fatigued they felt.

In theory, all participants experienced similar levels of muscle fatigue, but their perception of that fatigue varied.

Participants were next asked to complete a hand coordination task. People who reported less fatigue from the earlier force task had less accurate coordination; those who said they felt more fatigue were more accurate.

The hand coordination movement was designed to test motor control of the participants in light of their perceived fatigue. The movement itself was not physically fatiguing.

Agostina Casamento-Moran of Johns Hopkins University, the lead author of the study, was surprised to see such a difference between performance fatigue and perceived fatigue.

“When we started, we did not know that the subjective experience of fatigue would become the main focus of the story,” she said.

She, Celnik and others are increasingly using the term fatigability to refer to a decline in performance, and fatigue, to refer to a person’s perception of the experience.

There is immediate value in using more specific language, said Natalie Tronson, a behavioral neuroscientist at the University of Michigan.

“People often think about” fatigue “in terms of ‘oh, people are tired all the time.’ But fatigue is so much more pervasive and detrimental than that,” said Tronson, who was not involved in the study. “And so this understanding of perception vs. physical fatigue and what that means and how we should conceptualize it or talk about it is really, really important.”

Distinguishing between fatigability and fatigue would also help to better standardize scoring of perception of fatigue, making it easier to validate and compare data across different studies, said Bharat Biswal of the New Jersey Institute of Technology. Last year, Biswal published a study showing changes in the brains of covid-19 survivors experiencing fatigue.

“Some have a scale of 1 to 1oo, there are other studies where they have a scale of 1 to 5,” said Biswal, a professor of biomedical engineering, who was not involved in the study. “This is a good opportunity for us to figure it out.”

He also says it’s important to separate the neurological underpinnings of motor fatigue from mental fatigue because the associated brain regions can vary quite a bit. Being more precise about the affected brain regions could lead to better treatment options, Biswal said.

Could the cerebellum provide an answer? The cerebellum is a brain structure that sits above the brainstem. It is best-known for its role in coordinated movement and balance and it is important for cognition and emotion, including perception.

The study showed that people who reported less fatigue not only had worse motor control, but showed a reduction in activity in the cerebellum.

Celnik sees this as an indicator that perception of fatigue and motor control may fight for the cerebellum’s attention. “It’s a competition of resources,” he said, which may explain why people who reported less fatigue had worse motor control.

Limiting the brain’s resources this way could possibly be a protective mechanism for dealing with fatigue, Casamento-Moran said.

Having more accurate motor control when feeling fatigued could indicate improved body awareness, which may, for example, help prevent someone from overdoing it physically and possibly getting injured.

Any protective role the cerebellum might play is speculative, Casamento-Moran said.

“The findings represent incremental progress in understanding how we experience and regulate fatigue,” said Brian Walitt of the National Institutes of Health. Walitt studies the clinical and biological characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

But “as only healthy volunteers were part of this study,” said Walitt, who was not involved in the study, “it does not provide any direct insight into medically fatiguing conditions.”

Casamento-Moran is taking that next step. With what she and her colleagues learned from this new research, Casamento-Moran is studying perception of fatigue in people with long covid, probing “why they feel the way they feel” and how that impacts their cognitive and motor abilities, she said.

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Coping with fatigue

Based on these findings and other work the researchers have done related to fatigue, they recommend these strategies for people suffering from fatigue.

-Use a “pacing” strategy. With pacing, patients conserve energy the best they can by limiting their activity.

-Avoid trying to learn new information when fatigued. In a 2019 study, Celnik and collaborators found that when healthy participants performed a task that caused muscle fatigue (fatigability), and then were asked to learn a new physical skill, they did poorly compared with participants who were not experiencing muscle fatigue. In addition, it was harder for them to learn that new movement in the following days, suggesting that working past performance fatigue to learn a skill is counterproductive. Not only will you not learn as well in the moment, Celnik said, it could also negatively impact your ability to learn a new skill even days later.

-Be kind to yourself. Casamento-Moran says the field is progressing and hopes there will be more concrete advice and rehabilitation treatments, but there are still many intricacies concerning fatigue that experts don’t understand. “So if you’re tired, be nice to yourself. Take a break,” she said.



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