Suffering from fatigue? Study pinpoints brain regions that may control it

• Fatigue can affect anyone, and when it does, it can severely impact one's daily life
• Researchers at Johns Hopkins Medicine studied the brain region that may control fatigue
• Their findings may help scientists find therapies to assist those living with the condition

Fatigue, a condition characterised by feeling unusually tired or exhausted for no apparent reason, can take a toll on one’s personal and work life.

A new study by researchers at Johns Hopkins Medicine, however, is helping to advance the development of behavioural and other strategies that increase physical performance in healthy people.

Beyond this, their discoveries also illuminate the neural mechanisms that contribute to fatigue in people with depression, multiple sclerosis (MS) and stroke.

Using MRI scans and computer modelling, they have managed to further pinpoint areas of the human brain that regulate efforts to deal with fatigue.

Their work was published in Nature Communications.

Limited research on fatigue and the brain

“We know the physiologic processes involved in fatigue, such as lactic acid build-up in muscles, but we know far less about how feelings of fatigue are processed in the brain and how our brain decides how much and what kind of effort to make to overcome fatigue,” said Vikram Chib, assistant professor of biomedical engineering at the Johns Hopkins University School of Medicine in a news release.

If more is known about this, it might help scientists find therapies, added Chip. “It might not be ideal for your brain to simply power through fatigue,” says Chib. “It might be more beneficial for the brain to be more efficient about the signals it’s sending.”

Quantifying how people feel fatigue

For their study, the team developed a novel way to quantify how people "feel" fatigue. Physicians generally ask their patients to rate their fatigue on a scale of one to seven, but, similar to pain scales, these ratings are subjective and varied.

Chib and his team, therefore, standardised the metric for fatigue by asking 20 study participants to make risk-based decisions about making a specific physical effort.

Participants were between the ages of 18 and 34. The exercises included participants grasping and squeezing a sensor after training to recognise a scale of effort.

For example, zero was equal to no effort, and 50 was half the participant’s maximum force. When participants learned to associate units of effort with how much to squeeze, it helped the team to standardise the effort level.

After the participants repeated the grip exercises until they were fatigued, they were offered one of two choices regarding each effort: 

• One was a random ("risky") choice based on a coin flip, offering the chance to exert no effort, or a predetermined effort level. 
• The other was a predetermined set effort level. By introducing uncertainty, the researchers tapped into how each subject valued their effort (which sheds light on how their brains and minds decide how much effort to make).

Essentially, by using computerised programmes, the researchers assessed whether participants chose a risky option versus the predetermined one, and measured how participants felt about the prospect of exerting particular amounts of effort while they were fatigued.

What they found

“Unsurprisingly, we found that people tend to be more risk-averse – to avoid – effort,” said Chib.

Most of the participants (19 out of 20) opted for the risk-free choice of a predetermined effort level. This means that, when fatigued, they were less willing to take the chance of having to exert large amounts of effort.

“The predetermined amount had to get pretty high in relative effort for participants to choose the coin toss option,” added Chib.

A helpful step towards physical and chemical therapies

Using functional magnetic resonance imaging (fMRI) scans, the research team also evaluated participants' brain activity during the gripping exercises. These allowed for the tracking of participants’ blood flow through the brain, and showed researchers which neurons were firing most often.

The fMRI scans also allowed them to take a closer look at the motor cortex of the brain when the participants were fatigued – a region of the brain that is responsible for exerting the effort itself.

Results revealed that the motor cortex was deactivated at the time participants "decided" between the two effort choices, a finding consistent with previous studies, said Chib, adding that the body signals the motor cortex when fatigued.

Chib explained that their findings may advance the search for physical and chemical therapies that target this pathway in healthy people to advance performance, as well as in people with conditions that are associated with fatigue.

When should you worry about fatigue?

According to Harvard Health’s Dr Howard LeWine, if your fatigue lasts beyond a week or two, you should consult your doctor as it might be related to an underlying illness or infection. Symptoms to look out for include low-grade fever, shortness of breath, or loss of appetite.

LeWine also suggests that if you find yourself often waking up exhausted, despite sleeping well, and struggle to do ordinarily easy activities, it might also be a good idea to discuss this with your doctor as it could be symptoms of a sleep disorder or depression.