New Study Reveals Your Brain May Be the Real Source of Marathon Fatigue

If you’ve ever hit the wall in a marathon, you know how real fatigue feels, legs like cement, motivation gone, mind screaming to stop.

But a new study published this month in Sports Medicine argues that what you’re feeling in those moments might not be the result of your muscles giving out. It might be a signal from your brain that continuing could tip your body out of balance.

In the new paper, researchers Jeanne Dekerle, James G. Wrightson, and Aaron Greenhouse-Tucknott propose that exercise-induced fatigue is best understood as a “metacognitive inference”, a fancy way of saying that the brain makes a judgment call about how sustainable your effort is, and delivers the feeling of fatigue as a protective warning signal.

That might sound abstract, but the idea has very real implications for runners and endurance athletes. It means fatigue isn’t necessarily a sign that you’re out of energy or physically incapable of continuing.

Instead, it’s your brain predicting that you might soon be, based on everything it’s sensing, body temperature, heart rate, hydration status, mental strain, expectations, and even your past experiences with similar efforts.

The researchers call this framework Metacognitive Inference of Dyshomeostasis (MID).

It builds on a 2017 definition of fatigue as a “feeling of diminishing capacity to cope with physical or mental stressors, either imagined or real.” That “imagined or real” part matters, your brain doesn’t wait for a true physical breakdown, it reacts to the prediction of one.

“Fatigue,” the authors write, “arises not from muscles running out of energy, but from the brain’s forecast of how sustainable continued effort will be.”

The MID model draws from the neuroscience concept of predictive processing, which sees the brain as constantly generating predictions about what should happen next.

When those predictions don’t match incoming signals, for example, your heart rate spiking faster than expected, the brain updates its expectations and may conclude that you’re veering toward dyshomeostasis, or internal instability.

So, it sends out the sensation of fatigue. Not as a hard stop, but as a caution light. And yes, this means that fatigue, particularly the perceived fatigue so common in long-distance running, is at least partly shaped by what’s going on between your ears, not just in your quads or glycogen stores.

This theory could explain why elite marathoners are able to push deep into discomfort zones most of us would pull back from. Their brains may have learned, through training and exposure, that they can maintain homeostasis under extreme conditions, or at least hold off that warning signal a little longer.

For runners, this model reframes training not just as physical conditioning, but as teaching the brain what’s possible. Long runs, hard workouts, and even mental skills training may help recalibrate how your brain interprets distress signals.

Studies have shown, for example, that motivational self-talk can reduce perceived exertion and improve endurance. A 2014 study by Blanchfield et al. found that time-to-exhaustion improved significantly when athletes used pre-planned mental scripts.

The MID model also opens the door to understanding conditions like chronic fatigue syndrome (ME/CFS), where fatigue seems unlinked to measurable physical breakdowns. If the brain’s predictions about homeostatic stability are altered, overly cautious, or skewed by past illness, fatigue might be triggered prematurely and persistently.

Of course, this is still a theoretical model, and many questions remain. But the authors suggest it’s testable. Future studies could explore how modifying perception, interoception (our sense of the body’s internal state), or feedback changes fatigue during exercise.

For now, it’s a compelling reminder for runners that fatigue is real, but it’s also interpreted. You’re not weak for feeling it, and you’re not superhuman if you override it. You’re responding to a deeply complex, brain-body system that’s trying to keep you safe, even if, sometimes, it plays it a little too safe.