Feeling tired is something everyone experiences, but science still struggles to measure fatigue in an objective way.
A new international study led by the University of Michigan has taken an important step toward solving this problem by showing how brain activity changes across the entire day, down to the level of individual brain cells.
The research team used mice to explore how the brain works during wakefulness and sleep. Mice are often used in brain research because their brain structure and basic functions share similarities with humans. The study was published in the journal PLOS Biology and brings together scientists from the United States, Japan, and Switzerland.
The main goal of the study was to understand what happens in the brain as tiredness builds up during the day and how sleep helps restore normal brain function.
According to senior author Daniel Forger, a professor at the University of Michigan, the brain does not simply slow down when we get tired. Instead, it changes in deep and complex ways. As wake time increases, large shifts occur in which parts of the brain are active, and many of these changes seem to reset during sleep.
To study this process, researchers developed a new way to track brain activity across the whole brain over time. They combined advanced laboratory experiments with computer-based analysis.
In Japan and Switzerland, scientists created a special method to make active brain cells glow. When a brain cell became active, it lit up under a powerful microscope. This allowed researchers to see exactly which cells were working and when.
They used a technique called light sheet microscopy to create three-dimensional images of mouse brains. These images captured activity across the entire brain instead of focusing on just one small area. At the same time, the University of Michigan team designed computer tools to analyze the massive amount of data this process created.
What the researchers found was striking. When mice first woke up, brain activity started deep inside the brain, in areas that control basic functions such as alertness and movement.
As the mice stayed awake longer, activity gradually shifted toward the outer layer of the brain, known as the cortex. The cortex plays a major role in thinking, planning, and decision-making.
This shift suggests that the brain reorganizes itself throughout the day. Different brain regions take on more responsibility depending on how long the animal has been awake.
One scientist involved in the study compared this process to a city where traffic patterns change at different times of day. The roads stay the same, but which routes are busiest changes depending on the time.
These findings are important because people are often poor judges of their own fatigue. Many individuals believe they are fine to work even when their brain may be under strain.
This can be dangerous in jobs that require sharp attention, such as flying airplanes, performing surgery, or driving long distances. The researchers hope that their work could eventually lead to biological signs that show when someone is too tired to safely perform certain tasks.
Although the methods used in this study cannot be applied directly to humans, the ideas behind them can be adapted. The computer models developed by the team could be used alongside existing tools like brain scans or electrical brain recordings.
This means the research could help improve how fatigue is measured in people without needing invasive techniques.
The study may also have broader meaning beyond fatigue. Some researchers believe that the way brain activity shifts over time could help explain mental health conditions. Changes in how brain regions communicate may play a role in disorders such as depression or anxiety. Others are already using these methods to test how different drugs affect brain activity.
At the end of the project, the team dedicated the study to Steven Brown, a respected scientist who passed away during the research. He played a key role in bringing together ideas and people from different countries. His colleagues described him as a rare collaborator who helped connect science, creativity, and teamwork.
In reviewing the study’s findings, it is clear that this research changes how we think about fatigue. Instead of viewing tiredness as a simple loss of energy, the study shows it is linked to major changes in how the brain organizes itself. Sleep appears to play a vital role in restoring balance to these brain networks.
While more research is needed before this work can be used in everyday life, the study offers strong evidence that fatigue has clear biological patterns. Understanding these patterns could one day help protect health, improve safety, and deepen our understanding of the human brain.
If you care about health, please read studies that scientists find a core feature of depression and this metal in the brain strongly linked to depression.
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