Researchers in Japan uncover what helps the brain stay motivated when life gets harder

Brain motivation: Why do some people stay motivated even as a task becomes more demanding, while others give up? Researchers at Nagoya University in Japan believe part of the answer may lie in a specific group of brain cells known as orexin neurons.

In a study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), the researchers found that orexin neurons play an important role in sustaining motivated behavior, offering new insight into a brain mechanism that may help explain how goal-directed behavior is maintained as more effort is required.

Looking at the brain's role in motivation

Loss of motivation is common in conditions such as depression, addiction and ADHD, but the brain mechanisms behind these difficulties remain unclear.


The study was led by Hiroyuki Mizoguchi, associate professor, and Kiyofumi Yamada, professor emeritus, at Nagoya University's Graduate School of Medicine. Their team focused on orexin neurons, which help regulate functions including sleep, appetite and energy expenditure, as per a Sciencedaily report.

Although previous research suggested these neurons might also influence motivation, their specific role had remained uncertain.

Researchers tested how much effort rats would make for food

To investigate, the researchers created genetically modified "orexin-Cre" rats, allowing them to selectively target and manipulate orexin-producing neurons. Rats were chosen because they have stronger learning abilities than mice and are better suited to more complex behavioral tasks.

The team first activated orexin neurons using chemogenetics before placing the rats in a progressive ratio test. In this task, the animals had to make an increasing number of touches to receive each food reward.

The researchers measured motivation using the breakpoint, the point at which a rat stopped trying for the reward.

Rats with activated orexin neurons reached higher breakpoints, showing they were willing to perform more work for food. In contrast, rats whose orexin neurons had been selectively degenerated reached lower breakpoints, indicating weaker motivation.

Orexin neuron activity increased as more effort was required

The researchers also monitored orexin neuron activity in real time using fiber photometry while the rats anticipated and received food rewards.

Activity increased as the animals anticipated a reward and dropped after the food was delivered. When an expected reward did not appear, however, orexin neuron activity remained elevated.

The researchers also found that orexin neuron activity became stronger as the amount of work required to earn the reward increased. According to the team, this pattern may show how the brain connects the expectation of a reward with the effort needed to obtain it.

Orexin neurons helped sustain motivation

To determine whether these neurons directly influenced behavior, the team used optogenetics to control orexin neuron activity at the moment the rats expected a reward.

Suppressing orexin neuron activity caused the animals to take longer to complete effort-based tasks and lowered their breakpoints, indicating reduced motivation.

Increasing orexin neuron activity successfully activated the cells but did not make the rats work harder or produce any further increase in motivation.

The findings suggest that orexin neurons are required to maintain motivated behavior, but increasing their activity beyond normal levels may not be enough to produce additional motivation.

Mizoguchi said, "Our study demonstrated significant changes in orexin neuron activity depending on expected rewards and the effort required, suggesting a potential mechanism for translating expectations into sustained action," as quoted by Sciencedaily.

According to the report, future studies will examine the brain circuits connected to orexin neurons to better understand how they function and whether this knowledge could eventually contribute to new ways of addressing motivational deficits, including loss of motivation and difficulty maintaining goal-directed behavior.