Sunday, January 11, 2026

 

Why it is so hard to get started on an unpleasant task: Scientists identify a “motivation brake”



Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University

Figure 1. The VS–VP pathway acts like a “brake” that makes it harder to start unpleasant tasks. 

image: 

Monkeys were trained to perform two types of tasks: one with reward only, and another where the reward comes with a punishment. The VS–VP pathway was specifically suppressed using chemogenetics. In the reward-only task, motivation to initiate action was unchanged. In contrast, in the task that combined reward and punishment, suppression of the VS–VP pathway restored action initiation that had been reduced under stress, demonstrating that this pathway functions as a “brake” on taking the first step toward action.

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Credit: ASHBi/Kyoto University





Background

Most of us know the feeling: maybe it is making a difficult phone call, starting a report you fear will be criticized, or preparing a presentation that’s stressful just to think about. You understand what needs to be done, yet taking that very first step feels surprisingly hard. When this difficulty becomes severe, it is known medically as avolition. People with avolition are not lazy or unaware: they know what they need to do, but their brain seems unable to push the "go" button. Avolition is commonly seen in conditions such as depression, schizophrenia, and Parkinson's disease, and it seriously disrupts a person’s ability to manage daily life and maintain social functions.

Research in neuroscience and psychology has suggested that before we act, the brain weighs how much effort a task may cost. If the cost feels too high, motivation drops. But until now, it has been unclear how the brain turns this judgment into a decision not to act. To explore this question, a research team at WPI-ASHBi applied an advanced genetic technique called chemogenetics to highly intelligent macaque monkeys, allowing them to adjust communication temporarily and precisely between specific brain regions and identify a circuit that acts like a brake on motivation.

Methods and key findings

The monkeys were trained to perform two types of tasks. In one, completing the task earned a water reward. In the other, the reward came with an added downside: an unpleasant air puff to the face. Before each trial, the monkeys saw a cue and could freely decide whether to start or not. The researchers focused not on which option the monkeys chose, but on something more fundamental: did they take the first step at all? As expected, when the task involved only a reward, the monkeys usually got started without hesitation. But when the task involved an unpleasant air puff, they often held back, even though a reward was still available.

The researchers then temporarily weakened a specific brain connection linking two regions involved in motivation: the ventral striatum (VS) and the ventral pallidum (VP). In the reward-only task, suppressing this pathway had little effect on monkey behavior, and the monkeys initiated the task normally. In contrast, in tasks involving an unpleasant air puff, the mental brake to starting had eased: the monkeys became much more willing to start. Importantly, the monkeys' ability to judge rewards and punishments did not change. What changed was the step between knowing and doing.

The researchers took a closer look at what was actually happening in these brain regions during this process. Neural activity in the VS increased during the stressful task, suggesting it helps the brain register when a situation feels stressful. In contrast, activity in the VP gradually fell as the monkeys became less willing to start the task, showing that these two regions play different roles. Together, these findings show that the VS to VP pathway functions as a "motivation brake" that suppresses the internal "go" button, particularly when facing stressful or unpleasant tasks.

Future perspectives

This discovery of the VS–VP “motivation brake” may shed light on conditions such as depression and schizophrenia, where severe loss of motivation is common. In the future, interventions such as deep brain stimulation, non-invasive brain stimulation, or new drug strategies might aim to fine-tune this brake when it becomes too tight. But this “brake” exists for a reason. While an overly tight brake can lead to avolition, a brake that is too loose could make it harder to stop, even in excessively stressful situations, potentially leading to burnout. In other words, the VS–VP circuit may help keep motivation within a healthy range. “Over weakening the motivation brake could lead to dangerous behavior or excessive risk-taking,” said Ken-ichi Amemori, lead author of the study. “Careful validation and ethical discussion will be necessary to determine how and when such interventions should be used.”

In modern society, especially at a time when burnout is at an all-time high, these findings invite us to rethink what “motivation” really means. The brain can actively dampen the drive to act when tasks are unpleasant or stressful, so getting started is not simply about willpower. Rather than trying to forcibly boost motivation, the focus should shift toward how society can better support people in coping with stress. This is a question that warrants broader societal dialogue.

Glossary

  • Chemogenetics: A method for remotely controlling selected brain cells. Researchers first give specific neurons an artificial “switch” (a receptor) using a gene-delivery tool. They can then turn those neurons up or down for a short time by giving a drug that only works on that switch, letting them test the role of a particular circuit.
  • Ventral striatum (VS): A brain region involved in reward, motivation, and learning. Part of it is also called the nucleus accumbens.
  • Ventral pallidum (VP): A brain region that receives signals from the ventral striatum and helps pass them on to other parts of the brain. It is an important hub for turning motivation-related signals into action by relaying and combining information sent to areas such as the thalamus, midbrain, limbic system, and prefrontal cortex.

ANTI-ABORTION LAWS KILL

Targeted regulation of abortion providers laws and pregnancies conceived through fertility treatment



JAMA Health Forum





About The Study: 

The findings of this study suggest an increase in maternal morbidity among patients using fertility care in states that passed targeted regulation of abortion providers (TRAP) laws relative to states that did not.


Corresponding Author: To contact the corresponding author, Samuel J. F. Melville, MD, email melvills@ohsu.edu.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamahealthforum.2025.5920)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

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About JAMA Health Forum: JAMA Health Forum is an international, peer-reviewed, online, open access journal that addresses health policy and strategies affecting medicine, health and health care. The journal publishes original research, evidence-based reports and opinion about national and global health policy; innovative approaches to health care delivery; and health care economics, access, quality, safety, equity and reform. Its distribution will be solely digital and all content will be freely available for anyone to read.

 

A tug-of-war explains a decades-old question about how bacteria swim



Whether a bacterium’s tail spins clockwise or counter clockwise was previously thought to depend on a ‘domino effect’ among proteins inside the tail. However, new research proposes that a tug-of-war is the deciding factor.




Simons Foundation

Global Mechanical Coupling Graphic 

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Graphical depiction of the global mechanical coupling theory of how bacteria tails switch the direction of their spin.

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Credit: Lucy Reading-Ikkanda/Simons Foundation




Scientists have uncovered a new explanation for how swimming bacteria change direction, providing fresh insight into one of biology’s most intensively studied molecular machines.

Bacteria move through liquids using propellerlike tails called flagella, which alternate between clockwise and counterclockwise rotation. For decades, this switching behavior has been attributed to an equilibrium ‘domino effect’ model, in which proteins lining the bacterium’s tail exert pressure on their neighbors, prompting a change in rotational direction.

New research in Nature Physics from the Flatiron Institute’s Henry Mattingly and Yuhai Tu proposes a different mechanism, informed by experimental measurements of the molecular structure of the flagellar motor and an analysis of how flagella switch their spin. Rather than relying on passive pressure from neighboring proteins, the switch is driven by an active tug-of-war among distant proteins.

“People have known this switching behavior since the 1950s, but now having this simple molecular-level mechanism to explain it is very exciting,” says Tu, a senior research scientist at the Flatiron Institute’s Center for Computational Biology (CCB) and Center for Computational Neuroscience (CCN).

The Problem With the Domino Effect

The flagellar motor is a long-studied structure, and as Tu notes, it’s one of nature’s most beautiful molecular machines. It is composed of 34 proteins arranged in a large central ring, powered by smaller structures called stators — channels that allow electrically charged atoms to flow in and drive the rotation.

The ring proteins control whether the tail rotates clockwise or counterclockwise, depending on signals they receive from a molecule called CheY-P. If CheY-P binds to one of the proteins, it affects the protein’s conformation so that it promotes spinning in one direction or the other.

“CheY-P concentration depends on what the cell is experiencing outside, in its environment,” says Mattingly, an associate research scientist at the CCB. “It’s like a relay from what the cell senses to how it responds with changes in behavior.”

Depending on which proteins are bound by CheY-P, the ring proteins can end up in different states: Some bias the motor to move clockwise, while others favor counterclockwise rotation. In the original equilibrium model, scientists proposed that this disagreement among neighboring proteins would eventually be overcome through a domino effect. If a protein’s neighbors promoted a certain rotational direction, then that protein would be more likely to ‘fall in line’ and adopt that same state.

“The proteins cooperate with each other. If I’m in one state, my neighbor has a higher probability of joining me in that same state,” says Tu. “Once enough of them change state, the motor flips.”

However, when researchers examined the actual frequency with which flagella switched rotational direction, the distribution couldn’t be explained by the equilibrium model. Under that framework, motor switching should follow a memoryless statistical pattern, in which the likelihood of a flip doesn’t depend on how long the motor has been rotating in a given direction.

Instead, the experimental data revealed a peak in the distribution of time spent rotating in one direction rather than the other, which is not possible in an equilibrium system. “If you see this pattern, then the effect cannot be a purely equilibrium phenomenon,” says Tu. “There had to be something else going on.”

A Tug-of-War Inside the Tail

Mattingly and Tu reasoned that switching the motor’s rotational direction couldn’t be a passive equilibrium process — there must be energy injected into the system that somehow influences how and when the motor switches.

Several recent discoveries about the physical structure of the motor informed Mattingly and Tu’s theory. First, the ring of proteins in the flagellar motor, known as the C-ring, acts as one big central gear, with each protein acting as one tooth of the gear. Second, the stators aren’t just a general power source; they also function as smaller gears. These stators always rotate clockwise and make contact with the teeth of the large gear. How these teeth touch the stators determines which way they try to get the motor to turn.

The teeth of the large gear can change position to touch the small gears — the stators — on the stators’ outer edge or their inner edge. When the teeth touch the outer edge, the stators push the large gear clockwise; when they touch the inner edge, the stators push them counterclockwise. As a result, even though the small gears always rotate clockwise, the flagellum can rotate either way.

However, conflicts can arise when different teeth adopt different conformations. Some may contact their stators on the outside and favor a clockwise direction, while others contact their stators on the inside and try to turn the other way. According to the new model, this is where the tug-of-war emerges.

“Imagine all the teeth are in the same outer conformation. Then one of them flips,” says Mattingly. “As the gear turns, that lone dissenter eventually comes in contact with a stator that now pushes it in the opposite direction from all the others. Because the teeth are mechanically linked, that one tooth is feeling five active gears pushing one way and one pushing the other. Since it’s out of sync with the rest, the torque on it is much larger. It’s like a mechanical tug-of-war. If the mechanical force on it is too strong, it flips to join the majority. But if enough teeth dissent, then the entire motor changes direction.”

The team calls this process “global mechanical coupling.” The name is meant to underscore that the forces driving each tooth to turn one way or the other aren’t determined solely by the teeth’s interactions with their neighbors; rather, all teeth touching stators will impact one another across the motor in a collective process.

Global mechanical coupling can also produce the peak in the distribution seen in the earlier experiments. Since the stators are active players in the direction switching, not just general power sources for rotation, they inject energy into the system and drive it out of equilibrium.

“Global mechanical coupling explains what the earlier, purely equilibrium theory couldn’t, that switching is energy-driven, directional and cooperative,” says Tu.

Unraveling Mysteries in the Flagella and Beyond

With a new model in place, the team hopes it will inform our understanding of other nonequilibrium systems in living organisms.

“Our results make sense to me because I believe living systems always operate out of equilibrium,” says Tu. “They dissipate energy, and that energy is essential for biological function. This is a beautiful example of that principle.”

The researchers will continue to refine their model to integrate more experimental data. For example, their model predicts a peak in the distribution of counterclockwise durations, but on a shorter timescale than in experiments.

Understanding the flagella can also influence how scientists understand more complex systems.

“It’s so well studied that it becomes a perfect system to test ideas — and what we learn here often helps us think about more complex biology,” says Mattingly.

Tu adds that the new research is also exciting for the field of bacterial chemotaxis. “Every so often people say, ‘This is a dead field.’ Every time that turns out to be wrong. There’s always another layer.”

Information for the press


Bacteria propel themselves through liquids using propeller-like tails called flagellum. New research proposes a new explanation for how these tails flip from a counterclockwise to a clockwise rotation.

Credit

Hoi Chan for Simons Foundation