“Motivational Brake” Could Point to Schizophrenia and Depression Treatments

Many of us will recognize being in a situation where it’s really hard to get started on a task—whether it’s making a difficult phone call or preparing a presentation that’s stressful just to think about. We 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 brains seem unable to push the “go” button. Avolition is commonly seen in conditions such as depression, schizophrenia, and Parkinson’s disease, and it can seriously disrupt a person’s ability to manage daily life and maintain social functions.

Working with macaque monkeys trained to perform certain tasks, scientists at Kyoto University applied chemogenetics techniques to identify a pathway between the ventral striatum (VS) and ventral pallidum (VP) in the brain that functions as a “motivation brake,” suppressing this internal “go” button, particularly when facing stressful or unpleasant tasks. The results showed that chemogenetic suppression of this VS–VP pathway restored motivation in the animals under aversive conditions.

The team, headed by Ken-ichi Amemori, PhD, an associate professor at the Institute for the Advanced Study of Human Biology (WPI-ASHBi), and colleagues, suggests that the discovery of this VS–VP motivation brake may shed light on conditions such as depression and schizophrenia, where severe loss of motivation is common, and point to interventional strategies.

Amemori and colleagues reported on their findings in Current Biology, in a paper titled “Motivation under aversive conditions is regulated by a striatopallidal pathway in primates,” concluding that their results “identify the VS–VP pathway as a key circuit by which aversive contexts suppress effort-based behavioral initiation, highlighting it as a potential target for treating motivational deficits in depression and schizophrenia.

Motivation is the driving force that propels organisms to initiate and sustain goal-directed behavior, the authors explained, but motivation can often diminish under aversive conditions. 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. “Clinically, motivational deficits are linked to psychiatric disorders such as depression and schizophrenia, yet the neural mechanisms by which aversive contexts suppress motivation remain unclear,” the team further explained.

To explore this question, Amemori and team applied an advanced genetic technique called chemogenetics to macaque monkeys, making it possible to adjust communication temporarily and precisely between specific brain regions and identify a circuit that acts like a brake on motivation. Their study focused on the connected ventral striatum and ventral pallidum regions. “The ventral striatum (VS) and ventral pallidum (VP) are central components of motivational regulation within the basal ganglia,” the team noted. The VS is known to play a role in reward processing and incentive motivation, and its dysfunction has been implicated in motivational deficits observed in major depressive disorder.

The VP, they continued, “… encodes hedonic value and contributes to the generation of goal-directed output,” while both brain regions are involved in aversive motivation and effort-based decisions. For their reported study, the investigators tested whether the VS–VP pathway might play a role in motivation under aversive conditions.

The macaques were trained to perform two types of tasks. In one, completing the task earned a water reward, an approach-approach (Ap-Ap) task. In the other, the reward came with an added downside: an unpleasant air puff to the face, which they termed an approach-avoidance (Ap-Av) task. 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 whether, more fundamentally, the animals chose to 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 the ventral striatum and the ventral pallidum. They found that in the reward-only task, suppressing this pathway had little effect on monkey behavior, and the animals initiated the task normally. In contrast, in tasks involving an unpleasant air puff, the mental brake to starting had eased, and the monkeys became much more willing to start. “Using chemogenetic manipulation, we found that selective inhibition of the ventral striatum to ventral pallidum (VS–VP) pathway restored the motivation to initiate trials in the Ap-Av task without affecting goal valuation,” they stated. “No effects were observed in the Ap-Ap task.” Importantly, the animals’ 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.

“Electrophysiological recordings revealed rapid VS responses to aversive cues and a gradual decrease in VP activity, suggesting an inhibitory interaction in which elevated VS activity dampens VP output to limit initiation,” the scientists commented.

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. “These findings provide causal evidence that the VS-VP pathway mediates motivational suppression in aversive contexts.”

Discovery of the VS–VP motivation brake may help scientists better understand the lack of motivation commonly seen in individuals with depression and schizophrenia. In the future, the team suggests interventions such as deep brain stimulation, noninvasive brain stimulation, or new drug strategies might aim to fine-tune this brake when it becomes too tight. “From a clinical perspective, these findings provide mechanistic insight into motivational deficits central to psychiatric disorders. Avolition, diminished initiation despite preserved hedonic capacity, is a core symptom in MDD and schizophrenia, reflecting a dissociation between value representation and behavioral initiation,” they concluded. “Our results refine this view by identifying the VS–VP pathway as a key regulator of initiation under aversive conditions while leaving outcome valuation largely intact.”

However, this brake does exist 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. “Overweakening the motivation brake could lead to dangerous behavior or excessive risk-taking,” said Ken-ichi Amemori. “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.