Scientists discover how the brain keeps the urge to act under control
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This is the last race. Eight athletes lined the track, their feet tensed against the starting blocks. They hear a countdown: “On Your Marks!”, “Get Set,” and then, a split second before the shot, a runner jumps forward, disqualifying himself from the competition. It is at such times that an aspect of behavior that is usually neglected—action suppression—is painfully exposed.
A study published today in the journal Natural uncover how the brain stops us from jumping the gun. “We found an area of the brain that is responsible for prompting action and another for suppressing that impulse. We can also trigger impulsive behavior by manipulating the neurons in these areas,” said the study’s senior author, Joe Paton, Program Director of Champalimaud Neuroscience in Portugal.
Solve puzzles
Paton’s team set out to solve a puzzle that arose in part from Parkinson’s and Huntington’s Disease. This condition manifests as a movement disorder with very opposite symptoms. While Huntington’s patients suffer from involuntary and involuntary movements, Parkinson’s patients struggle with initiation of the action. Specifically, both conditions stem from dysfunction of the same brain region: the basal ganglia. How can the same structure support contradictory functions?
According to Paton, valuable clues emerge from previous research, which identified two main circuits in the basal ganglia: direct and indirect pathways. It is thought that while direct pathway activity promotes movement, indirect pathway suppresses it. However, the exact manner in which these interactions are carried out is largely unknown.
Timing tasks with a twist
Paton takes an original approach to this problem. Whereas previous research investigated the basal ganglia during movement, Paton’s team focused on suppressing active action instead.
The team designed a task in which mice had to determine whether the interval separating two notes was longer or shorter than 1.5 seconds. If it is shorter, the prize will be given on the left side of the box, and if it is longer, it will be available on the right.
“The key is that the rat has to stay still in the period between the two notes,” said Bruno Cruz, a doctoral student in the lab. “So even if the animal believes the 1.5 second mark has elapsed, it needs to suppress the urge to move until the second note sounds, and only then look for its reward.”
An impulsive ‘switch’
The researchers tracked the neural activity of both pathways as the mice performed the task. As in previous studies, activity levels were similar as the mice moved. However, things changed during the oppression-action period.
“Interestingly, unlike the coactivation we and others observed during movement, the activity patterns in the two pathways differed markedly during the action suppression period. The overall indirect pathway activity was higher and continued to increase as the mice waited for the second tone,” said Cruz.
According to the authors, these observations suggest that indirect pathways flexibly support animal behavioral goals. “Over time, the rat became more confident that it was in a ‘long interval’ experiment. And its urge to move became more and more difficult to resist. The possibility of this sustained increase in activity reflects this internal struggle,” explains Cruz. .
Inspired by this idea, Cruz tested the inhibitory effect of the indirect pathway. This manipulation caused the mice to behave impulsively more frequently, significantly increasing the number of trials in which they bolted to the reward port prematurely. With this innovative approach, the team effectively invented the “impulsive switch”.
“This discovery has far-reaching implications,” Paton mused. “In addition to its clear relevance for Parkinson’s and Huntington’s Diseases, it also provides a unique opportunity to investigate impulse control conditions, such as addiction and Obsessive-Compulsive Disorder.”
Looking for impetus to action
The team identified regions of the brain that actively suppress the urge to act, but where does that urge come from? Since the direct path is considered to be driving the action, the direct suspect is a direct path from the same area. However, the mice’s behavior was practically unaffected when the researchers inhibited them.
“We knew rats experienced a strong urge to act because removing suppression prompted such impulsive action. But it wasn’t immediately clear where else the action promotion site was. To answer this question, we decided to turn to computational modeling,” recalls Patton.
“Mathematical models are very useful for understanding complex systems, like these,” adds Gonçalo Guiomar, a doctoral student in the lab. “We took the accumulated knowledge about the basal ganglia, formulated it mathematically, and tested how the system processes information. We then combined the model’s predictions with evidence from previous research and identified a promising new candidate: the dorsomedial striatum.”
The team’s hypothesis was correct. Blocking neurons from direct pathways in this new region was enough to alter the behavior of mice. “Both areas we recorded are located in a part of the basal ganglia called the striatum. The first area is responsible for what is called ‘low-level’ motor sensor function and the second is dedicated to ‘high-level’ functions such as decision making,” explains Guiomar. .
From action to temptation and beyond
The authors argue that their findings contradict the common perception of how the basal ganglia operate, which is more centralized, and that their model offers a new perspective on how the basal ganglia operate.
“Our study shows that there are potentially multiple neural circuits in the brain that are constantly competing for which action to take next. These insights are important for a deeper understanding of how this system works, which is critical to treating certain movement disorders, but continues to grow.” . further afield,” said Paton. “Observation from neuroscience is at the core of many machine learning and AI techniques. The idea that decision making can occur through the interaction of multiple parallel circuits within the same system may prove useful for designing new types of intelligent systems,” he added.
Lastly, Paton suggests that perhaps one of the most unique aspects of the study is its ability to access inner cognitive experiences. “Impulsivity, temptation… These internal processes are some of the most interesting things the brain does, because they reflect our inner life. But these processes are also the most difficult to learn, because they don’t have as many outward signs as we can see. Setting up this new method is challenging , but now we have powerful tools to investigate internal mechanisms, such as those involved in resisting and yielding to temptation,” concluded Paton.
Mapping neural connections in Parkinson’s disease
Joseph Paton, Action suppression reveals the parallel control of the opponent through the striatal circuit, Natural (2022). DOI: 10.1038/s41586-022-04894-9. www.nature.com/articles/s41586-022-04894-9
Provided by Champalimaud Center for the Unknown
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