PARIS, July 11 (Benin News) –
A new study has discovered how the brain prevents us from making rash decisions. “We discovered an area of the brain responsible for inciting action and another for suppressing that impulse. We were also able to trigger impulsive behavior by manipulating neurons in these areas,” says study lead author Joe Paton, director of the Champalimaud Neuroscience Program in Portugal.
As published in the journal “Nature,” Paton’s team set out to solve a puzzle born in part of Parkinson’s and Huntington’s diseases. These diseases are manifested by movement disorders with very opposite symptoms. While Huntington’s disease patients suffer from involuntary and uncontrolled movements, Parkinson’s disease patients have difficulty initiating action. Interestingly, both conditions stem from dysfunction in the same brain region, the basal ganglia, and they wondered how the same structure can support conflicting functions.
According to Paton, a valuable clue emerged from previous studies, which identified two main circuits in the basal ganglia: direct and indirect pathways. It is believed that while activity in the direct pathway promotes movement, the indirect pathway suppresses it. However, the precise way in which this interaction occurs was largely unknown.
Paton took an original approach to the problem. Whereas previous studies focused on the basal ganglia during movement, Paton’s team focused on suppressing active action.
The team designed a task in which the mice had to determine whether an interval between two tones was longer or shorter than 1.5 seconds. If it was shorter, a reward was provided on the left of the box, and if it was longer, it was available on the right.
“The key was that the mouse had to remain perfectly still during the period between the two tones,” explains Bruno Cruz, a doctoral student in the lab. Thus, even if the animal was sure it had passed the 1.5-second mark, it had to suppress its urge to move until the second beep sounded, and only then go for the reward.
The researchers tracked neural activity in both pathways while the mouse performed the task. As in previous studies, activity levels were similar when the mouse was in motion. However, things changed during the destocking period.
“Interestingly, unlike the coactivation that we and others observed during movement, the activity patterns of the two pathways were markedly different during the suppressed period of action. The activity of the indirect pathway was generally higher and increased continuously while the mouse waited for the second beep”, adds Cruz.
According to the authors, this observation suggests that the indirect pathway flexibly supports the animal’s behavioral goals. “As time goes on, the mouse becomes more and more convinced that it is on a ‘long range’ test. Therefore, his desire to move becomes more and more difficult to contain. This continued increase in activity is likely to reflect this internal struggle,” he explains.
Inspired by this idea, Cruz tested the effect of inhibiting the indirect pathway. This manipulation caused the mice to behave impulsively more often, significantly increasing the number of trials in which they prematurely jumped to the reward port. Through this innovative approach, the team effectively discovered an “impulsivity switch.”
“This finding has broad implications,” says Paton. In addition to his obvious interest in Parkinson’s and Huntington’s diseases, he also offers a unique opportunity to study impulse control disorders, such as addiction and obsessive-compulsive disorders.
The team identified a region of the brain that actively suppresses the drive to act, but they wanted to know where that drive came from. Since the direct route is supposed to promote action, the immediate suspect was the direct route in the same area. However, the mice’s behavior was largely unaffected when the researchers inhibited it.
“We knew that the mice had a strong urge to act because the suppression of suppression promoted impulsive actions. But it wasn’t immediately clear where the venue for the action’s promotion might be. To answer this question, we decided to turn to computer modeling,” recalls Paton.
“Mathematical models are extremely useful for making sense of complex systems, like this one,” adds Gonçalo Guiomar, a doctoral student in the lab. We take the accumulated knowledge about the basal ganglia, formulate it mathematically, and check how the system processes the information. We then combined the model’s prediction with evidence from previous studies and identified a promising new candidate: the dorsomedial striatum.
The team’s assumption was correct. Inhibition of direct pathway neurons in this new region was sufficient to alter mouse behavior. “The two regions we recorded are located in a part of the basal ganglia called the striatum. The first area is responsible for so-called “low-level” motor and sensory functions, and the second is dedicated to “high-level” functions, such as decision-making,” explains Mr. Guiomar.
The authors say that their results run counter to the general perception of basal ganglia function, which is more centralized, and that their model offers a new perspective on basal ganglia function.
“Our study indicates that there are potentially multiple neural circuits in the brain that are constantly competing for what action to take next. This discovery is important to better understand how this system works, which is essential for treating certain movement disorders, but goes further”, says Paton. Observations from neuroscience are the basis for many machine learning and artificial intelligence techniques. The idea that decision making can be done by the interaction of many parallel circuits within a single system could be useful in designing new types of intelligent systems.
Finally, Paton suggests that perhaps one of the most unique aspects of the study is its ability to access internal cognitive experiences. “Impulsivity, temptation…. These internal processes are some of the most fascinating things the brain does because they reflect our inner lives. But they’re also the hardest to study, because they don’t have many external cues that we can measure.” It’s been a challenge to get this new method up and running, but now we have a powerful tool for studying internal mechanisms, such as those involved in resisting and overcome a temptation”, he concludes.