The researchers completed the first activity map of the mammalian brain in their groundbreaking duo and rewritten their understanding of how scientists’ decisions are made.
The project covers an area representing more than 95% of the brain, including dozens of labs and data from brain cells of over 600,000 individual mice. Findings from studies published in two Nature Journal papers suggest that decisions involve far more brains than previously thought.
The Mammoth Project was led by the International Brain Research Institute (IBL), a collaboration between experimental and theoretical neuroscientists across Europe and the United States.
“There was a problem with the way science was done,” said Matteo Carandini, a neuroscientist at the University of London, a core member of IBL.
In previous research on the brain, many separate labs have tried to answer big questions about organs, exploring how brain activity, for example, is related to behavior. However, each lab studied this question in different mouse brains and performed slightly different behavioral tasks on each set of rodents. Once each research group added uncertainty about how they defined different regions of the brain, these inconsistencies left the results muddy.
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“There were so many things different, so we don’t know if we actually agree or disagree,” Carandini told Live Science.
Related: The most detailed human brain map contains 3,300 cell types so far
Therefore, IBL came together to design a single, robust, standardized experiment on a scale that individual labs cannot tackle alone. This megatest was then combined with precision brain measurement tools and preset analysis methods to make the results as reproducible as possible. The purpose of the experiment is to overcome permanent obstacles in the field.
“One of the longest-existing challenges in neuroscience is deciphering how nervous system variation (both structural and functional) maps behavioral changes,” said Federico Turkheimer, a neuroscientist at King’s College London, who was not involved in the research, in a statement from the UK’s Science Media Centre.
The project ultimately included 139 mice spread across 12 labs around the world, with brain recording devices called neuropyxel probes embedded therein. The probe can record up to 1,000 individual neurons simultaneously. Researchers tested mice with a simple behavioral task where each dozen labs could reliably replicate. The researchers place the mouse in front of the screen, and a black-and-white striped marker flashes either right or left. If the mouse moved the small wheels in the same direction as the flash, they were rewarded.
Carandini said that based on what he read in neuroscience textbooks, he would expect brain activity that occurred during the experiment to follow a linear pathway. First, neurons from different parts of the brain, such as the prefrontal cortex, where images recognize cells fire and are known to be involved in abstract decisions. This information can be combined with additional activities that represent the mouse’s previous experience, i.e. memory, before being sent to the brain’s motor areas that control muscle responses.
The researchers’ findings supported part of this chain reaction. For example, it was the first one that became active. Still other discoveries clashed with team expectations.
“We found decision signals and signals that were related to previous information in brain regions more than we thought,” Karandini said. In summary, it is possible to infer whether mice received rewards using activities across almost every brain region studied.
In some experimental tests, researchers made the markers on the screen so faint that the mouse essentially had to guess how to move the wheel. The second nature paper focused on how mice used previous expectations based on the location of previous tests, informing them of speculation. The brain activity that flashed when the mouse guessed on these tasks was much more widely distributed in the brain than the team had expected.
IBL modeled approaches to understanding the brain with similar initiatives, such as particle physics experiments conducted to understand DNA in CERN and Human Genome Projects. To explain the impact of the project, Carandini arrives in yet another field: astronomy.
He stated that the earliest astronomers can look up at the night sky and see all the stars, but the details are very bad. The emergence of telescopes allowed us to explore individual celestial bodies. Previous work in neuroscience was, “As if someone pointed to a telescope only to one galaxy, and different astronomers pointed to a telescope in a different galaxy, saying, “My galaxy is doing this!” Or, “No, my galaxy does that!” he explained that the new project was something that allowed you to see all the features of the night sky at once and in close proximity.
While such work has only been possible with recent technological advancements and improved collaboration across the lab, Carandini hopes it can be used to address other big questions about the brain. As the findings of the current paper are only correlations, it is currently not possible to say whether observed brain activity directly triggers decisions or is only relevant to processes.
“I think that’s the next frontier,” he said, “it’s about adding causality to the research.”
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