The brain’s ability to connect external events with beneficial actions is crucial for our daily functioning. Neuroscientists have recently uncovered fascinating insights into how sensory input is transformed into motor action across multiple brain regions in mice. This groundbreaking research carried out at the Sainsbury Wellcome Centre at UCL has revealed that decision-making is a global process coordinated by learning.
These findings not only deepen our understanding of the brain but also have the potential to revolutionize artificial intelligence research by offering valuable insights into the design of more effective neural networks.
“This work unifies concepts previously described for individual brain areas into a coherent view that maps onto brain-wide neural dynamics. We now have a complete picture of what is happening in the brain as sensory input is transformed through a decision process into an action,” explained Professor Tom Mrsic-Flogel, Director of the Sainsbury Wellcome Centre at UCL and corresponding author on the paper.
The study unveils the cutting-edge use of Neuropixels probes, a state-of-the-art technology that enables simultaneous recordings across hundreds of neurons in multiple brain regions. The researchers delved into the minds of mice as they participated in a decision-making task meticulously crafted by Dr. Ivana Orsolic at SWC. This task not only allowed the team to dissect sensory processing and motor control but also shed light on the impact of learning by comparing trained animals with their naïve counterparts.
“We often make decisions based on ambiguous evidence. For example, when it starts to rain, you have to decide how high frequency the raindrops need to be before you open your umbrella. We studied this same ambiguous evidence integration in mice to understand how the brain processes perceptual decisions,” explained Dr Michael Lohse, Sir Henry Wellcome, Postdoctoral Fellow at SWC and joint first author on the paper.
Mice were trained to remain perfectly still as they observed a captivating visual pattern in motion on a screen. In order to earn a reward, the mice had to skillfully lick a spout the moment they detected a sustained increase in the speed of the visual pattern. The task was ingeniously designed so that the speed of the movement was never constant. Instead, it continuously fluctuated.
Furthermore, the timing of the increase in the average speed varied from trial to trial, preventing the mice from simply relying on memory. This required the mice to remain constantly vigilant, attentively integrating information to discern whether the increase in speed had occurred.
“By training the mice to stand still, the data analysis we could perform was much cleaner, and the task allowed us to look at how neurons track random fluctuations in speed before the mice took action. In trained mice, we found that there is no single brain region that integrates sensory evidence or orchestrates the process. Instead, we found neurons that are sparsely but broadly distributed across the brain link sensory evidence and action initiation,” explained Dr Andrei Khilkevich, Senior Research Fellow in the Mrsic-Flogel lab and joint first author on the paper.
The researchers meticulously recorded data from over 15,000 cells across 52 brain regions in 15 trained mice, conducting multiple recordings from each mouse. To delve into the realm of learning, the team compared the results to recordings from naïve mice.
“We found that when mice don’t know what the visual stimulus means, they only represent the information in the visual system in the brain and a few midbrain regions. After they have learned the task, cells integrate the evidence all over the brain,” explained Dr Lohse.
In this study, the team exclusively focused on both naïve animals and those that had mastered the task. However, in their upcoming endeavors, they are eager to unravel the mysteries of the learning process by tracking neurons over time to observe their transformation as the mice grasp the task. Additionally, the researchers aim to investigate whether specific brain areas serve as causal hubs in establishing connections between sensations and actions.
The study has sparked several intriguing questions, such as how the brain integrates an anticipation of when the speed of visual patterns will increase, allowing animals to react only when the information is relevant. The team is committed to delving deeper into these inquiries using the extensive dataset they have meticulously collected.
Journal reference:
- Andrei Khilkevich, Michael Lohse, Ryan Low, Ivana Orsolic, Tadej Bozic, Paige Windmill & Thomas D. Mrsic-Flogel. Brain-wide dynamics transforming sensation into action during decision-making. Nature, 2024; DOI: 10.1038/s41586-024-07908-w