In a First, Scientists Record Decision-Making as It Happens Across a Whole Mouse Brain

We’re constantly making decisions. If I get the pumpkin spice latte, would it make me happier than my usual black coffee? If I go the scenic route on a trip, would it be worth the extra time?

Past and current experiences affect each decision. By imaging the brain, scientists have long known multiple regions collaborate to pull in memories and integrate them with what we’re seeing, hearing, and thinking when weighing options. But because the resolution is relatively low, we’ve only had a rough sketch of the intricate neural connections involved.

A global collaboration is now digging deeper. In a technological feat, the International Brain Laboratory released a large, dynamic brain map of mice navigating a difficult decision-making task.

Launched in 2017, the group seeks to link brain activity with behavior, one of the holy grails in neuroscience. It’s been an uphill struggle. Prior attempts could only measure small regions, and individual teams used their own behavioral tests, making it difficult to integrate data.

The new collaboration gathered neural electrical recordings in mice from multiple labs across the globe using a standardized procedure. Overall, the scientists used nearly 700 brain implants to record neural activity in 139 mice, capturing the activity of 620,000 neurons across the brain.

“This is the first time anyone has produced a full, brain-wide map of the activity of single neurons during decision-making. The scale is unprecedented … [which] together represent[s] 95 percent of the mouse brain volume,” said study author Alexandre Pouget at the University of Geneva in a press release.

Should I Stay or Should I Go?

Despite decades of research, scientists still don’t fully understand how we make up our minds.

Say you’re hiking and encounter a bear. The brain immediately goes into hyper mode: The visual cortex identifies the brown thing as a bear and transmits this to the brain’s emotion centers. The latter activate to produce a sense of fear and ask the memory regions what to do. These calculations direct a motor response—back away, make yourself big, or quick-draw that bear spray.

Multiple neural networks fire up to reach the decision, but scientists are divided on how the system works. One camp thinks the brain could combine memories—say, YouTube videos of how to avoid bears—with the fact you’re seeing a bear in high-level brain regions. This hypothesis predicts memories, or prior information, only inform actions at later stages.

Another camp believes the opposite. Rather than waiting until the last second, all regions of the brain—including early sensory systems—incorporate memories to decide the best response. This process could better spread communication throughout the brain.

Neural Gambling

Like spies tapping phone lines, the authors of the new study hoped to settle the debate by listening in on the chatter of hundreds of thousands of brain cells.

The effort piggy-backed on an International Brain Laboratory dataset that used 699 Neuropixels, an open-source brain implant, to record the electrical firing of individual neurons in mice. The team strategically placed the devices across nearly 280 brain regions in over a hundred mice. They tried to keep the recordings relatively uniform as they tackled the same task across all collaborating labs.

“The scale is unprecedented as we recorded from over half a million neurons across mice…which together represent 95 percent of the mouse brain volume,” said Pouget.

Every lab taught the critters to perform the same difficult challenge. Each mouse entered an arcade of sorts and was shown a black-and-white grating—think zebra skin—on either the left or right side of a screen. They then had to use their front paws to turn a tiny wheel, moving the image to the center within a minute.

If they succeeded, they got a tasty reward. If they failed, they were blasted with a pop of white noise and a short time-out. Between trials, the mice tried to keep their paws on the wheel as they waited for the next test.

Here’s the crux: The game was rigged. There was an 80 percent chance the grate would appear in one direction, teaching the mice that was the best bet. As the trial went on, the grate slowly faded to the point it was almost impossible to see. The mice then had to decide whether to move it left or right based on what they’d previously learned as a best guess.

Each lab recorded brain signals as the mice made their choices and sent the data to a central database. In all, the consortium isolated nearly 76,000 neuron activity patterns across the brain. The recording sites were then stitched together using two-photon microscopy, a technology that impeccably lines up anatomical regions to maps of electrical activation in brain regions.

“We’d seen how successful large-scale collaborations in physics had been at tackling questions no single lab could answer, and we wanted to try that same approach in neuroscience,” said study author Tom Mrsic-Flogel at University College London. “The brain is the most complex structure we know of in the universe and understanding how it drives behavior requires international collaboration on a scale that matches that complexity.”

A Brainy Universe

Using data from the new brain map, the team realized that decision-making isn’t linear. Instead, multiple brain regions—including so-called “early” sensory ones—contribute to the final choice.

For example, brain regions in mice that process visual information sparked with activity upon seeing the grate. That activity then spread and ramped up in a wave-like pattern towards brain regions associated with emotion. These signals guided them to incorporate previous learning, called priors, into final decisions on what to do—move the wheel left or right.

Before, scientists thought priors were encoded in brain regions related to memory and higher cognition. But the new map suggests their signals also influence the early sensory processing regions that contribute to eventual responses.

“The efforts of our collaboration generated fundamental insights about the brain-wide circuits that support complex cognition,” said study author Anne Churchland at UCLA. “This is really exciting and a major step forward relative to the ‘piecemeal’ approach (1-2 brain areas at a time) that was previously the accepted method in the field.”

The International Brain Laboratory is releasing the entire database, with the goal of eventually understanding the brain’s computations within and across the brain regions behind decision-making. The dataset could shed light on neurological disorders with impaired decision-making, such as obsessive-compulsive disorders, Parkinson’s disease, and addiction.