Annual Report 2019

Neural Signals, Far and Wide

Simons Collaboration on the Global Brain

Neuroscientists have traditionally focused their efforts on discrete brain areas: People interested in vision studied the visual cortex, and people interested in movement studied the motor cortex. Though everyone knew such functions were not actually limited to specific regions, technological limitations made far-reaching experiments infeasible.

But that’s rapidly changing. The development of new technologies capable of recording from large populations of neurons in multiple brain regions — simultaneously — is now making it possible to examine how information is represented globally across the brain.

Early results suggest that neural signals for some cognitive functions are more widespread than anyone had predicted. Movement-related information seems to be particularly widespread, encoded all over the brain.

Even a twitch of a hind leg can produce abundant, widespread and high-dimensional activity in a mouse’s cortex. Researchers are investigating why even such small movements can engage the whole brain. Credit: Peter Diamond

Anne Churchland and her colleagues at Cold Spring Harbor Laboratory have shown that fidgeting — in mice, at least — activates not just the regions typically associated with movement but the entire brain. And a brief, apparently meaningless whisk or kick of a hind limb evokes a burst of neural activity over the entire cerebral cortex.

“It’s for sure made me wonder if, for certain organisms, including some humans, part of what it means to think is to move,” says Churchland, an investigator with the Simons Collaboration on the Global Brain (SCGB). “Movements and cognition for those subjects are deeply intertwined.”

“This type of research is essential to the Simons Collaboration on the Global Brain, which aims to understand how neurons work together to produce thoughts,” says David Tank, SCGB’s director and director of the Princeton Neuroscience Institute. “Uncovering how populations of neurons encode information across different regions of the brain is the first step in deciphering how these regions collaboratively integrate and process information.”

In Churchland’s experiment, published in Nature Neuroscience in September 2019, researchers monitored both neural activity and movement as mice learned to press left or right to receive a reward in response to a visual or auditory stimulus. The researchers expected to see just a handful of distinct cortical regions light up. “But what we actually saw was very different,” says Churchland. “Many, many brain structures were engaged. Many more than we anticipated, and to a much greater extent than we anticipated.”

Indeed, neural activity tied to random movements accounted for the majority of variability in neural responses from trial to trial — not just in the motor and somatosensory cortical areas, where fidget-related activity might be expected, but all over the cortex. Neuroscientists have long written off such variability as noise, but Churchland’s work suggests a significant chunk of it is actually signal.

The Churchland study followed a paper published in April in Science that used both calcium imaging and electrophysiology to monitor the activity of thousands of visual neurons in mice walking on a treadmill with little or no visual stimulation.

Uninstructed movements account for the majority of the variance in trial-to-trial neural activity. Credit: Musall et al./Nature Neuroscience 2019

Carsen Stringer and Marius Pachitariu, now at the Janelia Research Campus, working with Ken Harris and Matteo Carandini at University College London, both SCGB investigators, found that a mouse’s facial movements accounted for a significant amount of neural population activity in its visual cortex. Further experiments showed that this held true across the brain. They also found that the same neurons could encode both visual and behavioral information.

“The findings challenge the idea that the brain is modular. Every brain area contains behavioral information; therefore, sensory areas like visual cortex can no longer be thought of as simply visual,” Stringer says.

These two studies add to an expanding body of research exploring how an animal’s behavior profoundly influences the ways its brain processes sensory information and makes decisions. Previous research had mainly shown how single variables — such as running speed or pupil diameter (an indicator of arousal) — could account for changes in activity in sensory areas of the brain. This newer work shows both that movement-related neural activity is broadcast across the whole brain, and that the signals are more complex than previously described.

“Creatures evolved to have a brain to move the body, and cognitive tasks probably borrowed neural dynamics from movements,” Churchland says. She believes researchers should revisit the intersection between movement and thought and figure out how, exactly, the two are linked.

Different Distributions

Other types of information are also found across the brain, though not as extensively as movement-related information. In a study published in Nature in November 2019, SCGB investigator Nick Steinmetz, now at the University of Washington in Seattle, and collaborators found that different types of information can have very different patterns of neural activity distributed around the brain.

Researchers used Neuropixels probes, a newly developed, hair-thin probe densely packed with recording sites, to record from 30,000 neurons in 42 different brain regions in mice as they learned to turn a wheel left or right depending on a visual stimulus. They looked at neural activity linked to different aspects of the task, such as action (when the mouse started to turn the wheel), visual information (the content of the stimulus), choice (whether the animal moved the wheel left or right) and engagement (how likely the animal was to respond to the stimulus).

None of these factors were limited to one part of the brain. As was the case for the Churchland and Harris studies, movement-related information was broadly distributed around the brain. Visual information, however, was more limited, restricted largely to areas known to be involved in visual processing.

Neural activity tied to the animal’s level of engagement in the task and its eventual choice had unique representations. Choice-related signals were found in a subset of brain areas, including the prefrontal cortex, basal ganglia and midbrain, but not in the visual or parietal cortex. Engagement also had a distinctive pattern — less activity in the cortex and more activity in subcortical areas.

Researchers now need to figure out how different distributed networks of neurons coordinate with each other. “How is the flow of information controlled across networks?” asks Steinmetz.

The findings also challenge researchers to reconsider how cortical processing operates and to develop new models that incorporate behavior and the entire cortex. “You have moment-by-moment information about what you’re doing across the whole brain,” Stringer says. The question this poses for future research, she says, is: “What does the brain do with that information?”