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Researchers Find Order in the Language of the Brain

Research Highlight

Nerve cells in the brain, known as neurons , share information with each other. This is particularly true for neurons in gray matter of the cortex, the largest part of the brain where each neuron connects with thousands of other neurons in support of complex brain functions. Electrical neuronal activity spreads rapidly and extensively in this vast network, creating highly diverse patterns of activity that can last for long periods and involve millions of neurons.

This fluctuating neuronal activity lies at the core of information processing in the brain. Yet, it has been challenging to identify meaningful order in the constant activity fluctuations—a basic requirement to understand how the brain operates under normal conditions.

Early discoveries in understanding neuronal avalanches

Two decades ago, researchers in the National Institute of Mental Health (NIMH) Intramural Research Program (IRP) made a discovery that was a significant milestone in this effort. Trailblazing studies led by Dietmar Plenz, Ph.D., chief of the IRP Section on Critical Brain Dynamics, showed that the brain produces activity patterns of different sizes in a very organized way that follows a mathematical formula called a power law. This means that the brain produces activity patterns of different sizes at a constant rate.

This discovery led to the idea of "neuronal avalanches," in which groups of neurons firing together set off a chain reaction, causing other groups of neurons to fire in a cascade. The novel discovery also linked brain research to the field of self-organized criticality —a unifying theory that aims to explain how complex systems optimize information processing to operate at peak performance.

Current study examining properties of neuronal avalanches

In a new study supported by NIMH and the Brain Research Through Advancing Innovative Neurotechnologies® Initiative , or The BRAIN Initiative®, Dr. Plenz and colleagues have revealed how neuronal avalanches unfold over time. By showing that the synchronized activity of neuronal avalanches follows a precise order, the researchers essentially found order in the language of the brain—order that had been predicted by theory but that no one had shown experimentally at cellular resolution until now.

Using the latest methods in laser technology and image processing, the research team studied how the firing of individual neurons in an avalanche links to the firing of other neurons within the same avalanche. First, they inserted a prism into the mouse brain that provided a view of neurons in the opposite hemisphere (or side) of the brain. Then, they had the mouse run on a wheel for short periods over several days and observed neuronal activity in two brain areas—the primary visual cortex and the prefrontal cortex.

The researchers measured the firing of neurons using 2-photon imaging , a powerful technology for recording hundreds to thousands of neurons within a small brain region at the single-cell level. However, they needed to improve the imaging quality to reliably track the spread of neuronal activity. They did this using a machine-learning procedure called deep interpolation, which reduces noise in images to enhance their resolution, and Biowulf , the high-performance computational platform of NIH. With this combination of advanced tools, the researchers successfully reconstructed the firing of many neurons to get an in-depth look at how they fire together during neuronal avalanches.

Current study advances knowledge of neuronal avalanches

The researchers confirmed at the cellular level that neuronal avalanches occur in the visual cortex. For the first time, they also revealed that avalanches occur in the prefrontal cortex, which regulates thoughts, actions, and emotions through extensive connections with other brain regions.

The results showed that, under normal conditions, brain activity fluctuated in an extremely organized way that could be described with precise numbers. When groups of neurons in gray matter of the cortex fired together, they formed cascades of synchronized activity. These cascades unfolded in a specific pattern that took the form of a symmetrical inverted parabola (upside-down “U”)—with activity rising before leveling off and going back down—referred to as “parabolic avalanches.”

The researchers further demonstrated that parabolic avalanches grow rapidly at a constantly increasing quadratic rate. This feature enables maximum information storage.

These results held across various experimental conditions and for cascades of different durations. The researchers described this consistent organization as scale invariant—no matter at what scale you study the system, neuronal avalanches show the same universal time course over different brain regions.

Next steps for researchers studying neuronal avalanches

This study is a powerful example of how mathematical approaches can enhance understanding of how the brain works. The findings establish a scale-invariant, inverted parabola as a novel form of neuronal synchronization that defines organization of brain activity in the cortex.

The researchers’ discovery was only possible by making tremendous technical advancements that allowed them to track the firing of individual neurons within the cascades. Future researchers now have the tools to effectively visualize neuronal avalanches.

This study also propels efforts to identify the brain’s optimal state. It established, both experimentally and mathematically, the scale that defines the synchronization of neurons firing in the brain and the conditions under which the technology works best to track neuronal activity. The findings may make it possible to identify specific changes in brain activity that indicate altered brain function which could, in turn, open the door to many potential applications, such as the earlier identification of mental disorders.

Reference

Capek, E., Ribeiro, T. L., Kells, P., Srinivasan, K., Miller, S. R., Geist, E., Victor, M., Vakili, A., Pajevic, S., Chialvo, D. R., & Plenz, D. (2023). Parabolic avalanche scaling in the synchronization of cortical cell assemblies. Nature Communications, 14, Article 2555. https://doi.org/10.1038/s41467-023-37976-x 

Intramural funding

ZIAMH002797 , ZIAMH002971 

Grant

NS107464-01