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Post by Former NIMH Director Thomas Insel: The Brain’s Critical Balance

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Graphic of representation of brainWe have reached an interesting moment in our quest to understand how the brain works. Our current tools generate an abundance of data, but we are not sure how to turn this data into knowledge. In some ways, neuroscience today is where physics was half a century ago. The physicist Steven Weinberg reminds us, "Rather than being starved for data fifty years ago, we were deluged by data we could not understand. Progress when it came was generally initiated by theoretical advances, with experimentation serving as a referee between competing theories and providing occasional healthy surprises.”1

While we don’t have a unified field theory of the brain, some of the early projects in the BRAIN Initiative are providing models of how behavior emerges from brain activity.  One of the first grants issued by the BRAIN Initiative supported scientists at NIMH and the University of Maryland to understand how the activity of individual neurons is integrated into larger patterns of brain activity. This work builds on the observation that in nature, order sometimes emerges out of the chaos of individual interacting elements.2

This month, the NIMH team, led by Dietmar Plenz, reported that what might seem like chaotic, “noisy” firing of individual neurons in fact organizes across the brain in ways that can distinguish anesthetized and awake states and eventually could help distinguish healthy from disordered brain function.3 In awake rats the sporadic firing of individual neurons spontaneously organizes into avalanches, or cascades of activity within groups of neurons. Tracking neuronal firing using 2-photon imaging, which reveals the activity of individual cells in a behaving animal, the team found that avalanches were absent while the rats were anesthetized, but emerged as they awaken. While prior research in humans and animals has noted the presence of neuronal avalanches in the brain, this is the first link between the emergence of avalanches, the activity of excitatory neurons, and awakening. This finding depended not only on advanced imaging using genetically encoded fluorescent calcium sensors, but the ability to analyze complex patterns of neuronal firing.

Importantly, the frequency and magnitude of avalanches occur in a ratio that is consistent from small scale to large (reminiscent of fractals, repeating patterns that mirror themselves at every scale). This order in neuronal activity bursts, reflected in the above ratio, echoes a universal organizational pattern in nature, now observed in systems as diverse as social networks, power grids, economic systems, and the internet. Avalanche organization emerges as the many individual elements in each system engage in precisely balanced interactions. In the brain, the pace of neuronal avalanches depends on a balance between “excitatory” activity that causes neurons to fire, and “inhibitory” activity that prevents firing. Too much excitatory activity, and the system veers off balance, as in epilepsy, and possibly psychiatric disorders. It appears that the healthy brain is poised at “criticality,” ensuring the optimal ability to respond to the environment without tipping into instability.

There is an increasing recognition that understanding the brain in health and disease is going to require methods to make sense of the interactions of thousands, if not millions, of interacting, ever-changing assemblies of genes, proteins, and cells that form the circuits encoding our experience of the world. The BRAIN Initiative, beyond providing tools to measure, visualize, and monitor brain activity, is supporting scientists to develop a unifying framework and underlying principles for understanding how the estimated 86 billion neurons in the human brain act, en masse and in split second time frames, to enable consciousness and behavior.

References

1 Weinberg S. Physics: What We Do and Don’t Know.  The New York Review of Books. November 7, 2013.

2 Bak P. How Nature Works. Oxford. Oxford University Press. 1997.

3 Bellay T, Klaus A, Seshadri  S, Plenz D. Irregular spiking of pyramidal neurons organizes as scale-invariant neuronal avalanches in the awake state.  eLIFE. 2015 Jul 7;4. doi: 10.7554/eLife.07224.