Posted on by Dr. Francis Collins
One of life’s greatest mysteries is the brain’s ability to encode something as complex as human behavior. In an effort to begin to unravel this mystery, neuroscientists often zoom in to record the activities of individual neurons. Sometimes they expand their view to look at a specific region of the brain. But if they zoom out farther, neuroscientists can observe many thousands of neurons across the entire brain firing at once to produce electrical oscillations that somehow translate into behaviors as distinct as a smile and a frown. The complexity is truly daunting.
Rainbo Hultman, University of Iowa Carver College of Medicine, Iowa City, realized years ago that by zooming out and finding a way to map all those emergent signals, she could help to change the study of brain function fundamentally. She also realized doing so offered her an opportunity to chip away at cracking the complicated code of the electrical oscillations that translate into such complex behaviors. To pursue her work in this emerging area of “electrical connectomics,” Hultman recently received a 2020 NIH Director’s New Innovator Award to study the most common human neurological disorder: migraine headaches.
A few years ago, Hultman made some impressive progress in electrical connectomics as a post-doctoral researcher in the lab of Kafui Dzirasa at Duke University, Durham, NC. Hultman and her colleagues refined a way to use electrodes to collect electrical field potentials across an unprecedented seven separate mouse brain regions at once. Using machine learning to help make sense of all the data, they uncovered a dynamic, yet reproducible, electrical brain network encoding depression .
What’s more, they found that the specific features of this brain-wide network could predict which mice subjected to chronic stress would develop signs of major depressive disorder. As Hultman noted, when measured and mapped in this way, the broad patterns of electrical brain activity, or “Electome factors,” could indicate which mice were vulnerable to stress and which were more resilient.
Moving on to her latest area of research, Hultman is especially intrigued by the fact that people who endure regular migraine attacks often pass through a characteristic sequence of symptoms. These symptoms can include a painful headache on one side of the head; visual disturbances; sensitivity to light, odors, or sound; mood changes; nausea; trouble speaking; and sometimes even paralysis. By studying the broad electrical patterns and networks associated with migraine in mice—simultaneously capturing electrical recordings from 14 brain regions on a millisecond timescale—she wants to understand how brain circuits are linked and work together in ways that produce the complex sequences of migraine symptoms.
More broadly, Hultman wants to understand how migraine and many other disorders affecting the brain lead to a state of heightened sensory sensitivity and how that emerges from integrated neural circuits in the brain. In her studies of migraine, the researcher suspects she might observe some of the same patterns seen earlier in depression. In fact, her team is setting up its experiments to ensure it can identify any brain network features that are shared across important disease states.
By the way, I happen to be one of many people who suffer from migraines, although fortunately not very often in my case. The visual aura of flashing jagged images that starts in the center of my visual field and then gradually moves to the periphery over about 20 minutes is pretty dramatic—a free light show! I’ve wondered what the electrical component of that must be like. But, even with treatment, the headache that follows can be pretty intense.
Hultman also has seen in her own life and family how debilitating migraines can be. Her goal isn’t just to map these neural networks, but to use them to identify where to target future therapeutics. Ultimately, she hopes her work will pave the way for more precise approaches for treating migraine and other brain disorders that are based on the emergent electrical characteristics of each individual’s brain activity. It’s a fascinating proposition, and I certainly look forward to where this research leads and what it may reveal about the fundamentals of how our brains encode complex behaviors and emotions.
 Brain-wide electrical spatiotemporal dynamics encode depression vulnerability. Hultman R, Ulrich K, Sachs BD, Blount C, Carlson DE, Ndubuizu N, Bagot RC, Parise EM, Vu MT, Gallagher NM, Wang J, Silva AJ, Deisseroth K, Mague SD, Caron MG, Nestler EJ, Carin L, Dzirasa K. Cell. 2018 Mar 22;173(1):166-180.e14.
Migraine Information Page (National Institute of Neurological Disorders and Stroke/NIH)
Laboratory for Brain-Network Based Molecular Medicine (University of Iowa, Iowa City)
Hultman Project Information (NIH RePORTER)
NIH Director’s New Innovator Award (Common Fund)
NIH Support: Common Fund; National Institute of Mental Health
Posted on by Dr. Francis Collins
There is mounting evidence that predisposition to autism, schizophrenia, and many other devastating brain disorders may begin in the womb when genes are turned on or off at the wrong time during early brain development. But because our current maps of the developing brain are not nearly as detailed or dynamic as we would like, it has been a major challenge to identify and understand the precise roles of these genes.
So, I’m pleased to report that NIH-funded researchers at the Allen Institute for Brain Science in Seattle have produced a comprehensive 3-D map that reveals the activity of some 20,000 genes in 300 brain regions during mid-prenatal development . While this is just the first installment of what will be an atlas of gene activity covering the entire course of human brain development, this rich trove of data is already transforming the way we think about neurodevelopmental disorders.