Big Data and Imaging Analysis Yields High-Res Brain Map

The HCP’s multi-modal cortical parcellation

Caption: Map of 180 areas in the left and right hemispheres of the cerebral cortex.
Credit: Matthew F. Glasser, David C. Van Essen, Washington University Medical School, Saint Louis, Missouri

Neuroscientists have been working for a long time to figure out how the human brain works, and that has led many through the years to attempt to map its various regions and create a detailed atlas of their complex geography and functions. While great progress has been made in recent years, existing brain maps have remained relatively blurry and incomplete, reflecting only limited aspects of brain structure or function and typically in just a few people.

In a study reported recently in the journal Nature, an NIH-funded team of researchers has begun to bring this map of the human brain into much sharper focus [1]. By combining multiple types of cutting-edge brain imaging data from more than 200 healthy young men and women, the researchers were able to subdivide the cerebral cortex, the brain’s outer layer, into 180 specific areas in each hemisphere. Remarkably, almost 100 of those areas had never before been described. This new high-resolution brain map will advance fundamental understanding of the human brain and will help to bring greater precision to the diagnosis and treatment of many brain disorders.

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Making the Connections: Study Links Brain’s Wiring to Human Traits

The Human Connectome

Caption: The wiring diagram of a human brain, measured in a healthy individual, where the movement of water molecules is measured by diffuse tensor magnetic resonance imaging, revealing the connections. This is an example of the type of work being done by the Human Connectome Project.
Source: Courtesy of the Laboratory of Neuro Imaging and Martinos Center for Biomedical Imaging, Consortium of the Human Connectome Project

For questions about why people often think, act, and perceive the world so differently, the brain is clearly an obvious place to look for answers. However, because the human brain is packed with tens of billions of neurons, which together make trillions of connections, knowing exactly where and how to look remains profoundly challenging.

Undaunted by these complexities, researchers involved in the NIH-funded Human Connectome Project (HCP) have been making progress, as shown by some intriguing recent discoveries. In a study published in Nature Neuroscience [1], an HCP team found that the brains of individuals with “positive” traits—such as strong cognitive skills and a healthy sense of well-being—show stronger connectivity in certain areas of the brain than do those with more “negative” traits—such as tendencies toward anger, rule-breaking, and substance use. While these findings are preliminary, they suggest it may be possible one day to understand, and perhaps even modify, the connections within the brain that are associated with human behavior in all its diversity.

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If I Only Had a Brain? Tissue Chips Predict Neurotoxicity

Image of neurons, glial cells, and nuclei

Caption: 3D neural tissue chips contain neurons (green), glial cells (red), and nuclei (blue). To take this confocal micrograph, developing neural tissue was removed from a chip and placed on a glass-bottom Petri dish.
Credit: Michael Schwartz, Dept.  of Bioengineering, University of Wisconsin-Madison

A lot of time, money, and effort are devoted to developing new drugs. Yet only one of every 10 drug candidates entering human clinical trials successfully goes on to receive approval from the Food and Drug Administration (FDA) [1]. Many would-be drugs fall by the wayside because they prove toxic to the brain, liver, kidneys, or other organs—toxicity that, unfortunately, isn’t always detected in preclinical studies using mice, rats, or other animal models. That explains why scientists are working so hard to devise technologies that can do a better job of predicting early on which chemical compounds will be safe in humans.

As an important step in this direction, NIH-funded researchers at the Morgridge Institute for Research and University of Wisconsin-Madison have produced neural tissue chips with many features of a developing human brain. Each cultured 3D “organoid”—which sits comfortably in the bottom of a pea-sized well on a standard laboratory plate—comes complete with its very own neurons, support cells, blood vessels, and immune cells! As described in Proceedings of the National Academy of Sciences [2], this new tool is poised to predict earlier, faster, and less expensively which new or untested compounds—be they drug candidates or even ingredients in cosmetics and pesticides—might harm the brain, particularly at the earliest stages of development.

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Mice Learn Better with Help from Human Brain Cells

Photo image of human astrocytes

Human astrocytes in a mouse brain
Source: Steven Goldman, M.D., Ph.D., University of Rochester Medical Center

What happens when you implant human glia—a type of brain cell that protects and nurtures neurons—into the brains of newborn mice? Well, it turns out these glia mature into multi-talented astrocyte cells that provide nutrients, repair injuries, and modulate signals just like they do in a human brain. They even assume the same complex star shape!

We know the cells in question are indeed human astrocytes because they produce a group of specific proteins, which are tagged with a combination of dyes that together appear yellow in this image. In contrast, the mouse cells are blue.

This all looks very pretty, but you might wonder what impact these human astrocytes have on mouse cognition. Researchers found mice that received the implants were better able to learn and remember than those that didn’t. In short, the human cells seem to have made the mice smarter.

Interestingly, human astrocytes are larger, more complex, and more diverse than their counterparts in other species. So, perhaps these cells may hold some of the keys to our own unique cognitive abilities.

Reference:

Forebrain Engraftment
by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice. Xiaoning Han, Michael Chen, Fushun Wang, Martha Windrem, Su Wang, Steven Shanz, Qiwu Xu, Nancy Ann Oberheim, Lane Bekar,  Sarah Betstadt,  Alcino J. Silva, Takahiro Takano, Steven A. Goldman, and Maiken Nedergaard. Cell Stem Cell 12, 342–353, March 7, 2013.

NIH support: the National Institute of Mental Health; and the National Institute of Neurological Disorders and Stroke