Busy brain hubs go awry in disorders, study suggests

Schizophrenia, Alzheimer’s and other diseases target connection centers

BRAIN DRAIN  Some of the brain’s most highly connected hubs (large spheres) may malfunction in brain disorders, a new study suggests. Yellow and red spheres are associated with disorders.

N.A. Crossley et al/Brain 2014

In the brain, a handful of bustling hubs routinely handle heavy volumes of messages. In many cases, these key transit centers and the brain areas affected by brain disorders are one and the same, scientist report June 19 in Brain.    

The results highlight the importance of studying connections between nerve cells as well as discrete brain regions, an approach that may reveal a deeper understanding of the human mind (SN: 2/22/14, p. 22), says Nicolas Crossley, a neuroscientist at King’s College London.

With message-sending fibrils called axons, nerve cells in the brain form a complex web of connections that scientists call the connectome. Some parts of this web, called hubs, are especially rich in axons, both coming in and going out.

Computer simulations have suggested that these hubs are mission critical. When certain hubs or their connections are damaged in the simulations, the results are catastrophic for the entire brain (SN Online: 2/17/14).

Crossley and colleagues wanted to know whether people with brain disorders might also show signs of damaged hubs. To find brain regions implicated in brain disorders, the researchers analyzed published data that included nearly 10,000 patients with 26 brain disorders including Alzheimer’s disease, depression, autism and schizophrenia. Crossley and colleagues then compared the regions associated with these disorders with a composite map of a healthy brain’s connections, which the team created from diffusion tensor imaging scans of 56 volunteers. Diffusion tensor imaging indicates the strength and shape of bundles of axons in the brain.

Overall, regions implicated in brain disorders were more likely to be highly connected hubs than to be sleepier, out-of-the-way brain regions, the researchers found. Disorders didn’t all affect the same set of hubs. The regions implicated in Alzheimer’s disease were distinct from the hubs implicated in schizophrenia, for instance.

Hubs may have an outsized role in brain disorders for any of several reasons, the authors propose. Because of their high work load, hubs may require more energy than other brain regions. They also have longer connections. These features may render hubs particularly susceptible to damage, the authors suggest. Alternatively, damage to a hub might cause more problems than damage elsewhere, resulting in brain impairment.

The new study has “direct relevance to our understanding of major brain disorders,” says neuroscientist John Van Horn of the University of Southern California in Los Angeles. The link between disorders and highly connected hubs may help explain why some brain injuries appear small but can have big consequences, while other injuries appear disastrous but prove relatively benign.

Still, Van Horn cautions that the dataset used to compile the brain areas associated with disorders may be skewed. The data are based on published results, and scientists are more likely to publish results that pinpoint a connection between a disorder and a brain area than results that fail to find one. That effect might overestimate the importance of certain brain regions, Van Horn says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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