New research suggests that neurodegenerative diseases are neither diffuse nor random but specifically target large-scale functional networks in the human brain. The study, published by Cell Press in the April 16 issue of the journal Neuron, may drive a new generation of network-based strategies for diagnosing and monitoring neurodegenerative diseases.
Brain imaging studies have revealed the architecture of intrinsic functional networks in the human brain. These networks involve multiple functionally related groups of neurons that exhibit spontaneous synchronous baseline activity during task-free conditions. Previous work has established that connectivity within these networks can influence task performance, but it has remained unclear how fluctuations in neural network activity are correlated with brain structure in health and disease.
"Although some studies suggested that Alzheimer's disease may attack a specific large-scale network, we hypothesized that all neurodegenerative diseases target a distinct signature network," says lead study author Dr. William W. Seeley from the University of California, San Francisco. "If demonstrated as a class-wide phenomenon, this network degeneration framework could have major mechanistic significance, predicting that spatial patterning of disease relates to some structural, metabolic, or physiological aspect of neural network biology."
To examine whether large-scale neural networks are targeted by disease in living humans, Dr. Seeley and colleagues used neuroimaging to study patients with five distinct neurodegenerative syndromes and two healthy control groups. The researchers found that each of the neurodegenerative syndromes featured a distinct regional vulnerability pattern within one of five specific healthy human intrinsic networks.
Additionally, the authors found a direct link between intrinsic connectivity and normal brain structure. In the healthy individuals, nodes within each functional network exhibited tightly correlated gray matter tissue volumes. "These results provide a new, structure-based window into network organization," says Dr. Seeley. "It appears that regions that fire together also grow (in health) or atrophy (in disease) together."
These results provide strong support for the network degeneration hypothesis. "Our findings show that functional and structural network mapping approaches yield robust, convergent, anatomically predictable networks, and that specific neurodegenerative diseases target these patterned brain systems," says Dr. Seeley. "Future studies may clarify how these complex systems are assembled during development and undermined by disease."
The researchers include William W. Seeley, University of California, San Francisco, San Francisco, CA; Richard K. Crawford, University of California, San Francisco, San Francisco, CA; Juan Zhou, University of California, San Francisco, San Francisco, CA; Bruce L. Miller, University of California, San Francisco, San Francisco, CA; and Michael D. Greicius, Stanford University School of Medicine, Stanford, CA.
Journal
Neuron