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Neurodegenerative diseases target large-scale human brain networks.

ABSTRACT: During development, the healthy human brain constructs a host of large-scale, distributed, function-critical neural networks. Neurodegenerative diseases have been thought to target these systems, but this hypothesis has not been systematically tested in living humans. We used network-sensitive neuroimaging methods to show that five different neurodegenerative syndromes cause circumscribed atrophy within five distinct, healthy, human intrinsic functional connectivity networks. We further discovered a direct link between intrinsic connectivity and gray matter structure. Across healthy individuals, nodes within each functional network exhibited tightly correlated gray matter volumes. The findings suggest that human neural networks can be defined by synchronous baseline activity, a unified corticotrophic fate, and selective vulnerability to neurodegenerative illness. Future studies may clarify how these complex systems are assembled during development and undermined by disease.

SUBMITTER: Seeley WW

PROVIDER: S-EPMC2691647 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Neurodegenerative diseases target large-scale human brain networks.

Seeley William W WW Crawford Richard K RK Zhou Juan J Miller Bruce L BL Greicius Michael D MD

Neuron 20090401 1

During development, the healthy human brain constructs a host of large-scale, distributed, function-critical neural networks. Neurodegenerative diseases have been thought to target these systems, but this hypothesis has not been systematically tested in living humans. We used network-sensitive neuroimaging methods to show that five different neurodegenerative syndromes cause circumscribed atrophy within five distinct, healthy, human intrinsic functional connectivity networks. We further discover ...[more]

PMID: 19376066

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Project description:Fragile X syndrome (FXS) is an X-linked neurogenetic disorder characterized by a cognitive and behavioral phenotype resembling features of autism spectrum disorder. Until now, research has focused largely on identifying regional differences in brain structure and function between individuals with FXS and various control groups. Very little is known about the large-scale brain networks that may underlie the cognitive and behavioral symptoms of FXS.To identify large-scale, resting-state networks in FXS that differ from control individuals matched on age, IQ, and severity of behavioral and cognitive symptoms.Cross-sectional, in vivo neuroimaging study conducted in an academic medical center. Participants (aged 10-23 years) included 17 males and females with FXS and 16 males and females serving as controls.Univariate voxel-based morphometric analyses, fractional amplitude of low-frequency fluctuations (fALFF) analysis, and group-independent component analysis with dual regression.Patients with FXS showed decreased functional connectivity in the salience, precuneus, left executive control, language, and visuospatial networks compared with controls. Decreased fALFF in the bilateral insular, precuneus, and anterior cingulate cortices also was found in patients with FXS compared with control participants. Furthermore, fALFF in the left insular cortex was significantly positively correlated with IQ in patients with FXS. Decreased gray matter density, resting-state connectivity, and fALFF converged in the left insular cortex in patients with FXS.Fragile X syndrome results in widespread reductions in functional connectivity across multiple cognitive and affective brain networks. Converging structural and functional abnormalities in the left insular cortex, a region also implicated in individuals diagnosed with autism spectrum disorder, suggests that insula integrity and connectivity may be compromised in FXS. This method could prove useful in establishing an imaging biomarker for FXS.

Dataset Information

Neurodegenerative diseases target large-scale human brain networks.

Publications

Neurodegenerative diseases target large-scale human brain networks.

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