Neurodegenerative diseases target large-scale human brain networks

By William W. Seeley, Richard K. Crawford, Juan Zhou, Bruce L. Miller, Michael D. Greicius. Neuron, 2009

2,250 citations recorded by the source corpus.

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.

Subfields: Cognitive Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/64f9643cf5cefbce3cd9b4b950f57f2f1f37d844

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Citations in the corpus

Abnormal intrinsic brain functional network dynamics in Parkinson’s disease (2017, background): “Taken together, these observations seem to confirm the vulnerability of resting state networks in neurodegenerative conditions (Seeley et al., 2009; Zhou et al., 2012).”
A designer AAV variant permits efficient retrograde access to projection neurons (2016, background): “Projection neurons have also been impli- 372 Neuron 92, 372–382, October 19, 2016 ª 2016 Elsevier Inc. cated in the spread of several neurodegenerative diseases from spatially localized sites of onset (Guo and Lee, 2014; Seeley et al., 2009).”
Selective aberrant functional connectivity of resting state networks in social anxiety disorder (2010, background): “Resting state brain networks were often shown to present abnormalities in many neuropsychiatric disorders (Calhoun et al., 2008; 2009; Garrity et al., 2007; Greicius et al., 2004; 2007; Mohammadi et al., 2009; Seeley et al., 2009; Sorg et al., 2007).”
Multi-sensory gamma stimulation ameliorates Alzheimer’s-associated pathology and improves cognition. (2019, background): “However, AD affects multiple brain centers critical for learning and memory and other higher-order brain functions such as the hippocampus (HPC) and medial prefrontal cortex (mPFC) (Seeley et al., 2009; Sperling et al., 2010; Yamamoto et al., 2014; Spellman et al., 2015; Kim et al., 2016).”
Network centrality in the human functional connectome. (2012, background): “psychiatric disorders (Greicius 2008; Broyd et al. 2009; Seeley et al. 2009; Seeley 2010; Cole et al. 2011).”
Brain covariance selection: better individual functional connectivity models using population prior (2010, background): “Alzheimer’s disease–[7, 8], or in the study of brain lesions [9].”