Brain pathology recapitulates physiology: A network meta-analysis

Commun Biol. 2021 Mar 8;4(1):301. doi: 10.1038/s42003-021-01832-9.


Network architecture is a brain-organizational motif present across spatial scales from cell assemblies to distributed systems. Structural pathology in some neurodegenerative disorders selectively afflicts a subset of functional networks, motivating the network degeneration hypothesis (NDH). Recent evidence suggests that structural pathology recapitulating physiology may be a general property of neuropsychiatric disorders. To test this possibility, we compared functional and structural network meta-analyses drawing upon the BrainMap database. The functional meta-analysis included results from >7,000 experiments of subjects performing >100 task paradigms; the structural meta-analysis included >2,000 experiments of patients with >40 brain disorders. Structure-function network concordance was high: 68% of networks matched (pFWE < 0.01), confirming the broader scope of NDH. This correspondence persisted across higher model orders. A positive linear association between disease and behavioral entropy (p = 0.0006;R2 = 0.53) suggests nodal stress as a common mechanism. Corroborating this interpretation with independent data, we show that metabolic 'cost' significantly differs along this transdiagnostic/multimodal gradient.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / pathology*
  • Brain / physiopathology*
  • Brain Mapping
  • Case-Control Studies
  • Humans
  • Mental Disorders / diagnostic imaging
  • Mental Disorders / metabolism
  • Mental Disorders / pathology*
  • Mental Disorders / physiopathology*
  • Nerve Degeneration*
  • Nerve Net / pathology
  • Nerve Net / physiopathology
  • Network Meta-Analysis
  • Neurodegenerative Diseases / diagnostic imaging
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neurodegenerative Diseases / physiopathology*