The spatial correspondence and genetic influence of interhemispheric connectivity with white matter microstructure

Nat Neurosci. 2019 May;22(5):809-819. doi: 10.1038/s41593-019-0379-2. Epub 2019 Apr 15.

Abstract

Microscopic features (that is, microstructure) of axons affect neural circuit activity through characteristics such as conduction speed. To what extent axonal microstructure in white matter relates to functional connectivity (synchrony) between brain regions is largely unknown. Using MRI data in 11,354 subjects, we constructed multivariate models that predict functional connectivity of pairs of brain regions from the microstructural signature of white matter pathways that connect them. Microstructure-derived models provided predictions of functional connectivity that explained 3.5% of cross-subject variance on average (ranging from 1-13%, or r = 0.1-0.36) and reached statistical significance in 90% of the brain regions considered. The microstructure-function relationships were associated with genetic variants, co-located with genes DAAM1 and LPAR1, that have previously been linked to neural development. Our results demonstrate that variation in white matter microstructure predicts a fraction of functional connectivity across individuals, and that this relationship is underpinned by genetic variability in certain brain areas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • Brain / anatomy & histology*
  • Brain / growth & development
  • Brain / physiology*
  • Brain Mapping
  • Female
  • Genome-Wide Association Study
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Microfilament Proteins
  • Middle Aged
  • Models, Neurological
  • Multivariate Analysis
  • Neural Pathways / anatomy & histology
  • Neural Pathways / physiology
  • Phenotype*
  • Receptors, Lysophosphatidic Acid / genetics
  • White Matter / anatomy & histology*
  • White Matter / physiology*
  • rho GTP-Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • DAAM1 protein, human
  • LPAR1 protein, human
  • Microfilament Proteins
  • Receptors, Lysophosphatidic Acid
  • rho GTP-Binding Proteins