Regional white matter scaling in the human brain

Allysa Warling, P. Cassidy L. McDermott, P. Siyuan Liu, Jakob Seidlitz, Amanda L. Rodrigue, Ajay Nadig, Ruben C. Gur, Raquel E. Gur, David Roalf, Tyler M. Moore, David Glahn, Theodore D. Satterthwaite, Edward T. Bullmore, Armin Raznahan

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Anatomical organization of the primate cortex varies as a function of total brain size, where possession of a larger brain is accompanied by disproportionate expansion of associative cortices alongside a relative contraction of sensorimotor systems. However, equivalent scaling maps are not yet available for regional white matter anatomy. Here, we use three large-scale neuroimaging datasets to examine how regional white matter volume (WMV) scales with interindividual variation in brain volume among typically developing humans (combined N= 2391: 1247 females, 1144 males). We show that WMV scaling is regionally heterogeneous: larger brains have relatively greater WMV in anterior and posterior regions of cortical white matter, as well as the genu and splenium of the corpus callosum, but relatively less WMV in most subcortical regions. Furthermore, regions of positive WMV scaling tend to connect previously- defined regions of positive gray matter scaling in the cortex, revealing a coordinated coupling of regional gray and white matter organization with naturally occurring variations in human brain size. However, we also show that two commonly studied measures of white matter microstructure, fractional anisotropy (FA) and magnetization transfer (MT), scale negatively with brain size, and do so in a manner that is spatially unlike WMV scaling. Collectively, these findings provide a more complete view of anatomic scaling in the human brain, and offer new contexts for the interpretation of regional white matter variation in health and disease.

Original languageEnglish
Pages (from-to)7015-7028
Number of pages14
JournalJournal of Neuroscience
Issue number33
StatePublished - 18 Aug 2021
Externally publishedYes


  • Neuroimaging
  • Scaling
  • White matter


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