Comment; Interesting, how synapses seem to form, disassociate and re-form in other patterns that coincide with improving executive function; weighing pro’s and con’s of different courses of action.

Graham L. Baum, Zaixu Cui, David R. Roalf, Rastko Ciric, Richard F. Betzel, Bart Larsen, Matthew Cieslak, Philip A. Cook, Cedric H. Xia, Tyler M. Moore, Kosha Ruparel, Desmond J. Oathes,  View ORCID ProfileAaron F. Alexander-Bloch,  View ORCID ProfileRussell T. Shinohara, Armin Raznahan, Raquel E. Gur, Ruben C. Gur,  View ORCID ProfileDanielle S. Bassett, and  View ORCID ProfileTheodore D. SatterthwaitePNAS January 7, 2020 117 (1) 771-778; first published December 24, 2019

  1. Edited by Marcus E. Raichle, Washington University in St. Louis, St. Louis, MO, and approved November 27, 2019 (received for review July 12, 2019)


The human brain is organized into a hierarchy of functional systems that evolve in childhood and adolescence to support the dynamic control of attention and behavior. However, it remains unknown how developing white-matter architecture supports coordinated fluctuations in neural activity underlying cognition. We document marked remodeling of structure–function coupling in youth, which aligns with cortical hierarchies of functional specialization and evolutionary expansion. Further, we demonstrate that structure–function coupling in rostrolateral prefrontal cortex supports age-related improvements in executive ability. These findings have broad relevance for accounts of experience-dependent plasticity in healthy development and abnormal development associated with neuropsychiatric illness.


The protracted development of structural and functional brain connectivity within distributed association networks coincides with improvements in higher-order cognitive processes such as executive function. However, it remains unclear how white-matter architecture develops during youth to directly support coordinated neural activity. Here, we characterize the development of structure–function coupling using diffusion-weighted imaging and n-back functional MRI data in a sample of 727 individuals (ages 8 to 23 y). We found that spatial variability in structure–function coupling aligned with cortical hierarchies of functional specialization and evolutionary expansion. Furthermore, hierarchy-dependent age effects on structure–function coupling localized to transmodal cortex in both cross-sectional data and a subset of participants with longitudinal data (n = 294). Moreover, structure–function coupling in rostrolateral prefrontal cortex was associated with executive performance and partially mediated age-related improvements in executive function. Together, these findings delineate a critical dimension of adolescent brain development, whereby the coupling between structural and functional connectivity remodels to support functional specialization and cognition.


By quantifying regional patterns of structure–function coupling and characterizing their development during adolescence, our results inform network-level mechanisms of plasticity that support cognitive maturation. Describing how underlying white-matter architecture develops to support coordinated neural activity underlying executive function may offer critical insights into the basis for many sources of adolescent morbidity and mortality, such as risk taking and diverse neuropsychiatric syndromes which are prominently associated with failures of executive function.

Dr. Raymond Oenbrink