Is bigger always better? The importance of cortical configuration with respect to cognitive ability

Eero Vuoksimaa, Matthew S. Panizzon, Chi Hua Chen, Mark Fiecas, Lisa T. Eyler, Christine Fennema-Notestine, Donald J. Hagler, Carol E. Franz, Amy J. Jak, Michael J. Lyons, Michael C. Neale, Daniel A. Rinker, Wesley K. Thompson, Ming T. Tsuang, Anders M. Dale, William S. Kremen

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


General cognitive ability (GCA) has substantial explanatory power for behavioral and health outcomes, but its cortical substrate is still not fully established. GCA is highly polygenic and research to date strongly suggests that its cortical substrate is highly polyregional. We show in map-based and region-of-interest-based analyses of adult twins that a complex cortical configuration underlies GCA. Having relatively greater surface area in evolutionary and developmentally high-expanded prefrontal, lateral temporal, and inferior parietal regions is positively correlated with GCA, whereas relatively greater surface area in low-expanded occipital, medial temporal, and motor cortices is negatively correlated with GCA. Essentially the opposite pattern holds for relative cortical thickness. The phenotypic positive-to-negative gradients in our cortical-GCA association maps were largely driven by a similar pattern of genetic associations. The patterns are consistent with regional cortical stretching whereby relatively greater surface area is related to relatively thinner cortex in high-expanded regions. Thus, the typical "bigger is better" view does not adequately capture cortical-GCA associations. Rather, cognitive ability is influenced by complex configurations of cortical development patterns that are strongly influenced by genetic factors. Optimal cognitive ability appears to be driven both by the absolute size and the polyregional configuration of the entire cortex rather than by small, circumscribed regions.

Original languageEnglish (US)
Pages (from-to)356-366
Number of pages11
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
This work was supported by NIA grants R01 AG018386, AG022381, AG022982, AG050595 to WSK, R01 AG018384, AG050595 to MJL, K08 AG047903 to MSP, and R01 GM104400 to WKT, and Academy of Finland grant 257075 to EV, and resources of the VA San Diego Center of Excellence for Stress and Mental Health Healthcare System. The Cooperative Studies Program of the US Department of Veterans Affairs provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. NotesThe content is solely the responsibility of the authors and does not necessarily represent official views of the NIH or the VA. Numerous organizations provided invaluable assistance in the conduct of this study, including: Department of Defense; National Personnel Records Center, National Archives and Records Administration; the Internal Revenue Service; National Opinion Research Center; National Research Council, National Academy of Sciences; the Institute for Survey Research, and Temple University. We gratefully acknowledge the cooperation and participation of the members of the VET Registry and their families. Anders Dale is a founder and holds equity in CorTechs Laboratories and also serves on its Scientific Advisory Board. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. No other authors have any conflicts of interest to declare.


  • Cortical surface area
  • Cortical thickness
  • General cognitive ability
  • Neurodevelopment
  • Twin research

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