title: Is bigger always better? The importance of cortical configuration with respect to cognitive ability.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA; Department of Public Health, and Institute for Molecular Medicine (FIMM), University of Helsinki, Helsinki, Finland. Electronic address: eero.vuoksimaa@helsinki.fi.
authors.forename: Eero
authors.initials: E
authors.lastname: Vuoksimaa
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA; Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Chi-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Fiecas
authors.affiliation: Mental Illness Research Education and Clinical Center, VA San Diego Healthcare System, San Diego, CA, USA; Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Jak
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, MA 02215, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA 23220, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA; Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles, CA, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Rinker
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Wesley K
authors.initials: WK
authors.lastname: Thompson
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.affiliation: Department of Radiology, University of California, San Diego, La Jolla, CA 92093, USA; Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA; Center for Behavioral Genomics Twin Research Laboratory, University of California, San Diego, La Jolla, CA 92093, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, La Jolla, CA 92093, USA. Electronic address: wkremen@ucsd.edu.
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D001931:Brain Mapping; D002540:Cerebral Cortex / Q000033:anatomy & histology*; D003071:Cognition / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007360:Intelligence / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D014427:Twins
keywords: Cortical surface area; Cortical thickness; General cognitive ability; Neurodevelopment; Twin research
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