The biology of variation in anatomical brain asymmetries Proefschrift ter verkrijging van de graad van doctor aan de Radboud Universiteit Nijmegen op gezag van de rector magnificus prof. dr. J.H.J.M. van Krieken, volgens besluit van het college van decanen in het openbaar te verdedigen op donderdag 2 februari 2017 om 12.30 uur precies door Tulio Manuel Guadalupe Estrada geboren op 3 november 1982 te Moskou (Rusland) 1 507449-L-bw-Guadalupe Processed on: 11-1-2017 Promotor: Prof. dr. S.E. Fisher Copromotor: Dr. C. Francks (MPI) Manuscriptcommissie: Prof. dr. C.F. Beckmann Prof. dr. K.E. Watkins (University of Oxford, Verenigd Koninkrijk) Dr. S. Ocklenburg (Ruhr-Universität Bochum, Duitsland) 2 507449-L-bw-Guadalupe Processed on: 11-1-2017 The biology of variation in anatomical brain asymmetries Doctoral Thesis to obtain the degree of doctor from Radboud University Nijmegen on the authority of the Rector Magnificus prof. dr. J.H.J.M. van Krieken, according to the decision of the Council of Deans to be defended in public on Thursday, February 2, 2017 at 12.30 hours by Tulio Manuel Guadalupe Estrada Born on November 3, 1982 in Moscow (Russia) 3 507449-L-bw-Guadalupe Processed on: 11-1-2017 Supervisor: Prof. dr. S.E. Fisher Co-supervisor: Dr. C. Francks (MPI) Doctoral Thesis Committee: Prof. dr. C.F. Beckmann Prof. dr. K.E. Watkins (University of Oxford, United Kingdom) Dr. S. Ocklenburg (Ruhr-Universität Bochum, Germany) 4 507449-L-bw-Guadalupe Processed on: 11-1-2017 Table of Contents General introduction ..................................................................................................................................... 9 Asymmetries of human brain anatomy .................................................................................................. 10 Individual differences in brain asymmetry ............................................................................................. 11 Genetics of brain asymmetries ............................................................................................................... 14 Altered anatomical brain asymmetries and cognitive functions ............................................................ 16 Identifying biological factors related to anatomical brain asymmetries ................................................ 17 Summary of research chapters ............................................................................................................... 19 Differences in cerebral cortical anatomy of left- and right-handers .......................................................... 23 Abstract ................................................................................................................................................... 24 Introduction ............................................................................................................................................ 25 Methods .................................................................................................................................................. 27 Study dataset ...................................................................................................................................... 27 Image acquisition ................................................................................................................................ 28 Image processing ................................................................................................................................ 28 Cortical correlates of handedness ...................................................................................................... 29 Power analysis .................................................................................................................................... 29 Results ..................................................................................................................................................... 30 Discussion................................................................................................................................................ 33 Acknowledgements ................................................................................................................................. 36 Appendix ................................................................................................................................................. 37 Supplementary material ......................................................................................................................... 37 Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity ................................................................................. 49 Abstract ................................................................................................................................................... 50 Introduction ............................................................................................................................................ 51 Methods .................................................................................................................................................. 53 Study datasets ..................................................................................................................................... 53 Image acquisition ................................................................................................................................ 53 Image processing ................................................................................................................................ 54 Parcellation of cortical regions ........................................................................................................... 55 Regional asymmetry mapping by sex ................................................................................................. 56 5 507449-L-bw-Guadalupe Processed on: 11-1-2017 Total brain volume and asymmetry in the PT region .......................................................................... 56 Genotyping .......................................................................................................................................... 56 Genome-wide association scans ......................................................................................................... 57 Genome-wide association scan meta-analysis ................................................................................... 57 GWAS candidate pathway enrichment analysis ................................................................................. 58 Meta-VBM analysis of the rs785248 polymorphism .......................................................................... 59 Results ..................................................................................................................................................... 59 Sex and cerebral cortical asymmetry .................................................................................................. 59 Cortical parcellation with FreeSurfer .................................................................................................. 60 Total brain volume and PT asymmetry ............................................................................................... 62 Genetic analysis .................................................................................................................................. 64 Meta-VBM analysis of rs785248 ......................................................................................................... 66 Discussion................................................................................................................................................ 68 Asymmetry of the planum temporale is sexually dimorphic .............................................................. 68 HO probability map measures individual differences in PT regional asymmetry ............................... 69 Genes involved in steroid hormone biology influence population variance in PT asymmetry .......... 71 Additional sexually dimorphic cerebral asymmetries ......................................................................... 73 Acknowledgements ................................................................................................................................. 73 Appendix ................................................................................................................................................. 75 Supplementary material ..................................................................................................................... 75 Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets ....... 83 Abstract ................................................................................................................................................... 84 Introduction ............................................................................................................................................ 85 Methods .................................................................................................................................................. 87 Participant populations ....................................................................................................................... 87 Image acquisition ...............................................................................................................................