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01-01-2018 | Original Article

A large-scale study on the effects of sex on gray matter asymmetry

Authors: Christian Núñez, Constantina Theofanopoulou, Carl Senior, Maria Rosa Cambra, Judith Usall, Christian Stephan-Otto, Gildas Brébion

Published in: Brain Structure and Function | Issue 1/2018

Abstract

Research on sex-related brain asymmetries has not yielded consistent results. Despite its importance to further understanding of normal brain development and mental disorders, the field remains relatively unexplored. Here we employ a recently developed asymmetry measure, based on the Dice coefficient, to detect sex-related gray matter asymmetries in a sample of 457 healthy participants (266 men and 191 women) obtained from 5 independent databases. Results show that women’s brains are more globally symmetric than men’s (p < 0.001). Although the new measure accounts for asymmetries distributed all over the brain, several specific structures were identified as systematically more symmetric in women, such as the thalamus and the cerebellum, among other structures, some of which are typically involved in language production. These sex-related asymmetry differences may be defined at the neurodevelopmental stage and could be associated with functional and cognitive sex differences, as well as with proneness to develop a mental disorder.

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Biduła SP, Króliczak G (2015) Structural asymmetry of the insula is linked to the lateralization of gesture and language. Eur J Neurosci 41:1438–1447. doi:10.1111/ejn.12888 CrossRefPubMedPubMedCentral

Çetin MS, Christensen F, Abbott CC, Stephen JM, Mayer AR, Cańive JM, Bustillo JR, Pearlson GD, Calhoun VD (2014) Thalamus and posterior temporal lobe show greater inter-network connectivity at rest and across sensory paradigms in schizophrenia. Neuroimage 97:117–126. doi:10.1016/j.neuroimage.2014.04.009 CrossRefPubMedPubMedCentral

Clarke GM (1998) The genetic basis of developmental stability. IV. Individual and population asymmetry parameters. Heredity 80:553–561. doi:10.1046/j.1365-2540.1998.00326.x CrossRef

Corballis MC (2009) The evolution and genetics of cerebral asymmetry. Philos Trans R Soc Lond B Biol Sci 364:867–879. doi:10.1098/rstb.2008.0232 CrossRefPubMed

Dice LR (1945) Measures of the amount of ecologic association between species. Ecology 26:297–302. doi:10.2307/1932409 CrossRef

D’Mello AM, Moore DM, Crocetti D, Mostofsky SH, Stoodley CJ (2016) Cerebellar gray matter differentiates children with early language delay in autism. Autism Res 9:1191–1204. doi:10.1002/aur.1622 CrossRefPubMed

Fan L, Tang Y, Sun B, Gong G, Chen ZJ, Lin X, Yu T, Li Z, Evans AC, Liu S (2010) Sexual dimorphism and asymmetry in human cerebellum: an MRI-based morphometric study. Brain Res 1353:60–73. doi:10.1016/j.brainres.2010.07.031 CrossRefPubMed

Filová B, Ostatníková D, Celec P, Hodosy J (2013) The effect of testosterone on the formation of brain structures. Cells Tissues Organs 197:169–177. doi:10.1159/000345567 CrossRefPubMed

Frings L, Wagner K, Unterrainer J, Spreer J, Halsband U, Schulze-Bonhage A (2006) Gender-related differences in lateralization of hippocampal activation and cognitive strategy. Neuroreport 17:417–421. doi:10.1097/01.wnr.0000203623.02082.e3 CrossRefPubMed

Gollub RL, Shoemaker JM, King MD, White T, Ehrlich S, Sponheim SR, Clark VP, Turner JA, Mueller BA, Magnotta V, O’Leary D, Ho BC, Brauns S, Manoach DS, Seidman L, Bustillo JR, Lauriello J, Bockholt J, Lim KO, Rosen BR, Schulz SC, Calhoun VD, Andreasen NC (2013) The MCIC collection: a shared repository of multi-modal, multi-site brain image data from a clinical investigation of schizophrenia. Neuroinformatics 11:367–388. doi:10.1007/s12021-013-9184-3 CrossRefPubMedPubMedCentral

Good CD, Johnsrude I, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14:685–700. doi:10.1006/nimg.2001.0857 CrossRefPubMed

Gorgolewski KJ, Varoquaux G, Rivera G, Schwarz Y, Ghosh SS, Maumet C, Sochat VV, Nichols TE, Poldrack RA, Poline JB, Yarkoni T, Margulies DS (2015) NeuroVault.org: a web-based repository for collecting and sharing unthresholded statistical maps of the human brain. Front Neuroinform 9:8. doi:10.3389/fninf.2015.00008 CrossRefPubMedPubMedCentral

Gotts SJ, Jo HJ, Wallace GL, Saad ZS, Cox RW, Martin A (2013) Two distinct forms of functional lateralization in the human brain. Proc Natl Acad Sci USA 110:E3435–E3444. doi:10.1073/pnas.1302581110 CrossRefPubMedPubMedCentral

Guadalupe T, Zwiers MP, Wittfeld K, Teumer A, Vasquez AA, Hoogman M, Hagoort P, Fernandez G, Buitelaar J, van Bokhoven H, Hegenscheid K, Völzke H, Franke B, Fisher SE, Grabe HJ, Francks C (2015) Asymmetry within and around the human planum temporale is sexually dimorphic and influenced by genes involved in steroid hormone receptor activity. Cortex 62:41–55. doi:10.1016/j.cortex.2014.07.015 CrossRefPubMed

Guadalupe T, Mathias SR, vanErp TG, Whelan CD, Zwiers MP, Abe Y, Abramovic L, Agartz I, Andreassen OA, Arias-Vásquez A, Aribisala BS, Armstrong NJ, Arolt V, Artiges E, Ayesa-Arriola R, Baboyan VG, Banaschewski T, Barker G et al (2016) Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex. Brain Imaging Behav. doi:10.1007/s11682-016-9629-z (in press) PubMedCentral

Haier RJ, Jung RE, Yeo RA, Head K, Alkire MT (2004) Structural brain variation and general intelligence. Neuroimage 23:425–433. doi:10.1016/j.neuroimage.2004.04.025 CrossRefPubMed

Kang X, Herron TJ, Ettlinger M, Woods DL (2015) Hemispheric asymmetries in cortical and subcortical anatomy. Laterality 20:658–684. doi:10.1080/1357650X.2015.1032975 CrossRefPubMed

Karlebach G, Francks C (2015) Lateralization of gene expression in human language cortex. Cortex 67:30–36. doi:10.1016/j.cortex.2015.03.003 CrossRefPubMed

Kovalev VA, Kruggel F, von Cramon DY (2003) Gender and age effects in structural brain asymmetry as measured by MRI texture analysis. Neuroimage 19:895–905. doi:10.1016/S1053-8119(03)00140-X CrossRefPubMed

Kurth F, Gaser C, Luders E (2015) A 12-step user guide for analyzing voxel-wise gray matter asymmetries in statistical parametric mapping (SPM). Nat Protoc 10:293–304. doi:10.1038/nprot.2015.014 CrossRefPubMed

Mazure CM, Swendsen J (2016) Sex differences in Alzheimer’s disease and other dementias. Lancet Neurol 15:451–452. doi:10.1016/S1474-4422(16)00067-3 CrossRefPubMedPubMedCentral

McCarthy MM, Arnold AP, Ball GF, Blaustein JD, De Vries GJ (2012) Sex differences in the brain: the not so inconvenient truth. J Neurosci 32:2241–2247. doi:10.1523/jneurosci.5372-11.2012 CrossRefPubMedPubMedCentral

Mendrek A (2015) Is it important to consider sex and gender in neurocognitive studies? Front Psychiatry 6:83. doi:10.3389/fpsyt.2015.00083 CrossRefPubMedPubMedCentral

Muntané G, Santpere G, Verendeev A, Seeley WW, Jacobs B, Hopkins WD, Navarro A, Sherwood CC (2017) Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys. Brain Struct Funct. doi:10.1007/s00429-017-1401-7 (in press)

Núñez C, Paipa N, Senior C, Coromina M, Siddi S, Ochoa S, Brébion G, Stephan-Otto C (2017) Global brain asymmetry is increased in schizophrenia and related to avolition. Acta Psychiatr Scand 135:448–459. doi:10.1111/acps.12723 CrossRefPubMed

Ocklenburg S, Friedrich P, Güntürkün O, Genç E (2016) Voxel-wise grey matter asymmetry analysis in left- and right-handers. Neurosci Lett 633:210–214. doi:10.1016/j.neulet.2016.09.046 CrossRefPubMed

Özener B (2010) Brief communication: facial fluctuating asymmetry as a marker of sex differences of the response to phenotypic stresses. Am J Phys Anthropol 143:321–324. doi:10.1002/ajpa.21357 CrossRefPubMed

Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N (2014) Temporal specification and bilaterality of human neocortical topographic gene expression. Neuron 81:321–332. doi:10.1016/j.neuron.2013.11.018 CrossRefPubMed

Proverbio AM, Brignone V, Matarazzo S, Del Zotto M, Zani A (2006) Gender differences in hemispheric asymmetry for face processing. BMC Neurosci 7:44. doi:10.1186/1471-2202-7-44 CrossRefPubMedPubMedCentral

Pujol J, López A, Deus J, Cardoner N, Vallejo J, Capdevila A, Paus T (2002) Anatomical variability of the anterior cingulate gyrus and basic dimensions of human personality. Neuroimage 15:847–855. doi:10.1006/nimg.2001.1004 CrossRefPubMed

Ramnani N (2006) The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 7:511–522. doi:10.1038/nrn1953 CrossRefPubMed

Repovs G, Csernansky JG, Barch DM (2011) Brain network connectivity in individuals with schizophrenia and their siblings. Biol Psychiatry 69:967–973. doi:10.1016/j.biopsych.2010.11.009 CrossRefPubMed

Rippon G, Jordan-Young R, Kaiser A, Fine C (2014) Recommendations for sex/gender neuroimaging research: key principles and implications for research design, analysis, and interpretation. Front Hum Neurosci 8:650. doi:10.3389/fnhum.2014.00650 CrossRefPubMedPubMedCentral

Savic I (2014) Asymmetry of cerebral gray and white matter and structural volumes in relation to sex hormones and chromosomes. Front Neurosci 8:329. doi:10.3389/fnins.2014.00329 CrossRefPubMedPubMedCentral

Simmons LW, Rhodes G, Peters M, Koehler N (2004) Are human preferences for facial symmetry focused on signals of developmental instability? Behav Ecol 15:864–871. doi:10.1093/beheco/arh099 CrossRef

Stoodley CJ, Schmahmann JD (2010) Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 46:831–844. doi:10.1016/j.cortex.2009.11.008 CrossRefPubMedPubMedCentral

Stoodley CJ, Valera EM, Schmahmann JD (2012) Functional topography of the cerebellum for motor and cognitive tasks: an fMRI study. Neuroimage 59:1560–1570. doi:10.1016/j.neuroimage.2011.08.065 CrossRefPubMed

Strick PL, Dum RP, Fiez JA (2009) Cerebellum and nonmotor function. Annu Rev Neurosci 32:413–434. doi:10.1146/annurev.neuro.31.060407.125606 CrossRefPubMed

Toga AW, Thompson PM (2003) Mapping brain asymmetry. Nat Rev Neurosci 4:37–48. doi:10.1038/nrn1009 CrossRefPubMed

Toga AW, Thompson PM, Sowell ER (2006) Mapping brain maturation. Trends Neurosci 29:148–159. doi:10.1016/j.tins.2006.01.007 CrossRefPubMedPubMedCentral

Vernooij MW, Smits M, Wielopolski PA, Houston GC, Krestin GP, van der Lugt A (2007) Fiber density asymmetry of the arcuate fasciculus in relation to functional hemispheric language lateralization in both right- and left-handed healthy subjects: a combined fMRI and DTI study. Neuroimage 35:1064–1076. doi:10.1016/j.neuroimage.2006.12.041 CrossRefPubMed

Wang D, Buckner RL, Liu H (2013) Cerebellar asymmetry and its relation to cerebral asymmetry estimated by intrinsic functional connectivity. J Neurophysiol 109:46–57. doi:10.1152/jn.00598.2012 CrossRefPubMed

Watkins KE, Paus T, Lerch JP, Zijdenbos A, Collins DL, Neelin P, Taylor J, Worsley KJ, Evans AC (2001) Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cereb Cortex 11:868–877. doi:10.1093/cercor/11.9.868 CrossRefPubMed

Yücel M, Stuart GW, Maruff P, Velakoulis D, Crowe SF, Savage G, Pantelis C (2001) Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study. Cereb Cortex 11:17–25. doi:10.1093/cercor/11.1.17 CrossRefPubMed

Title: A large-scale study on the effects of sex on gray matter asymmetry
Authors: Christian Núñez
Constantina Theofanopoulou
Carl Senior
Maria Rosa Cambra
Judith Usall
Christian Stephan-Otto
Gildas Brébion
Publication date: 01-01-2018
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 1/2018
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-017-1481-4

At a glance: The STEP trials

Springer Medicine

A large-scale study on the effects of sex on gray matter asymmetry

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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