Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium
Authors: Kong Xiang-Zhen , Mathias Samuel R. , Guadalupe Tulio , Abé Christoph , Agartz Ingrid , Akudjedu Theophilus N. , Andre Aleman , Saud Alhusaini , Allen Nicholas B. , Ames David , Andreassen Ole A. , Arias Vasquez Alejandro , Armstrong Nicola J. , Bergo Felipe , Bastin Mark E. , Batalla Albert , Bauer Jochen , Baune Bernhard T , Baur Ramona , Biederman Joseph , Blaine Sara K. , Boedhoe Premika , Bøen Erlend , Bose Anushree , Bralten Janita , Brandeis Daniel , Brem Silvia , Brodaty Henry , Bröhl Henrieke , Brooks Samantha J. , Buitelaar Jan , Bürger Christian , Bülow Robin , Calhoun Vince , Calvo Anna , Canales-Rodríguez Erick Jorge , Canive Jose M. , Cannon Dara M. , Caparelli Elisabeth C. , Castellanos Francisco X. , Cavalleri Gianpiero L. , Cendes Fernando , Chaim-Avancini Tiffany Moukbel , Chantiluke Kaylita , Chen Qun-lin , Chen Xiayu , Cheng Yuqi , Christakou Anastasia , Clark Vincent P. , Coghill David , Connolly Colm G. , Conzelmann Annette , Cόrdova-Palomera Aldo , Cousijn Janna , Crow Tim , Cubillo Ana , Dannlowski Udo , de Bruttopilo Sara Ambrosino , Zeeuw Patrick de , Deary Ian J. , Delanty Norman , Demeter Damion V. , Martino Adriana Di , Dickie Erin W , Dietsche Bruno , Doan N. Trung , Doherty Colin P. , Doyle Alysa , Durston Sarah , Earl Eric , Ehrlich Stefan , Ekman Carl Johan , Elvsåshagen Torbjørn , Epstein Jeffery N. , Fair Damien A. , Faraone Stephen , Fatouros-Bergman Helena , Fernndez Guillen , Busatto Filho Geraldo , Flyckt Lena , Forster Katharina , Jean-Paul Fouche , Foxe John J. , Fuentes-Claramonte Paola , Fullerton Janice , Garavan Hugh , Garcia Danielle do Santos , Gotlib Ian H. , Goudriaan Anna E. , Jorgen Grabe Hans , Groenewold Nynke A. , Grotegerd Dominik , Gruber Oliver , Gurholt Tiril , Haavik Jan , Hahn Tim , Hansell Narelle K. , Harris Mathew A. , Hartman Catharina , Hernandez Maria del Carmen Valdes , Heslenfeld Dirk , Hester Robert , Hibar Derrek Paul , Ho Beng-Choon , Ho Tiffany C. , Hoekstra Pieter J. , van Holst Ruth J. , Hoogman Martine , Hovik Marie F. , Howells Fleur M. , Hugdahl Kenneth , Huyser Chaim , Ingvar Martind , Irwin Lourdes , Ishikawa Akari , James Anthony , Jahanshad Neda , Jernigan Terry L. , Jonsson Erik G , Kahler Claas , Kaleda Vasily , Kelly Clare , Kerich Michael , Keshavan Matcheri S , Khadka Sabin , Kircher Tilo , Kohls Gregor , Konrad Kerstin , Korucuoglu Ozlem , Kramer Bernd , Krug Axel , Kwon Jun Soo , Lambregts-Rommelse Nanda , Landen Mikael , Lazaro Luisa , Lebedeva Irina , Lenroot Rhoshel , Lesch Klaus-Peter , Li Qinqin , Lim Kelvin O. , Liu Jia , Lochner Christine , London Edythe D. , Lonning Vera , Lorenzetti Valentina , Luciano Michelle , Luijten Maartje , Lundervold Astri J. , Mackey Scott , MacMaster Frank P. , Maingault Sophie , Malpas Charles B. , Malt Ulrik F. , Mataix-Cols David , Martin-Santos Rocio , Mayer Andrew R. , McCarthy Hazel , Mitchell Philip B. , Mueller Bryon A. , Maniega Susana Munoz , Mazoyer Bernard , McDonald Colm , McLellan Quinn , McMahon Katie L. , McPhilemy Genevieve , Momenan Reza , Morales Angelica M. , Narayanaswamy Janardhanan C. , Moreira Jose Carlos Vasques , Nerland Stener , Nestor Liam , Nigg Joel T. , Nordvik Jan-Egil , Novotny Stephanie , Oberwelland Eileen , O'Gorman Ruth L. , Oosterlaan Jaap , Oranje Bob , Orr Catherine , Overs Bronwyn , Pauli Paul , Paulus Martin , Plessen Kerstin , von Polier Georg G. , Pomarol-Clotet Edith , Qiu Jiang , Radua Joaquim , Ramos-Quiroga Josep Antoni , Reddy Y.C. Janardhan , Reif Andreas , Roberts Gloria , Rosa Pedro , Rubia Katya , Sacchet Matthew D. , Sachdev Perminder S. , Salvador Raymond , Schmaal Lianne , Schweren Lisanne , Seidman Larry , Seitz Jochen , Serpa Mauricio Henriques , Shaw Philip , Shumskaya Elena , Silk Timothy J. , Simmons Alan N. , Simulionyte Egle , Sinha Rajita , Sjoerds Zsuzsika , Smelror Runar Elle , Soliva Joan Carlos , Solowij Nadia , Sponheim Scott R. , Stein Dan J. , Stein Elliot A. , Stevens Michael , Strike Lachlan T. , Sudre Gustavo , Sui Jing , Tamm Leanne , Temmingh Hendrik S. , Thoma Robert J. , Tomyshev Alexander , Tronchin Giulia , Turner Jessica , Uhlmann Anne , van Erp Theo G.M. , van den Heuvel Odile , van der Meer Dennis , van Eijk Liza , Vance Alasdair , Veer Ilya M. , Veltman Dick J. , Venkatasubramanian Ganesan , Vilarroya Oscar , Vives-Gilabert Yolanda , Voineskos Aristotle N. , Volzke Henry , Vuletic Daniella , Walitza Susanne , Walter Henrik , Walton Esther , Wardlaw Joanna M. , Wen Wei , Westlye Lars T. , Whelan Christopher D. , White Tonya , Wiers Reinout W. , Wright Margaret J. , Wittfeld Katharina , Yang Tony T. , Yasuda Clarissa L. , Yoncheva Yuliya , Yucel Murat , Yun Je-Yeon , Zanetti Marcus Vinicius , Zhen Zonglei , Zhu Xing-xing , Ziegler Georg C. , Zierhut Kathrin , de Zubicaray Greig I. , Zwiers Marcel ,   Karolinska Schizophrenia Project KaSP, Glahn David C. , Franke Barbara , Crivello Fabrice , Tzourio-Mazoyer Nathalie , Fisher Simon E. , Thompson Paul M. , Francks Clyde , Farde Lars , Engberg Goran , Erhardt Sophie , Cervenka Simon , Schwieler Lilly , Piehl Fredrik , Collste Karin , Victorsson Pauliina , Malmqvist Anna , Hedberg Mikael , Orhan Funda 
Published: October 2017

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N= 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

Significance Statement

Left-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.