Left-right asymmetry of the human brain is one of its cardinal features, and also a complex, multivariate trait. For example, language-related cerebral cortical regions and white matter tracts are well known to be structurally and functionally lateralized, with left-hemisphere dominance for language in the majority of people. Visuospatial cognition and hand motor control are also strongly lateralized. In addition, decades of research have suggested that brain asymmetry may be altered in psychiatric disorders. However, findings have been inconsistent and often based on small sample sizes.
In recent years, the ENIGMA-Laterality Working Group has published six studies of brain anatomical asymmetry based on total sample sizes of between roughly 3,500 and 17,000 individuals, which were between one and two orders of magnitude larger than those published in previous decades. In these studies we mapped brain anatomical asymmetry in healthy people, quantified the effects of age, sex and brain size on asymmetry, and also tested for changes of brain asymmetry in Autism Spectrum Disorder, Obsessive-Compulsive Disorder, and Major Depressive Disorder. ENIGMA’s multi-dataset approach supported an empirical illustration of reproducibility of hemispheric differences across datasets. We reported significant heritabilities of some measures of brain anatomical asymmetry, which sets a groundwork for molecular genetic studies. Please see below for links to our published papers.
On-going studies by the ENIGMA-Laterality group include analysis of brain anatomical changes in Attention Deficit/Hyperactivity Disorder, and in schizophrenia. If you are interested to join these and/or future efforts, please email Clyde Francks (clyde.francks@mpi.nl) at the Max Planck Institute, Nijmegen, The Netherlands, and Eileen Lueders (e.lueders@auckland.ac.nz) at the University of Auckland, New Zealand.
Papers from the ENIGMA-Laterality group:
Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium. Zhiqiang Sha, Daan van Rooij, Evdokia Anagnostou, Celso Arango, Guillaume Auzias, Marlene Behrmann, Boris Bernhardt, Sven Bolte, Geraldo F. Busatto, Sara Calderoni, Rosa Calvo, Eileen Daly, Christine Deruelle, Meiyu Duan, Fabio Luis Souza Duran, Sarah Durston, Christine Ecker, Stefan Ehrlich, Damien Fair, Jennifer Fedor, Jacqueline Fitzgerald, Dorothea L. Floris, Barbara Franke, Christine M. Freitag, Louise Gallagher, David C Glahn, Shlomi Haar, Liesbeth Hoekstra, Neda Jahanshad, Maria Jalbrzikowski, Joost Janssen, Joseph A. King, Luisa Lazaro, Beatriz Luna, Jane McGrath, Sarah E. Medland, Ciara Molloy, Filippo Muratori, Declan G.M. Murphy, Janina Neufeld, Kirsten O’Hearn, Bob Oranje, Mara Parellada, Jose C. Pariente, Merel C. Postema, Karl Lundin Remnelius, Alessandra Retico, Pedro Gomes Penteado Rosa, Katya Rubia, Devon Shook, Kristiina Tammimies, Margot J. Taylor, Michela Tosetti, Gregory L. Wallace, Fengfeng Zhou, Paul M. Thompson, Simon E. Fisher, Jan K. Buitelaar, Clyde Francks. (Preprint) bioRxiv 2021.05.05.442735.
Analysis of structural brain asymmetries in attention-deficit/hyperactivity disorder in 39 datasets. Postema MC, Hoogman M, Ambrosino S, Asherson P, Banaschewski T, Bandeira CE, Baranov A, Bau CHD, Baumeister S, Baur-Streubel R, Bellgrove MA, Biederman J, Bralten J, Brandeis D, Brem S, Buitelaar JK, Busatto GF, Castellanos FX, Cercignani M, Chaim-Avancini TM, Chantiluke KC, Christakou A, Coghill D, Conzelmann A, Cubillo AI, Cupertino RB, de Zeeuw P, Doyle AE, Durston S, Earl EA, Epstein JN, Ethofer T, Fair DA, Fallgatter AJ, Faraone SV, Frodl T, Gabel MC, Gogberashvili T, Grevet EH, Haavik J, Harrison NA, Hartman CA, Heslenfeld DJ, Hoekstra PJ, Hohmann S, Høvik MF, Jernigan TL, Kardatzki B, Karkashadze G, Kelly C, Kohls G, Konrad K, Kuntsi J, Lazaro L, Lera-Miguel S, Lesch KP, Louza MR, Lundervold AJ, Malpas CB, Mattos P, McCarthy H, Namazova-Baranova L, Nicolau R, Nigg JT, Novotny SE, Oberwelland Weiss E, O'Gorman Tuura RL, Oosterlaan J, Oranje B, Paloyelis Y, Pauli P, Picon FA, Plessen KJ, Ramos-Quiroga JA, Reif A, Reneman L, Rosa PGP, Rubia K, Schrantee A, Schweren LJS, Seitz J, Shaw P, Silk TJ, Skokauskas N, Soliva Vila JC, Stevens MC, Sudre G, Tamm L, Tovar-Moll F, van Erp TGM, Vance A, Vilarroya O, Vives-Gilabert Y, von Polier GG, Walitza S, Yoncheva YN, Zanetti MV, Ziegler GC, Glahn DC, Jahanshad N, Medland SE; ENIGMA ADHD Working Group, Thompson PM, Fisher SE, Franke B, Francks C. J Child Psychol Psychiatry. 2021 Oct;62(10):1202-1219. doi: 10.1111/jcpp.13396. Epub 2021 Mar 22. PMID: 33748971; PMCID: PMC8455726.
Reproducibility in the absence of selective reporting: An illustration from large-scale brain asymmetry research. Kong XZ; ENIGMA Laterality Working Group, Francks C. Hum Brain Mapp. 2020 Aug 25. doi: 10.1002/hbm.25154. Epub ahead of print. PMID: 32841457.
Mapping brain asymmetry in health and disease through the ENIGMA consortium. Kong XZ, Postema MC, Guadalupe T, de Kovel C, Boedhoe PSW, Hoogman M, Mathias SR, van Rooij D, Schijven D, Glahn DC, Medland SE, Jahanshad N, Thomopoulos SI, Turner JA, Buitelaar J, van Erp TGM, Franke B, Fisher SE, van den Heuvel OA, Schmaal L, Thompson PM, Francks C. Hum Brain Mapp. 2020 May 18. doi: 10.1002/hbm.25033. Epub ahead of print. PMID: 32420672.
Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets. Postema MC, van Rooij D, Anagnostou E, Arango C, Auzias G, Behrmann M, Filho GB, Calderoni S, Calvo R, Daly E, Deruelle C, Di Martino A, Dinstein I, Duran FLS, Durston S, Ecker C, Ehrlich S, Fair D, Fedor J, Feng X, Fitzgerald J, Floris DL, Freitag CM, Gallagher L, Glahn DC, Gori I, Haar S, Hoekstra L, Jahanshad N, Jalbrzikowski M, Janssen J, King JA, Kong XZ, Lazaro L, Lerch JP, Luna B, Martinho MM, McGrath J, Medland SE, Muratori F, Murphy CM, Murphy DGM, O'Hearn K, Oranje B, Parellada M, Puig O, Retico A, Rosa P, Rubia K, Shook D, Taylor MJ, Tosetti M, Wallace GL, Zhou F, Thompson PM, Fisher SE, Buitelaar JK, Francks C. Nat Commun. 2019 Oct 31;10(1):4958. doi: 10.1038/s41467-019-13005-8
No Alterations of Brain Structural Asymmetry in Major Depressive Disorder: An ENIGMA Consortium Analysis. de Kovel CGF, Aftanas L, Aleman A, Alexander-Bloch AF, Baune BT, Brack I, Bülow R, Busatto Filho G, Carballedo A, Connolly CG, Cullen KR, Dannlowski U, Davey CG, Dima D, Dohm K, Erwin-Grabner T, Frodl T, Fu CHY, Hall GB, Glahn DC, Godlewska B, Gotlib IH, Goya-Maldonado R, Grabe HJ, Groenewold NA, Grotegerd D, Gruber O, Harris MA, Harrison BJ, Hatton SN, Hickie IB, Ho TC, Jahanshad N, Kircher T, Krämer B, Krug A, Lagopoulos J, Leehr EJ, Li M, MacMaster FP, MacQueen G, McIntosh AM, McLellan Q, Medland SE, Mueller BA, Nenadic I, Osipov E, Papmeyer M, Portella MJ, Reneman L, Rosa PGP, Sacchet MD, Schnell K, Schrantee A, Sim K, Simulionyte E, Sindermann L, Singh A, Stein DJ, Ubani BN, Van der Wee NJA, Van der Werff SJA, Veer IM, Vives-Gilabert Y, Völzke H, Walter H, Walter M, Schreiner MW, Whalley H, Winter N, Wittfeld K, Yang TT, Yüksel D, Zaremba D, Thompson PM, Veltman DJ, Schmaal L, Francks C. Am J Psychiatry. 2019 Dec 1;176(12):1039-1049. doi: 10.1176/appi.ajp.2019.18101144
Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium. Kong XZ, Boedhoe PSW, Abe Y, Alonso P, Ameis SH, Arnold PD, Assogna F, Baker JT, Batistuzzo MC, Benedetti F, Beucke JC, Bollettini I, Bose A, Brem S, Brennan BP, Buitelaar J, Calvo R, Cheng Y, Cho KIK, Dallaspezia S, Denys D, Ely BA, Feusner J, Fitzgerald KD, Fouche JP, Fridgeirsson EA, Glahn DC, Gruner P, Gürsel DA, Hauser TU, Hirano Y, Hoexter MQ, Hu H, Huyser C, James A, Jaspers-Fayer F, Kathmann N, Kaufmann C, Koch K, Kuno M, Kvale G, Kwon JS, Lazaro L, Liu Y, Lochner C, Marques P, Marsh R, Martínez-Zalacaín I, Mataix-Cols D, Medland SE, Menchón JM, Minuzzi L, Moreira PS, Morer A, Morgado P, Nakagawa A, Nakamae T, Nakao T, Narayanaswamy JC, Nurmi EL, O'Neill J, Pariente JC, Perriello C, Piacentini J, Piras F, Piras F, Pittenger C, Reddy YCJ, Rus-Oswald OG, Sakai Y, Sato JR, Schmaal L, Simpson HB, Soreni N, Soriano-Mas C, Spalletta G, Stern ER, Stevens MC, Stewart SE, Szeszko PR, Tolin DF, Tsuchiyagaito A, van Rooij D, van Wingen GA, Venkatasubramanian G, Wang Z, Yun JY; ENIGMA OCD Working Group, Thompson PM, Stein DJ, van den Heuvel OA, Francks C. Biol Psychiatry. 2019 Apr 30. pii: S0006-3223(19)31292-2. doi: 10.1016/j.biopsych.2019.04.022.
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium. Kong XZ, Mathias SR, Guadalupe T; ENIGMA Laterality Working Group, Glahn DC, Franke B, Crivello F, Tzourio-Mazoyer N, Fisher SE, Thompson PM, Francks C. Proc Natl Acad Sci U S A. 2018 May 29;115(22):E5154-E5163. doi: 10.1073/pnas.1718418115.
Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex. Guadalupe T, Mathias SR, vanErp TGM, 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, Bastin ME, Baune BT, Blangero J, Bokde ALW, Boedhoe PSW, Bose A, Brem S, Brodaty H, Bromberg U, Brooks S, Büchel C, Buitelaar J, Calhoun VD, Cannon DM, Cattrell A, Cheng Y, Conrod PJ, Conzelmann A, Corvin A, Crespo-Facorro B, Crivello F, Dannlowski U, de Zubicaray GI, de Zwarte SMC, Deary IJ, Desrivières S, Doan NT, Donohoe G, Dørum ES, Ehrlich S, Espeseth T, Fernández G, Flor H, Fouche JP, Frouin V, Fukunaga M, Gallinat J, Garavan H, Gill M, Suarez AG, Gowland P, Grabe HJ, Grotegerd D, Gruber O, Hagenaars S, Hashimoto R, Hauser TU, Heinz A, Hibar DP, Hoekstra PJ, Hoogman M, Howells FM, Hu H, Hulshoff Pol HE, Huyser C, Ittermann B, Jahanshad N, Jönsson EG, Jurk S, Kahn RS, Kelly S, Kraemer B, Kugel H, Kwon JS, Lemaitre H, Lesch KP, Lochner C, Luciano M, Marquand AF, Martin NG, Martínez-Zalacaín I, Martinot JL, Mataix-Cols D, Mather K, McDonald C, McMahon KL, Medland SE, Menchón JM, Morris DW, Mothersill O, Maniega SM, Mwangi B, Nakamae T, Nakao T, Narayanaswaamy JC, Nees F, Nordvik JE, Onnink AMH, Opel N, Ophoff R, Paillère Martinot ML, Papadopoulos Orfanos D, Pauli P, Paus T, Poustka L, Reddy JY, Renteria ME, Roiz-Santiáñez R, Roos A, Royle NA, Sachdev P, Sánchez-Juan P, Schmaal L, Schumann G, Shumskaya E, Smolka MN, Soares JC, Soriano-Mas C, Stein DJ, Strike LT, Toro R, Turner JA, Tzourio-Mazoyer N, Uhlmann A, Hernández MV, van den Heuvel OA, van der Meer D, van Haren NEM, Veltman DJ, Venkatasubramanian G, Vetter NC, Vuletic D, Walitza S, Walter H, Walton E, Wang Z, Wardlaw J, Wen W, Westlye LT, Whelan R, Wittfeld K, Wolfers T, Wright MJ, Xu J, Xu X, Yun JY, Zhao J, Franke B, Thompson PM, Glahn DC, Mazoyer B, Fisher SE, Francks C. Brain Imaging Behav. 2017 Oct;11(5):1497-1514. doi: 10.1007/s11682-016-9629-z.
