Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

Abstract

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.Electronic supplementary materialThe online version of this article (doi:10.1007/s11682-016-9629-z) contains supplementary material, which is available to authorized users.

MR‐based age‐related effects on the striatum, globus pallidus, and thalamus in healthy individuals across the adult lifespan

“…However, given that some studies report sex effects in the aging literature (Coffey et al, 1998;Good et al, 2001;Guadalupe et al, 2017;Murphy et al, 1996;Pfefferbaum et al, 2013;Van der Werf et al, 2001;Xu et al, 2000; and other do not; Abedelahi, Hasanzadeh, Hadizadeh, & Joghataie, 2013;Fjell et al, 2009;Giedd et al, 1996;Greenberg et al, 2008;Lemaître et al, 2005;Narvacan et al, 2017;Raz et al, 2003;Sullivan et al, 2004;Wyciszkiewicz & Pawlak, 2014), we nonetheless examined whether there was a significant age by sex interaction in each of the models for each analysis (volume, surface area, and T1w/T2w), where once again AIC was used to determine the best fit for the age term (see Section 3.5 and Supplementary Results Section for more details). However, given that some studies report sex effects in the aging literature (Coffey et al, 1998;Good et al, 2001;Guadalupe et al, 2017;Murphy et al, 1996;Pfefferbaum et al, 2013;Van der Werf et al, 2001;Xu et al, 2000; and other do not; Abedelahi, Hasanzadeh, Hadizadeh, & Joghataie, 2013;Fjell et al, 2009;Giedd et al, 1996;Greenberg et al, 2008;Lemaître et al, 2005;Narvacan et al, 2017;Raz et al, 2003;Sullivan et al, 2004;Wyciszkiewicz & Pawlak, 2014), we nonetheless examined whether there was a significant age by sex interaction in each of the models for each analysis (volume, surface area, and T1w/T2w), where once again AIC was used to determine the best fit for the age term (see Section 3.5 and Supplementary Results Section for more deta...…”

“…While numerous studies have used magnetic resonance imaging (MRI) to demonstrate subcortical volumetric age relationships occurring across the lifespan in vivo (Courchesne et al, 2000;Brain Development Cooperative Group, 2012;Fjell et al, 2013;Fotenos, Snyder, Girton, Morris, & Buckner, 2005;Good et al, 2001;Goodro, Sameti, Patenaude, & Fein, 2012;Greenberg et al, 2008;Guadalupe et al, 2017;Inano et al, 2013;Jäncke, Mérillat, Liem, & Hänggi, 2015;Jernigan et al, 2001;Narvacan, Treit, Camicioli, Martin, & Beaulieu, 2017;Potvin et al, 2016;Raz et al, 2003Raz et al, , 2005Raz & Rodrigue, 2006;Raznahan et al, 2014;Sullivan, Rosenbloom, Serventi, & Pfefferbaum, 2004;Tamnes et al, 2013;Van Der Werf et al, 2001;Walhovd et al, 2005Walhovd et al, , 2011Ziegler et al, 2012), there are several discrepancies between the trajectories that have been previously reported. Different age-related relationships have been observed, with some studies suggesting linear decline beginning early in life Goodro et al, 2012;Greenberg et al, 2008;Gunning-Dixon, Head, McQuain, Acker, & Raz, 1998;Inano et al, 2013;Raz et al, 2003;Sullivan et al, 2004;Van Der Werf et al, 2001;Walhovd et al, 2005Walhovd et al, , 2011, whereas others report quadratic trajectories, with an increase in volume followed by a subsequent decline Goodro et al, 2012;…”

“…Specifically, these studies use various segmentation techniques (manual or computer-assisted methods (Greenberg et al, 2008;Gunning-Dixon et al, 1998;Jernigan et al, 2001;Raz et al, 2003Raz et al, , 2005Sullivan et al, 2004, Van Der Werf et al, 2001, FreeSurfer (Fischl et al, 2002;http://surfer.nmr.mgh.harvard. edu) Guadalupe et al, 2017;Inano et al, 2013;Jäncke et al, 2015;Narvacan et al, 2017;Potvin et al, 2016;Tamnes et al, 2013;Walhovd et al, 2005Walhovd et al, , 2011, FSL-FIRST (Patenaude, Smith, Kennedy, & Jenkinson, 2011;http://fsl.fmrib.ox.ac.uk) (Goodro et al, 2012)), all of which have differing segmentation criteria and definitions of the underlying anatomy. Specifically, these studies use various segmentation techniques (manual or computer-assisted methods (Greenberg et al, 2008;Gunning-Dixon et al, 1998;Jernigan et al, 2001;Raz et al, 2003Raz et al, , 2005Sullivan et al, 2004, Van Der Werf et al, 2001, FreeSurfer (Fischl et al, 2002;http://surfer.nmr.mgh.harvard. edu) Guadalupe et al, 2017;Inano et al, 2013;Jäncke et al, 2015;Narvacan et al, 2017;Potvin et al, 2016;Tamnes et al, 2013;Walhovd et al, 2005Walhovd et al, , 2011, FSL-FIRST …”

Genetic analysis of cortical sulci in 1,009 adults

“…This reduced the probability of Type 1 errors associated with multiple measurements. Apart from work by the ENIGMA Laterality group [16] most prior ENIGMA studies [1,17,18,19] performed analyses on pooled bilateral measures, averaging data from left and right hemispheres. To formally test whether this is acceptable when evaluating sulcal parameters, we performed a bivariate genetic analysis to estimate the genetic correlation between left and right sulcal measures.…”

Interhemispheric gene expression differences in the cerebral cortex of humans and macaque monkeys

“…However, functional and structural asymmetries have now been identified in many nonhuman primates and other species (Corballis, 2009; Frasnelli, 2013; Guadalupe et al, 2016; Ocklenburg et al, 2013a). It is still unclear whether cerebral lateralization is an effect of differential gene expression and when in development these patterns might arise.…”