Dataset Information

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.

SUBMITTER: Guadalupe T

PROVIDER: S-EPMC5540813 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Guadalupe Tulio T Mathias Samuel R SR vanErp Theo G M TGM Whelan Christopher D CD Zwiers Marcel P MP Abe Yoshinari Y Abramovic Lucija L Agartz Ingrid I Andreassen Ole A OA Arias-Vásquez Alejandro A Aribisala Benjamin S BS Armstrong Nicola J NJ Arolt Volker V Artiges Eric E Ayesa-Arriola Rosa R Baboyan Vatche G VG Banaschewski Tobias T Barker Gareth G Bastin Mark E ME Baune Bernhard T BT Blangero John J Bokde Arun L W ALW Boedhoe Premika S W PSW Bose Anushree A Brem Silvia S Brodaty Henry H Bromberg Uli U Brooks Samantha S Büchel Christian C Buitelaar Jan J Calhoun Vince D VD Cannon Dara M DM Cattrell Anna A Cheng Yuqi Y Conrod Patricia J PJ Conzelmann Annette A Corvin Aiden A Crespo-Facorro Benedicto B Crivello Fabrice F Dannlowski Udo U de Zubicaray Greig I GI de Zwarte Sonja M C SMC Deary Ian J IJ Desrivières Sylvane S Doan Nhat Trung NT Donohoe Gary G Dørum Erlend S ES Ehrlich Stefan S Espeseth Thomas T Fernández Guillén G Flor Herta H Fouche Jean-Paul JP Frouin Vincent V Fukunaga Masaki M Gallinat Jürgen J Garavan Hugh H Gill Michael M Suarez Andrea Gonzalez AG Gowland Penny P Grabe Hans J HJ Grotegerd Dominik D Gruber Oliver O Hagenaars Saskia S Hashimoto Ryota R Hauser Tobias U TU Heinz Andreas A Hibar Derrek P DP Hoekstra Pieter J PJ Hoogman Martine M Howells Fleur M FM Hu Hao H Hulshoff Pol Hilleke E HE Huyser Chaim C Ittermann Bernd B Jahanshad Neda N Jönsson Erik G EG Jurk Sarah S Kahn Rene S RS Kelly Sinead S Kraemer Bernd B Kugel Harald H Kwon Jun Soo JS Lemaitre Herve H Lesch Klaus-Peter KP Lochner Christine C Luciano Michelle M Marquand Andre F AF Martin Nicholas G NG Martínez-Zalacaín Ignacio I Martinot Jean-Luc JL Mataix-Cols David D Mather Karen K McDonald Colm C McMahon Katie L KL Medland Sarah E SE Menchón José M JM Morris Derek W DW Mothersill Omar O Maniega Susana Munoz SM Mwangi Benson B Nakamae Takashi T Nakao Tomohiro T Narayanaswaamy Janardhanan C JC Nees Frauke F Nordvik Jan E JE Onnink A Marten H AMH Opel Nils N Ophoff Roel R Paillère Martinot Marie-Laure ML Papadopoulos Orfanos Dimitri D Pauli Paul P Paus Tomáš T Poustka Luise L Reddy Janardhan Yc JY Renteria Miguel E ME Roiz-Santiáñez Roberto R Roos Annerine A Royle Natalie A NA Sachdev Perminder P Sánchez-Juan Pascual P Schmaal Lianne L Schumann Gunter G Shumskaya Elena E Smolka Michael N MN Soares Jair C JC Soriano-Mas Carles C Stein Dan J DJ Strike Lachlan T LT Toro Roberto R Turner Jessica A JA Tzourio-Mazoyer Nathalie N Uhlmann Anne A Hernández Maria Valdés MV van den Heuvel Odile A OA van der Meer Dennis D van Haren Neeltje E M NEM Veltman Dick J DJ Venkatasubramanian Ganesan G Vetter Nora C NC Vuletic Daniella D Walitza Susanne S Walter Henrik H Walton Esther E Wang Zhen Z Wardlaw Joanna J Wen Wei W Westlye Lars T LT Whelan Robert R Wittfeld Katharina K Wolfers Thomas T Wright Margaret J MJ Xu Jian J Xu Xiufeng X Yun Je-Yeon JY Zhao JingJing J Franke Barbara B Thompson Paul M PM Glahn David C DC Mazoyer Bernard B Fisher Simon E SE Francks Clyde C

Brain imaging and behavior 20171001 5

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 d ...[more]

PMID: 27738994

Similar Datasets

Project description:PurposeIn an increasingly aging society, it is of great importance to consider trajectories of subcortical volumes at different ages for understanding biological markers of aging. Thus, we investigated sex, age, and their interactions on subcortical volumes, including the basal ganglia (caudate, putamen, accumbens, and pallidum), thalamus, hippocampus, and amygdala.MethodsWe analyzed the adult lifespan trajectory of subcortical volumes and asymmetries in 563 healthy subjects aged from 19 to 86 using magnetic resonance imaging (MRI) data from the publicly available 7IXI data set.ResultsThe sex made strong contributions to the trajectories of subcortical volumes with aging, including the right putamen, right pallidum, bilateral thalamus, hippocampus, and amygdala. The volume of the right putamen, right pallidum, and right thalamus decreased more rapidly in males than in females, and the volume of the left thalamus, bilateral hippocampus, and amygdala in males followed a quadratic model, while those in females followed a linear decline model. The asymmetries in the caudate and hippocampus showed a linear decline, and a sex and age interaction was found in the hippocampus; that is, the asymmetry in the hippocampus decreased only in the males and not in the females. Changes in the accumbens and pallidum fit quadratic trajectories, in which females increased until 39.26 years old in the accumbens asymmetry and then began to rapidly decline, and males showed a linear decline. The asymmetry in the pallidum in males and females showed a slow decreasing period until almost 45 years of age and then increased.ConclusionThe results suggest that compared with females, males have a faster decline in the volume of the right putamen, right pallidum, and right thalamus, while aging occurred later but also faster in the left thalamus, bilateral hippocampus, and amygdala. Interestingly, we found the inflection point in the thalamus, bilateral hippocampus, and amygdala volume in the quadratic model, and after this point, the volume change accelerated with aging, which may have resulted from the stronger work pressure in the middle-aged men and the low levels of testosterone in the older adults. The interaction of age and sex on individual subcortical structures provides evidence to support the impact of sex on psychopathologies associated with degenerative brain disorders in the elderly. The findings may be significant to investigate the occurrence and prevalence of degenerative brain disorders in males and females. Future studies can focus on the functional and behavioral relations with subcortical structures for preventive measures of related disorders.

Project description:Age and sex can influence brain iron levels. We studied the influence of these variables on deep gray matter magnetic susceptibilities. In 183 healthy volunteers (44.7 ± 14.2 years, range 20-69, ♀ 49%), in vivo quantitative susceptibility mapping (QSM) at 1.5T was performed to estimate brain iron accumulation in the following regions of interest (ROIs): caudate nucleus (Cd), putamen (Pt), globus pallidus (Gp), thalamus (Th), pulvinar (Pul), red nucleus (Rn), substantia nigra (Sn) and the cerebellar dentate nuclei (Dn). We gauged the influence of age and sex on magnetic susceptibility by specifying a series of structural equation models. The distributions of susceptibility varied in degree across the structures, conforming to histologic findings (Hallgren and Sourander, 1958), with the highest degree of susceptibility in the Gp and the lowest in the Th. Iron increase correlated across several ROIs, which may reflect an underlying age-related process. Advanced age was associated with a particularly strong linear rise of susceptibility in the striatum. Nonlinear age trends were found in the Rn, where they were the most pronounced, followed by the Pul and Sn, while minimal nonlinear trends were observed for the Pt, Th, and Dn. Moreover, sex related variations were observed, so that women showed lower levels of susceptibility in the Sn after accounting for age. Regional susceptibility of the Pul increased linearly with age in men but exhibited a nonlinear association with age in women with a leveling off starting from midlife. Women expected to be post menopause (+51 years) showed lower total magnetic susceptibility in the subcortical gray matter. The current report not only is consistent with previous reports of age related variations of brain iron, but also adds to the current knowledge by reporting age-related changes in less studied, smaller subcortical nuclei. This is the first in-vivo report to show lower total subcortical brain iron levels selectively in women from midlife, compared to men and younger women. These results encourage further assessment of sex differences in brain iron. We anticipate that age and sex are important co-factors to take into account when establishing a baseline level for differentiating pathologic neurodegeneration from healthy aging. The variations in regional susceptibility reported herein should be evaluated further using a longitudinal study design to determine within-person changes in aging.

Project description:ImportanceNonlinear changes in brain function during aging are shaped by a complex interplay of factors, including sex, age, genetics, and modifiable health risk factors. However, the combined effects and underlying mechanisms of these factors on brain functional connectivity remain poorly understood.ObjectiveTo comprehensively investigate the combined associations of sex, age, APOE genotypes, and ten common modifiable health risk factors with brain functional connectivities during aging.Design setting and participantsThis analysis used data from 36,630 UK Biobank participants, aged 44-81, who were assessed for sex, age, APOE genotypes, 10 health risk factors, and brain functional connectivities through resting-state functional magnetic resonance imaging.Main outcomes and measuresBrain functional connectivities were evaluated through within- and between-network functional connectivities and connectivity strength. Associations between risk factors and brain functional connectivities, including their interaction effects, were analyzed.ResultsHypertension, BMI, and education were the top three influential factors. Sex-specific effects were also observed in interactions involving APOE4 gene, smoking, alcohol consumption, diabetes, BMI, and education. Notably, a negative sex-excessive alcohol interaction showed a stronger negative effect on functional connectivities in males, particularly between the dorsal attention network and the language network, while moderate alcohol consumption appeared to have protective effects. A significant negative interaction between sex and APOE4 revealed a greater reduction in functional connectivity between the cingulo-opercular network and the posterior multimodal network in male APOE4 carriers. Additional findings included a negative age-BMI interaction between the visual and dorsal attention networks, and a positive age-hypertension interaction between the frontoparietal and default mode networks.Conclusions and relevanceThe findings highlight significant sex disparities in the associations between age, the APOE-ε4 gene, modifiable health risk factors, and brain functional connectivity, emphasizing the necessity of jointly considering these factors to gain a deeper understanding of the complex processes underlying brain aging.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets