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

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

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes

Reduced right atrial contractile force in patients with left ventricular diastolic dysfunction: A study in human atrial fibers—contractile force and diastolic dysfunction

Background/Objective: The aim of our study was to evaluate right heart contractile force in patients with diastolic dysfunction (DD) with preserved left heart ejection fraction undergoing cardiac surgery. We examined the contractile properties of skinned human fibers obtained from the right auricle in two groups (DD and controls). Methods: Right atrial tissue from 64 patients, who were undergoing cardiac surgery, were collected before extracorporal circulation. Tissue was conserved and prepared as “skinned fibers”. We exposed the dissected fibers to increasing calcium concentrations and recorded the force values. Results: Patients with DD develop significantly less force at middle and higher calcium concentrations pCa 4.0: DD 2.58 ± 0.4 mN, controls 5.32 ± 0.4 mN, p = 0.02; pCa 5.5: DD 1.14 ± 0.3 mN, controls 1.45 ± 0.3 mN, p = 0.03. DD significantly correlates with left ventricular hypertrophy (LVH; p = 0.03). DD did not significantly occur more often in patients with mitral valve insufficiency, aortic insufficiency or stenosis, or coronary heart disease (all p > 0.10). LVH, which was associated with DD, correlated significantly with mitral valve prolapse (p = 0.05), aortic valve stenosis (p = 0.02), and mitral valve insufficiency (p = 0.03). Conclusion: Contractile force is significantly reduced in right atrial skinned human fibers with DD. DD is significantly associated with LVH, but emerges independently from underlying pathologies like valve diseases or coronary heart disease. This underlines the hypothesis that impairment of contractile capacity directly results from DD—independent from volume or pressure overload due to valvular or ischemic heart disease