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.

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Cortical and subcortical nuclei degenerate in the dementias, but less is known about changes in the white matter tracts that connect them. To better understand white matter changes in behavioral variant frontotemporal dementia (bvFTD) and early-onset Alzheimer’s disease (EOAD), we used a novel approach to extract full 3D profiles of fiber bundles from diffusion-weighted MRI (DWI) and map white matter abnormalities onto detailed models of each pathway. The result is a spatially complex picture of tract-by-tract microstructural changes. Our atlas of tracts for each disease consists of 21 anatomically clustered and recognizable white matter tracts generated from whole-brain tractography in 20 patients with bvFTD, 23 with age-matched EOAD, and 33 healthy elderly controls. To analyze the landscape of white matter abnormalities, we used a point-wise tract correspondence method along the 3D profiles of the tracts and quantified the pathway disruptions using common diffusion metrics – fractional anisotropy, mean, radial, and axial diffusivity. We tested the hypothesis that bvFTD and EOAD are associated with preferential degeneration in specific neural networks. We mapped axonal tract damage that was best detected with mean and radial diffusivity metrics, supporting our network hypothesis, highly statistically significant and more sensitive than widely studied fractional anisotropy reductions. From white matter diffusivity, we identified abnormalities in bvFTD in all 21 tracts of interest but especially in the bilateral uncinate fasciculus, frontal callosum, anterior thalamic radiations, cingulum bundles and left superior longitudinal fasciculus. This network of white matter alterations extends beyond the most commonly studied tracts, showing greater white matter abnormalities in bvFTD versus controls and EOAD patients. In EOAD, network alterations involved more posterior white matter – the parietal sector of the corpus callosum and parahipoccampal cingulum bilaterally. Widespread but distinctive white matter alterations are a key feature of the pathophysiology of these two forms of dementia.

Neuroimaging studies suggest that category-selective regions in higher-order visual cortex are topologically organized around specific anatomical landmarks: the mid-fusiform sulcus (MFS) in the ventral temporal cortex (VTC) and lateral occipital sulcus (LOS) in the lateral occipital cortex (LOC). To derive precise structure-function maps from direct neural signals, we collected intracranial EEG (icEEG) recordings in a large human cohort (n = 26) undergoing implantation of subdural electrodes. A surface-based approach to grouped icEEG analysis was used to overcome challenges from sparse electrode coverage within subjects and variable cortical anatomy across subjects. The topology of category-selectivity in bilateral VTC and LOC was assessed for five classes of visual stimuli—faces, animate non-face (animals/body-parts), places, tools, and words—using correlational and linear mixed effects analyses. In the LOC, selectivity for living (faces and animate non-face) and non-living (places and tools) classes was arranged in a ventral-to-dorsal axis along the LOS. In the VTC, selectivity for living and non-living stimuli was arranged in a latero-medial axis along the MFS. Written word-selectivity was reliably localized to the intersection of the left MFS and the occipito-temporal sulcus. These findings provide direct electrophysiological evidence for topological information structuring of functional representations within higher-order visual cortex.

Invasive intracranial EEG (icEEG) offers a unique opportunity to study human cognitive networks at an unmatched spatiotemporal resolution. To date, the contributions of icEEG have been limited to the individual-level analyses or cohorts whose data are not integrated in any way. Here we discuss how grouped approaches to icEEG overcome challenges related to sparse-sampling, correct for individual variations in response and provide statistically valid models of brain activity in a population. By the generation of whole-brain activity maps, grouped icEEG enables the study of intra and interregional dynamics between distributed cortical substrates exhibiting task-dependent activity. In this fashion, grouped icEEG analyses can provide significant advances in understanding the mechanisms by which cortical networks give rise to cognitive functions.