Introduction One important feature of the human brain is structural asymmetry in the homologous contralateral anatomical regions. Left-right asymmetries of cortical thickness and surface area exist widely across the cortical mantle but intracortical microstructure asymmetry is rarely studied. Here we evaluate the asymmetry of microstructural organization in the human cortex combining post mortem and in vivo datasets.
Methods We assessed asymmetry of microstructural intensity using a 20-μm ultra-high–resolution 3D histological reconstruction (cell-body staining) of a post mortem brain (BigBrain, male donor, age = 65 years), together with in vivo myelin-sensitive magnetic resonance imaging (MRI) data including young adult Human Connectome Project (HCP, n=1101) T1w/T2w maps and Microstructure-Informed Connectomics (MICA-MICs, n=50) quantitative T1 (qT1) relaxometry. We downsampled the cortical maps using a multi-modal parcellation and Cole-Anticevic network atlas. Asymmetry of intracortical organization was computed by using microstructure profile covariance (MPC) gradients of intracortical equivolumetric surfaces.
Results We observed layer-specific cytoarchitectural asymmetry of the human cortex using post mortem data (Figure 1A). All p-values displayed are less than 0.001. Layer IV showed highest spatial similarity between layers, with mean r = 0.739. We also observed increased rightward asymmetry with deeper intracortical depth in dorsal attention network (DAN, r = -0.679), and increased leftward asymmetry with deeper intracortical depth in networks including somatomotor (SMN), cingulate-opercular (CON, r = 0.652), language (Lan., r = 0.620), and posterior-multimodal (PMN, r = 0.856). Following, we evaluated asymmetry of intracortical profile covariance. The principal gradient of MPC (MPC G1) followed an anterior-position direction. Along this axis, visual cortices showed rightward asymmetries but posterior middle temporal gyrus and inferior parietal cortices showed leftward asymmetries (Figure 1B). Then, we evaluated whether similar patterns of asymmetry could be observed in vivo, using intra-cortical microstructural proxies. Visual and somatomotor cortices showed high myelination intensity for both qT1 and T1w/T2w data (Figure 1C). The left-right asymmetry of intensity followed an anterior-posterior direction (Figure 1D), as well as the asymmetry of MPC G1 (Figure 1E). T1w/T2w MPC G1 showed strongest leftward asymmetry in orbito-affective (OAN, Cohen’s d intra-hemisphere = 0.465, Cohen’s d inter-hemisphere = 0.478), frontoparietal (FPN, Cohen’s d intra-hemisphere = 1.314, Cohen’s d inter-hemisphere = 1.232), and language regions (Cohen’s d intra-hemisphere = 0.447, Cohen’s d inter-hemisphere = 0.414). Strongest rightward asymmetry was observed in PMN (Cohen’s d intra-hemisphere = -0.357, Cohen’s d inter-hemisphere = -0.265), SMN (Cohen’s d intra-hemisphere = -0.353, Cohen’s d inter-hemisphere = -0.769), and second visual network (Vis2, Cohen’s d intra-hemisphere = -0.600, Cohen’s d inter-hemisphere = -0.447). The spatial pattern is similar between T1w/T2w and qT1 (r intra-hemisphere = 0.556 and r inter-hemisphere = 0.542).
Conclusions In sum, we find that the cytoarchitectural asymmetry of the cortex differs between laminar structures, with intracortical changes in language, somatomotor, posterior multimodal, and dorsal attention networks, in particular in posterior cortical regions. Regarding the in vivo maps of intracortical microstructural asymmetry, our two measures suggest similar results in microstrural intensity but subtle differences in organization features.