A central goal in systems neuroscience is the parcellation of the cerebral cortex into discrete neurobiological "atoms". Resting-state functional magnetic resonance imaging (rs-fMRI) offers the possibility of in vivo human cortical parcellation. Almost all previous parcellations relied on 1 of 2 approaches. The local gradient approach detects abrupt transitions in functional connectivity patterns. These transitions potentially reflect cortical areal boundaries defined by histology or visuotopic fMRI. By contrast, the global similarity approach clusters similar functional connectivity patterns regardless of spatial proximity, resulting in parcels with homogeneous (similar) rs-fMRI signals. Here, we propose a gradient-weighted Markov Random Field (gwMRF) model integrating local gradient and global similarity approaches. Using task-fMRI and rs-fMRI across diverse acquisition protocols, we found gwMRF parcellations to be more homogeneous than 4 previously published parcellations. Furthermore, gwMRF parcellations agreed with the boundaries of certain cortical areas defined using histology and visuotopic fMRI. Some parcels captured subareal (somatotopic and visuotopic) features that likely reflect distinct computational units within known cortical areas. These results suggest that gwMRF parcellations reveal neurobiologically meaningful features of brain organization and are potentially useful for future applications requiring dimensionality reduction of voxel-wise fMRI data. Multiresolution parcellations generated from 1489 participants are publicly available (https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/brain_parcellation/Schaefer2018_LocalGlobal).
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.
Resting-state functional magnetic resonance imaging (rs-fMRI) offers the opportunity to delineate individual-specific brain networks. A major question is whether individual-specific network topography (i.e., location and spatial arrangement) is behaviorally relevant. Here, we propose a multi-session hierarchical Bayesian model (MS-HBM) for estimating individual-specific cortical networks and investigate whether individual-specific network topography can predict human behavior. The multiple layers of the MS-HBM explicitly differentiate intra-subject (within-subject) from inter-subject (between-subject) network variability. By ignoring intra-subject variability, previous network mappings might confuse intra-subject variability for inter-subject differences. Compared with other approaches, MS-HBM parcellations generalized better to new rs-fMRI and task-fMRI data from the same subjects. More specifically, MS-HBM parcellations estimated from a single rs-fMRI session (10 min) showed comparable generalizability as parcellations estimated by 2 state-of-the-art methods using 5 sessions (50 min). We also showed that behavioral phenotypes across cognition, personality, and emotion could be predicted by individual-specific network topography with modest accuracy, comparable to previous reports predicting phenotypes based on connectivity strength. Network topography estimated by MS-HBM was more effective for behavioral prediction than network size, as well as network topography estimated by other parcellation approaches. Thus, similar to connectivity strength, individual-specific network topography might also serve as a fingerprint of human behavior.
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