Abstract
Intersubject variability is a fundamental characteristic of brain organizations, and not just “noise”. Although intrinsic functional connectivity (FC) is unique to each individual and varies across brain gray-matter, the underlying mechanisms of intersubject functional variability in white-matter (WM) remain unknown. This study identified WMFC variabilities and determined the genetic basis and macroscale imaging in 45 healthy subjects. The functional localization pattern of intersubject variability across WM is heterogeneous, with most variability observed in the heteromodal cortex. The variabilities of heteromodal regions in expression profiles of genes are related to neuronal cells, involved in synapse-related and glutamic pathways, and associated with psychiatric disorders. In contrast, genes overexpressed in unimodal regions are mostly expressed in glial cells and were related to neurological diseases. Macroscopic variability recapitulates the functional and structural specializations and behavioral phenotypes. Together, our results provide clues to intersubject variabilities of the WMFC with convergent transcriptomic and cellular signatures, which relate to macroscale brain specialization.
Highlights
Intersubject variability is a fundamental characteristic of brain organizations, and not just “noise”
We found a significant overlap between the top-ranked PLS1 + gene list and genes associated with psychiatric disorders, such as schizophrenia, bipolar disorder, autism spectrum disorder, and depression, all of which were false discovery ratio (FDR)-corrected with P < 0.05 (Fig. 5a; Supplementary Result 6 and Supplementary Table 2)
We found that the intersubject variability of WM functional connectivity (WMFC) based on the Human Connectome Project (HCP) 7 T dataset showed a similar pattern with the intersubject variability across 12 WM functional networks in this work (r = 0.60, P = 0.04; Supplementary Fig. 7)
Summary
Intersubject variability is a fundamental characteristic of brain organizations, and not just “noise”. Intrinsic functional connectivity (FC) is unique to each individual and varies across brain gray-matter, the underlying mechanisms of intersubject functional variability in white-matter (WM) remain unknown. 1234567890():,; Blood-oxygenation-level-dependent-functional magnetic resonance imaging (BOLD-fMRI) has become the method of choice for evaluating the coherent signal fluctuations across the brain, because it has high spatial and temporal resolutions and is noninvasive[1,2,3]. This intrinsically inter-regional functional connectivity (FC) architecture is unique among individuals[4,5,6,7] and reflects cognitive or population variabilities[8,9]. The function of WM often overlaps with and is constrained by the physical substrate’s known anatomical pathways/microstructures[22]
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