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Correlation between cortical gene expression and resting-state functional network centrality in healthy young adults.

ABSTRACT: Resting-state functional connectivity in the human brain is heritable, and previous studies have investigated the genetic basis underlying functional connectivity. However, at present, the molecular mechanisms associated with functional network centrality are still largely unknown. In this study, functional networks were constructed, and the graph-theory method was employed to calculate network centrality in 100 healthy young adults from the Human Connectome Project. Specifically, functional connectivity strength (FCS), also known as the "degree centrality" of weighted networks, is calculated to measure functional network centrality. A multivariate technique of partial least squares regression (PLSR) was then conducted to identify genes whose spatial expression profiles best predicted the FCS distribution. We found that FCS spatial distribution was significantly positively correlated with the expression of genes defined by the first PLSR component. The FCS-related genes we identified were significantly enriched for ion channels, axon guidance, and synaptic transmission. Moreover, FCS-related genes were preferentially expressed in cortical neurons and young adulthood and were enriched in numerous neurodegenerative and neuropsychiatric disorders. Furthermore, a series of validation and robustness analyses demonstrated the reliability of the results. Overall, our results suggest that the spatial distribution of FCS is modulated by the expression of a set of genes associated with ion channels, axon guidance, and synaptic transmission.

SUBMITTER: Zhu D

PROVIDER: S-EPMC8046072 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionCannabis is the most commonly used illicit substance in the United States, and nearly 1 in 4 young adults are current cannabis users. Chronic cannabis use is associated with changes in resting state functional connectivity (RSFC) in the default mode network (DMN) in adolescents and young adults; results are somewhat inconsistent across studies, potentially due to methodological differences. The aims of the present study were to examine potential differences in DMN RSFC between cannabis users and controls, and to examine, as an exploratory analysis, if gender moderated any findings. We further examined whether differences in RSFC related to differences in performance on selected neuropsychological measures.Materials and methodsSeventy-seven 16-26-year-old participants underwent an MRI scan (including resting state scan), neuropsychological battery, toxicology screening, and drug use interview. Differences in DMN connectivity were examined between groups (cannabis vs. control) and with an exploratory group by gender interaction, using a left posterior cingulate cortex (PCC) seed-based analysis conducted in AFNI.ResultsCannabis users demonstrated weaker connectivity than controls between the left PCC and various DMN nodes, and the right Rolandic operculum/Heschl's gyrus. Cannabis users demonstrated stronger connectivity between the left PCC and the cerebellum and left supramarginal gyrus. The group by gender interaction was not significantly associated with connectivity differences. Stronger left PCC-cerebellum connectivity was associated with poorer performance on cognitive measures in cannabis users. In controls, intra-DMN connectivity was positively correlated with performance on a speeded selective/sustained attention measure.DiscussionConsistent with our hypotheses and other studies, cannabis users demonstrated weaker connectivity between the left PCC and DMN nodes. Chronic THC exposure may alter GABA and glutamate concentrations, which may alter brain communication. Future studies should be conducted with a larger sample size and examine gender differences and the mechanism by which these differences may arise.

Project description:Using voxel-wise degree centrality (DC), as measured by resting-state fMRI, we aimed to study alterations in the brain functional networks in patients with primary angle-closure glaucoma (PACG) and to reveal the plastic trajectories of surgery.A total of 23 preoperative PACG patients (49.48 ± 14.37 years old) were recruited to undergo a resting-state fMRI scan, and 9 of them were rescanned 3 months after surgery. All PACG patients underwent a complete ophthalmologic examination, including intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, vertical cup to disc ratio (V C/D), and average cup to disc ratio (A C/D). Another 23 gender- and age-matched healthy controls (48.18 ± 9.40 years old) underwent scanning once for comparison. The group difference in DC was calculated in each voxel, and the correlations between the DC value and each of the clinical variables were analyzed in the PACG patients.Preoperative PACG (pre-PACG) patients showed significantly decreased DC in the bilateral visual cortices but increased DC in the left anterior cingulate cortex (ACC) and caudate (p < 0.05, corrected) compared with the controls. Statistical analysis showed a significantly negative correlation between DC in the bilateral visual cortices and the IOP score and between DC in the anterior cingulate cortex (ACC) and both the A C/D and V C/D scores in the pre-PACG patients. Three months after surgery, these postoperative PACG (post-PACG) patients showed a significantly increased DC in both the bilateral visual cortices and the left precentral gyrus compared with the pre-PACG patients.Our results suggest that PACG may contribute to decreased functional centrality in the visual system and to increased degree centrality in cognition-emotional processing regions. Alterations in visual areas seem to parallel the cup to disc ratio, but not the duration of angle closure. The changes of functional centrality in PACG patients after operation may reveal the plasticity or degeneration of the visual-associated brain areas. Our findings may provide further understanding of the pathophysiology of PACG.

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Correlation between cortical gene expression and resting-state functional network centrality in healthy young adults.

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