Cerebral Blood Flow and Cardiovascular Risk Effects on Resting Brain Regional Homogeneity

Authors

Bhim M Adhikari
L Elliot Hong
Zhiwei Zhao
Danny J J Wang
Paul M Thompson
Neda Jahanshad
Alyssa H Zhu
Stefan Holiga
Jessica A Turner
Theo G M van Erp
Vince D Calhoun
Kathryn S Hatch
Heather Bruce
Stephanie M Hare
Joshua Chiappelli
Eric L Goldwaser
Mark D Kvarta
Yizhou Ma
Xiaoming Du
Thomas E Nichols
Alan R Shuldiner
Braxton D Mitchell
Juergen Dukart
Shuo Chen
Peter Kochunov

Publication Date

11-15-2022

Journal

Neuroimage

Abstract

Regional homogeneity (ReHo) is a measure of local functional brain connectivity that has been reported to be altered in a wide range of neuropsychiatric disorders. Computed from brain resting-state functional MRI time series, ReHo is also sensitive to fluctuations in cerebral blood flow (CBF) that in turn may be influenced by cerebrovascular health. We accessed cerebrovascular health with Framingham cardiovascular risk score (FCVRS). We hypothesize that ReHo signal may be influenced by regional CBF; and that these associations can be summarized as FCVRS→CBF→ReHo. We used three independent samples to test this hypothesis. A test-retest sample of N = 30 healthy volunteers was used for test-retest evaluation of CBF effects on ReHo. Amish Connectome Project (ACP) sample (N = 204, healthy individuals) was used to evaluate association between FCVRS and ReHo and testing if the association diminishes given CBF. The UKBB sample (N = 6,285, healthy participants) was used to replicate the effects of FCVRS on ReHo. We observed strong CBF→ReHo links (p<2.5 × 10−3) using a three-point longitudinal sample. In ACP sample, marginal and partial correlations analyses demonstrated that both CBF and FCVRS were significantly correlated with the whole-brain average (p<10−6) and regional ReHo values, with the strongest correlations observed in frontal, parietal, and temporal areas. Yet, the association between ReHo and FCVRS became insignificant once the effect of CBF was accounted for. In contrast, CBF→ReHo remained significantly linked after adjusting for FCVRS and demographic covariates (p<10−6). Analysis in N = 6,285 replicated the FCVRS→ReHo effect (p = 2.7 × 10−27). In summary, ReHo alterations in health and neuropsychiatric illnesses may be partially driven by region-specific variability in CBF, which is, in turn, influenced by cardiovascular factors.

Keywords

Arterial-spin labeling, Correlation, Local functional connectivity, Multivariate mediation analysis, Resting state functional MRI

Comments

Supplementary Materials

PMID: 35963506