Cerebral blood flow and cardiovascular risk effects on resting brain regional homogeneity
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
Affiliations
Bhim M. Adhikari
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
L. Elliot Hong
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Zhiwei Zhao
University of Maryland, College Park, MD 20742
Danny J.J. Wang
Laboratory of Functional MRI Technology, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90007
Paul M. Thompson
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292
Neda Jahanshad
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292
Alyssa H. Zhu
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA 90292
Stefan Holiga
Roche Innovation Center Basel, Basel, BS
Jessica A. Turner
Departments of Psychology and Neuroscience, Georgia State University, Atlanta, GA 30302
Theo G.M. van Erp
Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, School of Medicine, University of California, Irvine, CA 92697; Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA 92697
Vince D. Calhoun
Departments of Psychology and Neuroscience, Georgia State University, Atlanta, GA 30302; Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS): (Georgia State University, Georgia Institute of Technology, and Emory University), Atlanta, GA 30302
Kathryn S. Hatch
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Heather Bruce
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Stephanie M. Hare
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Joshua Chiappelli
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Eric L. Goldwaser
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Mark D. Kvarta
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Yizhou Ma
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Xiaoming Du
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Thomas E. Nichols
Nuffield Department of Population Health of the University of Oxford, Oxford, OX3 7LF, UK
Alan R. Shuldiner
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201
Braxton D. Mitchell
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201
Juergen Dukart
Institute of Neuroscience and Medicine - INM-7: Brain and Behaviour, Research Center Jülich, Wilhelm-Johnen-Straße, 52425 Jülich, Germany; Institute of Systems Neuroscience, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
Shuo Chen
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228
Peter Kochunov
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228; Corresponding author at: Maryland Psychiatry Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
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.
