The confound of hemodynamic response function variability in human resting-state functional MRI studies

D Rangaprakash; Robert L Barry; Gopikrishna Deshpande

doi:10.3389/fnins.2023.934138

The confound of hemodynamic response function variability in human resting-state functional MRI studies

Front Neurosci. 2023 Jul 14:17:934138. doi: 10.3389/fnins.2023.934138. eCollection 2023.

Authors

D Rangaprakash^{1

2}, Robert L Barry^{1

2

3}, Gopikrishna Deshpande^{4

5

6

7

8

9

10}

Affiliations

¹ Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
² Department of Radiology, Harvard Medical School, Boston, MA, United States.
³ Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Cambridge, MA, United States.
⁴ Department of Electrical and Computer Engineering, AU MRI Research Center, Auburn University, Auburn, AL, United States.
⁵ Department of Psychological Sciences, Auburn University, Auburn, AL, United States.
⁶ Center for Neuroscience, Auburn University, Auburn, AL, United States.
⁷ Alabama Advanced Imaging Consortium, Birmingham, AL, United States.
⁸ Key Laboratory for Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China.
⁹ Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India.
¹⁰ Centre for Brain Research, Indian Institute of Science, Bangalore, India.

Abstract

Functional magnetic resonance imaging (fMRI) is an indirect measure of neural activity with the hemodynamic response function (HRF) coupling it with unmeasured neural activity. The HRF, modulated by several non-neural factors, is variable across brain regions, individuals and populations. Yet, a majority of human resting-state fMRI connectivity studies continue to assume a non-variable HRF. In this article, with supportive prior evidence, we argue that HRF variability cannot be ignored as it substantially confounds within-subject connectivity estimates and between-subjects connectivity group differences. We also discuss its clinical relevance with connectivity impairments confounded by HRF aberrations in several disorders. We present limited data on HRF differences between women and men, which resulted in a 15.4% median error in functional connectivity estimates in a group-level comparison. We also discuss the implications of HRF variability for fMRI studies in the spinal cord. There is a need for more dialogue within the community on the HRF confound, and we hope that our article is a catalyst in the process.

Keywords: BOLD fMRI; HRF; aging; confound; resting state connectivity (rsfMRI); sex differences.

Abstract

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