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

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.

Cerebrovascular reactivity increases across development in multiple networks as revealed by a breath‐holding task: A longitudinal fMRI study

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Ophthalmic artery reversal predicts contralateral body weakness symptoms better than carotid Doppler velocity—preliminary results

“…The increase in local CO 2 reduces local arteriolar/capillary resistance which doubles local perfusion rate accompanied by doubling the oxygen extraction fraction to supply the required increase in power demand. The resultant oxygen saturation decrease is most easily measured with transcranial functional near-infrared spectroscopy (fNIRS, pulse-oximetry of the brain) ( 14 ) or fMRI blood oxygenation level dependent (BOLD) methods ( 15 ). To deliver the required increase in power density demand, the arteries supplying each cerebrosome must be adequate caliber and be unobstructed including the aorta, carotids and cerebral arteries.…”