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

Area of Science:

• Neuroimaging
• Cognitive Neuroscience
• Biomedical Engineering

Background:

• Functional magnetic resonance imaging (fMRI) measures neural activity indirectly via the hemodynamic response function (HRF).
• HRF is influenced by non-neural factors, leading to variability across brain regions, individuals, and populations.
• Current resting-state fMRI studies often assume a constant HRF, overlooking its inherent variability.

Purpose of the Study:

• To highlight the significant impact of HRF variability on fMRI connectivity analyses.
• To underscore the necessity of accounting for HRF variations in within-subject and between-subjects fMRI studies.
• To discuss the clinical implications of HRF aberrations in neurological disorders and fMRI research.

Main Methods:

• Review of existing literature supporting HRF variability.
• Analysis of preliminary data demonstrating sex-based HRF differences.
• Discussion of HRF variability implications for spinal cord fMRI.

Main Results:

• HRF variability substantially confounds functional connectivity estimates.
• Sex-based HRF differences can introduce median errors of 15.4% in group-level connectivity comparisons.
• HRF variability poses challenges for spinal cord fMRI research.

Conclusions:

• HRF variability is a critical confound in fMRI connectivity studies that cannot be ignored.
• Failure to account for HRF variations leads to inaccurate connectivity estimates and group comparisons.
• Further community dialogue and methodological advancements are needed to address the HRF confound in fMRI research.