Resting-state fMRI signals contain spectral signatures of local hemodynamic response timing

Abstract

Functional magnetic resonance imaging (fMRI) has proven to be a powerful tool for noninvasively measuring human brain activity; yet, thus far, fMRI has been relatively limited in its temporal resolution. A key challenge is understanding the relationship between neural activity and the blood-oxygenation-level-dependent (BOLD) signal obtained from fMRI, generally modeled by the hemodynamic response function (HRF). The timing of the HRF varies across the brain and individuals, confounding our ability to make inferences about the timing of the underlying neural processes. Here we show that resting-state fMRI signals contain information about HRF temporal dynamics that can be leveraged to understand and characterize variations in HRF timing across both cortical and subcortical regions. We found that the frequency spectrum of resting-state fMRI signals significantly differs between voxels with fast versus slow HRFs in human visual cortex. These spectral differences extended to subcortex as well, revealing significantly faster hemodynamic timing in the lateral geniculate nucleus of the thalamus. Ultimately, our results demonstrate that the temporal properties of the HRF impact the spectral content of resting-state fMRI signals and enable voxel-wise characterization of relative hemodynamic response timing. Furthermore, our results show that caution should be used in studies of resting-state fMRI spectral properties, as differences can arise from purely vascular origins. This finding provides new insight into the temporal properties of fMRI signals across voxels, which is crucial for accurate fMRI analyses, and enhances the ability of fast fMRI to identify and track fast neural dynamics.

Pupil size reflects activation of subcortical ascending arousal system nuclei during rest

“…The methods that have previously been used to examine co-fluctuations between pupil size and fMRI BOLD patterns worked under the assumption that the shape of the HRF during rest is homogeneous across the whole brain ( Breeden et al, 2017 ; DiNuzzo et al, 2019 ; Schneider et al, 2016 ; Yellin et al, 2015 ). This assumption may not be correct, and because even a 1 s latency difference between assumed HRF and actual HRF can have a significant impact on fMRI results ( Wall et al, 2009 ), it may be important to account for regional and individual differences ( Bailes et al, 2023 ; Handwerker et al, 2004 ) in the shape of the HRF. Indeed, subcortical structures have been characterized by faster BOLD responses (TTP 4–5 s; Lau et al, 2011 ; Lewis et al, 2018 ; Yen et al, 2011 ) compared to the cortex (TTP 5–6 s; Lewis et al, 2018 ; Friston et al, 2000 ).…”