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

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, because differences in fMRI frequency content 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. Functional magnetic resonance imaging (fMRI) is a tool that can be used to non-invasively measure the activity of the human brain. Active parts of the brain require more oxygen, which increases blood flow to these areas. fMRI can detect these changes, and its signal reflects the coupling between brain activity and changes in blood flow. The mechanism that couples brain activity to blood flow is known as the ‘hemodynamic response’, and its timing varies across the brain. Therefore, to interpret fMRI signals correctly and use them to measure underlying brain activity, it is necessary to understand how the response changes across the brain. Current methods for probing hemodynamic response variation are either limited to specific brain regions or require patients to hold their breath – something not all groups of patients can do. To solve this problem, Bailes et al. investigated whether resting-state fMRI signals contain information about how the hemodynamic response changes across the brain. This information could then be used to better infer brain activity from fMRI measurements. The experiments showed that resting-state fMRI signals can be used to characterize and predict the timing of the hemodynamic response. Specifically, the frequencies in resting-state fMRI signals are impacted by changes in the hemodynamic response and can therefore be used to predict hemodynamic timing. Additionally, Bailes et al. showed that these predictions are better than those obtained in experiments requiring patients to hold their breath, which is the current gold standard. The findings also demonstrate that the information from the frequencies of resting-state fMRI signals should be interpreted carefully, as differences in these frequencies can have a non-neural origin. Bailes et al. propose a highly generalizable approach for mapping and predicting variations of the hemodynamic response across the whole brain. These findings provide insights into the time-related properties of fMRI signals that are crucial for accurate analyses. This will be of particular importance as the field moves towards fMRI studies focused on rapid neural dynamics and higher-level cognition.