Abstract

The frequency characteristics of the resting-state BOLD fMRI (rs-fMRI) signal are of increasing scientific interest, as we discover more frequency-specific biological interpretations. In this work, we use variational mode decomposition (VMD) to precisely decompose the rs-fMRI time series into its intrinsic mode functions (IMFs) in a data-driven manner. The accuracy of the VMD decomposition of constituent IMFs is verified through simulations, with higher reconstruction accuracy and much-reduced mode mixing relative to previous methods. Furthermore, we examine the relative contribution of the VMD-derived modes (frequencies) to the rs-fMRI signal as well as functional connectivity measurements. Our primary findings are: (1) The rs-fMRI signal within the 0.01–0.25 Hz range can be consistently characterized by four intrinsic frequency clusters, centered at 0.028 Hz (IMF4), 0.080 Hz (IMF3), 0.15 Hz (IMF2) and 0.22 Hz (IMF1); (2) these frequency clusters were highly reproducible, and independent of rs-fMRI data sampling rate; (3) not all frequencies were associated with equivalent network topology, in contrast to previous findings. In fact, while IMF4 is most likely associated with physiological fluctuations due to respiration and pulse, IMF3 is most likely associated with metabolic processes, and IMF2 with vasomotor activity. Both IMF3 and IMF4 could produce the brain-network topology typically observed in fMRI, whereas IMF1 and IMF2 could not. These findings provide initial evidence of feasibility in decomposing the rs-fMRI signal into its intrinsic oscillatory frequencies in a reproducible manner.

Highlights

  • The frequency characteristics of the resting-state BOLD fMRI signal are of increasing scientific interest (Salvador et al, 2005; Niazy et al, 2011; Kalcher et al, 2014), as we discover more frequency-specific biological interpretations within the conventional data-acquisition bandwidth of 0–0.25 Hz (Golestani et al, 2015; Hocke et al, 2016)

  • The main differences between methods based intrinsic-modal decomposition and those based on bandpass filtering are: (1) results and interpretations of band-pass filtering are sensitive to the shape of the band-pass filter; (2) band-pass filtering is sensitive to non-linearity in the signal, such as introduced when the signal is non-stationary

  • Our work is novel in the following aspects: (1) instead of relying on the assumption that our data-driven method accurately decomposes the modes of the signal, we test this accuracy using rs-fMRI-informed simulations; (2) we compared the findings from short-TR acquisitions with those based on conventional acquisitions (TR = 2 s), and assessed the reproducibility of these results for both scenarios; (3) instead of defining the rs-fMRI spectral information by broad frequency ranges, we target the frequency range typically used in functional-connectivity analyses (

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Summary

INTRODUCTION

The frequency characteristics of the resting-state BOLD fMRI (rs-fMRI) signal are of increasing scientific interest (Salvador et al, 2005; Niazy et al, 2011; Kalcher et al, 2014), as we discover more frequency-specific biological interpretations within the conventional data-acquisition bandwidth of 0–0.25 Hz (Golestani et al, 2015; Hocke et al, 2016). The variational model assesses the bandwidth of the modes by minimizing the Gaussian-regularized mean-square error between the signal and its representation as a series of Wiener filters, with the modal instantaneous frequency being determined as the center of mass of the power-spectral density function of each IMF This approach increases the robustness of the model to estimation uncertainties. Prior work (using EMD and CEEMD) have suggested that resting-state networks (RSNs) measured through rs-fMRI are frequency independent, we hypothesize that existing results are affected by modal mixing and limited frequency precision as described To address this hypothesis, we re-examine the frequency dependence of functional connectivity of RSNs using VMD

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