Percent amplitude of fluctuation: a simple measure for resting-state fMRI signal at single voxel level

Abstract

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxels ALFF by the global mean ALFF. However, this makes the individual voxels ALFF dependent on the global mean. Although Fractional ALFF (fALFF), proposed as a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. We proposed a new standardized, stand-alone, single-voxel metrics for RS-fMRI, namely percent amplitude of fluctuation (PerAF). PerAF is an analog to the percent signal change that has been widely used in the task fMRI communities, which allows it to be a straightforward measurement of BOLD signal fluctuations during resting state. We further conducted a test-retest reliability analysis comparing the relevant metrics, which indicated that PerAF was generally more reliable than the ALFF and fALFF. In a real RS-fMRI application, we further demonstrated that with and without standardization by global mean PerAF yielded prominently different results when comparing eyes open with eyes closed resting conditions, suggesting that future study should provide both with and without global mean standardization. The above results suggest that PerAF is a more reliable, straightforward and promising measurement for voxelwise brain activity-based RS-fMRI studies. For prompting future application of PerAF, we also implemented this method into a user-friendly toolbox REST-PerAF.