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Recent BOLD-fMRI studies have revealed spatial distinction between variability- and mean-based between-condition differences, suggesting that BOLD variability could offer complementary and even orthogonal views of brain function with traditional activation. However, these findings were mainly observed in block-designed fMRI studies. As block design may not be appreciate for characterizing the low-frequency dynamics of BOLD signal, the evidences suggesting the distinction between BOLD variability and mean are less convincing. Based on the high reproducibility of signal variability modulation between continuous eyes-open (EO) and eyes-closed (EC) states, here we employed EO/EC paradigm and BOLD-fMRI to compare variability- and mean-based EO/EC differences while the subjects were in light. The comparisons were made both on block-designed and continuous EO/EC data. Our results demonstrated that the spatial patterns of variability- and mean-based EO/EC differences were largely distinct with each other, both for block-designed and continuous data. For continuous data, increases of BOLD variability were found in secondary visual cortex and decreases were mainly in primary auditory cortex, primary sensorimotor cortex and medial nuclei of thalamus, whereas no significant mean-based differences were observed. For the block-designed data, the pattern of increased variability resembled that of continuous data and the negative regions were restricted to medial thalamus and a few clusters in auditory and sensorimotor networks, whereas activation regions were mainly located in primary visual cortex and lateral nuclei of thalamus. Furthermore, with the expanding window analyses we found variability results of continuous data exhibited a rather slower dynamical process than typically considered for task activation, suggesting block design is less optimal than continuous design in characterizing BOLD variability. In sum, we provided more solid evidences that variability-based modulation could represent orthogonal views of brain function with traditional mean-based activation.

Distinction Between Variability-Based Modulation and Mean-Based Activation Revealed by BOLD-fMRI and Eyes-Open/Eyes-Closed Contrast