Altered frequency architecture of spontaneous brain activity in asymptomatic carotid stenosis: a wavelet-based resting-state fMRI study

The intrinsic brain activity measured by resting-state fMRI (rs-fMRI) consists of synchronized neural oscillations across a broad range of low frequencies. Although previous studies have linked frequency-specific changes to cognitive function and impairment, the alterations of these frequency-specific spatiotemporal patterns in chronic occlusive cerebrovascular disease remain unclear. In this study, we investigated the cross-frequency structure underlying cognitive impairment in patients with severe asymptomatic carotid stenosis (SACS) using wavelet-transformed amplitude of low-frequency fluctuation (wavelet-ALFF) of rs-fMRI. We found that, in healthy controls, frequency-specific wavelet-ALFF exhibited a spatial distribution from lower to higher frequencies, aligned with the functional hierarchy extending from the default mode network (DMN) to primary somatomotor and subcortical regions. In contrast, SACS patients exhibited frequency-dependent changes, including significantly decreased wavelet-ALFF in the anteromedial DMN at lower frequencies and the posteromedial DMN at higher frequencies. Further spatiotemporal decomposition analysis revealed that SACS patients exhibited abnormal cross-frequency coupling in the DMN. Our findings suggest that frequency-specific changes underlying cognitive impairment in SACS arise from spatiotemporally abnormal cross-frequency interplay within the DMN. These insights may contribute to a better understanding of other major brain diseases.