The influence of the amplitude of low-frequency fluctuations on resting-state functional connectivity

Studies of brain functional connectivity have provided a better understanding of organization and integration of large-scale brain networks. Functional connectivity using resting-state functional magnetic resonance imaging (fMRI) is typically based upon the correlations of the low-frequency fluctuation of fMRI signals. Reproducible spatial maps in the brain have also been observed using the amplitude of low-frequency fluctuations (ALFF) in resting-state. However, little is known about the influence of the ALFF on the functional connectivity measures. In the present study, we analyzed resting-state fMRI data on 79 healthy old individuals. Spatial independent component analysis (ICA) and regions of interest (ROIs) based connectivity analysis were first performed to obtain measures of functional connectivity. ALFF maps were also calculated. First, voxel-matched inter-subject correlations were computed between back-reconstructed IC and ALFF maps. For all the resting-state networks, there was a consistent correlation between ALFF variability and network strengths (within regions that had high IC strengths). Next, inter-subject variance of correlations across 160 functionally defined ROIs were correlated with the corresponding ALFF variance. Several of these ROIs and their connections to other regions were more likely to correlate with its own regional ALFF. These regions were mainly located in the anterior cingulate cortex, medial prefrontal cortex, precuneus, insula, basal ganglia, and thalamus. These associations may suggest a functional significance of functional connectivity modulations. Alternatively, the fluctuation amplitudes may arise from physiological noises, and therefore, need to be controlled when studying resting-state functional connectivity.