Characterizations of resting-state modulatory interactions in the human brain

Functional connectivity between two brain regions, measured using functional MRI (fMRI), has been shown to be modulated by other regions even in a resting state, i.e., without performing specific tasks. We aimed to characterize large-scale modulatory interactions by performing region-of-interest (ROI)-based physiophysiological interaction analysis on resting-state fMRI data. Modulatory interactions were calculated for every possible combination of three ROIs among 160 ROIs sampling the whole brain. Firstly, among all of the significant modulatory interactions, there were considerably more negative than positive effects; i.e., in more cases, an increase of activity in one region was associated with decreased functional connectivity between two other regions. Next, modulatory interactions were categorized as to whether the three ROIs were from one single network module, two modules, or three different modules (defined by a modularity analysis on their functional connectivity). Positive modulatory interactions were more represented than expected in cases in which the three ROIs were from a single module, suggesting an increase within module processing efficiency through positive modulatory interactions. In contrast, negative modulatory interactions were more represented than expected in cases in which the three ROIs were from two modules, suggesting a tendency of between-module segregation through negative modulatory interactions. Regions that were more likely to have modulatory interactions were then identified. The numbers of significant modulatory interactions for different regions were correlated with the regions' connectivity strengths and connection degrees. These results demonstrate whole-brain characteristics of modulatory interactions and may provide guidance for future studies of connectivity dynamics in both resting state and task state.