Negative functional connectivity and its dependence on the shortest path length of positive network in the resting-state human brain.

It is suggested that structurally segregated and functionally specialized brain regions are mediated by synchrony over large-scale networks in order to provide the formation of dynamic links and integration functions. The existence of negative synchrony, or negative functional connectivity (NFC), however, has been a subject of debate in terms of its origin, interpretation, relationship with structural connectivity, and possible neurophysiological function. The present study, which incorporated 20 cognitively healthy elderly human subjects, focused on testing the hypothesis that NFC significantly correlates with the shortest path length (SPL) in the human brain network. Our theoretical calculation, simulated data, and human study results support this hypothesis. In the human study, we find that (1) the percentage of NFC connections among all connections between brain regions significantly correlates with spatial Euclidian distance; (2) the strength of the NFC between the right amygdala and the left dorsolateral prefrontal cortex is significantly correlated with the SPL across the 20 human subjects; (3) such a significant relationship between the NFC and SPL exists in all the NFC connections in the whole brain; and (4) the correlations between the NFC and SPL also are frequency bandwidth dependent. These results suggest that an accumulated phased delay gives rise to the NFC, along the shortest path in the large-scale brain functional network. It is suggested that our study can be extended to examine a variety of neurological diseases and psychiatric disorders by measuring the changes of SPL and functional reorganization in the brain.