Brain-wide resting-state connectivity regulation by the hippocampus and medial prefrontal cortex is associated with fluid intelligence.

The connectivity hub property of the hippocampus (HIP) and the medial prefrontal cortex (MPFC) is essential for their widespread involvement in cognition; however, the cooperation mechanism between them is far from clear. Herein, using resting-state functional MRI and Gaussian Bayesian network to describe the directed organizing architecture of the HIP-MPFC pathway with regions in the brain, we demonstrated that the HIP and the MPFC have central roles as the driving hub and aggregating hub, respectively. The status of the HIP and the MPFC is dominant in communications between the HIP and the default-mode network, between the HIP and core neurocognitive networks, including the default-mode, frontoparietal, and salience networks, and between brain-wide representative regions, suggesting a strong and robust central position of the two regions in regulating the dynamics of large-scale brain activity. Furthermore, we found that the directed connectivity and flow from the right HIP to the MPFC is significantly linked to fluid intelligence. Together, these results clarify the different roles of the HIP and the MPFC that jointly contribute to network dynamics and cognitive ability from a data-driven insight via the use of the directed connectivity method.