Altered dynamic effective connectivity of the default mode network in newly diagnosed drug-naïve juvenile myoclonic epilepsy

Juvenile myoclonic epilepsy (JME) has been repeatedly revealed to be associated with brain dysconnectivity in the default mode network (DMN). However, the implicit assumption of stationary and nondirectional functional connectivity (FC) in most previous resting-state fMRI studies raises an open question of JME-related aberrations in dynamic causal properties of FC. Here, we introduces an empirical method incorporating sliding-window approach and a multivariate Granger causality analysis to investigate, for the first time, the reorganization of dynamic effective connectivity (DEC) in DMN for patients with JME. DEC was obtained from resting-state fMRI of 34 patients with newly diagnosed and drug-naïve JME and 34 matched controls. Through clustering analysis, we found two distinct states that characterize the DEC patterns (i.e., a less frequent, strongly connected state (State 1) and a more frequent, weakly connected state (State 2)). Patients showed altered ECs within DMN subnetworks in the State 2, whereas abnormal ECs between DMN subnetworks were found in the State 1. Furthermore, we observed that the causal influence flows of the medial prefrontal cortex and angular gyrus were altered in a manner of state specificity, and associated with disease severity of patients. Overall, our findings extend the dysconnectivity hypothesis in JME from static to dynamic causal FC and demonstrate that aberrant DEC may underlie abnormal brain function in JME at early phase of illness.