Abstract
OBJECTIVE: The objective of this study was to explore the distributed network effects of intracranial electrical stimulation in patients with medically refractory epilepsy using dynamic functional connectivity (dFC) and graph indicators. METHODS: The time-varying connectivity patterns of dFC (state-based metrics) as well as topological properties of static functional connectivity (sFC) and dFC (graph indicators) were assessed before and after the intracranial electrical stimulation. The sliding window method and k-means clustering were used for the analysis of dFC states, which were characterized by connectivity strength, occupancy rate, dwell time, and transition. Graph indicators for sFC and dFC were obtained using group statistical tests. RESULTS: DFCs were clustered into two connectivity configurations: a strongly connected state (state 1) and a sparsely connected state (state 2). After electrical stimulation, the dwell time and occupancy rate of state 1 decreased, while that of state 2 increased. Connectivity strengths of both state 1 and state 2 decreased. For graph indicators, the clustering coefficient, k-core, global efficiency, and local efficiency of patients showed a significant decrease, but the brain networks of patients exhibited higher modularity after electrical stimulation. Especially, for state 1, there was a significant decrease in functional connectivity strength after stimulation within and between the frontal lobe and temporary lobe, both of which are associated with the seizure onset. CONCLUSION: Our findings demonstrated that intracranial electrical stimulation significantly changed the time-varying connectivity patterns and graph indicators of the brain in patients with medically refractory epilepsy. Specifically, the electrical stimulation decreased functional connectivity strength in both local-level and global-level networks. This might provide a mechanism of understanding for the distributed network effects of intracranial electrical stimulation and extend the knowledge of the pathophysiological network of medically refractory epilepsy.