Brain stimulation for the treatment of epilepsy: Current application and outlook of network neuromodulation

Brain stimulation provides an alternative, reversible, and adjustable treatment option for patients with drug-resistant epilepsy (DRE). Deep brain stimulation (DBS) and responsive neural stimulation (RNS) have been applied in patients in the past decade, partly filling an essential gap for patients with DRE who are ineligible or unwilling to receive irreversible surgical treatments. Another new type of brain stimulation, chronic subthreshold cortical stimulation (CSCS), also deserves attention. In the past decade, clinical data about those therapies’ long-term safety and efficacy have been accumulated, and their clinical effectiveness has been further confirmed. Nonetheless, the therapeutic mechanisms of brain stimulation have been found far more complicated than the original design. The clinical effects of different stimulation targets of DBS and the indications for patient selection remain to be further demonstrated and clarified. There is a growing consensus that the efficacy of RNS is likely due to a long-term neuromodulatory effect on the epileptogenic network, rather than only arresting seizures. Triggering strategy (open-loop versus closed-loop) could not be seen as the essential difference between DBS and RNS in the neuromodulation mechanism for epilepsy. In addition to excitability inhibition and desynchronization for the epileptogenic zone, stimulation-induced modification of the connection and plasticity of the distributed network were identified. Further in-depth understanding of the modulatory mechanism will contribute to creating novel modulation systems and improving the efficacy of brain stimulation in the treatment of epilepsy.