Stimulation strategies for absence seizures: targeted therapy of the focus in coupled thalamocortical model

Abstract

Motivated by the recent experimental findings that thalamic reticular nucleus (TRN) may be a pacemaker of absence seizures, we explore whether changes in the level of TRN activation can induce absence seizures by using a coupled thalamocortical model. We first simulate different firing states by considering the interaction of pathway between cortical excitatory pyramidal neuronal population (PY)–TRN and specific relay nucleus (SRN)–TRN. By simultaneously increasing the coupling strength of each of these pathways, we can reproduce the absence seizures, which indicates that epileptic seizures may be caused by activating the TRN. We further infer that the TRN may be an epileptogenic focus. Following this, different stimulation strategies, including deep brain stimulation, 1:0 coordinated reset stimulation (CRS) and 3:2 CRS, are applied in TRN. By qualitatively analyzing the efficacy of three different stimulation methods, we find that 3:2 CRS is a more effective and safe method to control absence seizures in the first compartment, for which we then further explore the impact of 3:2 CRS in the second compartment. The results show that the additional stimulation in the second compartment also can lead to a considerable decrease in the spike-and-wave discharges (SWD) oscillation region. Therefore, we conclude that TRN-3:2 CRS is an optimal electrical stimulation method for our modeling and simulation studies. Furthermore, we hope that these numerical simulation results can provide some references for the treatment of real epilepsy patients in the future.