Possible regulatory mechanisms of typical and atypical absence seizures through an equivalent projection from the subthalamic nucleus to the cortex: Evidence in a computational model.

The subthalamic nucleus (STN) is an important structure that regulates basal ganglia output and has been involved in the pathophysiology of epilepsy disease. In this paper, we propose an equivalent inhibitory pathway directly projecting from the STN to the cortex and systematically study its regulatory effect on absence seizures. Interestingly, we find that this equivalent inhibitory projection is a key factor for assisting in the development of atypical absence seizures. Through computational simulation and model analysis, we find that the enhancement of coupling strength on this equivalent STN-cortex projection can effectively suppress typical and atypical spike and wave discharges (TSWDs and ASWDs) during absence seizures. Furthermore, altering the activation level of STN through external stimuli can also control seizures, and the presence of equivalent STN-cortex projection makes the control effect more easier to achieve. Several direct and indirect pathways related to the STN can achieve inhibition of SWDs by regulating the activation level of STN, and relevant control strategies have high biological plausibility. Therefore, the STN may be an effective target for the deep brain stimulation (DBS) to control absence seizures. Importantly, we observe that the control effect of DBS-STN on SWDs is significantly superior to other basal ganglia targets in this model. Moreover, we find that the parameter range and value with high biological plausibility for the coupling weight in this equivalent STN-cortex projection can be effectively estimated in this model. Our results imply that the inhibitory effect from the STN to the cortex plays a crucial role in regulating both typical and atypical SWDs, and the STN might be a potential and reasonable DBS target for the treatment of absence epilepsy.