Multi-pathway synergistic regulation and epileptic state transitions in a thalamocortical coupled model

Epilepsy is a prevalent and disabling neurological disorder worldwide. Existing studies confirm that thalamocortical circuits dominate the generation of spike-and-wave discharges (SWDs) in absence epilepsy, and interhemispheric coupling modulates epileptic progression. However, the synergistic regulatory roles of excitatory interneurons (EIN) and thalamic inhibitory interneurons (TIN) in bilateral neural networks remain unclear. This study constructs a bilaterally coupled thalamocortical model containing EIN and TIN subgroups. Centering on the pyramidal (PY) neuron→TIN→TC disynaptic feedforward inhibitory cascade, we explore the synergistic regulation of EIN-mediated excitatory input to PY neurons and intrathalamic inhibition from TIN to thalamocortical (TC) neurons. We also compare the inhibitory effects of single deep brain stimulation (DBS), Electromagnetic Stimulation(EMS) and their combined intervention on epileptiform oscillations. The results demonstrate that weakened signal transmission along the full PY→TIN→TC feedforward inhibitory cascade disrupts thalamic negative feedback loops. The co-enhanced EIN→PY and TIN→TC pathways exert synergistic antiepileptic effects, and single high-frequency DBS presents better efficacy than combined strategies with no linear superposition. This study clarifies the multi-pathway regulatory mechanism centered on the PY→TIN→TC circuit and provides theoretical references for optimizing targeted intervention strategies for epilepsy.