Deep brain stimulation of the anterior nucleus of the thalamus in animal models of mesial temporal lobe epilepsy: A literature review.

Epilepsy affects approximately 1 % of the global population, presenting as a complex and heterogeneous disorder characterized by spontaneous, recurrent seizures. Focal onset seizures comprise half of all epilepsy cases. Mesial temporal lobe epilepsy (MTLE), the most prevalent form of focal seizures in adults, originates in the temporal lobe and is challenging to manage with standard antiseizure medications. Deep brain stimulation (DBS) targeting the anterior nucleus of the thalamus (ANT) has emerged as a therapeutic option for drug-resistant cases. Although clinical effects are well documented, pre-clinical research remains limited. To date, only 28 studies have been published, mostly in rodents and few in primates and sheep. This narrative review examines the anatomical organization of the ANT across human, rodent, and non-human primate models and synthesizes findings from the preclinical studies investigating ANT-DBS in experimental MTLE animal models. Collectively, these studies demonstrate an approximate 50 % reduction in seizure frequency, mirroring recent clinical outcomes. However, the majority of studies have focused on high-frequency stimulation (>100 Hz), with few exploring multiple stimulation frequencies. Additionally, outcomes from intermittent ON/OFF stimulation were inconclusive or showed worsening effects in two out of three studies. Thus, several crucial parameters, including stimulation frequency, pattern, and other variables remain inadequately explored in preclinical MTLE models yet hold potential to enhance therapeutic efficacy and patient outcomes.