Thesis defense Lili Huang (Donders Series 180)

11 March 2015

Promotor: Prof.dr. G. van Luijtelaar

The subiculum: a promising new target of deep brain stimulation in temporal lobe epilepsy. Investigation of closed-loop and open-loop high frequency stimulation of the subiculum in seizure and epilepsy models in rats

Deep brain stimulation (DBS) is one viable alternative treatment for refractory epilepsy such as temporal lobe epilepsy (TLE). DBS, especially high frequency stimulation (HFS) has been applied to patients with refractory epilepsy and has achieved moderate to positive effects. The hippocampus plays an important role in the generation and propagation of temporal lobe seizures and the subiculum is one major output structure in the hippocampus. One main goal of the current thesis was to investigate whether the subiculum is a potential target of DBS in different seizure and epilepsy models of TLE in rats. Closed-loop stimulation that is dependent on occurrence of seizures was also investigated and compared to classic open-loop stimulation in these rat models.

In the current thesis, a high rate of acute induced seizures can be repeatedly and reliably induced by focal administration of kainic acid (KA) in the CA3 area in rats. The early online detection of seizures is also possible with development of automatic seizure detection algorithm in a brain computer interface system. The outcomes also showed that both closed-loop and open-loop stimulation had beneficial effects on acute induced seizures and spontaneous seizures. Importantly, high efficacy of closed-loop stimulation indicates that the subiculum is sensitive to timing of stimulation and can be a proper target for closed-loop stimulation. Such anticonvulsant effects of subicular stimulation varied with different seizure induction protocols, the severity and types of seizures: immediate and lasting effects on focal seizures, and delayed effects on generalized seizures. Subicular stimulation had no or even proconvulsant effects on the rats that reached status epilepticus (SE), indicating stimulation should be avoided to patients who have SE if possible. In sum, the outcomes of these animal studies suggest that the subiculum could be a promising new target of DBS for epilepsy treatment.