The Effect of Electrical Stimulation of the Subthalamic Nucleus on Seizures Is Frequency Dependent

Abstract

Summary:Purpose: Animal studies and anecdotal human case reports have indicated that the subthalamic nucleus (STN) may be a site of anticonvulsant action.Methods: We tested the hypothesis that continuous electrical stimulation of the STN inhibits seizures acutely. We determined the effects of three stimulation frequencies, 130 Hz, 260 Hz, and 800 Hz, on generalized clonic and tonic-clonic flurothyl seizures. Adult male rats were implanted with concentric bipolar stimulating electrodes in the STN bilaterally. After recovery, rats underwent flurothyl seizures to compare the effects of each stimulation frequency on seizure threshold. Rats were tested 4 times, twice in the stimulated condition, and twice in the unstimulated condition. The order of trials was random, except that stimulation trials alternated with control trials. Flurothyl seizure thresholds under each stimulation condition were compared with control values from the same animal.Results: Bilateral stimulation of the STN at 130 Hz produced a significant increase in the seizure threshold for clonic flurothyl seizures, whereas stimulation at 260 Hz did not appear to have any effect on seizures. STN stimulation at 800 Hz significantly lowered seizure threshold for tonic-clonic seizures.Conclusions: We conclude that electrical stimulation of the STN can be anticonvulsant, but the effects appear to depend on the stimulation frequency and the type of seizure.

Deep Brain Stimulation for Epilepsy

“…30 On the other hand, lowfrequency (8 Hz) DBS was proconvulsant, as noted in earlier studies. 18,31 Bilateral ANT DBS may also prolong the latency of onset of status epilepticus after administration of pilocarpine. 32 Nevertheless, efficacy of ANT DBS for epilepsy in animal models is still debated, given its lack of effect reported from numerous studies, as well as an exacerbation of seizure frequency by chronic ANT DBS.…”

Deep brain stimulation for medically refractory epilepsy

“…42 Seizures can be induced in guinea pigs by microinjection into the ANT of the excitatory agents kainic acid, bicuculline, or pentylenetetrazol. 55 Interrupting the mammilothalamic tracts by electrolytic lesions offers protection from the epileptogenic action of pentylenetetrazol.…”

“…An average reduction in seizure frequency of 67% (range 44-94%), was noted during the sham interval. Once the stimulators were turned on, a 49% (range 35-76%) reduction in seizure frequency was noted over the subsequent follow-up period (mean 43.8 months, range [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48]. In 1 patient the stimulator was inadvertently turned off during months 7-12, during which period the seizure frequency increased compared to baseline.…”

“…42 A microthalamotomy effect has been postulated based on the observation that some patients obtain a reduction in seizure fre- …”

“…6 Moreover, at high frequencies DBS may abolish cortical epileptiform activity. 42 A microthalamotomy effect has been postulated based on the observation that some patients obtain a reduction in seizure fre-quency prior to activation of the pulse generator. 3,50 Other studies have failed to detect a lesioning effect in the immediate postoperative period.…”