Abstracts

Rationale: Stimulation of white matter tracts provides an alternative method for suppressing seizures by lowering excitability in a large portion of the brain simultaneously. Low-frequency stimulation of the corpus callosum has been shown to suppress seizures in an acute model of focal cortical seizures by more than 90%. Stimulation was shown to be selective for the region of the cortex innervated by the corresponding section of the corpus callosum. It is therefore possible that stimulation of the corpus callosum could be targeted to the specific cortical region of seizure origin. Two high-frequency grey matter stimulation technologies, focal high-frequency stimulation (FHFS) and stimulation of the anterior nucleus of the thalamus (SANT) may also prove to be effective at suppressing seizures. Methods: 4-aminopyridine (4-AP) was injected in the primary somatosensory cortex of 28 rats (4 groups of 7) under anesthesia. Recording electrodes were placed in the ipsilateral and contralateral somatosensory cortex. For the three different stimulation groups, local field potentials were recorded for one hour before stimulation as well as one hour during and following stimulation to determine the effect of stimulation on seizure duration. Stimulation was delivered in the corpus callosum low frequency (CCLFS) group as a 20 Hz bipolar pulse, whereas stimulation for FHFS and SANT was set to 200 Hz. The results from our first study in the motor cortex were compared to the seizure suppression in the somatosensory cortex.  Results: Corpus callosum stimulation was effective at suppressing seizures at 20Hz in the primary motor cortex by 95% (p<0.001, n=14). Secondarily generalized seizures in the hippocampus were eliminated when seizures in the cortical focus were suppressed. In the somatosensory cortex, a suppression of 65% in the seizure focus was observed and a 97% (p<0.01, n=7) reduction in the mirror focus. However, there was no observable effect of either FHFS or SANT on seizure duration or frequency. The fact that low-frequency stimulation of the corpus callosum suppressed seizures by such a significant amount despite the severity of the model suggests that such a technique may prove more useful in treating refractory epilepsies than currently available DBS paradigms. Conclusions: Low-frequency fiber tract stimulation of the corpus callosum could suppress cortical seizures in two acute models of focal cortical seizures. The stimulation paradigm is selective as it is only effective when targeted to specific regions of the corpus callosum that project maximally to cortical regions generating the seizure activity. In comparison, focal grey matter stimulation did not have any effect on seizures in the somatosensory model. Funding: 5T32EB004314