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 (1-4). Low-frequency stimulation of the hippocampal commissure has yielded a greater than 90% reduction in seizure frequency in in-vitro experiments, chronic animal studies, and in one clinical trial for patients with mesial temporal lobe epilepsy (1-4). For cortical seizures, a similar approach would be to target the corpus callosum. Methods: 4-aminopyridine (4-AP) was injected in the primary motor cortex of 24 rats under anesthesia. Recording electrodes were placed in the contralateral motor cortex and hippocampus. Three pairs of stimulating electrodes were inserted into the corpus callosum along its longitudinal axis. Local field potentials were recorded one hour before, during, and after stimulation to determine the effect of stimulation on seizure duration. Stimulation was delivered from each pair of electrodes independently in separate experiments at 1, 10, 20, and 30Hz. Furthermore, electrical stimulation was injected from the region of the corpus callosum with the highest degree of innervation of the seizure focus as measured by the amplitude of the evoked potential. Evoked potentials were measured in order to determine the selectivity of this stimulation paradigm. Results: Corpus callosum stimulation was effective at suppressing seizures at 10 Hz by 76% (p < 0.05, n=5) and 20 Hz by 95% (p>0.9999, n=5). Furthermore, stimulation was only effective at suppressing seizures only when the pair of electrodes were placed within the section of corpus callosum fibers innervating the seizure focus. Secondarily generalized seizures in the hippocampus were eliminated when seizures in the cortical focus were suppressed. Conclusions: Low-frequency fiber tract stimulation of the corpus callosum could suppress both cortical and hippocampal seizures in an acute model of focal cortical epilepsy. 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. Selective placement of stimulation electrodes along the corpus callosum could be used as a patient specific treatment for cortical epilepsies.References1. Koubeissi MZ, Kahriman E, Syed TU, et al. Low-frequency electrical stimulation of a fiber tract in temporal lobe epilepsy. Annals of Neurology. 2013;74:223-231.2. Rashid S, Pho G, Czigler M, et al. Low frequency stimulation of ventral hippocampal commissures reduces seizures in a rat model of chronic temporal lobe epilepsy. Epilepsia. 2012;53:147-156.3. Tang Y, Durand DM. A novel electrical stimulation paradigm for the suppression of epileptiform activity in an in vivo model of mesial temporal lobe status epilepticus. International Journal of Neural Systems. 2012;22:1250006.4. Toprani S, Durand DM. Fiber tract stimulation can reduce epileptiform activity in an in-vitro bilateral hippocampal slice preparation. Experimental Neurology. 2013;240:28-43. Funding: National Institutes of Health, Grant/Award Number: 2R01NS060757-05A1