Abstracts

Rationale: The postictal period immediately following seizures is characterized by electrophysiological cortical depression, decreased cortical blood flow and often neurocognitive disturbance including decreased level of consciousness. For patients suffering from medically and surgically refractory epilepsy, the use of deep brain stimulation (DBS) to improve consciousness during the postictal period may have a major benefit on quality of life. Previous work in a rodent model of limbic seizures has shown that bilateral stimulation of the thalamic intralaminar central lateral nucleus (CL) during the postictal period of seizures improved behavioral arousal while restoring normal-appearing cortical electrophysiology. Here, using the same rodent model of limbic seizures, our aim is to further investigating the effect of this stimulation on purposeful behavior. Methods: By implementation of a lever-press escape/avoidance (E/A) task, we evaluated task performance during natural sleep and the postictal period, and assessed the effect of DBS. During successive sessions, animals were trained to press a lever to avoid foot-shock when an auditory stimulus occurs. After they completed training, bilateral CL and unilateral hippocampal and orbital frontal cortex electrodes were implanted. Animals were reevaluated in the task after recovering from surgery and retrained until they achieved >90% avoidance, at which point sessions with seizure trials began. Within sessions, seizures were induced by 2 second 60 Hz hippocampal stimulation. Following the appearance of slow-wave activity during the post-ictal period, the CL was stimulated at 100 Hz while recording electrophysiology and behavior. We also compared behavior elicited during sleep to that measured during the post-ictal period as a natural control for behavior during an inattentive state. Results: E/A task performance was impaired during the postictal period with cortical slow wave activity (avoidance percentage: 17 ± 9.6, response time: 63 ± 3.4 s, n=8 seizures from 3 rats) when compared with the natural sleep slow-wave period (avoidance percentage: 79 ± 20.8, response time: 13 ± 3.8 s, n=17 seizures from 3 rats) (P Conclusions: This is the first instance in which we developed a paradigm to evaluate behavioral responses during the postictal period in a rodent model. Using this behavior task, a difference in task performance ability was identified when comparing normal sleep and the postictal slow-wave period in rats. Moreover, the DBS in bilateral CL increased the ability to perform the E/A task in the postictal period which further supports the potential role of targeted DBS to improve consciousness and cognitive function in patients following seizures. Funding: NIH R01 NS066974 and R01 NS096088