Abstracts

Rationale: Impaired consciousness during and after seizure from medically and surgically refractory epilepsy has a dramatic impact on morbidity, mortality, and overall quality of life. The ability to improve consciousness in the ictal and postictal periods would be highly beneficial to patients. We have developed a partial limbic seizure rodent model which mimics the human cortical EEG signature of neocortical slow waves and behavioral arrest, which is associated with loss of consciousness in temporal lobe epilepsy. We have additionally shown EEG and fMRI suppression of the arousal system, including the brainstem cholinergic and intralaminar thalamic nuclei. This model allows us to investigate different interventions that may positively impact loss of consciousness during limbic seizures.Methods: We investigated the effects of dual-site intralaminar thalamic and pontine stimulation on cortical arousal in the rodent limbic seizure model. Electrodes were targeted to the intralaminar central lateral thalamus (CL) and pontine nucleus oralis (PnO), and localization was confirmed via histologic staining. Seizures were induced by brief 2 second hippocampal stimulation at 60 Hz. Stimulation of the bilateral intralaminar thalamic CL at 100 Hz and PnO at 50 Hz was then applied at varying current intensities during the ensuing seizure for up to 120 seconds while we synchronously recorded electrophysiology and behavior.Results: Dual-site CL and PnO stimulation during seizures reduced cortical slow waves by more than 85% while simultaneously eliciting robust behavioral arousal as measured by spontaneous exploratory behavior (n=6). This effect of dual-site PnO and CL stimulation on cortical slow waves and behavioral arousal resembled those seen with stimulation during physiological sleep (n=6) and under anesthesia (n=6). This was in contrast to stimulation of just CL or PnO alone, which was insufficient to produce reliable cortical desynchronization and behavioral improvement during seizures (n=12).Conclusions: These data suggest a novel potential therapeutic approach to improving consciousness during and after seizures. Further, pairing this with responsive neurostimulation algorithms may lead to rapid implementation of a therapy for preventing impaired consciousness during and after seizures in epilepsy patients. Studying this model with explicit behavioral tasks will help to determine the degree of recovery in the ictal and postictal periods. Finally, other states of decreased consciousness, such as vegetative and minimally conscious states, may similarly benefit from multi-site stimulation within the arousal networks.