Abstracts

Rationale: Impaired consciousness during and following seizures has a dramatic impact on quality of life, morbidity and mortality. Restoring consciousness after seizures would be highly beneficial to patients. In prior work, we developed a rat model of limbic seizures which recapitulates the neocortical slow waves, depressed subcortical arousal and behavioral arrest associated with loss of consciousness in human temporal lobe epilepsy. Prior work has also shown that central thalamic nuclei neurostimulation can improve behavioral arousal in human disorders of consciousness, suggesting this therapeutic modality could be used to improve postictal unconsciousness. Methods: We stereotactically implanted electrodes in bilateral central lateral thalamus and confirmed localization with histology. We stimulated bilateral intralaminar thalami at 100 Hz and varying current intensities for 20 seconds while synchronously recording electrophysiology and behavior. We induced seizures with 2-second 60 Hz hippocampal stimulation. Results: Here we explored the effects of intralaminar thalamic stimulation on cortical arousal in our rat limbic seizure model. Intralaminar thalamic neurostimulation under deep anesthesia produced loss of cortical slow waves, sustained increases in tonic cortical neuronal firing, and signs of activity with exploratory behavior. Similar beneficial effects on cortical physiology and behavioral arousal were seen when thalamic stimulation was applied in the postictal period in lightly anesthetized or awake behaving rats. Conclusions: These data suggest a novel therapeutic strategy for improving postictal impairments in consciousness. When paired with responsive neurostimulation algorithms, we may be able to rapidly translate this approach to improve impaired consciousness after seizures in patients.