Abstracts

Rationale: Medically refractory epilepsy is highly debilitating and lethal (mortality rate is 5 times higher than that of the general population). Surgical treatment is often the only option, but current conventional surgical interventions are frequently associated with failures, complications and high costs. Many patients are not candidates for respective surgery and have few treatment options available. One of the major impediments to improving the diagnosis and treatment of refractory epilepsy is a basic lack of knowledge about how seizures are organized, how they start, spread and terminate. Intracranial monitoring of brain activity via stereo-electroencephalography (SEEG) has been employed to study electrophysiological signatures of seizures, in order to identify the epileptogenic zone (EZ) for possible resection or neuromodulation. However, despite considerable evidence for subcortical involvement in epilepsy collected over the past century, such studies now focus mainly on examining seizures in cortical brain regions, leaving largely unexplored the vast thalamocortical networks that are known to underlie many aspects of cortical synchronization.

Methods: In order to characterize the patterns of ictal functional connectivity between thalamic nuclei and related cortical structures that are characteristic of medically refractory focal epilepsy, we have studied 11 patients with MRE who were implanted with SEEG depth electrodes that simultaneously explore thalamic nuclei and cortical regions. Areas of interest included the anterior and pulvinar thalamic nuclei as well as frontal and posterior quadrant cortical regions. Specific patterns of synchronized activity between subcortical and cortical regions were quantified in the pre-ictal, ictal and post-ictal periods. We hypothesized that peri-ictal synchronization of local field potentials occurs between the cortical EZ and the associated thalamic nuclei.

Results: Indeed, in preliminary analyses, we found that high-frequency (75-300 Hz) phase synchrony selectively increased during seizures between the pulvinar nucleus and EZ identified in occipital cortex; whereas the anterior nucleus showed similar synchronization with EZ located in frontal cortical areas. Furthermore, in a patient with posterior quadrant epilepsy, high frequency pulvinar stimulation (30 seconds train duration, 100 Hz) produced a suppression of epileptiform activity in the EZ during the stimulation epoch. The effect appeared to be frequency and location dependent, with optimal responses at 100 Hz stimulation applied in the posterior lateral pulvinar nucleus.

Conclusions: These results support the hypothesis that thalamo-cortical networks critically participate in seizure initiation and termination via their reciprocal connections. This knowledge will advance the development of treatment options by defining optimal neuromodulation targets and parameters of therapeutic electrical stimulation intended to modify these networks.

Funding: Please list any funding that was received in support of this abstract.: Hamot Health Foundation. "The Role of Basal Ganglia in Language and Motor Control."