Abstracts

Rationale: Interictal spikes (IISs) are the hallmarks of the presence of an active epileptic focus. However, the relationship between IIS and ictal events has been widely debated. While some studies indicate that IIS may trigger an interictal-to-ictal transition, it is also reported that interictal events may play a role in the control of seizures. The main reason for this debate relies on the lack of knowledge on the initiation dynamics of both IIS and ictal events. Here, we observe the initiation processes of both IIS and ictal events in a focal neocortex epilepsy model. Methods: The focal epilepsy model was created by local injection of 4-Aminopyridine (15mM, 0.5 μl) (4-AP) and the local field potential was recorded from the 4-AP injection electrode. Wide field calcium imaging was employed for wide-field recording of neuronal activity.  Multielectrode arrays (10 by 10 grid, 40 µm spacing) were used to recorded local field potential and multiunit activity.  In some experiments, local field potentials were recorded from both the neocortex and the thalamus. A bipolar electrode with an interelectrod distance of 150 μm was employed to deliver single or train squire wave stimulation to the ventrolbasal thalamus. Results: The 4-AP induced ictal events were focally distributed near the 4-AP injection site, the ictal focus. On the other hand, the ictal first spike and IISs propagated to the whole field of view. Both IIS and the first spike initiated from cortical areas far removed from the ictal focus and propagated back into the focus. During both the first spike and IIS, thalamic involvement reliably lead the cortical activity. These results indicate that both ictal events and the IIS were triggered by thalamocortical connections. This was further supported by the observation that TTx injection into the thalamus suspended both IIS and ictal events. We then delivered electrical stimulation to the ventrolbasal thalamus. Single or a train of square-wave stimulation was found to trigger the onset of both the first spike of ictal event and the IIS. Conclusions: We demonstrate that IIS and the first spike of ictal events have similar spatiotemporal dynamics and are both triggered by thalamocortical input. Our data indicates that IIS and ictal events may be arise as different cortical response to a global thalamic input. Funding: NSF-1264948