Abstracts

Rationale: Intracranial recordings in patients with drug-resistant epilepsy provide a means to study hippocampal neurophysiology in vivo. Yet, the sparse coverage of linear depth electrodes limits the understanding of how oscillations and other transient phenomena propagate within this structure. We recently described the existence of bidirectional traveling waves moving up and down the hippocampal structure using novel conformal thin-film micro-grid arrays over its surface. Here, we extend our examination to the spatiotemporal properties of transient bursts of activity including both runs (bouts) of oscillations and interictal epileptiform discharges (IEDs) in the hippocampus.

Methods: Six participants undergoing epilepsy surgery (five with medically-refractory seizures and one with a circumscribed lateral temporal lobe glioma) underwent limited excision of the antero-lateral temporal lobe for clinical purposes, exposing the ventricular hippocampal surface. Four had a right-sided surgery and were under general anesthesia and two were left-sided and in the awake state. A 32-channel micro-grid array (4 x 8 layout, 2mm spacing, 1.22mm diameter platinum/iridium contacts) was carefully placed and conformed onto the lateral hippocampal surface. This provided relatively homogenous sampling of the anterior-intermediate CA1 region, and hippocampal activity was recorded at 24 kHz from all 32 contacts for approximately 8-22 minutes for each participant.

Results: Traveling low-frequency (1-15 Hz) oscillations occurred in bouts similar to findings in depth electrode studies, with median bout durations ranging from approximately 1.2 to 3.0 seconds. Using two-dimensional regression modeling, we found that each bout nearly always traveled in a single direction until stopping, with subsequent bouts starting in either a similar or reverse direction. Maximum bout durations ranged from 3.4 to 9.3 seconds, and there was no correlation between this parameter and oscillation frequency (Spearman’s rho: -0.432, p=0.141). IEDs were observed in all participants except the one undergoing resection for a lateral temporal tumor who had a presumably normal hippocampus. IED rates ranged from 2.13 to 15.71 per minute (median 5.97) across participants. Preliminary results using a template matching algorithm suggested IEDs were generated from one or occasionally two consistent spatial sources that were distinct for each participant.

Conclusions: Low-frequency traveling oscillations occur in short (seconds-long) bouts, translating to several or dozens of continuous cycles flowing toward either the septal or temporal hippocampal pole. These transient timescales may support information processing (online and offline) by facilitating frequent diverse exchanges between the hippocampus and cortical structures interconnected along its axis. The two-dimensional spatial perspective also suggested that IEDs are consistently generated from intrahippocampal sources that show little spatial variation (within millimeters), likely representing the concrete pathophysiological circuitry that can be targeted with epilepsy surgery.

Funding: Please list any funding that was received in support of this abstract.: Dr. Kleen was funded by NIH / NINDS grant K23NS110920.