Novel visualization of the spatiotemporal relationship between ictal spiking and LFP supports the involvement of mid-range excitatory circuits during human focal seizures

Abstract

AbstractThe relationship between action potentials and the associated local field potential (LFP) in neural recordings is typically studied only in the temporal domain using the spike-triggered average (STA). In this study, we present a novel approach, termed the spatiotemporal spike-centered average (st-SCA), that allows for visualization of the spike-LFP relationship in both the temporal and spatial domains. In this method, a 3D spatiotemporal topography of spike-associated LFP is calculated from a 2D spatial average of the LFP centered around the time and location of individual spikes. We applied this method to 25 microelectrode array (MEA) recordings obtained from seven patients with pharmacoresistant focal epilepsy during ictal and interictal states. Five patients in this dataset had MEA implants in recruited cortex, and two had implants in unrecruited cortex. Of the five patients with arrays implanted in recruited territory, three showed STAs that resembled sine cardinal (sinc) functions, and two showed non-sinc functions. Using the st-SCA, we found that the patients who showed a sinc-function pattern in the temporal domain showed a donut-shaped ring of LFP activity in the spatial domain. This observation was corroborated by a theoretical model describing an ictal spike as measured by a macroelectrode. The model also revealed a special symmetry wherein temporal component of the st-SCA predicts the spatial component when they both approximate sinc-functions. Supporting this theoretical derivation, a radial cut of the donut-shaped st-SCA showed a spatial pattern consistent with a sinc-function. This spatial sinc-function had peaks separated by ∼2.5mm—a measurement that supports the role of mid-range excitatory connections during ictal activity. In sum these findings suggest that patients whose seizures engage mid-range connections may be identifiable by the spatiotemporal features of ictal spike-associated LFP activity.