Multivariate regression methods for estimating velocity of ictal discharges from human microelectrode recordings

Abstract

Objective Epileptiform discharges, an electrophysiological hallmark of seizures, can propagate across cortical tissue in a manner similar to traveling waves. Recent work has focused attention on the origination and propagation patterns of these discharges, yielding important clues to their source location and mechanism of travel. However, systematic studies of methods for measuring propagation are lacking. Approach We analyzed epileptiform discharges in microelectrode array recordings of human seizures. The array records multiunit activity and local field potentials at 400-micron spatial resolution, from a small cortical site free of obstructions. We evaluated several computationally efficient statistical methods for calculating traveling wave velocity, benchmarking them to analyses of associated neuronal burst firing. Main results Over 90% of discharges met statistical criteria for propagation across the sampled cortical territory. Detection rate, direction and speed estimates derived from a multiunit estimator were compared to four field potential-based estimators: negative peak, maximum descent, high gamma power, and cross-correlation. Interestingly, the methods that were computationally simplest and most efficient (negative peak and maximal descent) offer non-inferior results in predicting neuronal traveling wave velocities compared to the other two, more complex methods. Moreover, the negative peak and maximal descent methods proved to be more robust against reduced spatial sampling challenges. Using least absolute deviation in place of least squares error minimized the impact of outliers, and reduced the discrepancies between local field potential-based and multiunit estimators. Significance Our findings suggest that ictal epileptiform discharges typically take the form of exceptionally strong, rapidly traveling waves, with propagation detectable across millimeter distances. The sequential activation of neurons in space can be inferred from clinically-observable EEG data, with a variety of straightforward computation methods available. This opens possibilities for systematic assessments of ictal discharge propagation in clinical and research settings.

A theoretical model for focal seizure initiation, propagation, termination, and progression

“…Also, our model predicts that outward traveling waves move at a lower speed than inward traveling waves because inhibition outside the ictal wavefront is initially intact ( Figure 4B). In agreement with our prediction, as shown in Figure 4C, a similar dependence of traveling wave speed on the direction relative to the ictal wavefront has been observed in human recordings Liou et al, 2017).…”

“…All inward traveling waves in this case are directed in a centripetal pattern uniformly towards the center point, with no directional preference within the ictal core (Figures 6A, Supplementary Video 2). However, ictal EEG discharges recorded from epilepsy patients clearly demonstrate stable preferred traveling wave directions Liou et al, 2017;Martinet et al, 2017). Although preferred directions that correspond to existing functional pathways have been demonstrated (Rossi et al, 2017), we found that they may also occur due to random fluctuations in background neural activity.…”

“…Ictal wavefront annihilation and the pre-termination stage Previously, based on analysis of human multiscale recordings, our group proposed that dissipation of the ictal wavefront is a key event preceding wide-area, simultaneous seizure termination Liou et al, 2017). This process is also evident in the model seizures.…”

“…Recovered inhibition then attenuates burst intensity ( Figure 3A & 3C), desynchronizes the neuronal populations ( Figure 3D), and slows the speed of the inward traveling waves ( Figure 3E). For the raw electrophysiology signals of traveling waves and methods of determining their velocities, see our previous publications Liou et al, 2017).…”

“…the classic Jacksonian march (York and Steinberg, 2011). As it advances, the ictal wavefront generates fast-moving ictal discharges (Trevelyan, 2009;Smith et al, 2016), directed inward towards the initiation point, at speeds two orders of magnitude higher than the wavefront propagation Liou et al, 2017). These fast-moving ictal discharges are the basis of the well-recognized high amplitude field potential deflections that are the hallmark of electrographic seizures.…”