448 Analysis of Bipolar Re-Referencing on Spectral Composition and Spike Detection in Human Electrocorticography

Abstract

INTRODUCTION: Electrocorticography (ECoG) enables the localization of epileptic seizure foci prior to surgical resection. Improving the signal-to-noise ratio is paramount, and can be accomplished with bipolar re-referencing. METHODS: Intracranial recordings for drug-resistant epilepsy were performed at UCSF using high-density ECoG grid (4 mm inter-electrode pitch), strip (10 mm), and penetrating depth (5 mm) electrodes. Raw voltages for each participant (n = 11) were systematically re-referenced (bipolar subtraction) at increasing scales (4 mm-50 mm) and a multi-taper power spectrum (2-200 Hz) was generated around spike-free baseline windows. Cluster based permutation tests (p < 0.05) were used to compare spectral composition features after z-scoring log power features by frequency and binning by bipolar distance. High-density and low-density (4mm vs 8mm) re-referencing schemes were used for spike localization by applying a line length transform to highlight epileptiform features in peri-spike windows and comparing to baseline windows using cluster-based permutation tests. RESULTS: Bipolar pair distances <10 mm decreased low-frequency (<30 Hz) power, whereas both low and high frequency (30-200 Hz) power increased by longer bipolar distances. These findings were consistent across different components (grids, strips, depths). The detection of high gamma (50-200 Hz) neural activity in the STG related to an audio stimulus was enhanced at bipolar distances of <45 mm but attenuated at higher distances. Similar spike detection (duration and number of channels involved) was seen between high- vs. low-density bipolar re-referencing. CONCLUSIONS: Re-referencing at <10 mm bipolar distance preferentially attenuated low-frequency signal while standard clinical and larger distances systematically augmented broadband (2-200 Hz) signals. Shorter distances, especially high-density, augmented spatial delineation of neural activity when compared to more widely spaced arrays, however, standard clinical arrays capture the general spatio-temporal extent of spike waveforms.