Spike sorting is a critical first step in extracting neural signals from large-scale electrophysiological data. This manuscript describes an efficient, reliable pipeline for spike sorting on dense multi-electrode arrays (MEAs), where neural signals appear across many electrodes and spike sorting currently represents a major computational bottleneck. We present several new techniques that make dense MEA spike sorting more robust and scalable.

New silicon technology is enabling large-scale electrophysiological recordings in vivo from hundreds to thousands of channels. Interpreting these recordings requires scalable and accurate automated methods for spike sorting, which should minimize the time required for manual curation of the results. Here we introduce KiloSort, a new integrated spike sorting framework that uses template matching both during spike detection and during spike clustering. KiloSort models the electrical voltage as a sum of template waveforms triggered on the spike times, which allows overlapping spikes to be identified and resolved. Unlike previous algorithms that compress the data with PCA, KiloSort operates on the raw data which allows it to construct a more accurate model of the waveforms. Processing times are faster than in previous algorithms thanks to batch-based optimization on GPUs. We compare KiloSort to an established algorithm and show favorable performance, at much reduced processing times. A novel post-clustering merging step based on the continuity of the templates further reduced substantially the number of manual operations required on this data, for the neurons with near-zero error rates, paving the way for fully automated spike sorting of multichannel electrode recordings.

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In the method section of our paper, we describe the general encoding-decoding paradigm. We provide a brief overview of our data preprocessing pipeline, which involves the following steps. We employ the method of Boussard et al. (2021) to estimate the location of Decentralized registration (Windolf et al., 2022) is applied to track and correct Figure 6: Motion drift in "good" and "bad" sorting recordings. "bad" sorting example, which is still affected by drift even after registration. To decode binary behaviors, such as the mouse's left or right choices, we utilize In this section, we provide visualizations to gain insights into the effectiveness of our proposed decoder.

Unlike the case for text--wherein every document written in a given language shares a basic lexicon for tokenization--there is no one-to-one correspondence between neurons in different individuals.