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Mildren, R.

Publications and source records attributed to Mildren, R..

2 recordsLinked to original sources

CUSP: Complex Spike Sorting from Multi-electrode Array Recordings with U-net Sequence-to-Sequence Prediction

BackgroundComplex spikes (CSs) in cerebellar Purkinje cells convey unique signals complementary to Simple spike (SS) action potentials, but are infrequent and variable in waveform. Their variability and low spike counts, combined with recording artifacts such as electrode drift, make automated detection challenging. New MethodWe introduce CUSP (CS sorting via U-net Sequence Prediction), a fully automated deep learning framework for CS sorting in high-density multi-electrode array recordings. CUSP uses a U-Net architecture with hybrid self-attention inception blocks to integrate local field potential and action potential signals and outputs CS event probabilities in a sequence-to-sequence manner. Detected events are clustered and paired with concurrently detected SSs to reconstruct the complete Purkinje cell activity. ResultsTrained on cerebellar neuropixels recordings in rhesus macaques, CUSP achieves human-expert performance (F1 = 0.83 {+/-} 0.03) and even captures valid CS events overlooked during manual annotation. Comparison with Existing MethodsCUSP outperforms traditional and state-of-the-art CS and SS sorting algorithms on CS detection. It remains robust to waveform variability, spikelet composition, and electrode drift, enabling accurate CS tracking in long-term recordings. In contrast, existing methods often show false-positive biases or degrade under drift. ConclusionsCUSP provides a scalable, robust framework for analyzing burst-like or dynamically complex spike patterns. Its generalizability makes it valuable for large-scale cerebellar datasets and other neural systems, such as hippocampal pyramidal cells, where complex bursts are critical for computation. By combining expert-level accuracy with automation, CUSP offers a broadly applicable solution for studying information coding across circuits.

neuroscience↗

SLAy-ing oversplitting errors in high-density electrophysiology spike sorting

The growing channel count of silicon probes has substantially increased the number of neurons recorded in electrophysiology (ephys) experiments, rendering traditional manual spike sorting impractical. Instead, modern ephys recordings are processed with automated methods that use waveform template matching to isolate putative single neurons. While scalable, automated methods rely on assumptions that often fail to account for biophysical changes in action potential waveforms, leading to systematic oversplitting of individual neurons into multiple putative units. Consequently, manual curation of these errors, which is both time-consuming and lacking in reproducibility, remains necessary. To improve efficiency and reproducibility in the spike-sorting pipeline, we introduce the Spike-sorting Lapse Amelioration System (SLAy), an algorithm that automatically merges oversplit spike units. SLAy employs two novel metrics: (1) a waveform similarity metric that uses a neural network to obtain spatially informed, nonlinear waveform representations, and (2) a cross-correlogram significance metric based on the earth movers distance between the observed and null cross-correlograms. To improve reproducibility and remove the need for manual tuning, we also develop an automatic parameter setting procedure for SLAy that accounts for dataset-specific characteristics. On simulated oversplitting across a diverse set of animal models, brain regions, and probe geometries, SLAy substantially outperforms an existing merging algorithm, achieving high recall without merging extraneous units. On the original datasets without simulated oversplitting, SLAy recovers [~] 95% of merges found by human curators and human curators agree with [~] 90% of merges suggested by SLAy. SLAy leverages multithreading for computational efficiency, running in less than 10 minutes for all recordings we tested. SLAy is also compatible with SpikeInterface, making it a practical and flexible solution for large-scale ephys data analysis across acquisition systems and spike sorters.

neuroscience↗