End-to-end multimodal deep learning for real-time decoding of months-long neural activity from the same cells

Long-term, stable, and real-time decoding of behavior-dependent neural dynamics from the same cells is critical for brain-computer interfaces (BCIs) and for understanding neural evolution during learning, and memory, and disease progression. Recent advances in flexible and high-density electrodes have enabled the stability required for long-term tracking but generate vast datasets that challenge existing analysis methods. Current spike sorting approaches rely heavily on manual curation and lack scalability for large-scale, real-time processing. Here, we introduce AutoSort, an end-to-end multimodal deep neural network-based method that enables real-time tracking and decoding of the same neurons over months. AutoSort uses a scalable strategy by learning deep representations from initial recordings and applying the trained model in real-time. It integrates multimodal features, including waveform features, distribution patterns, and inferred neuron spatial locations, to ensure robustness and accuracy. AutoSort outperforms existing methods in both simulated and long-term recordings, reducing computational demands by using only 10% of the time and 25% of the memory compared to conventional methods. By combining AutoSort with high-density flexible probes, we track neural dynamics in real-time during motor learning and skill acquisition over 2 months, capturing intrinsic neural manifold drift, stabilization, and post-learning representational drift. AutoSort offers a promising solution for studying long-term neural intrinsic dynamics and enabling real-time BCI decoding.