Real-time decoding of neural activity is central to neuroscience and neurotechnology applications, from closed-loop experiments to brain-computer interfaces, where models are subject to strict latency constraints. Traditional methods, including simple recurrent neural networks, are fast and lightweight but often struggle to generalize to unseen data. In contrast, recent Transformer-based approaches leverage large-scale pretraining for strong generalization performance, but typically have much larger computational requirements and are not always suitable for low-resource or real-time settings. To address these shortcomings, we present POSSM, a novel hybrid architecture that combines individual spike tokenization via a cross-attention module with a recurrent state-space model (SSM) backbone to enable (1) fast and causal online prediction on neural activity and (2) efficient generalization to new sessions, individuals, and tasks through multi-dataset pretraining. We evaluate POSSM's decoding performance and inference speed on intracortical decoding of monkey motor tasks, and show that it extends to clinical applications, namely handwriting and speech decoding in human subjects. Notably, we demonstrate that pretraining on monkey motor-cortical recordings improves decoding performance on the human handwriting task, highlighting the exciting potential for cross-species transfer. In all of these tasks, we find that POSSM achieves decoding accuracy comparable to state-of-the-art Transformers, at a fraction of the inference cost (up to 9x faster on GPU). These results suggest that hybrid SSMs are a promising approach to bridging the gap between accuracy, inference speed, and generalization when training neural decoders for real-time, closed-loop applications.

Our ability to use deep learning approaches to decipher neural activity would likely benefit from greater scale, in terms of both the model size and the datasets. However, the integration of many neural recordings into one unified model is challenging, as each recording contains the activity of different neurons from different individual animals. In this paper, we introduce a training framework and architecture designed to model the population dynamics of neural activity across diverse, large-scale neural recordings. Our method first tokenizes individual spikes within the dataset to build an efficient representation of neural events that captures the fine temporal structure of neural activity. We then employ cross-attention and a PerceiverIO backbone to further construct a latent tokenization of neural population activities. Utilizing this architecture and training framework, we construct a large-scale multi-session model trained on large datasets from seven nonhuman primates, spanning over 158 different sessions of recording from over 27,373 neural units and over 100 hours of recordings. In a number of different tasks, we demonstrate that our pretrained model can be rapidly adapted to new, unseen sessions with unspecified neuron correspondence, enabling few-shot performance with minimal labels. This work presents a powerful new approach for building deep learning tools to analyze neural data and stakes out a clear path to training at scale for neural decoding models.