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This research introduces a discrete generative model using vector-quantized autoencoders and masked transformers to efficiently represent sparse neural spiking data from high-density microelectrode arrays. By learning a shared vocabulary of spatiotemporal motifs, the approach achieves significantly higher reconstruction precision than flat tokenizers while demonstrating that neural activity patterns are broadly reusable across different tissue types. This scalable framework offers a robust foundation for simulating population activity in diverse applications, including disease modeling and closed-loop experimentation without relying on assay-specific parameters.
A discrete generative model of neuronal spiking activity on microelectrode arrays
arXiv:2609.23907v1 Announce Type: new Abstract: Generative models of neural activity could help characterize tissue dynamics, compare experimental conditions, and simulate population activity for applications ranging from disease and drug-response studies to closed-loop experimentation. Existing approaches, however, typically assume a fixed set of sorted neurons, whereas high-density microelectrode arrays produce extremely sparse, array-wide binary spike volumes in which the observed subset of electrodes varies across assays. We introduce a discrete generative model that represents this activity using a shared vocabulary of spatiotemporal motifs. A residual vector-quantized autoencoder learns the motif vocabulary, while a factorized masked transformer predicts where activity occurs and which motif appears at each active location. We evaluate the model on 31 assays spanning human brain organoids and acute \emph{ex vivo} human hippocampal tissue. The learned motifs are broadly reused: assay identity explains only $9%$ of the entropy in motif use, and motif overlap across tissue types is comparable to overlap within them. When representation quality is evaluated independently of the generative prior, our approach achieves $5.2\times$ the voxel-level reconstruction average precision of a matched flat tokenizer. For masked completion and free generation, the full model achieves $1.4$--$2.6\times$ the site-level average precision of the matched generative baseline and outperforms it across all four families of generation metrics. These results establish a compact, reusable representation for array-wide spiking activity without learned assay-specific parameters, providing a scalable foundation for generative modeling across diverse neural preparations.
Abstract:Generative models of neural activity could help characterize tissue dynamics, compare experimental conditions, and simulate population activity for applications ranging from disease and drug-response studies to closed-loop experimentation. Existing approaches, however, typically assume a fixed set of sorted neurons, whereas high-density microelectrode arrays produce extremely sparse, array-wide binary spike volumes in which the observed subset of electrodes varies across assays. We introduce a discrete generative model that represents this activity using a shared vocabulary of spatiotemporal motifs. A residual vector-quantized autoencoder learns the motif vocabulary, while a factorized masked transformer predicts where activity occurs and which motif appears at each active location. We evaluate the model on 31 assays spanning human brain organoids and acute \emph{ex vivo} human hippocampal tissue. The learned motifs are broadly reused: assay identity explains only $9%$ of the entropy in motif use, and motif overlap across tissue types is comparable to overlap within them. When representation quality is evaluated independently of the generative prior, our approach achieves $5.2\times$ the voxel-level reconstruction average precision of a matched flat tokenizer. For masked completion and free generation, the full model achieves $1.4$--$2.6\times$ the site-level average precision of the matched generative baseline and outperforms it across all four families of generation metrics. These results establish a compact, reusable representation for array-wide spiking activity without learned assay-specific parameters, providing a scalable foundation for generative modeling across diverse neural preparations.
Machine Learning (cs.LG); Signal Processing (eess.SP); Neurons and Cognition (q-bio.NC)
arXiv:2609.23907 [cs.LG]
(or arXiv:2609.23907v1 [cs.LG] for this version)
https://doi.org/10.48550/arXiv.2609.23907 Focus to learn more arXiv-issued DOI via DataCite (pending registration)
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