A discrete generative model of neuronal spiking activity on microelectrode arrays

2026-09-20

AI Summary

本文提出一种离散生成模型，通过学习时空模体词汇表来表示高密度微电极阵列上的神经元放电活动，解决了现有方法无法处理可变观测电极子集的问题。

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.

Problem

• discrete generative model
• neuronal spiking activity
• microelectrode arrays
• spatiotemporal motifs
• residual vector-quantized autoencoder

Innovation

• discrete generative model
• spatiotemporal motifs
• vector-quantized autoencoder
• factorized masked transformer