GRAFT: Gain-Recalibrated Adapters for Transformer-Based Neural Population Activity Modeling

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.

Large-scale calcium imaging has created an opportunity to build foundation-style models for neural population dynamics, but a central question remains unresolved: \textbf{whether a model pretrained on one collection of recordings can generalize to new datasets, experimental paradigms, and even species.} Existing approaches are often designed for specific tasks and evaluated on a single dataset, making it unclear whether their learned representations are reusable for new calcium trace datasets. To tackle this gap, we present \textbf{CAPT}, a \textbf{C}ontinuous \textbf{A}utoregressive \textbf{P}opulation \textbf{T}ransformer for calcium population dynamics. CAPT models continuous calcium traces directly through a continuous patch tokenization strategy and is trained autoregressively, enabling end-to-end pretraining and adaptation to diverse downstream tasks. We first pretrain CAPT on a large-scale mouse calcium imaging dataset and evaluate its transferability across independent mouse, larval zebrafish, and \textit{C. elegans} datasets collected by different laboratories. In these transfer settings, the pretrained backbone is frozen and only adaptation modules are updated. Across neural population forecasting and behavior decoding tasks, CAPT consistently outperforms specialized and general-purpose baselines. Alongside predictive performance, multimodal analyses using NeuroPAL annotations in \textit{C. elegans} datasets show that CAPT embeddings form a shared functional space across datasets and capture anatomical cell-identity-related structure. These results suggest that the continuous autoregressive modeling opens up possibilities for a simple route towards general-purpose neural foundation models for calcium imaging, which can generalize across datasets, experimental paradigms, and species. Code is available at https://github.com/TSuXinH/CAPT.

Closed-loop brain-computer interfaces often require both a forecast of upcoming neural population activity and a readout of the animal's behavioral state. A single Mamba forecaster, trained only on next-step spike counts at Neuropixels scale, can deliver both in one forward pass. A lightweight per-session linear head reading the model's predicted rates decodes behavior better than the same linear classifier reading the raw spike counts, under matched temporal context. We test on the Steinmetz visual-discrimination benchmark, which spans 39 sessions, roughly 27,000 neurons, and 1,994 held-out trials. Across three training seeds, Mamba's predicted rates decode mouse choice at 75.7$\pm$0.2% trial vote, roughly 2.3 times chance level, and stimulus side at 66.1$\pm$0.6%, about twice chance. Compared to a matched 500 ms-context linear decoder on the raw spike counts, Mamba wins at trial vote by 4-6 pp on response and 4-6 pp on stimulus side. A session-start calibration block of about 100-150 trials brings the readout within 1-2 pp of asymptote, and the full pipeline fits inside the 50 ms bin budget on workstation-class GPUs typical of tethered chronic Neuropixels recordings.