Integrative neurocybernetic modeling in the era of large-scale neuroscience
Authors: Il Memming Park, Ayesha Vermani, Gonzalo G. de Polavieja, Juan Álvaro Gallego, Kathleen Esfahany, Shreya Saxena, Michael Orger, Auke Ijspeert, +6 more
Organizations: Champalimaud Centre for the Unknown, Champalimaud Foundation, Lisbon, Portugal · Harvard University, Cambridge, MA, USA · Yale University, New Haven, CT, USA · École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland · RyvivyR Inc, NY, USA · Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA
Abstract
Large-scale neuroscience is generating rich datasets across animals, brain areas and behavioral contexts, yet our modeling efforts remains fragmented across isolated experiments. We argue that understanding behavior requires integrative neurocybernetic models: understandable dynamical models that capture the closed-loop coupling of brain, body and environment, treat the brain as a controller pursuing latent objectives, represent structured variation across scales, and scale to heterogeneous datasets. Such models shift the goal from predicting neural recordings in isolation to inferring the organizing principles that govern neural and behavioral dynamics. We outline a practical route toward this goal by combining nonlinear state-space models and meta-dynamical extensions with scalable inference, knowledge distillation, mixed open- and closed-loop training, and connectomics-informed architectures. By pooling complementary constraints from recordings, behavior, perturbations and anatomy, integrative neurocybernetic models can provide statistical amplification, few-shot generalization, and mechanistic insight into shared dynamical structure, individual variation, and the control objectives that govern behavior. This agenda offers a model-centric path from fragmented data to a mechanistic science of how brains produce behavior.
Recent developments in brain recording are driving a demand for machine learning tools capable of decoding the latent structure of large populations of neurons. In this paper, we provide a comprehensive survey that outlines the trajectory of Latent Variable Models (LVMs) from early state-space models to more recent deep generative models. We organize the literature into three closely related domains: (1) Single-Region Latent Dynamics, which includes models such as linear dynamical systems to more complex dynamics represented by Recurrent Neural Networks (RNNs) and Neural Ordinary Differential Equations (ODEs); (2) Multi-Region Communication, which employs probabilistic as well as subspace methods to study how information is transferred across different brain areas considering synaptic propagation delays and network connectivity; and (3) Behavior-Aligned Modeling, which seeks to disentangle neural activity related to task performance from other internal states via supervised or contrastive learning. This survey also includes large-scale neural foundation models, such as Transformers and diffusion models, that rely on large-scale pre-training for optimal performance across subjects. Finally, we conclude and discuss benchmarks, evaluation criteria, and open challenges, such as the ability to identify causal links or directionality of communication, to facilitate future research for bridging interpretable brain dynamics with reliable neural decoding.
Scaling data and artificial neural networks has transformed AI, driving breakthroughs in language and vision. Whether similar principles apply to modeling brain activity remains unclear. Here we leveraged a dataset of 3.1 million neurons from the visual cortex of 73 mice across 323 sessions, totaling more than 150 billion neural tokens recorded during natural movies, images and parametric stimuli, and behavior. We train multi-modal, multi-task models that support three regimes flexibly at test time: neural prediction, behavioral decoding, neural forecasting, or any combination of the three. OmniMouse achieves state-of-the-art performance, outperforming specialized baselines across nearly all evaluation regimes. We find that performance scales reliably with more data, but gains from increasing model size saturate. This inverts the standard AI scaling story: in language and computer vision, massive datasets make parameter scaling the primary driver of progress, whereas in brain modeling -- even in the mouse visual cortex, a relatively simple system -- models remain data-limited despite vast recordings. The observation of systematic scaling raises the possibility of phase transitions in neural modeling, where larger and richer datasets might unlock qualitatively new capabilities, paralleling the emergent properties seen in large language models. Code available at https://github.com/enigma-brain/omnimouse.
Konstantin F. Willeke, Polina Turishcheva, Alex Gilbert +18
Decoding continuous motor trajectories from neural activity is essential for developing practical brain-computer interfaces (BCIs). However, current neural decoders are constrained by the limited scale and heterogeneity of neural recordings. In contrast, behavioral data can be collected more readily and at substantially larger scale from humans, animals, simulations, and robotic systems. Here, we introduce NeuroPB, a framework that scales neural decoding by transferring knowledge from pretrained behavioral representations. NeuroPB first pretrains a motor encoder on large-scale motor behavior data and then aligns neural activity with the resulting behavioral representation space using a limited set of paired neural-behavioral recordings. A neural encoder and lightweight motor decoder are subsequently optimized to reconstruct continuous movement from the aligned neural representations. Across multiple macaque motor datasets, behavioral pretraining improves trajectory decoding, including an 11% R2 increase on center-out and 8% on random-target compared with training the motor encoder from scratch. Notably, pretraining on robotic trajectories achieves performance comparable to pretraining on macaque trajectories, demonstrating that transferable kinematic structure is shared across biological and artificial models. Moreover, decoding performance improves as the scale and diversity of robotic pretraining data increase, when the amount of neural data is fixed. Pretraining also enhances generalization across recording sessions, subjects, and motor tasks, with only 10% calibration needed to match training from scratch. Overall, these results establish behavioral pretraining as a scalable source for neural decoding and provide a promising route toward high-performance and calibration-efficient BCIs under limited neural data.