Liam Paninski

Yanchen Wang, Lenny Aharon, Wangshu Zhu et al.

Multi-view video recordings are increasingly used to capture the 3D movements of animals in experimental settings, yet extracting rich 3D representations from these recordings remains challenging. Supervised pose estimation requires extensive manual annotation, while general-purpose 3D reconstruction models trained on generic scene datasets fail on the specialized imagery and sparse-view setting of laboratory experiments. We address these limitations with BEAST3D, a self-supervised pretraining framework that learns 3D visual representations from unlabeled, calibrated multi-view video. BEAST3D uses a vision transformer to predict 3D Gaussian splats that reconstruct held-out views through differentiable rendering, while simultaneously segmenting the animal from the background. BEAST3D reconstructs 3D structure with as few as four views by conditioning directly on known camera parameters--unlike general-purpose models, which must estimate camera geometry from dense overlapping viewpoints that are seldom available in lab settings. Through comprehensive evaluation across four species, we demonstrate that BEAST3D produces rich, viewpoint-invariant features that transfer effectively to three downstream tasks: novel view synthesis, which validates the quality of the learned 3D representations; multi-view pose estimation, which provides the sparse keypoint trajectories widely used in behavioral analysis; and neural encoding, which relates 3D behavioral features to simultaneously recorded neural activity. BEAST3D thus establishes a versatile framework for behavioral analysis that leverages 3D structure in modern multi-view laboratory recordings.

Yizi Zhang, Yanchen Wang, Donato Jimenez-Beneto et al. · gatech

Neuroscience research has made immense progress over the last decade, but our understanding of the brain remains fragmented and piecemeal: the dream of probing an arbitrary brain region and automatically reading out the information encoded in its neural activity remains out of reach. In this work, we build towards a first foundation model for neural spiking data that can solve a diverse set of tasks across multiple brain areas. We introduce a novel self-supervised modeling approach for population activity in which the model alternates between masking out and reconstructing neural activity across different time steps, neurons, and brain regions. To evaluate our approach, we design unsupervised and supervised prediction tasks using the International Brain Laboratory repeated site dataset, which is comprised of Neuropixels recordings targeting the same brain locations across 48 animals and experimental sessions. The prediction tasks include single-neuron and region-level activity prediction, forward prediction, and behavior decoding. We demonstrate that our multi-task-masking (MtM) approach significantly improves the performance of current state-of-the-art population models and enables multi-task learning. We also show that by training on multiple animals, we can improve the generalization ability of the model to unseen animals, paving the way for a foundation model of the brain at single-cell, single-spike resolution.

Ari Blau, Christoph Gebhardt, Andres Bendesky et al.

Multi-animal pose estimation is essential for studying animals' social behaviors in neuroscience and neuroethology. Advanced approaches have been proposed to support multi-animal estimation and achieve state-of-the-art performance. However, these models rarely exploit unlabeled data during training even though real world applications have exponentially more unlabeled frames than labeled frames. Manually adding dense annotations for a large number of images or videos is costly and labor-intensive, especially for multiple instances. Given these deficiencies, we propose a novel semi-supervised architecture for multi-animal pose estimation, leveraging the abundant structures pervasive in unlabeled frames in behavior videos to enhance training, which is critical for sparsely-labeled problems. The resulting algorithm will provide superior multi-animal pose estimation results on three animal experiments compared to the state-of-the-art baseline and exhibits more predictive power in sparsely-labeled data regimes.

Ari Blau, Evan S Schaffer, Neeli Mishra et al. · princeton

Action segmentation of behavioral videos is the process of labeling each frame as belonging to one or more discrete classes, and is a crucial component of many studies that investigate animal behavior. A wide range of algorithms exist to automatically parse discrete animal behavior, encompassing supervised, unsupervised, and semi-supervised learning paradigms. These algorithms -- which include tree-based models, deep neural networks, and graphical models -- differ widely in their structure and assumptions on the data. Using four datasets spanning multiple species -- fly, mouse, and human -- we systematically study how the outputs of these various algorithms align with manually annotated behaviors of interest. Along the way, we introduce a semi-supervised action segmentation model that bridges the gap between supervised deep neural networks and unsupervised graphical models. We find that fully supervised temporal convolutional networks with the addition of temporal information in the observations perform the best on our supervised metrics across all datasets.

Yizi Zhang, Yanchen Wang, Mehdi Azabou et al. · gatech

Recent work has demonstrated that large-scale, multi-animal models are powerful tools for characterizing the relationship between neural activity and behavior. Current large-scale approaches, however, focus exclusively on either predicting neural activity from behavior (encoding) or predicting behavior from neural activity (decoding), limiting their ability to capture the bidirectional relationship between neural activity and behavior. To bridge this gap, we introduce a multimodal, multi-task model that enables simultaneous Neural Encoding and Decoding at Scale (NEDS). Central to our approach is a novel multi-task-masking strategy, which alternates between neural, behavioral, within-modality, and cross-modality masking. We pretrain our method on the International Brain Laboratory (IBL) repeated site dataset, which includes recordings from 83 animals performing the same visual decision-making task. In comparison to other large-scale models, we demonstrate that NEDS achieves state-of-the-art performance for both encoding and decoding when pretrained on multi-animal data and then fine-tuned on new animals. Surprisingly, NEDS's learned embeddings exhibit emergent properties: even without explicit training, they are highly predictive of the brain regions in each recording. Altogether, our approach is a step towards a foundation model of the brain that enables seamless translation between neural activity and behavior.

Yanchen Wang, Han Yu, Ari Blau et al.

The brain can only be fully understood through the lens of the behavior it generates -- a guiding principle in modern neuroscience research that nevertheless presents significant technical challenges. Many studies capture behavior with cameras, but video analysis approaches typically rely on specialized models requiring extensive labeled data. We address this limitation with BEAST (BEhavioral Analysis via Self-supervised pretraining of Transformers), a novel and scalable framework that pretrains experiment-specific vision transformers for diverse neuro-behavior analyses. BEAST combines masked autoencoding with temporal contrastive learning to effectively leverage unlabeled video data. Through comprehensive evaluation across multiple species, we demonstrate improved performance in three critical neuro-behavioral tasks: extracting behavioral features that correlate with neural activity, and pose estimation and action segmentation in both the single- and multi-animal settings. Our method establishes a powerful and versatile backbone model that accelerates behavioral analysis in scenarios where labeled data remains scarce.

Yizi Zhang, Linyang He, Chaofei Fan et al.

Speech brain-computer interfaces (BCIs) aim to restore communication for people with paralysis by translating neural activity into text. Most systems use cascaded frameworks that decode phonemes before assembling sentences with an n-gram language model (LM), preventing joint optimization of all stages simultaneously. Here, we introduce an end-to-end Brain-to-Text (BIT) framework that translates neural activity into coherent sentences using a single differentiable neural network. Central to our approach is a cross-task, cross-species pretrained neural encoder, whose representations transfer to both attempted and imagined speech. In a cascaded setting with an n-gram LM, the pretrained encoder establishes a new state-of-the-art (SOTA) on the Brain-to-Text '24 and '25 benchmarks. Integrated end-to-end with audio large language models (LLMs) and trained with contrastive learning for cross-modal alignment, BIT reduces the word error rate (WER) of the prior end-to-end method from 24.69% to 10.22%. Notably, we find that small-scale audio LLMs markedly improve end-to-end decoding. Beyond record-setting performance, BIT aligns attempted and imagined speech embeddings to enable cross-task generalization. Altogether, our approach advances the integration of large, diverse neural datasets, paving the way for an end-to-end decoding framework that supports seamless, differentiable optimization.

Lenny Aharon, Keemin Lee, Karan Sikka et al.

Multi-view pose estimation is essential for quantifying animal behavior in scientific research, yet current methods struggle to achieve accurate tracking with limited labeled data and suffer from poor uncertainty estimates. We address these challenges with a comprehensive framework combining novel training and post-processing techniques, and a model distillation procedure that leverages the strengths of these techniques to produce a more efficient and effective pose estimator. Our multi-view transformer (MVT) utilizes pretrained backbones and enables simultaneous processing of information across all views, while a novel patch masking scheme learns robust cross-view correspondences without camera calibration. For calibrated setups, we incorporate geometric consistency through 3D augmentation and a triangulation loss. We extend the existing Ensemble Kalman Smoother (EKS) post-processor to the nonlinear case and enhance uncertainty quantification via a variance inflation technique. Finally, to leverage the scaling properties of the MVT, we design a distillation procedure that exploits improved EKS predictions and uncertainty estimates to generate high-quality pseudo-labels, thereby reducing dependence on manual labels. Our framework components consistently outperform existing methods across three diverse animal species (flies, mice, chickadees), with each component contributing complementary benefits. The result is a practical, uncertainty-aware system for reliable pose estimation that enables downstream behavioral analyses under real-world data constraints.

Yueqi Wang, Yoonho Lee, Pallab Basu et al.

Learning community structures in graphs has broad applications across scientific domains. While graph neural networks (GNNs) have been successful in encoding graph structures, existing GNN-based methods for community detection are limited by requiring knowledge of the number of communities in advance, in addition to lacking a proper probabilistic formulation to handle uncertainty. We propose a simple framework for amortized community detection, which addresses both of these issues by combining the expressive power of GNNs with recent methods for amortized clustering. Our models consist of a graph representation backbone that extracts structural information and an amortized clustering network that naturally handles variable numbers of clusters. Both components combine into well-defined models of the posterior distribution of graph communities and are jointly optimized given labeled graphs. At inference time, the models yield parallel samples from the posterior of community labels, quantifying uncertainty in a principled way. We evaluate several models from our framework on synthetic and real datasets, and demonstrate improved performance compared to previous methods. As a separate contribution, we extend recent amortized probabilistic clustering architectures by adding attention modules, which yield further improvements on community detection tasks.

Xue-Xin Wei, Ding Zhou, Andres Grosmark et al.

Calcium imaging is a critical tool for measuring the activity of large neural populations. Much effort has been devoted to developing "pre-processing" tools for calcium video data, addressing the important issues of e.g., motion correction, denoising, compression, demixing, and deconvolution. However, statistical modeling of deconvolved calcium signals (i.e., the estimated activity extracted by a pre-processing pipeline) is just as critical for interpreting calcium measurements, and for incorporating these observations into downstream probabilistic encoding and decoding models. Surprisingly, these issues have to date received significantly less attention. In this work we examine the statistical properties of the deconvolved activity estimates, and compare probabilistic models for these random signals. In particular, we propose a zero-inflated gamma (ZIG) model, which characterizes the calcium responses as a mixture of a gamma distribution and a point mass that serves to model zero responses. We apply the resulting models to neural encoding and decoding problems. We find that the ZIG model outperforms simpler models (e.g., Poisson or Bernoulli models) in the context of both simulated and real neural data, and can therefore play a useful role in bridging calcium imaging analysis methods with tools for analyzing activity in large neural populations.

Ding Zhou, Yuanjun Gao, Liam Paninski

The Hierarchical Dirichlet Process Hidden Markov Model (HDP-HMM) has been used widely as a natural Bayesian nonparametric extension of the classical Hidden Markov Model for learning from sequential and time-series data. A sticky extension of the HDP-HMM has been proposed to strengthen the self-persistence probability in the HDP-HMM. However, the sticky HDP-HMM entangles the strength of the self-persistence prior and transition prior together, limiting its expressiveness. Here, we propose a more general model: the disentangled sticky HDP-HMM (DS-HDP-HMM). We develop novel Gibbs sampling algorithms for efficient inference in this model. We show that the disentangled sticky HDP-HMM outperforms the sticky HDP-HMM and HDP-HMM on both synthetic and real data, and apply the new approach to analyze neural data and segment behavioral video data.

Jackson Loper, David Blei, John P. Cunningham et al.

Gaussian Processes (GPs) provide powerful probabilistic frameworks for interpolation, forecasting, and smoothing, but have been hampered by computational scaling issues. Here we investigate data sampled on one dimension (e.g., a scalar or vector time series sampled at arbitrarily-spaced intervals), for which state-space models are popular due to their linearly-scaling computational costs. It has long been conjectured that state-space models are general, able to approximate any one-dimensional GP. We provide the first general proof of this conjecture, showing that any stationary GP on one dimension with vector-valued observations governed by a Lebesgue-integrable continuous kernel can be approximated to any desired precision using a specifically-chosen state-space model: the Latent Exponentially Generated (LEG) family. This new family offers several advantages compared to the general state-space model: it is always stable (no unbounded growth), the covariance can be computed in closed form, and its parameter space is unconstrained (allowing straightforward estimation via gradient descent). The theorem's proof also draws connections to Spectral Mixture Kernels, providing insight about this popular family of kernels. We develop parallelized algorithms for performing inference and learning in the LEG model, test the algorithm on real and synthetic data, and demonstrate scaling to datasets with billions of samples.

Ari Pakman, Yueqi Wang, Catalin Mitelut et al.

Probabilistic clustering models (or equivalently, mixture models) are basic building blocks in countless statistical models and involve latent random variables over discrete spaces. For these models, posterior inference methods can be inaccurate and/or very slow. In this work we introduce deep network architectures trained with labeled samples from any generative model of clustered datasets. At test time, the networks generate approximate posterior samples of cluster labels for any new dataset of arbitrary size. We develop two complementary approaches to this task, requiring either O(N) or O(K) network forward passes per dataset, where N is the dataset size and K the number of clusters. Unlike previous approaches, our methods sample the labels of all the data points from a well-defined posterior, and can learn nonparametric Bayesian posteriors since they do not limit the number of mixture components. As a scientific application, we present a novel approach to neural spike sorting for high-density multielectrode arrays.

Ari Pakman, Liam Paninski

We develop methods for efficient amortized approximate Bayesian inference over posterior distributions of probabilistic clustering models, such as Dirichlet process mixture models. The approach is based on mapping distributed, symmetry-invariant representations of cluster arrangements into conditional probabilities. The method parallelizes easily, yields iid samples from the approximate posterior of cluster assignments with the same computational cost of a single Gibbs sampler sweep, and can easily be applied to both conjugate and non-conjugate models, as training only requires samples from the generative model.

Daniel Hernandez, Antonio Khalil Moretti, Ziqiang Wei et al.

Latent variable models have been widely applied for the analysis of time series resulting from experimental neuroscience techniques. In these datasets, observations are relatively smooth and possibly nonlinear. We present Variational Inference for Nonlinear Dynamics (VIND), a variational inference framework that is able to uncover nonlinear, smooth latent dynamics from sequential data. The framework is a direct extension of PfLDS; including a structured approximate posterior describing spatially-dependent linear dynamics, as well as an algorithm that relies on the fixed-point iteration method to achieve convergence. We apply VIND to electrophysiology, single-cell voltage and widefield imaging datasets with state-of-the-art results in reconstruction error. In single-cell voltage data, VIND finds a 5D latent space, with variables akin to those of Hodgkin-Huxley-like models. VIND's learned dynamics are further quantified by predicting future neural activity. VIND excels in this task, in some cases substantially outperforming current methods.

E. Kelly Buchanan, Ian Kinsella, Ding Zhou et al.

Calcium imaging has revolutionized systems neuroscience, providing the ability to image large neural populations with single-cell resolution. The resulting datasets are quite large, which has presented a barrier to routine open sharing of this data, slowing progress in reproducible research. State of the art methods for analyzing this data are based on non-negative matrix factorization (NMF); these approaches solve a non-convex optimization problem, and are effective when good initializations are available, but can break down in low-SNR settings where common initialization approaches fail. Here we introduce an approach to compressing and denoising functional imaging data. The method is based on a spatially-localized penalized matrix decomposition (PMD) of the data to separate (low-dimensional) signal from (temporally-uncorrelated) noise. This approach can be applied in parallel on local spatial patches and is therefore highly scalable, does not impose non-negativity constraints or require stringent identifiability assumptions (leading to significantly more robust results compared to NMF), and estimates all parameters directly from the data, so no hand-tuning is required. We have applied the method to a wide range of functional imaging data (including one-photon, two-photon, three-photon, widefield, somatic, axonal, dendritic, calcium, and voltage imaging datasets): in all cases, we observe ~2-4x increases in SNR and compression rates of 20-300x with minimal visible loss of signal, with no adjustment of hyperparameters; this in turn facilitates the process of demixing the observed activity into contributions from individual neurons. We focus on two challenging applications: dendritic calcium imaging data and voltage imaging data in the context of optogenetic stimulation. In both cases, we show that our new approach leads to faster and much more robust extraction of activity from the data.

Scott W. Linderman, Gonzalo E. Mena, Hal Cooper et al.

Many matching, tracking, sorting, and ranking problems require probabilistic reasoning about possible permutations, a set that grows factorially with dimension. Combinatorial optimization algorithms may enable efficient point estimation, but fully Bayesian inference poses a severe challenge in this high-dimensional, discrete space. To surmount this challenge, we start with the usual step of relaxing a discrete set (here, of permutation matrices) to its convex hull, which here is the Birkhoff polytope: the set of all doubly-stochastic matrices. We then introduce two novel transformations: first, an invertible and differentiable stick-breaking procedure that maps unconstrained space to the Birkhoff polytope; second, a map that rounds points toward the vertices of the polytope. Both transformations include a temperature parameter that, in the limit, concentrates the densities on permutation matrices. We then exploit these transformations and reparameterization gradients to introduce variational inference over permutation matrices, and we demonstrate its utility in a series of experiments.

Scott W. Linderman, Andrew C. Miller, Ryan P. Adams et al.

Many natural systems, such as neurons firing in the brain or basketball teams traversing a court, give rise to time series data with complex, nonlinear dynamics. We can gain insight into these systems by decomposing the data into segments that are each explained by simpler dynamic units. Building on switching linear dynamical systems (SLDS), we present a new model class that not only discovers these dynamical units, but also explains how their switching behavior depends on observations or continuous latent states. These "recurrent" switching linear dynamical systems provide further insight by discovering the conditions under which each unit is deployed, something that traditional SLDS models fail to do. We leverage recent algorithmic advances in approximate inference to make Bayesian inference in these models easy, fast, and scalable.

Ari Pakman, Dar Gilboa, David Carlson et al.

We introduce a novel stochastic version of the non-reversible, rejection-free Bouncy Particle Sampler (BPS), a Markov process whose sample trajectories are piecewise linear. The algorithm is based on simulating first arrival times in a doubly stochastic Poisson process using the thinning method, and allows efficient sampling of Bayesian posteriors in big datasets. We prove that in the BPS no bias is introduced by noisy evaluations of the log-likelihood gradient. On the other hand, we argue that efficiency considerations favor a small, controllable bias in the construction of the thinning proposals, in exchange for faster mixing. We introduce a simple regression-based proposal intensity for the thinning method that controls this trade-off. We illustrate the algorithm in several examples in which it outperforms both unbiased, but slowly mixing stochastic versions of BPS, as well as biased stochastic gradient-based samplers.

Kamiar Rahnama Rad, Timothy A. Machado, Liam Paninski

A common analytical problem in neuroscience is the interpretation of neural activity with respect to sensory input or behavioral output. This is typically achieved by regressing measured neural activity against known stimuli or behavioral variables to produce a "tuning function" for each neuron. Unfortunately, because this approach handles neurons individually, it cannot take advantage of simultaneous measurements from spatially adjacent neurons that often have similar tuning properties. On the other hand, sharing information between adjacent neurons can errantly degrade estimates of tuning functions across space if there are sharp discontinuities in tuning between nearby neurons. In this paper, we develop a computationally efficient block Gibbs sampler that effectively pools information between neurons to de-noise tuning function estimates while simultaneously preserving sharp discontinuities that might exist in the organization of tuning across space. This method is fully Bayesian and its computational cost per iteration scales sub-quadratically with total parameter dimensionality. We demonstrate the robustness and scalability of this approach by applying it to both real and synthetic datasets. In particular, an application to data from the spinal cord illustrates that the proposed methods can dramatically decrease the experimental time required to accurately estimate tuning functions.

Yuanjun Gao, Evan Archer, Liam Paninski et al.

A body of recent work in modeling neural activity focuses on recovering low-dimensional latent features that capture the statistical structure of large-scale neural populations. Most such approaches have focused on linear generative models, where inference is computationally tractable. Here, we propose fLDS, a general class of nonlinear generative models that permits the firing rate of each neuron to vary as an arbitrary smooth function of a latent, linear dynamical state. This extra flexibility allows the model to capture a richer set of neural variability than a purely linear model, but retains an easily visualizable low-dimensional latent space. To fit this class of non-conjugate models we propose a variational inference scheme, along with a novel approximate posterior capable of capturing rich temporal correlations across time. We show that our techniques permit inference in a wide class of generative models.We also show in application to two neural datasets that, compared to state-of-the-art neural population models, fLDS captures a much larger proportion of neural variability with a small number of latent dimensions, providing superior predictive performance and interpretability.

David Carlson, Patrick Stinson, Ari Pakman et al.

Partition functions of probability distributions are important quantities for model evaluation and comparisons. We present a new method to compute partition functions of complex and multimodal distributions. Such distributions are often sampled using simulated tempering, which augments the target space with an auxiliary inverse temperature variable. Our method exploits the multinomial probability law of the inverse temperatures, and provides estimates of the partition function in terms of a simple quotient of Rao-Blackwellized marginal inverse temperature probability estimates, which are updated while sampling. We show that the method has interesting connections with several alternative popular methods, and offers some significant advantages. In particular, we empirically find that the new method provides more accurate estimates than Annealed Importance Sampling when calculating partition functions of large Restricted Boltzmann Machines (RBM); moreover, the method is sufficiently accurate to track training and validation log-likelihoods during learning of RBMs, at minimal computational cost.

Evan Archer, Il Memming Park, Lars Buesing et al.

Latent variable time-series models are among the most heavily used tools from machine learning and applied statistics. These models have the advantage of learning latent structure both from noisy observations and from the temporal ordering in the data, where it is assumed that meaningful correlation structure exists across time. A few highly-structured models, such as the linear dynamical system with linear-Gaussian observations, have closed-form inference procedures (e.g. the Kalman Filter), but this case is an exception to the general rule that exact posterior inference in more complex generative models is intractable. Consequently, much work in time-series modeling focuses on approximate inference procedures for one particular class of models. Here, we extend recent developments in stochastic variational inference to develop a `black-box' approximate inference technique for latent variable models with latent dynamical structure. We propose a structured Gaussian variational approximate posterior that carries the same intuition as the standard Kalman filter-smoother but, importantly, permits us to use the same inference approach to approximate the posterior of much more general, nonlinear latent variable generative models. We show that our approach recovers accurate estimates in the case of basic models with closed-form posteriors, and more interestingly performs well in comparison to variational approaches that were designed in a bespoke fashion for specific non-conjugate models.

Josh Merel, David Carlson, Liam Paninski et al.

Neuroprosthetic brain-computer interfaces function via an algorithm which decodes neural activity of the user into movements of an end effector, such as a cursor or robotic arm. In practice, the decoder is often learned by updating its parameters while the user performs a task. When the user's intention is not directly observable, recent methods have demonstrated value in training the decoder against a surrogate for the user's intended movement. We describe how training a decoder in this way is a novel variant of an imitation learning problem, where an oracle or expert is employed for supervised training in lieu of direct observations, which are not available. Specifically, we describe how a generic imitation learning meta-algorithm, dataset aggregation (DAgger, [1]), can be adapted to train a generic brain-computer interface. By deriving existing learning algorithms for brain-computer interfaces in this framework, we provide a novel analysis of regret (an important metric of learning efficacy) for brain-computer interfaces. This analysis allows us to characterize the space of algorithmic variants and bounds on their regret rates. Existing approaches for decoder learning have been performed in the cursor control setting, but the available design principles for these decoders are such that it has been impossible to scale them to naturalistic settings. Leveraging our findings, we then offer an algorithm that combines imitation learning with optimal control, which should allow for training of arbitrary effectors for which optimal control can generate goal-oriented control. We demonstrate this novel and general BCI algorithm with simulated neuroprosthetic control of a 26 degree-of-freedom model of an arm, a sophisticated and realistic end effector.