Adam S. Charles

Eva Yezerets, En Yang, Misha B. Ahrens et al.

Brain-wide recordings of large-scale networks of neurons now provide an unprecedented view into how the brain drives behavior. However, brain activity contains both information directly related to behavior as well as the potential for many internal computations. Moreover, observable behavior is executed not only by the brain, but also by the spinal cord and peripheral nervous system. Behavior is a coarse-grained product of neural activity, and we thus take the view that it can be best represented by lower-dimensional latent neural dynamics. Capturing this indirect relationship while disambiguating behavior-generating networks from internal computations running in parallel requires new modeling approaches that can embody the parallel and distributed nature of large-scale neural populations. We thus present behavior-decomposed linear dynamical systems (b-dLDS) to disentangle simultaneously recorded subsystems and identify how the latent neural subsystems relate to behavior. We demonstrate the ability of b-dLDS to decouple behavioral vs. internal computations on controlled, simulated data, showing improvements over a state-of-the-art model that uses behavior to supervise all dynamics based on behavior. We also demonstrate b-dLDS's interpretability benefits on a task-driven RNN dataset featuring a nonlinear relationship between behavior and activations. We then show that b-dLDS can further scale up to tens of thousands of neurons by applying our model to a large-scale recording of a zebrafish hindbrain during the complex positional homeostasis behavior, wherein b-dLDS highlights asymmetry in behavior-related dynamic connectivity networks.

Noga Mudrik, Yenho Chen, Eva Yezerets et al.

Learning interpretable representations of neural dynamics at a population level is a crucial first step to understanding how observed neural activity relates to perception and behavior. Models of neural dynamics often focus on either low-dimensional projections of neural activity, or on learning dynamical systems that explicitly relate to the neural state over time. We discuss how these two approaches are interrelated by considering dynamical systems as representative of flows on a low-dimensional manifold. Building on this concept, we propose a new decomposed dynamical system model that represents complex non-stationary and nonlinear dynamics of time series data as a sparse combination of simpler, more interpretable components. Our model is trained through a dictionary learning procedure, where we leverage recent results in tracking sparse vectors over time. The decomposed nature of the dynamics is more expressive than previous switched approaches for a given number of parameters and enables modeling of overlapping and non-stationary dynamics. In both continuous-time and discrete-time instructional examples we demonstrate that our model can well approximate the original system, learn efficient representations, and capture smooth transitions between dynamical modes, focusing on intuitive low-dimensional non-stationary linear and nonlinear systems. Furthermore, we highlight our model's ability to efficiently capture and demix population dynamics generated from multiple independent subnetworks, a task that is computationally impractical for switched models. Finally, we apply our model to neural "full brain" recordings of C. elegans data, illustrating a diversity of dynamics that is obscured when classified into discrete states.

Sai Koukuntla, Joshua B. Julian, Jesse C. Kaminsky et al.

Studying complex real-world phenomena often involves data from multiple views (e.g. sensor modalities or brain regions), each capturing different aspects of the underlying system. Within neuroscience, there is growing interest in large-scale simultaneous recordings across multiple brain regions. Understanding the relationship between views (e.g., the neural activity in each region recorded) can reveal fundamental insights into each view and the system as a whole. However, existing methods to characterize such relationships lack the expressivity required to capture nonlinear relationships, describe only shared sources of variance, or discard geometric information that is crucial to drawing insights from data. Here, we present SPLICE: a neural network-based method that infers disentangled, interpretable representations of private and shared latent variables from paired samples of high-dimensional views. Compared to competing methods, we demonstrate that SPLICE 1) disentangles shared and private representations more effectively, 2) yields more interpretable representations by preserving geometry, and 3) is more robust to incorrect a priori estimates of latent dimensionality. We propose our approach as a general-purpose method for finding succinct and interpretable descriptions of paired data sets in terms of disentangled shared and private latent variables.

Yenho Chen, Noga Mudrik, Kyle A. Johnsen et al.

Time-varying linear state-space models are powerful tools for obtaining mathematically interpretable representations of neural signals. For example, switching and decomposed models describe complex systems using latent variables that evolve according to simple locally linear dynamics. However, existing methods for latent variable estimation are not robust to dynamical noise and system nonlinearity due to noise-sensitive inference procedures and limited model formulations. This can lead to inconsistent results on signals with similar dynamics, limiting the model's ability to provide scientific insight. In this work, we address these limitations and propose a probabilistic approach to latent variable estimation in decomposed models that improves robustness against dynamical noise. Additionally, we introduce an extended latent dynamics model to improve robustness against system nonlinearities. We evaluate our approach on several synthetic dynamical systems, including an empirically-derived brain-computer interface experiment, and demonstrate more accurate latent variable inference in nonlinear systems with diverse noise conditions. Furthermore, we apply our method to a real-world clinical neurophysiology dataset, illustrating the ability to identify interpretable and coherent structure where previous models cannot.

Noga Mudrik, Gal Mishne, Adam S. Charles

Time series data across scientific domains are often collected under distinct states (e.g., tasks), wherein latent processes (e.g., biological factors) create complex inter- and intra-state variability. A key approach to capture this complexity is to uncover fundamental interpretable units within the data, Building Blocks (BBs), which modulate their activity and adjust their structure across observations. Existing methods for identifying BBs in multi-way data often overlook inter- vs. intra-state variability, produce uninterpretable components, or do not align with properties of real-world data, such as missing samples and sessions of different duration. Here, we present a framework for Similarity-driven Building Block Inference using Graphs across States (SiBBlInGS). SiBBlInGS offers a graph-based dictionary learning approach for discovering sparse BBs along with their temporal traces, based on co-activity patterns and inter- vs. intra-state relationships. Moreover, SiBBlInGS captures per-trial temporal variability and controlled cross-state structural BB adaptations, identifies state-specific vs. state-invariant components, and accommodates variability in the number and duration of observed sessions across states. We demonstrate SiBBlInGS's ability to reveal insights into complex phenomena as well as its robustness to noise and missing samples through several synthetic and real-world examples, including web search and neural data.

Noga Mudrik, Adam S. Charles

While recent advancements in artificial intelligence (AI) language models demonstrate cutting-edge performance when working with English texts, equivalent models do not exist in other languages or do not reach the same performance level. This undesired effect of AI advancements increases the gap between access to new technology from different populations across the world. This unsought bias mainly discriminates against individuals whose English skills are less developed, e.g., non-English speakers children. Following significant advancements in AI research in recent years, OpenAI has recently presented DALL-E: a powerful tool for creating images based on English text prompts. While DALL-E is a promising tool for many applications, its decreased performance when given input in a different language, limits its audience and deepens the gap between populations. An additional limitation of the current DALL-E model is that it only allows for the creation of a few images in response to a given input prompt, rather than a series of consecutive coherent frames that tell a story or describe a process that changes over time. Here, we present an easy-to-use automatic DALL-E storytelling framework that leverages the existing DALL-E model to enable fast and coherent visualizations of non-English songs and stories, pushing the limit of the one-step-at-a-time option DALL-E currently offers. We show that our framework is able to effectively visualize stories from non-English texts and portray the changes in the plot over time. It is also able to create a narrative and maintain interpretable changes in the description across frames. Additionally, our framework offers users the ability to specify constraints on the story elements, such as a specific location or context, and to maintain a consistent style throughout the visualization.

Noga Mudrik, Yuxi Chen, Gal Mishne et al.

Many fields collect large-scale temporal data through repeated measurements (trials), where each trial is labeled with a set of metadata variables spanning several categories. For example, a trial in a neuroscience study may be linked to a value from category (a): task difficulty, and category (b): animal choice. A critical challenge in time-series analysis is to understand how these labels are encoded within the multi-trial observations, and disentangle the distinct effect of each label entry across categories. Here, we present MILCCI, a novel data-driven method that i) identifies the interpretable components underlying the data, ii) captures cross-trial variability, and iii) integrates label information to understand each category's representation within the data. MILCCI extends a sparse per-trial decomposition that leverages label similarities within each category to enable subtle, label-driven cross-trial adjustments in component compositions and to distinguish the contribution of each category. MILCCI also learns each component's corresponding temporal trace, which evolves over time within each trial and varies flexibly across trials. We demonstrate MILCCI's performance through both synthetic and real-world examples, including voting patterns, online page view trends, and neuronal recordings.

Noga Mudrik, Adam S. Charles

Across many scientific fields, measurements often represent the number of times an event occurs. For example, a document can be represented by word occurrence counts, neural activity by spike counts per time window, or online communication by daily email counts. These measurements yield high-dimensional count data that often approximate a Poisson distribution, frequently with low rates that produce substantial sparsity and complicate downstream analysis. A useful approach is to embed the data into a low-dimensional space that preserves meaningful structure, commonly termed dimensionality reduction. Yet existing dimensionality reduction methods, including both linear (e.g., PCA) and nonlinear approaches (e.g., t-SNE), often assume continuous Euclidean geometry, thereby misaligning with the discrete, sparse nature of low-rate count data. Here, we propose p-SNE (Poisson Stochastic Neighbor Embedding), a nonlinear neighbor embedding method designed around the Poisson structure of count data, using KL divergence between Poisson distributions to measure pairwise dissimilarity and Hellinger distance to optimize the embedding. We test p-SNE on synthetic Poisson data and demonstrate its ability to recover meaningful structure in real-world count datasets, including weekday patterns in email communication, research area clusters in OpenReview papers, and temporal drift and stimulus gradients in neural spike recordings.

Shashwat Kumar, Dominic M. Padova, Binish Narang et al.

Synapses are densely packed submicron structures that dynamically reorganize during learning and memory formation. Longitudinal \textit{in vivo} imaging of fluorescently tagged synaptic receptors offers a promising opportunity to study large-scale synaptic dynamics and how these processes are disrupted in neurological disease. However, in vivo imaging with 2-photon microscopy uses low laser power and therefore suffers from low signal-to-noise ratio (SNR) and high shot noise, nonlinear tissue motion between days, nonstationary fluctuations in synaptic fluorescence, and significant blur induced by the microscope point spread function (PSF). Together, these factors make it challenging to detect and track synapses, especially in regions with high synaptic density. This paper presents a novel template-based framework for modeling synapses as varying luminance point sources that move under a nonlinear tissue deformation. Taking a unified Bayesian approach, we apply this model to microscopy data by deriving a posterior that incorporates a diffeomorphic mapping for domain warping, a Gaussian point spread function for the imaging process, and a Poisson observation model for raw photon counts. The Bayesian solution simultaneously: (1) Constructs a probabilistic template of synapse locations, (2) denoises and deconvolves the image data, (3) infers fluorescence intensities, (4) performs diffeomorphic image registration to correct for tissue motion, and (5) provides confidence regions for these parameter estimates. We demonstrate the framework on both a 2D+t simulated dataset and a 3D+t longitudinal \textit{in vivo} microscopy dataset of fluorescent synapses imaged in a mouse over two weeks.

Scott Gigante, Adam S. Charles, Smita Krishnaswamy et al.

Understanding why and how certain neural networks outperform others is key to guiding future development of network architectures and optimization methods. To this end, we introduce a novel visualization algorithm that reveals the internal geometry of such networks: Multislice PHATE (M-PHATE), the first method designed explicitly to visualize how a neural network's hidden representations of data evolve throughout the course of training. We demonstrate that our visualization provides intuitive, detailed summaries of the learning dynamics beyond simple global measures (i.e., validation loss and accuracy), without the need to access validation data. Furthermore, M-PHATE better captures both the dynamics and community structure of the hidden units as compared to visualization based on standard dimensionality reduction methods (e.g., ISOMAP, t-SNE). We demonstrate M-PHATE with two vignettes: continual learning and generalization. In the former, the M-PHATE visualizations display the mechanism of "catastrophic forgetting" which is a major challenge for learning in task-switching contexts. In the latter, our visualizations reveal how increased heterogeneity among hidden units correlates with improved generalization performance. An implementation of M-PHATE, along with scripts to reproduce the figures in this paper, is available at https://github.com/scottgigante/M-PHATE.

Adam S. Charles

Theoretical understanding of deep learning is one of the most important tasks facing the statistics and machine learning communities. While deep neural networks (DNNs) originated as engineering methods and models of biological networks in neuroscience and psychology, they have quickly become a centerpiece of the machine learning toolbox. Unfortunately, DNN adoption powered by recent successes combined with the open-source nature of the machine learning community, has outpaced our theoretical understanding. We cannot reliably identify when and why DNNs will make mistakes. In some applications like text translation these mistakes may be comical and provide for fun fodder in research talks, a single error can be very costly in tasks like medical imaging. As we utilize DNNs in increasingly sensitive applications, a better understanding of their properties is thus imperative. Recent advances in DNN theory are numerous and include many different sources of intuition, such as learning theory, sparse signal analysis, physics, chemistry, and psychology. An interesting pattern begins to emerge in the breadth of possible interpretations. The seemingly limitless approaches are mostly constrained by the lens with which the mathematical operations are viewed. Ultimately, the interpretation of DNNs appears to mimic a type of Rorschach test --- a psychological test wherein subjects interpret a series of seemingly ambiguous ink-blots. Validation for DNN theory requires a convergence of the literature. We must distinguish between universal results that are invariant to the analysis perspective and those that are specific to a particular network configuration. Simultaneously we must deal with the fact that many standard statistical tools for quantifying generalization or empirically assessing important network features are difficult to apply to DNNs.

Qi She, Xiaoli Wu, Beth Jelfs et al.

Accurate statistical models of neural spike responses can characterize the information carried by neural populations. But the limited samples of spike counts during recording usually result in model overfitting. Besides, current models assume spike counts to be Poisson-distributed, which ignores the fact that many neurons demonstrate over-dispersed spiking behaviour. Although the Negative Binomial Generalized Linear Model (NB-GLM) provides a powerful tool for modeling over-dispersed spike counts, the maximum likelihood-based standard NB-GLM leads to highly variable and inaccurate parameter estimates. Thus, we propose a hierarchical parametric empirical Bayes method to estimate the neural spike responses among neuronal population. Our method integrates both Generalized Linear Models (GLMs) and empirical Bayes theory, which aims to (1) improve the accuracy and reliability of parameter estimation, compared to the maximum likelihood-based method for NB-GLM and Poisson-GLM; (2) effectively capture the over-dispersion nature of spike counts from both simulated data and experimental data; and (3) provide insight into both neural interactions and spiking behaviours of the neuronal populations. We apply our approach to study both simulated data and experimental neural data. The estimation of simulation data indicates that the new framework can accurately predict mean spike counts simulated from different models and recover the connectivity weights among neural populations. The estimation based on retinal neurons demonstrate the proposed method outperforms both NB-GLM and Poisson-GLM in terms of the predictive log-likelihood of held-out data. Codes are available in https://doi.org/10.5281/zenodo.4704423

Adam S. Charles, Han Lun Yap, Christopher J. Rozell

Cortical networks are hypothesized to rely on transient network activity to support short term memory (STM). In this paper we study the capacity of randomly connected recurrent linear networks for performing STM when the input signals are approximately sparse in some basis. We leverage results from compressed sensing to provide rigorous non asymptotic recovery guarantees, quantifying the impact of the input sparsity level, the input sparsity basis, and the network characteristics on the system capacity. Our analysis demonstrates that network memory capacities can scale superlinearly with the number of nodes, and in some situations can achieve STM capacities that are much larger than the network size. We provide perfect recovery guarantees for finite sequences and recovery bounds for infinite sequences. The latter analysis predicts that network STM systems may have an optimal recovery length that balances errors due to omission and recall mistakes. Furthermore, we show that the conditions yielding optimal STM capacity can be embodied in several network topologies, including networks with sparse or dense connectivities.