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Adam S. Charles

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Published work

8 published item(s)

preprint2026arXiv

Bayesian In Vivo Tracking of Synapses using Joint Poisson Deconvolution and Diffeomorphic Registration

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.

preprint2026arXiv

Partitioning Neural Co-Variability

Trial-to-trial variability of neural responses has been linked to important aspects of neural computation and is essential for understanding how neuronal populations respond. While current overdispersion models treat each neuron's gain as independent of each other, this assumption fails to capture the network statistics of neuronal populations. As no existing model can capture overdispersed structured spiking gain-modulation across a neural population, network-level gain covariance remains largely unstudied. We thus present the Poisson matrix-normal latent variable (PMNLV) model, which extends single-neuron overdispersion to neural populations by placing a matrix-normal prior over the latent gain with a Kronecker-factored covariance. Spike counts are Poisson-distributed with a rate equal to the sum of a per-neuron stimulus tuning term and a matrix-normal gain, passed through a quadratic soft-rectifying link. We derive two complementary estimation algorithms: a variational EM (VEM) with a matrix-normal posterior that recovers dense Kronecker factors without structural assumptions, and a Kernel Tournament Method (KTM) that performs data-driven selection over a biologically motivated kernel dictionary and composite likelihood. On simulated data, both algorithms recover the inter-neuron and temporal covariance factors and accurate tuning curves. Applying VEM to Neuropixel recordings across four cortical regions of mouse visual hierarchy, we replicate a previous finding that single-neuron marginal variability changes little across cortical areas. We then show that shared population co-variability, invisible to scalar summaries e.g., the Fano factor, peaks in primary visual cortex and declines in higher visual areas. The PMNLV framework is applicable to any simultaneously recorded population where structured gain covariance is of scientific interest.

preprint2026arXiv

Stable Filtering for Efficient Dimensionality Reduction of Streaming Manifold Data

Many areas in science and engineering now have access to technologies that enable the rapid collection of overwhelming data volumes. While these datasets are vital for understanding phenomena from physical to biological and social systems, the sheer magnitude of the data makes even simple storage, transmission, and basic processing highly challenging. To enable efficient and accurate execution of these data processing tasks, we require new dimensionality reduction tools that 1) do not need expensive, time-consuming training, and 2) preserve the underlying geometry of the data that has the information required to understand the measured system. Specifically, the geometry to be preserved is that induced by the fact that in many applications, streaming high-dimensional data evolves on a low-dimensional attractor manifold. Importantly, we may not know the exact structure of this manifold a priori. To solve these challenges, we present randomized filtering (RF), which leverages a specific instantiation of randomized dimensionality reduction to provably preserve non-linear manifold structure in the embedded space while remaining data-independent and computationally efficient. In this work we build on the rich theoretical promise of randomized dimensionality reduction to develop RF as a real, practical approach. We introduce novel methods, analysis, and experimental verification to illuminate the practicality of RF in diverse scientific applications, including several simulated and real-data examples that showcase the tangible benefits of RF.

preprint2022arXiv

Data Processing of Functional Optical Microscopy for Neuroscience

Functional optical imaging in neuroscience is rapidly growing with the development of new optical systems and fluorescence indicators. To realize the potential of these massive spatiotemporal datasets for relating neuronal activity to behavior and stimuli and uncovering local circuits in the brain, accurate automated processing is increasingly essential. In this review, we cover recent computational developments in the full data processing pipeline of functional optical microscopy for neuroscience data and discuss ongoing and emerging challenges.

preprint2020arXiv

Efficient Tracking of Sparse Signals via an Earth Mover's Distance Dynamics Regularizer

Tracking algorithms such as the Kalman filter aim to improve inference performance by leveraging the temporal dynamics in streaming observations. However, the tracking regularizers are often based on the $\ell_p$-norm which cannot account for important geometrical relationships between neighboring signal elements. We propose a practical approach to using the earth mover's distance (EMD) via the earth mover's distance dynamic filtering (EMD-DF) algorithm for causally tracking time-varying sparse signals when there is a natural geometry to the coefficient space that should be respected (e.g., meaningful ordering). Specifically, this paper presents a new Beckmann formulation that dramatically reduces computational complexity, as well as an evaluation of the performance and complexity of the proposed approach in imaging and frequency tracking applications with real and simulated neurophysiology data.

preprint2015arXiv

Re-Weighted l_1 Dynamic Filtering for Time-Varying Sparse Signal Estimation

Signal estimation from incomplete observations improves as more signal structure can be exploited in the inference process. Classic algorithms (e.g., Kalman filtering) have exploited strong dynamic structure for time-varying signals while modern work has often focused on exploiting low-dimensional signal structure (e.g., sparsity in a basis) for static signals. Few algorithms attempt to merge both static and dynamic structure to improve estimation for time-varying sparse signals (e.g., video). In this work we present a re-weighted l_1 dynamic filtering scheme for causal signal estimation that utilizes both sparsity assumptions and dynamic structure. Our algorithm leverages work on hierarchical Laplacian scale mixture models to create a dynamic probabilistic model. The resulting algorithm incorporates both dynamic and sparsity priors in the estimation procedure in a robust and efficient algorithm. We demonstrate the results in simulation using both synthetic and natural data.

preprint2015arXiv

Short Term Memory Capacity in Networks via the Restricted Isometry Property

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.

preprint2011arXiv

Analog Sparse Approximation with Applications to Compressed Sensing

Recent research has shown that performance in signal processing tasks can often be significantly improved by using signal models based on sparse representations, where a signal is approximated using a small number of elements from a fixed dictionary. Unfortunately, inference in this model involves solving non-smooth optimization problems that are computationally expensive. While significant efforts have focused on developing digital algorithms specifically for this problem, these algorithms are inappropriate for many applications because of the time and power requirements necessary to solve large optimization problems. Based on recent work in computational neuroscience, we explore the potential advantages of continuous time dynamical systems for solving sparse approximation problems if they were implemented in analog VLSI. Specifically, in the simulated task of recovering synthetic and MRI data acquired via compressive sensing techniques, we show that these systems can potentially perform recovery at time scales of 10-20μs, supporting datarates of 50-100 kHz (orders of magnitude faster that digital algorithms). Furthermore, we show analytically that a wide range of sparse approximation problems can be solved in the same basic architecture, including approximate $\ell^p$ norms, modified $\ell^1$ norms, re-weighted $\ell^1$ and $\ell^2$, the block $\ell^1$ norm and classic Tikhonov regularization.