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1. Dynamic Analysis of Higher-Order Coordination in Neuronal Assemblies via De-Sparsified Orthogonal Matching Pursuit

   Mukherjee, Shoutik; Babadi, Behtash (January 2021, Advances in Neural Information Processing Systems 34 (NeurIPS 2021))

   Coordinated ensemble spiking activity is widely observable in neural recordings and central in the study of population codes, with hypothesized roles including robust stimulus representation, interareal communication of neural information, and learning and memory formation. Model-free measures of synchrony characterize the coherence of pairwise activity, but not higher-order interactions; this limitation is transcended by statistical models of ensemble spiking activity. However, existing model-based analyses often impose assumptions about the relevance of higher-order interactions and require multiple repeated trials in order to characterize dynamics in the correlational structure of ensemble activity. To address these shortcomings, we propose an adaptive greedy filtering algorithm based on a discretized mark point-process model of ensemble spiking and a corresponding precise statistical inference framework to identify significant coordinated higher-order spiking activity. In the course of developing the statistical inference procedures, we also show that confidence intervals can be constructed for greedily estimated parameters. We demonstrate the utility of our proposed methods on simulated neuronal assemblies. Applied to multi-electrode recordings of human cortical ensembles, our proposed methods provide new insights into the dynamics underlying localized population activity during transitions between brain states. 

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2. Dynamic Analysis of Higher-Order Coordination in Neuronal Assemblies via De-Sparsified Orthogonal Matching Pursuit

   Mukherjee, Shoutik; Babadi, Behtash (January 2021, Advances in neural information processing systems)

   Coordinated ensemble spiking activity is widely observable in neural recordings and central in the study of population codes, with hypothesized roles including robust stimulus representation, interareal communication of neural information, and learning and memory formation. Model-free measures of synchrony characterize the coherence of pairwise activity, but not higher-order interactions; this limitation is transcended by statistical models of ensemble spiking activity. However, existing model-based analyses often impose assumptions about the relevance of higher-order interactions and require multiple repeated trials in order to characterize dynamics in the correlational structure of ensemble activity. To address these shortcomings, we propose an adaptive greedy filtering algorithm based on a discretized mark point process model of ensemble spiking and a corresponding precise statistical inference framework to identify significant coordinated higher-order spiking activity. In the course of developing the statistical inference procedures, we also show that confidence intervals can be constructed for greedily estimated parameters. We demonstrate the utility of our proposed methods on simulated neuronal assemblies. Applied to multi-electrode recordings of human cortical ensembles, our proposed methods provide new insights into the dynamics underlying localized population activity during transitions between brain states. 

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3. Calibrating Bayesian decoders of neural spiking activity

   https://doi.org/10.1523/JNEUROSCI.2158-23.2024  

   Wei, Ganchao; Tajik_Mansouri, Zeinab; Wang, Xiaojing; Stevenson, Ian H (March 2024, The Journal of Neuroscience)

   Accurately decoding external variables from observations of neural activity is a major challenge in systems neuroscience. Bayesian decoders, that provide probabilistic estimates, are some of the most widely used. Here we show how, in many common settings, the probabilistic predictions made by traditional Bayesian decoders are overconfident. That is, the estimates for the decoded stimulus or movement variables are more certain than they should be. We then show how Bayesian decoding with latent variables, taking account of low-dimensional shared variability in the observations, can improve calibration, although additional correction for overconfidence is still needed. Using data from males, we examine: 1) decoding the direction of grating stimuli from spike recordings in primary visual cortex in monkeys, 2) decoding movement direction from recordings in primary motor cortex in monkeys, 3) decoding natural images from multi-region recordings in mice, and 4) decoding position from hippocampal recordings in rats. For each setting we characterize the overconfidence, and we describe a possible method to correct miscalibration post-hoc. Properly calibrated Bayesian decoders may alter theoretical results on probabilistic population coding and lead to brain machine interfaces that more accurately reflect confidence levels when identifying external variables. Significance Statement Bayesian decoding is a statistical technique for making probabilistic predictions about external stimuli or movements based on recordings of neural activity. These predictions may be useful for robust brain machine interfaces or for understanding perceptual or behavioral confidence. However, the probabilities produced by these models do not always match the observed outcomes. Just as a weather forecast predicting a 50% chance of rain may not accurately correspond to an outcome of rain 50% of the time, Bayesian decoders of neural activity can be miscalibrated as well. Here we identify and measure miscalibration of Bayesian decoders for neural spiking activity in a range of experimental settings. We compare multiple statistical models and demonstrate how overconfidence can be corrected. 

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4. CREIMBO: Cross-Regional Ensemble Interactions in Multi-view Brain Observations

   Mudrik, Noga; Ly, Ryan; Ruebel, Oliver; Charles, Adam S (January 2025, The International Conference on Learning Representations)

   Modern recordings of neural activity provide diverse observations of neurons across brain areas, behavioral conditions, and subjects; presenting an exciting opportunity to reveal the fundamentals of brain-wide dynamics. Current analysis methods, however, often fail to fully harness the richness of such data, as they provide either uninterpretable representations (e.g., via deep networks) or oversimplify models (e.g., by assuming stationary dynamics or analyzing each session independently). Here, instead of regarding asynchronous neural recordings that lack alignment in neural identity or brain areas as a limitation, we leverage these diverse views into the brain to learn a unified model of neural dynamics. Specifically, we assume that brain activity is driven by multiple hidden global sub-circuits. These sub-circuits represent global basis interactions between neural ensembles—functional groups of neurons—such that the time-varying decomposition of these sub-circuits defines how the ensembles’ interactions evolve over time non-stationarily and non-linearly. We discover the neural ensembles underlying non-simultaneous observations, along with their non-stationary evolving interactions, with our new model, CREIMBO (Cross-Regional Ensemble Interactions in Multi-view Brain Observations). CREIMBO identifies the hidden composition of per-session neural ensembles through novel graph-driven dictionary learning and models the ensemble dynamics on a low-dimensional manifold spanned by a sparse time-varying composition of the global sub-circuits. Thus, CREIMBO disentangles overlapping temporal neural processes while preserving interpretability due to the use of a shared underlying sub-circuit basis. Moreover, CREIMBO distinguishes session-specific computations from global (session-invariant) ones by identifying session covariates and variations in sub-circuit activations. We demonstrate CREIMBO’s ability to recover true components in synthetic data, and uncover meaningful brain dynamics in human high-density electrode recordings, including cross-subject neural mechanisms as well as inter- vs. intra-region dynamical motifs. Furthermore, using mouse whole-brain recordings, we show CREIMBO’s ability to discover dynamical interactions that capture task and behavioral variables and meaningfully align with the biological importance of the brain areas they represent 

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5. Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings

   https://doi.org/10.1038/s41467-024-55571-6  

   Rahmani, Keivan; Yang, Yang; Foster, Ethan Paul; Tsai, Ching-Ting; Meganathan, Dhivya Pushpa; Alvarez, Diego D; Gupta, Aayush; Cui, Bianxiao; Santoro, Francesca; Bloodgood, Brenda L; et al (December 2025, Nature Communications)

   Abstract Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells’ electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput. However, accessing intracellular potentials with NEAs remains challenging. This study presents an AI-supported technique that leverages thousands of synchronous eAP and iAP pairs from stem-cell-derived cardiomyocytes on NEAs. Our analysis revealed strong correlations between specific eAP and iAP features, such as amplitude and spiking velocity, indicating that extracellular signals could be reliable indicators of intracellular activity. We developed a physics-informed deep learning model to reconstruct iAP waveforms from extracellular recordings recorded from NEAs and Microelectrode arrays (MEAs), demonstrating its potential for non-invasive, long-term, high-throughput drug cardiotoxicity assessments. This AI-based model paves the way for future electrophysiology research across various cell types and drug interactions. 

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