Granger Sensori-Behavioral Taxonomy of Neuronal Ensemble Activity from Two-Photon Calcium Imaging Data

Understanding how neuronal populations interact to encode and transform sensory information is a fundamental challenge in computational neuroscience. Most existing studies, however, study neural encoding, behavioral readout, and functional connectivity as disjoint problems. Two-photon calcium imaging enables simultaneous recording of large neuronal ensembles in vivo, driven by diverse stimuli and eliciting distinct behaviors. However, extracting directional functional connectivity metrics as well as encoding and readout properties of neurons from such data remains difficult due to indirect and noisy observations of spiking activity, slow temporal dynamics, and the latent interplay between external stimuli and endogenous neural processes. Here, we introduce a unified conceptual and operational modeling and inference framework for directly extracting functional Granger causal (GC) effects between neurons, from external stimuli to neurons, and from neurons to behavior, from two-photon imaging data, in the sense of Granger. Inspired by the intersection information framework, we also identify neurons that encode features of sensory stimuli that inform behavioral readout. The resulting GC networks together with the taxonomy of functional sensori-behavioral relevance, which we call G-taxonomy, provides a powerful statistical analysis framework, enabled by the integration of several techniques including state-space modeling and inference, variational inference, and point processes. We applied the proposed framework to simulated and experimentally-recorded two-photon imaging from the mouse auditory cortex (A1) during both passive listening and active tone discrimination. Our simulation studies reveal significant improvement of our proposed methodology over existing techniques. Analysis of experimental data from the mouse A1 identifies distinct groups of cells with diverse sensori-behavioral relevance, as well as changes in functional connectivity associated with correct vs. incorrect behavior. In summary, this work provides a principled and data-driven methodology for uncovering directional interactions among the neurons, sensory stimuli, and behavior, all within the same statistical framework, offering new insights into how distributed cortical populations transform sensory inputs into behaviorally relevant representations. Author SummaryThe brain processes sensory inputs through the coordinated activity of large networks of neurons and produces readouts that elicit behavior. Understanding how information flows and is processed through these networks is a central goal of neuroscience. In this study, we present a new computational framework that identifies directional interactions among neurons in an ensemble as well as from sensory stimuli to neurons and from neurons to behavior. Utilizing the Granger formalism to identify directional effects, as opposed to common correlational measures, our framework extracts said effects directly from two-photon calcium imaging data. We tested our proposed method on both simulated data and recordings from the auditory cortex of mice during passive listening and active tone discrimination tasks. Our method revealed diverse groups of neurons in the auditory cortex with distinct functional roles and relevance to sensori-behavioral integration. Our framework provides a new way to study the flow of information in the brain and can be broadly applied to uncover neural computations across sensory and cognitive systems.