Gaussian processes are now commonly used in dimensionality reduction approaches tailored to neuroscience, especially to describe changes in high-dimensional neural activity over time. As recording capabilities expand to include neuronal populations across multiple brain areas, cortical layers, and cell types, interest in extending Gaussian process factor models to characterize multi-population interactions has grown. However, the cubic runtime scaling of current methods with the length of experimental trials and the number of recorded populations (groups) precludes their application to large-scale multi-population recordings. Here, we improve this scaling from cubic to linear in both trial length and group number. We present two approximate approaches to fitting multi-group Gaussian process factor models based on (1) inducing variables and (2) the frequency domain. Empirically, both methods achieved orders of magnitude speed-up with minimal impact on statistical performance, in simulation and on neural recordings of hundreds of neurons across three brain areas. The frequency domain approach, in particular, consistently provided the greatest runtime benefits with the fewest trade-offs in statistical performance. We further characterize the estimation biases introduced by the frequency domain approach and demonstrate effective strategies to mitigate them. This work enables a powerful class of analysis techniques to keep pace with the growing scale of multi-population recordings, opening new avenues for exploring brain function.

Adaptive stimulus selection methods in neuroscience have primarily focused on maximizing the firing rate of a single recorded neuron. When recording from a population of neurons, it is usually not possible to find a single stimulus that maximizes the firing rates of all neurons. This motivates optimizing an objective function that takes into account the responses of all recorded neurons together. We propose "Adept," an adaptive stimulus selection method that can optimize population objective functions. In simulations, we first confirmed that population objective functions elicited more diverse stimulus responses than single-neuron objective functions. Then, we tested Adept in a closed-loop electrophysiological experiment in which population activity was recorded from macaque V4, a cortical area known for mid-level visual processing. To predict neural responses, we used the outputs of a deep convolutional neural network model as feature embeddings. Natural images chosen by Adept elicited mean neural responses that were 20% larger than those for randomly-chosen natural images, and also evoked a larger diversity ofneural responses. Such adaptive stimulus selection methods can facilitate experiments that involve neurons far from the sensory periphery, for which it is often unclear which stimuli to present.

Developments in neural recording technology are rapidly enabling the recording of populations of neurons in multiple brain areas simultaneously, as well as the identification of the types of neurons being recorded (e.g., excitatory vs. inhibitory). There is a growing need for statistical methods to study the interaction among multiple, labeled populations of neurons. Rather than attempting to identify direct interactions between neurons (where the number of interactions grows with the number of neurons squared), we propose to extract a smaller number of latent variables from each population and study how the latent variables interact. Specifically, we propose extensions to probabilistic canonical correlation analysis (pCCA) to capture the temporal structure of the latent variables, as well as to distinguish within-population dynamics from across-population interactions (termed Group Latent Auto-Regressive Analysis, gLARA). We then applied these methods to populations of neurons recorded simultaneously in visual areas V1 and V2, and found that gLARA provides a better description of the recordings than pCCA. This work provides a foundation for studying how multiple populations of neurons interact and how this interaction supports brain function.

We consider the problem of recovering a symmetric, positive semidefinite (SPSD) matrix from a subset of its entries, possibly corrupted by noise. In contrast to previous matrix recovery work, we drop the assumption of a random sampling of entries in favor of a deterministic sampling of principal submatrices of the matrix. We develop a set of sufficient conditions for the recovery of a SPSD matrix from a set of its principal submatrices, present necessity results based on this set of conditions and develop an algorithm that can exactly recover a matrix when these conditions are met. The proposed algorithm is naturally generalized to the problem of noisy matrix recovery, and we provide a worst-case bound on reconstruction error for this scenario. Finally, we demonstrate the algorithm's utility on noiseless and noisy simulated datasets.

Simultaneous recordings of many neurons embedded within a recurrently-connected cortical network may provide concurrent views into the dynamical processes of that network, and thus its computational function. In principle, these dynamics might be identified by purely unsupervised, statistical means. Here, we show that a Hidden Switching Linear Dynamical Systems (HSLDS) model---in which multiple linear dynamical laws approximate a nonlinear and potentially non-stationary dynamical process---is able to distinguish different dynamical regimes within single-trial motor cortical activity associated with the preparation and initiation of hand movements. The regimes are identified without reference to behavioural or experimental epochs, but nonetheless transitions between them correlate strongly with external events whose timing may vary from trial to trial. The HSLDS model also performs better than recent comparable models in predicting the firing rate of an isolated neuron based on the firing rates of others, suggesting that it captures more of the "shared variance" of the data. Thus, the method is able to trace the dynamical processes underlying the coordinated evolution of network activity in a way that appears to reflect its computational role.

Neurons in the neocortex code and compute as part of a locally interconnected population. Large-scale multi-electrode recording makes it possible to access these population processes empirically by fitting statistical models to unaveraged data. What statistical structure best describes the concurrent spiking of cells within a local network? We argue that in the cortex, where firing exhibits extensive correlations in both time and space and where a typical sample of neurons still reflects only a very small fraction of the local population, the most appropriate model captures shared variability by a low-dimensional latent process evolving with smooth dynamics, rather than by putative direct coupling. We test this claim by comparing a latent dynamical model with realistic spiking observations to coupled generalised linear spike-response models (GLMs) using cortical recordings. We find that the latent dynamical approach outperforms the GLM in terms of goodness-of-fit, and reproduces the temporal correlations in the data more accurately. We also compare models whose observations models are either derived from a Gaussian or point-process models, finding that the non-Gaussian model provides slightly better goodness-of-fit and more realistic population spike counts.

We consider the problem of extracting smooth low-dimensional ``neural trajectories'' that summarize the activity recorded simultaneously from tens to hundreds of neurons on individual experimental trials. Beyond the benefit of visualizing the high-dimensional noisy spiking activity in a compact denoised form, such trajectories can offer insight into the dynamics of the neural circuitry underlying the recorded activity. Current methods for extracting neural trajectories involve a two-stage process: the data are first ``denoised'' by smoothing over time, then a static dimensionality reduction technique is applied. We first describe extensions of the two-stage methods that allow the degree of smoothing to be chosen in a principled way, and account for spiking variability that may vary both across neurons and across time. We then present a novel method for extracting neural trajectories, Gaussian-process factor analysis (GPFA), which unifies the smoothing and dimensionality reduction operations in a common probabilistic framework. We applied these methods to the activity of 61 neurons recorded simultaneously in macaque premotor and motor cortices during reach planning and execution. By adopting a goodness-of-fit metric that measures how well the activity of each neuron can be predicted by all other recorded neurons, we found that GPFA provided a better characterization of the population activity than the two-stage methods. From the extracted single-trial neural trajectories, we directly observed a convergence in neural state during motor planning, an effect suggestive of attractor dynamics that was shown indirectly by previous studies.

Neuronal activity, particularly in cerebral cortex, is highly variable.

Spiking activity from neurophysiological experiments often exhibits dynamics beyond that driven by external stimulation, presumably reflecting the extensive recurrence of neural circuitry. Characterizing these dynamics may reveal important features of neural computation, particularly during internally-driven cognitive operations. For example, the activity of premotor cortex (PMd) neurons during an instructed delay period separating movement-target specification and a movementinitiation cue is believed to be involved in motor planning. We show that the dynamics underlying this activity can be captured by a lowdimensional nonlinear dynamical systems model, with underlying recurrent structure and stochastic point-process output.

Spiking activity from neurophysiological experiments often exhibits dynamics beyondthat driven by external stimulation, presumably reflecting the extensive recurrence of neural circuitry. Characterizing these dynamics may reveal important features of neural computation, particularly duringinternally-driven cognitive operations. For example, the activity of premotor cortex (PMd) neurons during an instructed delay periodseparating movement-target specification and a movementinitiation cueis believed to be involved in motor planning. We show that the dynamics underlying this activity can be captured by a lowdimensional non-lineardynamical systems model, with underlying recurrent structure and stochastic point-process output.