With the accelerated development of neural recording technology over the past few decades, research in integrative neuroscience has become increasingly reliant on data analysis methods that are scalable to high-dimensional recordings and computationally tractable. Latent process models have shown promising results in estimating the dynamics of cognitive processes using individual models for each neuron's receptive field. However, scaling these models to work on high-dimensional neural recordings remains challenging. Not only is it impractical to build receptive field models for individual neurons of a large neural population, but most neural data analyses based on individual receptive field models discard the local history of neural activity, which has been shown to be critical in the accurate inference of the underlying cognitive processes. Here, we propose a novel, scalable latent process model that can directly estimate cognitive process dynamics without requiring precise receptive field models of individual neurons or brain nodes. We call this the direct discriminative decoder (DDD) model. The DDD model consists of (1) a discriminative process that characterizes the conditional distribution of the signal to be estimated, or state, as a function of both the current neural activity and its local history, and (2) a state transition model that characterizes the evolution of the state over a longer time period. While this modeling framework inherits advantages of existing latent process modeling methods, its computational cost is tractable. More important, the solution can incorporate any information from the history of neural activity at any timescale in computing the estimate of the state process. There are many choices in building the discriminative process, including deep neural networks or gaussian processes, which adds to the flexibility of the framework. We argue that these attributes of the proposed methodology, along with its applicability to different modalities of neural data, make it a powerful tool for high-dimensional neural data analysis. We also introduce an extension of these methods, called the discriminative-generative decoder (DGD). The DGD includes both discriminative and generative processes in characterizing observed data. As a result, we can combine physiological correlates like behavior with neural data to better estimate underlying cognitive processes. We illustrate the methods, including steps for inference and model identification, and demonstrate applications to multiple data analysis problems with high-dimensional neural recordings. The modeling results demonstrate the computational and modeling advantages of the DDD and DGD methods.

It is of great interest to characterize the spiking activity of individual neurons in a cell ensemble. Many different mechanisms, such as synaptic coupling and the spiking activity of itself and its neighbors, drive a cell's firing properties. Though this is a widely studied modeling problem, there is still room to develop modeling solutions by simplifications embedded in previous models. The first shortcut is that synaptic coupling mechanisms in previous models do not replicate the complex dynamics of the synaptic response. The second is that the number of synaptic connections in these models is an order of magnitude smaller than in an actual neuron. In this research, we push this barrier by incorporating a more accurate model of the synapse and propose a system identification solution that can scale to a network incorporating hundreds of synaptic connections. Although a neuron has hundreds of synaptic connections, only a subset of these connections significantly contributes to its spiking activity. As a result, we assume the synaptic connections are sparse, and to characterize these dynamics, we propose a Bayesian point-process state-space model that lets us incorporate the sparsity of synaptic connections within the regularization technique into our framework. We develop an extended expectation-maximization. algorithm to estimate the free parameters of the proposed model and demonstrate the application of this methodology to the problem of estimating the parameters of many dynamic synaptic connections. We then go through a simulation example consisting of the dynamic synapses across a range of parameter values and show that the model parameters can be estimated using our method. We also show the application of the proposed algorithm in the intracellular data that contains 96 presynaptic connections and assess the estimation accuracy of our method using a combination of goodness-of-fit measures.

Marked point process models have recently been used to capture the coding properties of neural populations from multiunit electrophysiological recordings without spike sorting. These clusterless models have been shown in some instances to better describe the firing properties of neural populations than collections of receptive field models for sorted neurons and to lead to better decoding results. To assess their quality, we previously proposed a goodness-of-fit technique for marked point process models based on time rescaling, which for a correct model produces a set of uniform samples over a random region of space. However, assessing uniformity over such a region can be challenging, especially in high dimensions. Here, we propose a set of new transformations in both time and the space of spike waveform features, which generate events that are uniformly distributed in the new mark and time spaces. These transformations are scalable to multidimensional mark spaces and provide uniformly distributed samples in hypercubes, which are well suited for uniformity tests. We discuss the properties of these transformations and demonstrate aspects of model fit captured by each transformation. We also compare multiple uniformity tests to determine their power to identify lack-of-fit in the rescaled data. We demonstrate an application of these transformations and uniformity tests in a simulation study. Proofs for each transformation are provided in the appendix.

Cognitive processes, such as learning and cognitive flexibility, are both difficult to measure and to sample continuously using objective tools because cognitive processes arise from distributed, high-dimensional neural activity. For both research and clinical applications, that dimensionality must be reduced. To reduce dimensionality and measure underlying cognitive processes, we propose a modeling framework in which a cognitive process is defined as a low-dimensional dynamical latent variable—called a cognitive state, which links high-dimensional neural recordings and multidimensional behavioral readouts. This framework allows us to decompose the hard problem of modeling the relationship between neural and behavioral data into separable encoding-decoding approaches. We first use a state-space modeling framework, the behavioral decoder, to articulate the relationship between an objective behavioral readout (e.g., response times) and cognitive state. The second step, the neural encoder, involves using a generalized linear model (GLM) to identify the relationship between the cognitive state and neural signals, such as local field potential (LFP). We then use the neural encoder model and a Bayesian filter to estimate cognitive state using neural data (LFP power) to generate the neural decoder. We provide goodness-of-fit analysis and model selection criteria in support of the encoding-decoding result. We apply this framework to estimate an underlying cognitive state from neural data in human participants ( N = 8 ) performing a cognitive conflict task. We successfully estimated the cognitive state within the 95% confidence intervals of that estimated using behavior readout for an average of 90% of task trials across participants. In contrast to previous encoder-decoder models, our proposed modeling framework incorporates LFP spectral power to encode and decode a cognitive state. The framework allowed us to capture the temporal evolution of the underlying cognitive processes, which could be key to the development of closed-loop experiments and treatments.