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BackgroundA central goal of systems neuroscience is to understand the relationships amongst constituent units in neural populations, and their modulation by external factors, using high-dimensional and stochastic neural recordings. Parametric statistical models (e.g., coupling, encoding, and decoding models), play an instrumental role in accomplishing this goal. However, extracting conclusions from a parametric model requires that it is fit using an inference algorithm capable of selecting the correct parameters and properly estimating their values. Traditional approaches to parameter inference have been shown to suffer from failures in both selection and estimation. The recent development of algorithms that ameliorate these deficiencies raises the question of whether past work relying on such inference procedures have produced inaccurate systems neuroscience models, thereby impairing their interpretation.New methodWe used algorithms based on Union of Intersections, a statistical inference framework based on stability principles, capable of improved selection and estimation.ComparisonWe fit functional coupling, encoding, and decoding models across a battery of neural datasets using both UoI and baseline inference procedures (e.g., ℓ1-penalized GLMs), and compared the structure of their fitted parameters.ResultsAcross recording modality, brain region, and task, we found that UoI inferred models with increased sparsity, improved stability, and qualitatively different parameter distributions, while maintaining predictive performance. We obtained highly sparse functional coupling networks with substantially different community structure, more parsimonious encoding models, and decoding models that relied on fewer single-units.ConclusionsTogether, these results demonstrate that improved parameter inference, achieved via UoI, reshapes interpretation in diverse neuroscience contexts.

Simultaneous recordings from the cortex have revealed that neural activity is highly variable and that some variability is shared across neurons in a population. Further experimental work has demonstrated that the shared component of a neuronal population's variability is typically comparable to or larger than its private component. Meanwhile, an abundance of theoretical work has assessed the impact that shared variability has on a population code. For example, shared input noise is understood to have a detrimental impact on a neural population's coding fidelity. However, other contributions to variability, such as common noise, can also play a role in shaping correlated variability. We present a network of linear-nonlinear neurons in which we introduce a common noise input to model-for instance, variability resulting from upstream action potentials that are irrelevant to the task at hand. We show that by applying a heterogeneous set of synaptic weights to the neural inputs carrying the common noise, the network can improve its coding ability as measured by both Fisher information and Shannon mutual information, even in cases where this results in amplification of the common noise. With a broad and heterogeneous distribution of synaptic weights, a population of neurons can remove the harmful effects imposed by afferents that are uninformative about a stimulus. We demonstrate that some nonlinear networks benefit from weight diversification up to a certain population size, above which the drawbacks from amplified noise dominate over the benefits of diversification. We further characterize these benefits in terms of the relative strength of shared and private variability sources. Finally, we studied the asymptotic behavior of the mutual information and Fisher information analytically in our various networks as a function of population size. We find some surprising qualitative changes in the asymptotic behavior as we make seemingly minor changes in the synaptic weight distributions.

Network formation from neural activity is a foundational problem in systems neuroscience. Functional networks, after downstream analysis, can provide key insights into the nature of neurobiological structure and computation. The validity of such insights hinges on accurate selection and estimation of the edges connecting nodes. However, commonly used statistical inference procedures generally fail to identify the correct features, and further introduce consequential bias in the estimates. To address these issues, we developed Union of Intersections (UoI), a flexible, modular, and scalable framework for enhanced statistical feature selection and estimation. Methods based on UoI perform feature selection and feature estimation through intersection and union operations, respectively. In the context of linear regression (specifically UoI Lasso ), we summarize extensive numerical investigation on synthetic data to demonstrate tight control of false-positives and false-negatives in feature selection with low-bias and low-variance estimates of selected parameters, while maintaining high-quality prediction accuracy. We demonstrate, with UoI Lasso , the extraction of sparse, predictive, and interpretable functional networks from human electrocorticography recordings during speech production and the inference of parsimonious coupling models from nonhuman primate single-unit recordings during reaching tasks. Our results establish that UoI Lasso generates interpretable and predictive functional connectivity networks.