Dataset Information

A Low-Rank Method for Characterizing High-Level Neural Computations.

ABSTRACT: The signal transformations that take place in high-level sensory regions of the brain remain enigmatic because of the many nonlinear transformations that separate responses of these neurons from the input stimuli. One would like to have dimensionality reduction methods that can describe responses of such neurons in terms of operations on a large but still manageable set of relevant input features. A number of methods have been developed for this purpose, but often these methods rely on the expansion of the input space to capture as many relevant stimulus components as statistically possible. This expansion leads to a lower effective sampling thereby reducing the accuracy of the estimated components. Alternatively, so-called low-rank methods explicitly search for a small number of components in the hope of achieving higher estimation accuracy. Even with these methods, however, noise in the neural responses can force the models to estimate more components than necessary, again reducing the methods' accuracy. Here we describe how a flexible regularization procedure, together with an explicit rank constraint, can strongly improve the estimation accuracy compared to previous methods suitable for characterizing neural responses to natural stimuli. Applying the proposed low-rank method to responses of auditory neurons in the songbird brain, we find multiple relevant components making up the receptive field for each neuron and characterize their computations in terms of logical OR and AND computations. The results highlight potential differences in how invariances are constructed in visual and auditory systems.

SUBMITTER: Kaardal JT

PROVIDER: S-EPMC5534486 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A Low-Rank Method for Characterizing High-Level Neural Computations.

Kaardal Joel T JT Theunissen Frédéric E FE Sharpee Tatyana O TO

Frontiers in computational neuroscience 20170731

The signal transformations that take place in high-level sensory regions of the brain remain enigmatic because of the many nonlinear transformations that separate responses of these neurons from the input stimuli. One would like to have dimensionality reduction methods that can describe responses of such neurons in terms of operations on a large but still manageable set of relevant input features. A number of methods have been developed for this purpose, but often these methods rely on the expan ...[more]

PMID: 28824408

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Project description:In many brain areas, sensory responses are heavily modulated by factors including attentional state, context, reward history, motor preparation, learned associations, and other cognitive variables. Modelling the effect of these modulatory factors on sensory responses has proven challenging, mostly due to the time-varying and nonlinear nature of the underlying computations. Here we present a computational model capable of capturing and dissociating multiple time-varying modulatory effects on neuronal responses on the order of milliseconds. The model's performance is tested on extrastriate perisaccadic visual responses in nonhuman primates. Visual neurons respond to stimuli presented around the time of saccades differently than during fixation. These perisaccadic changes include sensitivity to the stimuli presented at locations outside the neuron's receptive field, which suggests a contribution of multiple sources to perisaccadic response generation. Current computational approaches cannot quantitatively characterize the contribution of each modulatory source in response generation, mainly due to the very short timescale on which the saccade takes place. In this study, we use a high spatiotemporal resolution experimental paradigm along with a novel extension of the generalized linear model framework (GLM), termed the sparse-variable GLM, to allow for time-varying model parameters representing the temporal evolution of the system with a resolution on the order of milliseconds. We used this model framework to precisely map the temporal evolution of the spatiotemporal receptive field of visual neurons in the middle temporal area during the execution of a saccade. Moreover, an extended model based on a factorization of the sparse-variable GLM allowed us to disassociate and quantify the contribution of individual sources to the perisaccadic response. Our results show that our novel framework can precisely capture the changes in sensitivity of neurons around the time of saccades, and provide a general framework to quantitatively track the role of multiple modulatory sources over time.

Project description:BackgroundHigh throughput microfluidic protocols in single cell RNA sequencing (scRNA-seq) collect mRNA counts from up to one million individual cells in a single experiment; this enables high resolution studies of rare cell types and cell development pathways. Determining small sets of genetic markers that can identify specific cell populations is thus one of the major objectives of computational analysis of mRNA counts data. Many tools have been developed for marker selection on single cell data; most of them, however, are based on complex statistical models and handle the multi-class case in an ad-hoc manner.ResultsWe introduce RANKCORR, a fast method with strong mathematical underpinnings that performs multi-class marker selection in an informed manner. RANKCORR proceeds by ranking the mRNA counts data before linearly separating the ranked data using a small number of genes. The step of ranking is intuitively natural for scRNA-seq data and provides a non-parametric method for analyzing count data. In addition, we present several performance measures for evaluating the quality of a set of markers when there is no known ground truth. Using these metrics, we compare the performance of RANKCORR to a variety of other marker selection methods on an assortment of experimental and synthetic data sets that range in size from several thousand to one million cells.ConclusionsAccording to the metrics introduced in this work, RANKCORR is consistently one of most optimal marker selection methods on scRNA-seq data. Most methods show similar overall performance, however; thus, the speed of the algorithm is the most important consideration for large data sets (and comparing the markers selected by several methods can be fruitful). RANKCORR is fast enough to easily handle the largest data sets and, as such, it is a useful tool to add into computational pipelines when dealing with high throughput scRNA-seq data. RANKCORR software is available for download at https://github.com/ahsv/RankCorr with extensive documentation.

Dataset Information

A Low-Rank Method for Characterizing High-Level Neural Computations.

Publications

A Low-Rank Method for Characterizing High-Level Neural Computations.

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