Search bioRxivSearch

bioRxiv · 10.1101/2020.06.16.154377

Estimating Transfer Entropy in Continuous Time Between Neural Spike Trains or Other Event-Based Data

Abstract

Transfer entropy (TE) is a widely used measure of directed information flows in a number of domains including neuroscience. Many real-world time series in which we are interested in information flows come in the form of (near) instantaneous events occurring over time, including the spiking of biological neurons, trades on stock markets and posts to social media. However, there exist severe limitations to the current approach to TE estimation on such event-based data via discretising the time series into time bins: it is not consistent, has high bias, converges slowly and cannot simultaneously capture relationships that occur with very fine time precision as well as those that occur over long time intervals. Building on recent work which derived a theoretical framework for TE in continuous time, we present an estimation framework for TE on event-based data and develop a k-nearest-neighbours estimator within this framework. This estimator is provably consistent, has favourable bias properties and converges orders of magnitude more quickly than the discrete-time estimator on synthetic examples. We also develop a local permutation scheme for generating null surrogate time series to test for the statistical significance of the TE and, as such, test for the conditional independence between the history of one point process and the updates of another -- signifying the lack of a causal connection under certain weak assumptions. Our approach is capable of detecting conditional independence or otherwise even in the presence of strong pairwise time-directed correlations. The power of this approach is further demonstrated on the inference of the connectivity of biophysical models of a spiking neural circuit inspired by the pyloric circuit of the crustacean stomatogastric ganglion, succeeding where previous related estimators have failed. AUTHOR SUMMARYTransfer Entropy (TE) is an information-theoretic measure commonly used in neuroscience to measure the directed statistical dependence between a source and a target time series, possibly also conditioned on other processes. Along with measuring information flows, it is used for the inference of directed functional and effective networks from time series data. The currently-used technique for estimating TE on neural spike trains first time-discretises the data and then applies a straightforward or "plug-in" information-theoretic estimation procedure. This approach has numerous drawbacks: it is very biased, it cannot capture relationships occurring on both fine and large timescales simultaneously, converges very slowly as more data is obtained, and indeed does not even converge to the correct value. We present a new estimator for TE which operates in continuous time, demonstrating via application to synthetic examples that it addresses these problems, and can reliably differentiate statistically significant flows from (conditionally) independent spike trains. Further, we also apply it to more biologically-realistic spike trains obtained from a biophysical model of the pyloric circuit of the crustacean stomatogastric ganglion; our correct inference of the underlying connection structure here provides an important validation for our approach where similar methods have previously failed

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Shorten, D., Spinney, R., Lizier, J.. 2020-06-16. Estimating Transfer Entropy in Continuous Time Between Neural Spike Trains or Other Event-Based Data. https://doi.org/10.1101/2020.06.16.154377

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience