9 research outputs found
False discovery rate regression: an application to neural synchrony detection in primary visual cortex
Many approaches for multiple testing begin with the assumption that all tests
in a given study should be combined into a global false-discovery-rate
analysis. But this may be inappropriate for many of today's large-scale
screening problems, where auxiliary information about each test is often
available, and where a combined analysis can lead to poorly calibrated error
rates within different subsets of the experiment. To address this issue, we
introduce an approach called false-discovery-rate regression that directly uses
this auxiliary information to inform the outcome of each test. The method can
be motivated by a two-groups model in which covariates are allowed to influence
the local false discovery rate, or equivalently, the posterior probability that
a given observation is a signal. This poses many subtle issues at the interface
between inference and computation, and we investigate several variations of the
overall approach. Simulation evidence suggests that: (1) when covariate effects
are present, FDR regression improves power for a fixed false-discovery rate;
and (2) when covariate effects are absent, the method is robust, in the sense
that it does not lead to inflated error rates. We apply the method to neural
recordings from primary visual cortex. The goal is to detect pairs of neurons
that exhibit fine-time-scale interactions, in the sense that they fire together
more often than expected due to chance. Our method detects roughly 50% more
synchronous pairs versus a standard FDR-controlling analysis. The companion R
package FDRreg implements all methods described in the paper
A Semiparametric Bayesian Model for Detecting Synchrony Among Multiple Neurons
We propose a scalable semiparametric Bayesian model to capture dependencies
among multiple neurons by detecting their co-firing (possibly with some lag
time) patterns over time. After discretizing time so there is at most one spike
at each interval, the resulting sequence of 1's (spike) and 0's (silence) for
each neuron is modeled using the logistic function of a continuous latent
variable with a Gaussian process prior. For multiple neurons, the corresponding
marginal distributions are coupled to their joint probability distribution
using a parametric copula model. The advantages of our approach are as follows:
the nonparametric component (i.e., the Gaussian process model) provides a
flexible framework for modeling the underlying firing rates; the parametric
component (i.e., the copula model) allows us to make inference regarding both
contemporaneous and lagged relationships among neurons; using the copula model,
we construct multivariate probabilistic models by separating the modeling of
univariate marginal distributions from the modeling of dependence structure
among variables; our method is easy to implement using a computationally
efficient sampling algorithm that can be easily extended to high dimensional
problems. Using simulated data, we show that our approach could correctly
capture temporal dependencies in firing rates and identify synchronous neurons.
We also apply our model to spike train data obtained from prefrontal cortical
areas in rat's brain
Establishing a Statistical Link between Network Oscillations and Neural Synchrony
Pairs of active neurons frequently fire action potentials or “spikes” nearly synchronously (i.e., within 5 ms of each other). This spike synchrony may occur by chance, based solely on the neurons’ fluctuating firing patterns, or it may occur too frequently to be explicable by chance alone. When spike synchrony above chances levels is present, it may subserve computation for a specific cognitive process, or it could be an irrelevant byproduct of such computation. Either way, spike synchrony is a feature of neural data that should be explained. A point process regression framework has been developed previously for this purpose, using generalized linear models (GLMs). In this framework, the observed number of synchronous spikes is compared to the number predicted by chance under varying assumptions about the factors that affect each of the individual neuron’s firing-rate functions. An important possible source of spike synchrony is network-wide oscillations, which may provide an essential mechanism of network information flow. To establish the statistical link between spike synchrony and network-wide oscillations, we have integrated oscillatory field potentials into our point process regression framework. We first extended a previously-published model of spike-field association and showed that we could recover phase relationships between oscillatory field potentials and firing rates. We then used this new framework to demonstrate the statistical relationship between oscillatory field potentials and spike synchrony in: 1) simulated neurons, 2) in vitro recordings of hippocampal CA1 pyramidal cells, and 3) in vivo recordings of neocortical V4 neurons. Our results provide a rigorous method for establishing a statistical link between network oscillations and neural synchrony
Graph quilting: graphical model selection from partially observed covariances
We investigate the problem of conditional dependence graph estimation when
several pairs of nodes have no joint observation. For these pairs even the
simplest metric of covariability, the sample covariance, is unavailable. This
problem arises, for instance, in calcium imaging recordings where the
activities of a large population of neurons are typically observed by recording
from smaller subsets of cells at once, and several pairs of cells are never
recorded simultaneously. With no additional assumption, the unavailability of
parts of the covariance matrix translates into the unidentifiability of the
precision matrix that, in the Gaussian graphical model setting, specifies the
graph. Recovering a conditional dependence graph in such settings is
fundamentally an extremely hard challenge, because it requires to infer
conditional dependences between network nodes with no empirical evidence of
their covariability. We call this challenge the "graph quilting problem". We
demonstrate that, under mild conditions, it is possible to correctly identify
not only the edges connecting the observed pairs of nodes, but also a superset
of those connecting the variables that are never observed jointly. We propose
an regularized graph estimator based on a partially observed sample
covariance matrix and establish its rates of convergence in high-dimensions. We
finally present a simulation study and the analysis of calcium imaging data of
ten thousand neurons in mouse visual cortex.Comment: 6 figure
Point process modeling as a framework to dissociate intrinsic and extrinsic components in neural systems
Understanding the factors shaping neuronal spiking is a central problem in neuroscience. Neurons may have complicated sensitivity and, often, are embedded in dynamic networks whose ongoing activity may influence their likelihood of spiking. One approach to characterizing neuronal spiking is the point process generalized linear model (GLM), which decomposes spike probability into explicit factors. This model represents a higher level of abstraction than biophysical models, such as Hodgkin-Huxley, but benefits from principled approaches for estimation and validation.
Here we address how to infer factors affecting neuronal spiking in different types of neural systems. We first extend the point process GLM, most commonly used to analyze single neurons, to model population-level voltage discharges recorded during human seizures. Both GLMs and descriptive measures reveal rhythmic bursting and directional wave propagation. However, we show that GLM estimates account for covariance between these features in a way that pairwise measures do not. Failure to account for this covariance leads to confounded results. We interpret the GLM results to speculate the mechanisms of seizure and suggest new therapies.
The second chapter highlights flexibility of the GLM. We use this single framework to analyze enhancement, a statistical phenomenon, in three distinct systems. Here we define the enhancement score, a simple measure of shared information between spike factors in a GLM. We demonstrate how to estimate the score, including confidence intervals, using simulated data. In real data, we find that enhancement occurs prominently during human seizure, while redundancy tends to occur in mouse auditory networks. We discuss implications for physiology, particularly during seizure.
In the third part of this thesis, we apply point process modeling to spike trains recorded from single units in vitro under external stimulation. We re-parameterize models in a low-dimensional and physically interpretable way; namely, we represent their effects in principal component space. We show that this approach successfully separates the neurons observed in vitro into different classes consistent with their gene expression profiles.
Taken together, this work contributes a statistical framework for analyzing neuronal spike trains and demonstrates how it can be applied to create new insights into clinical and experimental data sets