The effect of different spectro-temporal representations of an input auditory stimulus on the fitting of a point process model of auditory neurons

We compare the effect of the use of three different spectro-temporal representations of an input auditory stimulus on the fitting of a point process model of auditory neuron firing. The three spectro-temporal representations considered are the spectrogram, a gammatone filterbank and the Hilbert spectrum. We firstly investigate how the model fits the recorded neuronal data when using either one of the three representations and secondly how well do the estimated parameters of the model correspond to their experimentally measured counterparts. It is observed that all three representations yield a model that fits well the recorded data. However, the characteristic frequencies obtained with the spectro-temporal parameters of the model using the gammatone filterbank corresponds better to the experimentally measured characteristic frequency than the characteristic frequency obtained with the models using the other two spectro-temporal representations. Therefore, it is concluded that the quality of the fitted parameters can be affected by the choice of the spectro-temporal representation and that, as could have been expected, the gammatone filterbank seems to more accurately extract the relevant spectro-temporal characteristics of the input auditory stimulus.Fonds quebecois de la recherche sur la nature et les technologiesNational Institutes of Health (U.S.) (Grant DP1-OD003646

A comparison of spike time prediction and receptive field mapping with point process generalized linear models, Wiener-Voltera kernels, and spike-triggered averaging methods

Poster presentation: Characterizing neuronal encoding is essential for understanding information processing in the brain. Three methods are commonly used to characterize the relationship between neural spiking activity and the features of putative stimuli. These methods include: Wiener-Volterra kernel methods (WVK), the spike-triggered average (STA), and more recently, the point process generalized linear model (GLM). We compared the performance of these three approaches in estimating receptive field properties and orientation tuning of 251 V1 neurons recorded from 2 monkeys during a fixation period in response to a moving bar. The GLM consisted of two formulations of the conditional intensity function for a point process characterization of the spiking activity: one with a stimulus only component and one with the stimulus and spike history. We fit the GLMs by maximum likelihood using GLMfit in Matlab. Goodness-of-fit was assessed using cross-validation with Kolmogorov-Smirnov (KS) tests based on the time-rescaling theorem to evaluate the accuracy with which each model predicts the spiking activity of individual neurons and for each movement direction (4016 models in total, for 251 neurons and 16 different directions). The GLMs that considered spike history of up to 35 ms, accurately predicted neuronal spiking activity (95% confidence intervals for KS test) with a performance of 97.0% (3895/4016) for the training data, and 96.5% (3876/4016) for the test data. If spike history was not considered, performance dropped to 73,1% in the training and 71.3% in the testing data. In contrast, the WVF and the STA predicted spiking accurately for 24.2% and 44.5% of the test data examples respectively. The receptive field size estimates obtained from the GLM (with and without history), WVF and STA were comparable. Relative to the GLM orientation tuning was underestimated on average by a factor of 0.45 by the WVF and the STA. The main reason for using the STA and WVF approaches is their apparent simplicity. However, our analyses suggest that more accurate spike prediction as well as more credible estimates of receptive field size and orientation tuning can be computed easily using GLMs implemented in Matlab with standard functions such as GLMfit

Algorithms for the analysis of ensemble neural spiking activity using simultaneous-event multivariate point-process models

Understanding how ensembles of neurons represent and transmit information in the patterns of their joint spiking activity is a fundamental question in computational neuroscience. At present, analyses of spiking activity from neuronal ensembles are limited because multivariate point process (MPP) models cannot represent simultaneous occurrences of spike events at an arbitrarily small time resolution. Solo recently reported a simultaneous-event multivariate point process (SEMPP) model to correct this key limitation. In this paper, we show how Solo's discrete-time formulation of the SEMPP model can be efficiently fit to ensemble neural spiking activity using a multinomial generalized linear model (mGLM). Unlike existing approximate procedures for fitting the discrete-time SEMPP model, the mGLM is an exact algorithm. The MPP time-rescaling theorem can be used to assess model goodness-of-fit. We also derive a new marked point-process (MkPP) representation of the SEMPP model that leads to new thinning and time-rescaling algorithms for simulating an SEMPP stochastic process. These algorithms are much simpler than multivariate extensions of algorithms for simulating a univariate point process, and could not be arrived at without the MkPP representation. We illustrate the versatility of the SEMPP model by analyzing neural spiking activity from pairs of simultaneously-recorded rat thalamic neurons stimulated by periodic whisker deflections, and by simulating SEMPP data. In the data analysis example, the SEMPP model demonstrates that whisker motion significantly modulates simultaneous spiking activity at the 1 ms time scale and that the stimulus effect is more than one order of magnitude greater for simultaneous activity compared with non-simultaneous activity. Together, the mGLM, the MPP time-rescaling theorem and the MkPP representation of the SEMPP model offer a theoretically sound, practical tool for measuring joint spiking propensity in a neuronal ensemble

A Point Process Model for Auditory Neurons Considering Both Their Intrinsic Dynamics and the Spectrotemporal Properties of an Extrinsic Signal

We propose a point process model of spiking activity from auditory neurons. The model takes account of the neuron's intrinsic dynamics as well as the spectrotemporal properties of an input stimulus. A discrete Volterra expansion is used to derive the form of the conditional intensity function. The Volterra expansion models the neuron's baseline spike rate, its intrinsic dynamics-spiking history-and the stimulus effect which in this case is the analog of the spectrotemporal receptive field (STRF). We performed the model fitting efficiently in a generalized linear model framework using ridge regression to address properly this ill-posed maximum likelihood estimation problem. The model provides an excellent fit to spiking activity from 55 auditory nerve neurons. The STRF-like representation estimated jointly with the neuron's intrinsic dynamics may offer more accurate characterizations of neural activity in the auditory system than current ones based solely on the STRF

A Granger Causality Measure for Point Process Models of Ensemble Neural Spiking Activity

The ability to identify directional interactions that occur among multiple neurons in the brain is crucial to an understanding of how groups of neurons cooperate in order to generate specific brain functions. However, an optimal method of assessing these interactions has not been established. Granger causality has proven to be an effective method for the analysis of the directional interactions between multiple sets of continuous-valued data, but cannot be applied to neural spike train recordings due to their discrete nature. This paper proposes a point process framework that enables Granger causality to be applied to point process data such as neural spike trains. The proposed framework uses the point process likelihood function to relate a neuron’s spiking probability to possible covariates, such as its own spiking history and the concurrent activity of simultaneously recorded neurons. Granger causality is assessed based on the relative reduction of the point process likelihood of one neuron obtained excluding one of its covariates compared to the likelihood obtained using all of its covariates. The method was tested on simulated data, and then applied to neural activity recorded from the primary motor cortex (MI) of a Felis catus subject. The interactions present in the simulated data were predicted with a high degree of accuracy, and when applied to the real neural data, the proposed method identified causal relationships between many of the recorded neurons. This paper proposes a novel method that successfully applies Granger causality to point process data, and has the potential to provide unique physiological insights when applied to neural spike trains.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant R01-EB006385

State-space solutions to the dynamic magnetoencephalography inverse problem using high performance computing

Determining the magnitude and location of neural sources within the brain that are responsible for generating magnetoencephalography (MEG) signals measured on the surface of the head is a challenging problem in functional neuroimaging. The number of potential sources within the brain exceeds by an order of magnitude the number of recording sites. As a consequence, the estimates for the magnitude and location of the neural sources will be ill-conditioned because of the underdetermined nature of the problem. One well-known technique designed to address this imbalance is the minimum norm estimator (MNE). This approach imposes an $L^2$ regularization constraint that serves to stabilize and condition the source parameter estimates. However, these classes of regularizer are static in time and do not consider the temporal constraints inherent to the biophysics of the MEG experiment. In this paper we propose a dynamic state-space model that accounts for both spatial and temporal correlations within and across candidate intracortical sources. In our model, the observation model is derived from the steady-state solution to Maxwell's equations while the latent model representing neural dynamics is given by a random walk process.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS483 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

General Anesthesia and Altered States of Arousal: A Systems Neuroscience Analysis

Placing a patient in a state of general anesthesia is crucial for safely and humanely performing most surgical and many nonsurgical procedures. How anesthetic drugs create the state of general anesthesia is considered a major mystery of modern medicine. Unconsciousness, induced by altered arousal and/or cognition, is perhaps the most fascinating behavioral state of general anesthesia. We perform a systems neuroscience analysis of the altered arousal states induced by five classes of intravenous anesthetics by relating their behavioral and physiological features to the molecular targets and neural circuits at which these drugs are purported to act. The altered states of arousal are sedation-unconsciousness, sedation-analgesia, dissociative anesthesia, pharmacologic non-REM sleep, and neuroleptic anesthesia. Each altered arousal state results from the anesthetic drugs acting at multiple targets in the central nervous system. Our analysis shows that general anesthesia is less mysterious than currently believed.Massachusetts General Hospital. Dept. of Anesthesia and Critical CareNational Institutes of Health (U.S.) (Director's Pioneer Award DP10D003646)National Institutes of Health (U.S.) (New Innovator Award DP2OD006454)National Institutes of Health (U.S.) (Grant K25-NS057580)National Institutes of Health (U.S.) (Training Program in Sleep, Circadian and Respiratory Neurobiology HL07901

On the uncertainty in single molecule fluorescent lifetime and energy emission measurements

Time-correlated single photon counting has recently been combined with mode-locked picosecond pulsed excitation to measure the fluorescent lifetimes and energy emissions of single molecules in a flow stream. Maximum likelihood (ML) and least square methods agree and are optimal when the number of detected photons is large however, in single molecule fluorescence experiments the number of detected photons can be less than 20, 67% of those can be noise and the detection time is restricted to 10 nanoseconds. Under the assumption that the photon signal and background noise are two independent inhomogeneous poisson processes, we derive the exact joint arrival time probably density of the photons collected in a single counting experiment performed in the presence of background noise. The model obviates the need to bin experimental data for analysis, and makes it possible to analyze formally the effect of background noise on the photon detection experiment using both ML or Bayesian methods. For both methods we derive the joint and marginal probability densities of the fluorescent lifetime and fluorescent emission. the ML and Bayesian methods are compared in an analysis of simulated single molecule fluorescence experiments of Rhodamine 110 using different combinations of expected background nose and expected fluorescence emission. While both the ML or Bayesian procedures perform well for analyzing fluorescence emissions, the Bayesian methods provide more realistic measures of uncertainty in the fluorescent lifetimes. The Bayesian methods would be especially useful for measuring uncertainty in fluorescent lifetime estimates in current single molecule flow stream experiments where the expected fluorescence emission is low. Both the ML and Bayesian algorithms can be automated for applications in molecular biology