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Emery N Brown

Publications and source records attributed to Emery N Brown.

31 records · Page 2Linked to original sources

Spatiotemporal wavelet analysis for functional MRI.

Characterizing the spatiotemporal behavior of the BOLD signal in functional Magnetic Resonance Imaging (fMRI) is a central issue in understanding brain function. While the nature of functional activation clusters is fundamentally heterogeneous, many current analysis approaches use spatially invariant models that can degrade anatomic boundaries and distort the underlying spatiotemporal signal. Furthermore, few analysis approaches use true spatiotemporal continuity in their statistical formulations. To address these issues, we present a novel spatiotemporal wavelet procedure that uses a stimulus-convolved hemodynamic signal plus correlated noise model. The wavelet fits, computed by spatially constrained maximum-likelihood estimation, provide efficient multiscale representations of heterogeneous brain structures and give well-identified, parsimonious spatial activation estimates that are modulated by the temporal fMRI dynamics. In a study of both simulated data and actual fMRI memory task experiments, our new method gave lower mean-squared error and seemed to result in more localized fMRI activation maps compared to models using standard wavelet or smoothing techniques. Our spatiotemporal wavelet framework suggests a useful tool for the analysis of fMRI studies.

Algorithms↗

Multiple neural spike train data analysis: state-of-the-art and future challenges.

Multiple electrodes are now a standard tool in neuroscience research that make it possible to study the simultaneous activity of several neurons in a given brain region or across different regions. The data from multi-electrode studies present important analysis challenges that must be resolved for optimal use of these neurophysiological measurements to answer questions about how the brain works. Here we review statistical methods for the analysis of multiple neural spike-train data and discuss future challenges for methodology research.

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Dynamic analyses of information encoding in neural ensembles.

Neural spike train decoding algorithms and techniques to compute Shannon mutual information are important methods for analyzing how neural systems represent biological signals. Decoding algorithms are also one of several strategies being used to design controls for brain-machine interfaces. Developing optimal strategies to design decoding algorithms and compute mutual information are therefore important problems in computational neuroscience. We present a general recursive filter decoding algorithm based on a point process model of individual neuron spiking activity and a linear stochastic state-space model of the biological signal. We derive from the algorithm new instantaneous estimates of the entropy, entropy rate, and the mutual information between the signal and the ensemble spiking activity. We assess the accuracy of the algorithm by computing, along with the decoding error, the true coverage probability of the approximate 0.95 confidence regions for the individual signal estimates. We illustrate the new algorithm by reanalyzing the position and ensemble neural spiking activity of CA1 hippocampal neurons from two rats foraging in an open circular environment. We compare the performance of this algorithm with a linear filter constructed by the widely used reverse correlation method. The median decoding error for Animal 1 (2) during 10 minutes of open foraging was 5.9 (5.5) cm, the median entropy was 6.9 (7.0) bits, the median information was 9.4 (9.4) bits, and the true coverage probability for 0.95 confidence regions was 0.67 (0.75) using 34 (32) neurons. These findings improve significantly on our previous results and suggest an integrated approach to dynamically reading neural codes, measuring their properties, and quantifying the accuracy with which encoded information is extracted.

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Dynamic analysis of neural encoding by point process adaptive filtering.

Neural receptive fields are dynamic in that with experience, neurons change their spiking responses to relevant stimuli. To understand how neural systems adapt their representations of biological information, analyses of receptive field plasticity from experimental measurements are crucial. Adaptive signal processing, the well-established engineering discipline for characterizing the temporal evolution of system parameters, suggests a framework for studying the plasticity of receptive fields. We use the Bayes' rule Chapman-Kolmogorov paradigm with a linear state equation and point process observation models to derive adaptive filters appropriate for estimation from neural spike trains. We derive point process filter analogues of the Kalman filter, recursive least squares, and steepest-descent algorithms and describe the properties of these new filters. We illustrate our algorithms in two simulated data examples. The first is a study of slow and rapid evolution of spatial receptive fields in hippocampal neurons. The second is an adaptive decoding study in which a signal is decoded from ensemble neural spiking activity as the receptive fields of the neurons in the ensemble evolve. Our results provide a paradigm for adaptive estimation for point process observations and suggest a practical approach for constructing filtering algorithms to track neural receptive field dynamics on a millisecond timescale.

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A statistical model of diurnal variation in human growth hormone.

The diurnal pattern of growth hormone (GH) serum levels depends on the frequency and amplitude of GH secretory events, the kinetics of GH infusion into and clearance from the circulation, and the feedback of GH on its secretion. We present a two-dimensional linear differential equation model based on these physiological principles to describe GH diurnal patterns. The model characterizes the onset times of the secretory events, the secretory event amplitudes, as well as the infusion, clearance, and feedback half-lives of GH. We illustrate the model by using maximum likelihood methods to fit it to GH measurements collected in 12 normal, healthy women during 8 h of scheduled sleep and a 16-h circadian constant-routine protocol. We assess the importance of the model components by using parameter standard error estimates and Akaike's Information Criterion. During sleep, both the median infusion and clearance half-life estimates were 13.8 min, and the median number of secretory events was 2. During the constant routine, the median infusion half-life estimate was 12.6 min, the median clearance half-life estimate was 11.7 min, and the median number of secretory events was 5. The infusion and clearance half-life estimates and the number of secretory events are consistent with current published reports. Our model gave an excellent fit to each GH data series. Our analysis paradigm suggests an approach to decomposing GH diurnal patterns that can be used to characterize the physiological properties of this hormone under normal and pathological conditions.

Adult↗

Single neurons in the monkey hippocampus and learning of new associations.

The medial temporal lobe is crucial for the ability to learn and retain new declarative memories. This form of memory includes the ability to quickly establish novel associations between unrelated items. To better understand the patterns of neural activity during associative memory formation, we recorded the activity of hippocampal neurons of macaque monkeys as they learned new associations. Hippocampal neurons signaled learning by changing their stimulus-selective response properties. This change in the pattern of selective neural activity occurred before, at the same time as, or after learning, which suggests that these neurons are involved in the initial formation of new associative memories.

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Persistent activity and memory in the entorhinal cortex.

The entorhinal cortex (EC) is an essential component of the medial temporal lobe long-term-memory system. Recently, Egorov et al. demonstrated that neurons in layer 5 of the EC show graded persistent activity: each neuron could maintain a constant rate firing over several minutes, even in the absence of input from other neurons. These findings suggest that layer-5 EC neurons could play a central role in the formation of associations among stimuli that occur at different times.

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An application of reversible-jump Markov chain Monte Carlo to spike classification of multi-unit extracellular recordings.

Multi-electrode recordings in neural tissue contain the action potential waveforms of many closely spaced neurons. While we can observe the action potential waveforms, we cannot observe which neuron is the source for which waveform nor how many source neurons are being recorded. Current spike-sorting algorithms solve this problem by assuming a fixed number of source neurons and assigning the action potentials given this fixed number. We model the spike waveforms as an anisotropic Gaussian mixture model and present, as an alternative, a reversible-jump Markov chain Monte Carlo (MCMC) algorithm to simultaneously estimate the number of source neurons and to assign each action potential to a source. We derive this MCMC algorithm and illustrate its application using simulated three-dimensional data and real four-dimensional feature vectors extracted from tetrode recordings of rat entorhinal cortex neurons. In the analysis of the simulated data our algorithm finds the correct number of mixture components (sources) and classifies the action potential waveforms with minimal error. In the analysis of real data, our algorithm identifies clusters closely resembling those previously identified by a user-dependent graphical clustering procedure. Our findings suggest that a reversible-jump MCMC algorithm could offer a new strategy for designing automated spike-sorting algorithms.

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Estimating a state-space model from point process observations.

A widely used signal processing paradigm is the state-space model. The state-space model is defined by two equations: an observation equation that describes how the hidden state or latent process is observed and a state equation that defines the evolution of the process through time. Inspired by neurophysiology experiments in which neural spiking activity is induced by an implicit (latent) stimulus, we develop an algorithm to estimate a state-space model observed through point process measurements. We represent the latent process modulating the neural spiking activity as a gaussian autoregressive model driven by an external stimulus. Given the latent process, neural spiking activity is characterized as a general point process defined by its conditional intensity function. We develop an approximate expectation-maximization (EM) algorithm to estimate the unobservable state-space process, its parameters, and the parameters of the point process. The EM algorithm combines a point process recursive nonlinear filter algorithm, the fixed interval smoothing algorithm, and the state-space covariance algorithm to compute the complete data log likelihood efficiently. We use a Kolmogorov-Smirnov test based on the time-rescaling theorem to evaluate agreement between the model and point process data. We illustrate the model with two simulated data examples: an ensemble of Poisson neurons driven by a common stimulus and a single neuron whose conditional intensity function is approximated as a local Bernoulli process.

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Contrasting patterns of receptive field plasticity in the hippocampus and the entorhinal cortex: an adaptive filtering approach.

Neural receptive fields are frequently plastic: a neural response to a stimulus can change over time as a result of experience. We developed an adaptive point process filtering algorithm that allowed us to estimate the dynamics of both the spatial receptive field (spatial intensity function) and the interspike interval structure (temporal intensity function) of neural spike trains on a millisecond time scale without binning over time or space. We applied this algorithm to both simulated data and recordings of putative excitatory neurons from the CA1 region of the hippocampus and the deep layers of the entorhinal cortex (EC) of awake, behaving rats. Our simulation results demonstrate that the algorithm accurately tracks simultaneous changes in the spatial and temporal structure of the spike train. When we applied the algorithm to experimental data, we found consistent patterns of plasticity in the spatial and temporal intensity functions of both CA1 and deep EC neurons. These patterns tended to be opposite in sign, in that the spatial intensity functions of CA1 neurons showed a consistent increase over time, whereas those of deep EC neurons tended to decrease, and the temporal intensity functions of CA1 neurons showed a consistent increase only in the "theta" (75-150 msec) region, whereas those of deep EC neurons decreased in the region between 20 and 75 msec. In addition, the minority of deep EC neurons whose spatial intensity functions increased in area over time fired in a significantly more spatially specific manner than non-increasing deep EC neurons. We hypothesize that this subset of deep EC neurons may receive more direct input from CA1 and may be part of a neural circuit that transmits information about the animal's location to the neocortex.

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Motion and ballistocardiogram artifact removal for interleaved recording of EEG and EPs during MRI.

Artifacts generated by motion (e.g., ballistocardiac) of the head inside a high magnetic field corrupt recordings of EEG and EPs. This paper introduces a method for motion artifact cancellation. This method is based on adaptive filtering and takes advantage of piezoelectric motion sensor information to estimate the motion artifact noise. This filter estimates the mapping between motion sensor and EEG space, subtracting the motion-related noise from the raw EEG signal. Due to possible subject motion and changes in electrode impedance, a time-varying mapping of the motion versus EEG is required. We show that this filter is capable of removing both ballistocardiogram and gross motion artifacts, restoring EEG alpha waves (8-13 Hz), and visual evoked potentials (VEPs). This adaptive filter outperforms the simple band-pass filter for alpha detection because it is also capable of reducing noise within the frequency band of interest. In addition, this filter also removes the transient responses normally visible in the EEG window after echo planar image acquisition, observed during interleaved EEG/fMRI recordings. Our adaptive filter approach can be implemented in real-time to allow for continuous monitoring of EEG and fMRI during clinical and cognitive studies.

Adult↗

The time-rescaling theorem and its application to neural spike train data analysis.

Measuring agreement between a statistical model and a spike train data series, that is, evaluating goodness of fit, is crucial for establishing the model's validity prior to using it to make inferences about a particular neural system. Assessing goodness-of-fit is a challenging problem for point process neural spike train models, especially for histogram-based models such as perstimulus time histograms (PSTH) and rate functions estimated by spike train smoothing. The time-rescaling theorem is a well-known result in probability theory, which states that any point process with an integrable conditional intensity function may be transformed into a Poisson process with unit rate. We describe how the theorem may be used to develop goodness-of-fit tests for both parametric and histogram-based point process models of neural spike trains. We apply these tests in two examples: a comparison of PSTH, inhomogeneous Poisson, and inhomogeneous Markov interval models of neural spike trains from the supplementary eye field of a macque monkey and a comparison of temporal and spatial smoothers, inhomogeneous Poisson, inhomogeneous gamma, and inhomogeneous inverse gaussian models of rat hippocampal place cell spiking activity. To help make the logic behind the time-rescaling theorem more accessible to researchers in neuroscience, we present a proof using only elementary probability theory arguments. We also show how the theorem may be used to simulate a general point process model of a spike train. Our paradigm makes it possible to compare parametric and histogram-based neural spike train models directly. These results suggest that the time-rescaling theorem can be a valuable tool for neural spike train data analysis.

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