thesis

Advances in point process filters and their application to sympathetic neural activity

Abstract

This thesis is concerned with the development of techniques for analyzing the sequences of stereotypical electrical impulses within neurons known as spikes. Sequences of spikes, also called spike trains, transmit neural information; decoding them often provides details about the physiological processes generating the neural activity. Here, the statistical theory of event arrivals, called point processes, is applied to human muscle sympathetic spike trains, a peripheral nerve signal responsible for cardiovascular regulation. A novel technique that uses observed spike trains to dynamically derive information about the physiological processes generating them is also introduced. Despite the emerging usage of individual spikes in the analysis of human muscle sympathetic nerve activity, the majority of studies in this field remain focused on bursts of activity at or below cardiac rhythm frequencies. Point process theory applied to multi-neuron spike trains captured both fast and slow spiking rhythms. First, analysis of high-frequency spiking patterns within cardiac cycles was performed and, surprisingly, revealed fibers with no cardiac rhythmicity. Modeling spikes as a function of average firing rates showed that individual nerves contribute substantially to the differences in the sympathetic stressor response across experimental conditions. Subsequent investigation of low-frequency spiking identified two physiologically relevant frequency bands, and modeling spike trains as a function of hemodynamic variables uncovered complex associations between spiking activity and biophysical covariates at these two frequencies. For example, exercise-induced neural activation enhances the relationship of spikes to respiration but does not affect the extremely precise alignment of spikes to diastolic blood pressure. Additionally, a novel method of utilizing point process observations to estimate an internal state process with partially linear dynamics was introduced. Separation of the linear components of the process model and reduction of the sampled space dimensionality improved the computational efficiency of the estimator. The method was tested on an established biophysical model by concurrently computing the dynamic electrical currents of a simulated neuron and estimating its conductance properties. Computational load reduction, improved accuracy, and applicability outside neuroscience establish the new technique as a valuable tool for decoding large dynamical systems with linear substructure and point process observations

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