Introducing a Comprehensive Framework to Measure Spike-LFP Coupling

Measuring the coupling of single neuron's spiking activities to the local field potentials (LFPs) is a method to investigate neuronal synchronization. The most important synchronization measures are phase locking value (PLV), spike field coherence (SFC), pairwise phase consistency (PPC), and spike-triggered correlation matrix synchronization (SCMS). Synchronization is generally quantified using the PLV and SFC. PLV and SFC methods are either biased on the spike rates or the number of trials. To resolve these problems the PPC measure has been introduced. However, there are some shortcomings associated with the PPC measure which is unbiased only for very high spike rates. However evaluating spike-LFP phase coupling (SPC) for short trials or low number of spikes is a challenge in many studies. Lastly, SCMS measures the correlation in terms of phase in regions around the spikes inclusive of the non-spiking events which is the major difference between SCMS and SPC. This study proposes a new framework for predicting a more reliable SPC by modeling and introducing appropriate machine learning algorithms namely least squares, Lasso, and neural networks algorithms where through an initial trend of the spike rates, the ideal SPC is predicted for neurons with low spike rates. Furthermore, comparing the performance of these three algorithms shows that the least squares approach provided the best performance with a correlation of 0.99214 and R2 of 0.9563 in the training phase, and correlation of 0.95969 and R2 of 0.8842 in the test phase. Hence, the results show that the proposed framework significantly enhances the accuracy and provides a bias-free basis for small number of spikes for SPC as compared to the conventional methods such as PLV method. As such, it has the general ability to correct for the bias on the number of spike rates

Effective influences in neuronal networks : attentional modulation of effective influences underlying flexible processing and how to measure them

Selective routing of information between brain areas is a key prerequisite for flexible adaptive behaviour. It allows to focus on relevant information and to ignore potentially distracting influences. Selective attention is a psychological process which controls this preferential processing of relevant information. The neuronal network structures and dynamics, and the attentional mechanisms by which this routing is enabled are not fully clarified. Based on previous experimental findings and theories, a network model is proposed which reproduces a range of results from the attention literature. It depends on shifting of phase relations between oscillating neuronal populations to modulate the effective influence of synapses. This network model might serve as a generic routing motif throughout the brain. The attentional modifications of activity in this network are investigated experimentally and found to employ two distinct channels to influence processing: facilitation of relevant information and independent suppression of distracting information. These findings are in agreement with the model and previously unreported on the level of neuronal populations. Furthermore, effective influence in dynamical systems is investigated more closely. Due to a lack of a theoretical underpinning for measurements of influence in non-linear dynamical systems such as neuronal networks, often unsuited measures are used for experimental data that can lead to erroneous conclusions. Based on a central theorem in dynamical systems, a novel theory of effective influence is developed. Measures derived from this theory are demonstrated to capture the time dependent effective influence and the asymmetry of influences in model systems and experimental data. This new theory holds the potential to uncover previously concealed interactions in generic non-linear systems studied in a range of disciplines, such as neuroscience, ecology, economy and climatology

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

Estimating Neural Signal Dynamics in the Human Brain

Although brain imaging methods are highly effective for localizing the effects of neural activation throughout the human brain in terms of the blood oxygenation level dependent (BOLD) response, there is currently no way to estimate the underlying neural signal dynamics in generating the BOLD response in each local activation region (except for processes slower than the BOLD time course). Knowledge of the neural signal is critical if spatial mapping is to progress to the analysis of dynamic information flow through the cortical networks as the brain performs its tasks. We introduce an analytic approach that provides a new level of conceptualization and specificity in the study of brain processing by non-invasive methods. This technique allows us to use brain imaging methods to determine the dynamics of local neural population responses to their native temporal resolution throughout the human brain, with relatively narrow confidence intervals on many response properties. The ability to characterize local neural dynamics in the human brain represents a significant enhancement of brain imaging capabilities, with potential applications ranging from general cognitive studies to assessment of neuropathologies