Assessing dynamics, spatial scale, and uncertainty in task-related brain network analyses

This is the publisher's version, also available electronically from http://journal.frontiersin.org/Journal/10.3389/fncom.2014.00031/abstractThe brain is a complex network of interconnected elements, whose interactions evolve dynamically in time to cooperatively perform specific functions. A common technique to probe these interactions involves multi-sensor recordings of brain activity during a repeated task. Many techniques exist to characterize the resulting task-related activity, including establishing functional networks, which represent the statistical associations between brain areas. Although functional network inference is commonly employed to analyze neural time series data, techniques to assess the uncertainty—both in the functional network edges and the corresponding aggregate measures of network topology—are lacking. To address this, we describe a statistically principled approach for computing uncertainty in functional networks and aggregate network measures in task-related data. The approach is based on a resampling procedure that utilizes the trial structure common in experimental recordings. We show in simulations that this approach successfully identifies functional networks and associated measures of confidence emergent during a task in a variety of scenarios, including dynamically evolving networks. In addition, we describe a principled technique for establishing functional networks based on predetermined regions of interest using canonical correlation. Doing so provides additional robustness to the functional network inference. Finally, we illustrate the use of these methods on example invasive brain voltage recordings collected during an overt speech task. The general strategy described here—appropriate for static and dynamic network inference and different statistical measures of coupling—permits the evaluation of confidence in network measures in a variety of settings common to neuroscience

Characterizing dynamically evolving functional networks in humans with application to speech

Understanding how communication between brain areas evolves to support dynamic function remains a fundamental challenge in neuroscience. One approach to this question is functional connectivity analysis, in which statistical coupling measures are employed to detect signatures of interactions between brain regions. Because the brain uses multiple communication mechanisms at different temporal and spatial scales, and because the neuronal signatures of communication are often weak, powerful connectivity inference methodologies require continued development specific to these challenges. Here we address the challenge of inferring task-related functional connectivity in brain voltage recordings. We first develop a framework for detecting changes in statistical coupling that occur reliably in a task relative to a baseline period. The framework characterizes the dynamics of connectivity changes, allows inference on multiple spatial scales, and assesses statistical uncertainty. This general framework is modular and applicable to a wide range of tasks and research questions. We demonstrate the flexibility of the framework in the second part of this thesis, in which we refine the coupling statistics and hypothesis tests to improve statistical power and test different proposed connectivity mechanisms. In particular, we introduce frequency domain coupling measures and define test statistics that exploit theoretical properties and capture known sampling variability. The resulting test statistics use correlation, coherence, canonical correlation, and canonical coherence to infer task-related changes in coupling. Because canonical correlation and canonical coherence are not commonly used in functional connectivity analyses, we derive the theoretical values and statistical estimators for these measures. In the third part of this thesis, we present a sample application of these techniques to electrocorticography data collected during an overt reading task. We discuss the challenges that arise with task-related human data, which is often noisy and underpowered, and present functional connectivity results in the context of traditional and contemporary within-electrode analytics. In two of nine subjects we observe time-domain and frequency-domain network changes that accord with theoretical models of information routing during motor processing. Taken together, this work contributes a methodological framework for inferring task-related functional connectivity across spatial and temporal scales, and supports insight into the rapid, dynamic functional coupling of human speech

Definition of Neurophysiological Indices to Describe and Quantify the Cortical Plasticity Induced by Neuro-Rehabilitation

The general objective of the PhD project was to develop a methodology for the definition and analysis of neurophysiological indices able to provide a stable and reliable measure of changes induced by a rehabilitative intervention in the brain activity and organization, with the aim to: i) provide a neurophysiological description of the modifications subtending a functional recovery; ii) allow the evaluation of the effects of rehabilitation treatments in terms of brain reorganization; iii) describe specific properties in the brain general organization to be correlated with the outcome of the intervention, with possible prognostic/decision support value. For this purpose, the research activity was focused on the development of an approach for the extraction of neurophysiological indices from non-invasive estimation of the cerebral activity and connectivity based on electroencephalographic recordings. Brain activity and its changes in time were investigated at three different interconnected levels: spectral analysis, connectivity estimation and graph theory. For each of these, the state of the art methods were evaluated and methodological advancements were proposed on the basis of open problems presented by the nature of the data and by the clinical problem. Experimental data were acquired from 56 stroke patients subjected to a rehabilitative intervention based on Motor Imagery (MI). A subgroup of randomly selected patients were trained in the MI task with the support of Brain Computer Interface. New spectral and functional indices were defined and computed from EEG recorded during the execution of specific tasks (e.g. motor execution), but also from resting state brain activity, to capture both specific and general brain functional modifications. The application of the developed methods allowed to return a proof of the nature, quality and properties of the brain description and quantitative indices that can be derived from data easily recordable from a wide range of patients

Contributions to statistical analysis methods for neural spiking activity

With the technical advances in neuroscience experiments in the past few decades, we have seen a massive expansion in our ability to record neural activity. These advances enable neuroscientists to analyze more complex neural coding and communication properties, and at the same time, raise new challenges for analyzing neural spiking data, which keeps growing in scale, dimension, and complexity. This thesis proposes several new statistical methods that advance statistical analysis approaches for neural spiking data, including sequential Monte Carlo (SMC) methods for efficient estimation of neural dynamics from membrane potential threshold crossings, state-space models using multimodal observation processes, and goodness-of-fit analysis methods for neural marked point process models. In a first project, we derive a set of iterative formulas that enable us to simulate trajectories from stochastic, dynamic neural spiking models that are consistent with a set of spike time observations. We develop a SMC method to simultaneously estimate the parameters of the model and the unobserved dynamic variables from spike train data. We investigate the performance of this approach on a leaky integrate-and-fire model. In another project, we define a semi-latent state-space model to estimate information related to the phenomenon of hippocampal replay. Replay is a recently discovered phenomenon where patterns of hippocampal spiking activity that typically occur during exploration of an environment are reactivated when an animal is at rest. This reactivation is accompanied by high frequency oscillations in hippocampal local field potentials. However, methods to define replay mathematically remain undeveloped. In this project, we construct a novel state-space model that enables us to identify whether replay is occurring, and if so to estimate the movement trajectories consistent with the observed neural activity, and to categorize the content of each event. The state-space model integrates information from the spiking activity from the hippocampal population, the rhythms in the local field potential, and the rat's movement behavior. Finally, we develop a new, general time-rescaling theorem for marked point processes, and use this to develop a general goodness-of-fit framework for neural population spiking models. We investigate this approach through simulation and a real data application

Characteristic time courses of electrocorticographic signals during speech

Electrophysiology has produced a wealth of information concerning characteristic patterns of neural activity underlying movement control in non-human primates. Such patterns differentiate functional classes of neurons and illuminate neural computations underlying different stages of motor planning and execution. The scarcity of high-resolution electrophysiological recordings in humans has hindered such descriptions of brain activity during uniquely human acts such as speech production. The goal of this dissertation was to identify and quantitatively characterize canonical temporal profiles of neural activity measured using surface and depth electrocorticography electrodes while pre-surgical epilepsy patients read aloud monosyllabic utterances. An unsupervised iterative clustering procedure was combined with a novel Kalman filter-based trend analysis to identify characteristic activity time courses that occurred across multiple subjects. A nonlinear distance measure was used to emphasize similarity at key portions of the activity profiles, including signal peaks. Eight canonical activity patterns were identified. These activity profiles fell broadly into two classes: symmetric profiles in which activity rises and falls at approximately the same rate, and ramp profiles in which activity rises relatively quickly and falls off gradually. Distinct characteristic time courses were found during four different task stages: early processing of the orthographic stimulus, phonological-to-motor processing, motor execution, and auditory processing of self-produced speech, with activity offset ramps in earlier stages approximately matching activity onset rates in later stages. The addition of an anatomical constraint to the distance measure to encourage clusters to form within local brain regions did not significantly change results. The anatomically constrained results showed a further subdivision of the eight canonical activity patterns, with the subdivisions primarily stemming from sub-clusters that are anatomically distinct across different brain regions, but maintained the base activity pattern of their parent cluster from the analysis without the anatomically constrained distance measure. The analysis tools developed herein provide a powerful means for identifying and quantitatively characterizing the neural computations underlying human speech production and may apply to other cognitive and behavioral domains