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

Statistical causality in the EEG for the study of cognitive functions in healthy and pathological brains

Understanding brain functions requires not only information about the spatial localization of neural activity, but also about the dynamic functional links between the involved groups of neurons, which do not work in an isolated way, but rather interact together through ingoing and outgoing connections. The work carried on during the three years of PhD course returns a methodological framework for the estimation of the causal brain connectivity and its validation on simulated and real datasets (EEG and pseudo-EEG) at scalp and source level. Important open issues like the selection of the best algorithms for the source reconstruction and for time-varying estimates were addressed. Moreover, after the application of such approaches on real datasets recorded from healthy subjects and post-stroke patients, we extracted neurophysiological indices describing in a stable and reliable way the properties of the brain circuits underlying different cognitive states in humans (attention, memory). More in detail: I defined and implemented a toolbox (SEED-G toolbox) able to provide a useful validation instrument addressed to researchers who conduct their activity in the field of brain connectivity estimation. It may have strong implication, especially in methodological advancements. It allows to test the ability of different estimators in increasingly less ideal conditions: low number of available samples and trials, high inter-trial variability (very realistic situations when patients are involved in protocols) or, again, time varying connectivity patterns to be estimate (where stationary hypothesis in wide sense failed). A first simulation study demonstrated the robustness and the accuracy of the PDC with respect to the inter-trials variability under a large range of conditions usually encountered in practice. The simulations carried on the time-varying algorithms allowed to highlight the performance of the existing methodologies in different conditions of signals amount and number of available trials. Moreover, the adaptation of the Kalman based algorithm (GLKF) I implemented, with the introduction of the preliminary estimation of the initial conditions for the algorithm, lead to significantly better performance. Another simulation study allowed to identify a tool combining source localization approaches and brain connectivity estimation able to provide accurate and reliable estimates as less as possible affected to the presence of spurious links due to the head volume conduction. The developed and tested methodologies were successfully applied on three real datasets. The first one was recorded from a group of healthy subjects performing an attention task that allowed to describe the brain circuit at scalp and source level related with three important attention functions: alerting, orienting and executive control. The second EEG dataset come from a group of healthy subjects performing a memory task. Also in this case, the approaches under investigation allowed to identify synthetic connectivity-based descriptors able to characterize the three main memory phases (encoding, storage and retrieval). For the last analysis I recorded EEG data from a group of stroke patients performing the same memory task before and after one month of cognitive rehabilitation. The promising results of this preliminary study showed the possibility to follow the changes observed at behavioural level by means of the introduced neurophysiological indices

Effect of inter-trials variability on the estimation of cortical connectivity by Partial Directed Coherence

Partial Directed Coherence (PDC) is a powerful estimator of effective connectivity. In neuroscience it is used in different applications with the aim to investigate the communication between brain regions during the execution of different motor or cognitive tasks. When multiple trials are available, PDC can be computed over multiple realizations, provided that the assumption of stationarity across trials is verified. This allows to improve the amount of data, which is an important constraint for the estimation accuracy. However, the stationarity of the data across trials is not always guaranteed, especially when dealing with patients. In this study we investigated how the inter-trials variability of an EEG dataset affects the PDC accuracy. Effects of density variations and of changes of connectivity values across trials were first investigated with a simulation study and then tested on real EEG data collected from two post-stroke patients during a motor imagery task and characterized by different inter-trials variability. Results showed the effect of different factors on the PDC accuracy and the robustness of such estimator in a range of conditions met in practical applications