The complex process of gait is rendered partially automatic by central pattern generators (CPGs). To further our understanding of their role in gait control in healthy subjects, we applied a paradigm of anti-phase, or syncopated, movement to gait. To provide a context for our results, we reviewed the literature on in-phase, or synchronized, gait. The review results are as follows. Auditory cueing increased step/stride rate for older subjects, but not younger. Stride rate variability decreased for younger subjects, perhaps because the metronome’s cue acted as a temporal ‘anchor point’ for each step. Step width increased in half of the treadmill studies, but none of the overground ones, suggesting a cumulative effect of the attentional demands of synchronizing gait while on a treadmill. Time series analysis revealed that the α exponent was the most sensitive parameter reported, decreasing toward anti-persistence in almost all cued-gait studies. This project compares in-phase (IN) and anti-phase gait (ANTI) in young and old healthy subjects. We expected gait to be less disrupted during ANTI trials at preferred speed, when the facilitating effect of CPGs would be strongest. The measures step time variability, jerk index, and harmonic ratio quantified gait perturbation: none indicated that ANTI was easiest at preferred walking speed. Surprisingly, the gait of older subjects was no more perturbed than that of younger subjects. When they successfully matched the pace of the beat, they unwittingly synchronized to it. The temporal relationship of their steps to the beat was the same in the IN and ANTI conditions. Younger subjects, visibly struggling during ANTI trials, were able to walk in syncopation. This result suggests that cognitive resources available only to the younger group are required to resist synchronizing to the beat.

Gleno-humeral joint (GHJ) is the most mobile joint of the human body. This is related to theincongr uence between the large humeral head articulating with the much smaller glenoid (ratio 3:1). The GHJ laxity is the ability of the humeral head to be passively translated on the glenoid fossa and, when physiological, it guarantees the normal range of motion of the joint. Three-dimensional GHJ linear displacements have been measured, both in vivo and in vitro by means of different instrumental techniques. In vivo gleno-humeral displacements have been assessed by means of stereophotogrammetry, electromagnetic tracking sensors, and bio-imaging techniques. Both stereophotogrammetric systems and electromagnetic tracking devices, due to the deformation of the soft tissues surrounding the bones, are not capable to accurately assess small displacements, such as gleno-humeral joint translations. The bio-imaging techniques can ensure for an accurate joint kinematic (linear and angular displacement) description, but, due to the radiation exposure, most of these techniques, such as computer tomography or fluoroscopy, are invasive for patients. Among the bioimaging techniques, an alternative which could provide an acceptable level of accuracy and that is innocuous for patients is represented by magnetic resonance imaging (MRI). Unfortunately, only few studies have been conducted for three-dimensional analysis and very limited data is available in situations where preset loads are being applied. The general aim of this doctoral thesis is to develop a non-invasive methodology based on open-MRI for in-vivo evaluation of the gleno-humeral translation components in healthy subjects under the application of external loads. / L’articolazione gleno-omerale rappresenta l’articolazione più mobile del corpo umano. Le ragioni di ciò sono da ricondursi alla parziale congruenza tra la testa omerale che si articola con la più piccola cavità glenoidea (rapporto 3:1). La lassità dell’articolazione gleno-omerale rappresenta l’attitudine della testa omerale a essere traslata passivamente rispetto alla cavità glenoidea; essa garantisce, quando fisiologica, il normale range di movimento dell’articolazione. Gli spostamenti lineari tridimensionali (lassità) sono stati misurati, sia in vivo sia in vitro per mezzo di diverse tecniche strumentali. In vivo gli spostamenti dell’articolazione gleno-omerale sono stati valutati con sistemi stereofotogrammetrici, sensori di tracciamento elettromagnetici, e tecniche di bio-imaging. Sia i sistemi stereofotogrammetrici sia i dispositivi di tracciamento elettromagnetici, a causa della deformazione dei tessuti molli che circondano le ossa, non sono adatti a stimare accuratamente piccoli spostamenti, come possono essere le traslazioni dell’articolazione gleno-omerale. Le tecniche di bioimaging possono garantire un’accurata descrizione della cinematica articolare (spostamenti lineari e angolari), ma a causa dell’esposizione alle radiazioni molte di queste tecniche, come la tomografia assiale computerizzata e la fluoroscopia, sono invasive per i pazienti. Tra le tecniche di bio-imaging, un’alternativa che può garantire un accettabile livello di accuratezza e che risulta innocua per i pazienti è rappresentata dall’imaging di risonanza magnetica (RM). Sfortunatamente, solo pochi studi sono stati condotti sull’analisi tridimensionale e pochi dati sono disponibili in situazioni in cui l’articolazione è soggetta all’azione di carichi esterni noti. L’obiettivo generale di questa tesi di dottorato è di sviluppare una metodologia non invasiva basata sulla RM aperta per la valutazione in vivo delle componenti traslazionali dell’articolazione glenoomerale in soggetti sani e con l’applicazione di carichi esterni.

Falls are caused by complex interaction between multiple risk factors which may be modified by age, disease and environment. A variety of methods and tools for fall risk assessment have been proposed, but none of which is universally accepted. Existing tools are generally not capable of providing a quantitative predictive assessment of fall risk. The need for objective, cost-effective and clinically applicable methods would enable quantitative assessment of fall risk on a subject-specific basis. Tracking objectively falls risk could provide timely feedback about the effectiveness of administered interventions enabling intervention strategies to be modified or changed if found to be ineffective. Moreover, some of the fundamental factors leading to falls and what actually happens during a fall remain unclear. Objectively documented and measured falls are needed to improve knowledge of fall in order to develop more effective prevention strategies and prolong independent living. In the last decade, several research groups have developed sensor-based automatic or semi-automatic fall risk assessment tools using wearable inertial sensors. This approach may also serve to detect falls. At the moment, i) several fall-risk assessment studies based on inertial sensors, even if promising, lack of a biomechanical model-based approach which could provide accurate and more detailed measurements of interests (e.g., joint moments, forces) and ii) the number of published real-world fall data of older people in a real-world environment is minimal since most authors have used simulations with healthy volunteers as a surrogate for real-world falls. With these limitations in mind, this thesis aims i) to suggest a novel method for the kinematics and dynamics evaluation of functional motor tasks, often used in clinics for the fall-risk evaluation, through a body sensor network and a biomechanical approach and ii) to define the guidelines for a fall detection algorithm based on a real-world fall database availability.

The surface electrocardiogram (ECG) is an established diagnostic tool for the detection of abnormalities in the electrical activity of the heart. The interest of the ECG, however, extends beyond the diagnostic purpose. In recent years, studies in cognitive psychophysiology have related heart rate variability (HRV) to memory performance and mental workload. The aim of this thesis was to analyze the variability of surface ECG derived rhythms, at two different time scales: the discrete-event time scale, typical of beat-related features (Objective I), and the “continuous” time scale of separated sources in the ECG (Objective II), in selected scenarios relevant to psychophysiological and clinical research, respectively. Objective I) Joint time-frequency and non-linear analysis of HRV was carried out, with the goal of assessing psychophysiological workload (PPW) in response to working memory engaging tasks. Results from fourteen healthy young subjects suggest the potential use of the proposed indices in discriminating PPW levels in response to varying memory-search task difficulty. Objective II) A novel source-cancellation method based on morphology clustering was proposed for the estimation of the atrial wavefront in atrial fibrillation (AF) from body surface potential maps. Strong direct correlation between spectral concentration (SC) of atrial wavefront and temporal variability of the spectral distribution was shown in persistent AF patients, suggesting that with higher SC, shorter observation time is required to collect spectral distribution, from which the fibrillatory rate is estimated. This could be time and cost effective in clinical decision-making. The results held for reduced leads sets, suggesting that a simplified setup could also be considered, further reducing the costs. In designing the methods of this thesis, an online signal processing approach was kept, with the goal of contributing to real-world applicability. An algorithm for automatic assessment of ambulatory ECG quality, and an automatic ECG delineation algorithm were designed and validated.

This thesis is mainly devoted to show how EEG data and related phenomena can be reproduced and analyzed using mathematical models of neural masses (NMM). The aim is to describe some of these phenomena, to show in which ways the design of the models architecture is influenced by such phenomena, point out the difficulties of tuning the dozens of parameters of the models in order to reproduce the activity recorded with EEG systems during different kinds of experiments, and suggest some strategies to cope with these problems. In particular the chapters are organized as follows: chapter I gives a brief overview of the aims and issues addressed in the thesis; in chapter II the main characteristics of the cortical column, of the EEG signal and of the neural mass models will be presented, in order to show the relationships that hold between these entities; chapter III describes a study in which a NMM from the literature has been used to assess brain connectivity changes in tetraplegic patients; in chapter IV a modified version of the NMM is presented, which has been developed to overcomes some of the previous version’s intrinsic limitations; chapter V describes a study in which the new NMM has been used to reproduce the electrical activity evoked in the cortex by the transcranial magnetic stimulation (TMS); chapter VI presents some preliminary results obtained in the simulation of the neural rhythms associated with memory recall; finally, some general conclusions are drawn in chapter VII.

Finite element techniques for solving the problem of fluid-structure interaction of an elastic solid material in a laminar incompressible viscous flow are described. The mathematical problem consists of the Navier-Stokes equations in the Arbitrary Lagrangian-Eulerian formulation coupled with a non-linear structure model, considering the problem as one continuum. The coupling between the structure and the fluid is enforced inside a monolithic framework which computes simultaneously for the fluid and the structure unknowns within a unique solver. We used the well-known Crouzeix-Raviart finite element pair for discretization in space and the method of lines for discretization in time. A stability result using the Backward-Euler time-stepping scheme for both fluid and solid part and the finite element method for the space discretization has been proved. The resulting linear system has been solved by multilevel domain decomposition techniques. Our strategy is to solve several local subproblems over subdomain patches using the Schur-complement or GMRES smoother within a multigrid iterative solver. For validation and evaluation of the accuracy of the proposed methodology, we present corresponding results for a set of two FSI benchmark configurations which describe the self-induced elastic deformation of a beam attached to a cylinder in a laminar channel flow, allowing stationary as well as periodically oscillating deformations, and for a benchmark proposed by COMSOL multiphysics where a narrow vertical structure attached to the bottom wall of a channel bends under the force due to both viscous drag and pressure. Then, as an example of fluid-structure interaction in biomedical problems, we considered the academic numerical test which consists in simulating the pressure wave propagation through a straight compliant vessel. All the tests show the applicability and the numerical efficiency of our approach to both two-dimensional and three-dimensional problems.

This thesis aimed at addressing some of the issues that, at the state of the art, avoid the P300-based brain computer interface (BCI) systems to move from research laboratories to end users’ home. An innovative asynchronous classifier has been defined and validated. It relies on the introduction of a set of thresholds in the classifier, and such thresholds have been assessed considering the distributions of score values relating to target, non-target stimuli and epochs of voluntary no-control. With the asynchronous classifier, a P300-based BCI system can adapt its speed to the current state of the user and can automatically suspend the control when the user diverts his attention from the stimulation interface. Since EEG signals are non-stationary and show inherent variability, in order to make long-term use of BCI possible, it is important to track changes in ongoing EEG activity and to adapt BCI model parameters accordingly. To this aim, the asynchronous classifier has been subsequently improved by introducing a self-calibration algorithm for the continuous and unsupervised recalibration of the subjective control parameters. Finally an index for the online monitoring of the EEG quality has been defined and validated in order to detect potential problems and system failures. This thesis ends with the description of a translational work involving end users (people with amyotrophic lateral sclerosis-ALS). Focusing on the concepts of the user centered design approach, the phases relating to the design, the development and the validation of an innovative assistive device have been described. The proposed assistive technology (AT) has been specifically designed to meet the needs of people with ALS during the different phases of the disease (i.e. the degree of motor abilities impairment). Indeed, the AT can be accessed with several input devices either conventional (mouse, touchscreen) or alterative (switches, headtracker) up to a P300-based BCI. / Questa tesi affronta alcune delle problematiche che, allo stato dell'arte, limitano l'usabilità delle interfacce cervello computer (Brain Computer Interface - BCI) al di fuori del contesto sperimentale. E' stato inizialmente definito e validato un classificatore asincrono. Quest'ultimo basa il suo funzionamento sull'inserimento di un set di soglie all'interno del classificatore. Queste soglie vengono definite considerando le distribuzioni dei valori di score relativi agli stimoli target e non-target e alle epoche EEG in cui il soggetto non intendeva effettuare nessuna selezione (no-control). Con il classificatore asincrono, un BCI basato su potenziali P300 può adattare la sua velocità allo stato corrente dell'utente e sospendere automaticamente il controllo quando l'utente non presta attenzione alla stimolazione. Dal momento che i segnali EEG sono non-stazionari e mostrano una variabilità intrinseca, al fine di rendere possibile l'utilizzo dei sistemi BCI sul lungo periodo, è importante rilevare i cambiamenti dell'attività EEG e adattare di conseguenza i parametri del classificatore. A questo scopo, il classificatore asincrono è stato successivamente migliorato introducendo un algoritmo di autocalibrazione per la continua e non supervisionata ricalibrazione dei parametri di controllo soggettivi. Infine è stato definito e validato un indice per monitorare on-line la qualità del segnale EEG, in modo da rilevare potenziali problemi e malfunzionamenti del sistema. Questa tesi si conclude con la descrizione di un lavoro che ha coinvolto gli utenti finali (persone affette da sclerosi laterale amiotrofica-SLA). In particolare, basandosi sui principi dell’user-centered design, sono state descritte le fasi relative alla progettazione, sviluppo e validazione di una tecnologia assistiva (TA) innovativa. La TA è stata specificamente progettata per rispondere alla esigenze delle persone affetta da SLA durante le diverse fasi della malattia. Infatti, la TA proposta può essere utilizzata sia mediante dispositivi d’input tradizionali (mouse, tastiera) che alternativi (bottoni, headtracker) fino ad arrivare ad un BCI basato su potenziali P300.

The monitoring of cognitive functions aims at gaining information about the current cognitive state of the user by decoding brain signals. In recent years, this approach allowed to acquire valuable information about the cognitive aspects regarding the interaction of humans with external world. From this consideration, researchers started to consider passive application of brain–computer interface (BCI) in order to provide a novel input modality for technical systems solely based on brain activity. The objective of this thesis is to demonstrate how the passive Brain Computer Interfaces (BCIs) applications can be used to assess the mental states of the users, in order to improve the human machine interaction. Two main studies has been proposed. The first one allows to investigate whatever the Event Related Potentials (ERPs) morphological variations can be used to predict the users’ mental states (e.g. attentional resources, mental workload) during different reactive BCI tasks (e.g. P300-based BCIs), and if these information can predict the subjects’ performance in performing the tasks. In the second study, a passive BCI system able to online estimate the mental workload of the user by relying on the combination of the EEG and the ECG biosignals has been proposed. The latter study has been performed by simulating an operative scenario, in which the occurrence of errors or lack of performance could have significant consequences. The results showed that the proposed system is able to estimate online the mental workload of the subjects discriminating three different difficulty level of the tasks ensuring a high reliability. / La valutazione delle funzioni cognitive ha l’obbiettivo di ottenere informazioni sullo stato mentale attuale dell'utente, attraverso la decodifica dei segnali cerebrali. Negli ultimi anni, questo approccio ha consentito di indagare informazioni preziose sugli aspetti cognitivi riguardanti l'interazione tra l’uomo ed il mondo esterno. In base a queste considerazioni, recentemente si è considerata in letteratura la possibilità di utilizzare le interfacce cervello computer passive (BCI passivi) per interagire con dispositivi esterni, sfruttando l’attività spontanea dell’utente. L'obiettivo di questa tesi è quello di dimostrare come le interfacce cervello computer passive possano essere utilizzate per valutare lo stato mentale dell’utente, al fine di migliorare l'interazione uomo-macchina. Sono stati presentati due studi principali. Il primo ha l’obbiettivo di investigare le variazioni morfologiche dei potenziali evento correlati (ERP), al fine di associarle agli stati mentali dell’utente (es. attenzione, carico di lavoro mentale) durante l’utilizzo di BCI reattive, e come predittori delle performance raggiunte dai soggetti. Nel secondo studio è stato sviluppato e validato un sistema BCI passivo in grado di stimare il carico di lavoro mentale dell'utente durante task operative, attraverso la combinazione del segnale elettroencefalografico (EEG) ed elettrocardiografico (ECG). Quest'ultimo studio è stato effettuato simulando uno scenario operativo, in cui il verificarsi di errori da parte dell’operatore o il calo di prestazioni poteva avere conseguenze importanti. I risultati hanno mostrato che il sistema proposto è in grado di discriminare il carico di lavoro mentale percepito dall’utente su tre livelli di difficoltà, garantendo un’elevata affidabilità.

In this work I tried to explore many aspects of cognitive visual science, each one based on different academic fields, proposing mathematical models capable to reproduce both neuro-physiological and phenomenological results that were described in the recent literature. The structure of my thesis is mainly composed of three chapters, corresponding to the three main areas of research on which I focused my work. The results of each work put the basis for the following, and their ensemble form an homogeneous and large-scale survey on the spatio-temporal properties of the architecture of the visual cortex of mammals.

Abstract and concrete concepts are generally considered fundamentally distinct categories. However, many concepts have both concrete and abstract senses, for instance "book" can refer to both a physical object (as in "a torn book") and the abstract content (as in "an interesting book"). How is the meaning of such concepts represented in the brain? In this thesis, we address this question in the light of Pustejovsky’s dot-object hypothesis (Pustejovsky, 1995, 2011). According to the hypothesis, words such as "book" and "lunch" are dot-objects: a class of logically polysemous words which have multiple senses that are closely bound together. As a result of the close binding, both senses can be accessed simultaneously (as in "read the book"), however sometimes only a single aspect is emphasised by the context (e.g. "the book burned", "he summarised the book"). We argue that the complex meanings of the dot-objects are represented and manipulated in semantic hubs in the brain, where all aspects of conceptual knowledge converge and are represented in a modality-independent manner (thus accommodating diverse aspects of knowledge such as that cakes are made of pastry and are related to both birthdays and diabetes). We present three experiments investigating the neural representation of three dot-object categories with clear concrete and abstract senses: print matter such as "book" (OBJECT • INFORMATION), meal concepts such as "lunch" (FOOD • EVENT), and institution such as "church" (BUILDING • ORGANISATION). In all the experiments, participants read the dot-objects in a minimal context which elicited either the concrete or the abstract interpretation (e.g. "open the book" / "consult the book", "cook the lunch" / "organise the lunch"). We found the neural distinction between the concrete and abstract interpretations of the dot-objects differed from the concrete-abstract distinction observed for mono-sense nouns; instead the differential effect was most evident in the anterior temporal lobe (ATL), an area argue to be the semantic hub. The result suggests that 1) the distinct senses of a dot-object are associated with a single, unspecified structure in the mental lexicon, thus aligning with the dot-object theory; 2) when in context, the semantic representation is specified by instantiation to a particular sense. In addition, we also observed variations between the book-like and the lunch-like dot-objects, suggesting a graded representation mechanism within the ATL. Finally the third experiment showed that the MEG gamma-band frequency power could distinguish the neural correlates of the concrete and abstract interpretations; notably the divergence occurred 400ms and later post-stimulus onset. Given the established role in the literature of the gamma-band in integration processes, we conclude that the meaning instantiation only occurred at the later integration stage.