The growing interest in neuroimaging technologies generates a massive amount of biomedical data that exhibit high dimensionality. Tensor-based analysis of brain imaging data has by now been recognized as an effective approach exploiting its inherent multi-way nature. In particular, the advantages of tensorial over matrix-based methods have previously been demonstrated in the context of functional magnetic resonance imaging (fMRI) source localization; the identification of the regions of the brain which are activated at specific time instances. However, such methods can also become ineffective in realistic challenging scenarios, involving, e.g., strong noise and/or significant overlap among the activated regions. Moreover, they commonly rely on the assumption of an underlying multilinear model generating the data. In the first part of this thesis, we aimed at investigating the possible gains from exploiting the 3-dimensional nature of the brain images, through a higher-order tensorization ...

Epilepsy is a neurological condition that manifests in epileptic seizures as a result of an abnormal, synchronous activity of a large group of neurons. Depending on the affected brain regions, seizures produce various severe clinical symptoms. Epilepsy cannot be cured and in many cases is not controlled by medication either. Surgical resection of the region responsible for generating the epileptic seizures might offer remedy for these patients. Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) measure the changes of brain activity in time over different locations of the brain. As such, they provide valuable information on the nature, the timing and the spatial origin of the epileptic activity. Unfortunately, both techniques record activity of different brain and artefact sources as well. Hence, EEG and fMRI signals are characterised by low signal to noise ratio. Data quality and the vast amount ...

A complex physical system like the human brain can only be comprehended by the use of a combination of various medical imaging techniques, each of which shed light on only a specific aspect of the neural processes that take place beneath the skull. Electroencephalography (EEG) and functional magnetic resonance (fMRI) are two such modalities, which enable the study of brain (dys)function. While the EEG is measured with a limited set of scalp electrodes which record rapid electrical changes resulting from neural activity, fMRI offers a superior spatial resolution at the expense of only picking up slow fluctuations of oxygen concentration that takes place near active brain cells. Hence, combining these very complementary modalities is an appealing, but complicated task due to their heterogeneous nature. In this thesis, we devise advanced signal processing techniques which integrate the multimodal data stemming from ...

Understanding the cognitive processes that are going on in the human brain, requires the combination of several types of observations. For this reason, since several years, neuroscience research started to focus on multimodal approaches. One such multimodal approach is the combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). The non-invasive character of these two modalities makes their combination not only harmless and painless, but also especially suited for widespread research in both clinical and experimental applications. Moreover, the complementarity between the high temporal resolution of the EEG and the high spatial resolution of the fMRI, allows obtaining a more complete picture of the processes under study. However, the combination of EEG and fMRI is challenging, not only on the level of the data acquisition, but also when it comes to extracting the activity of interest and interpreting the ...

Magnetic Resonance Imaging (MRI) constitutes a non-invasive medical imaging technique that allows the exploration of the inner anatomy, tissues, and physiological processes of the body. Among the different MRI applications, functional Magnetic Resonance Imaging (fMRI) has slowly become an essential tool for investigating the brain behavior and, nowadays, it plays a fundamental role in clinical and neurophysiological research. Due to its particular nature, specialized signal processing techniques are required in order to analyze the fMRI data properly. Among the various related techniques that have been developed over the years, the General Linear Model (GLM) is one of the most widely used approaches, and it usually appears as a default in many specialized software toolboxes for fMRI. On the other end, Blind Source Separation (BSS) methods constitute the most common alternative to GLM, especially when no prior information regarding the brain ...

Preterm birth is a major pediatric health problem that perturbs the genetically determined program of corticogenesis of the developing brain. As a consequence, prematurity has been strongly associated with adverse long-term neurodevelopmental outcome that may persist even into adulthood. Early characterization of the underlying neuronal mechanisms and early identification of infants at risk is of paramount importance since it allows better development of early therapeutic interventions aiming to prevent adverse outcomes through resilience. This dissertation aims to investigate the consequences of preterm birth on brain function and structure and their relation to adverse neurodevelopmental outcome, as well as to unveil the effect of an early music intervention on brain function. Research to date has mainly focused on the effect of early interventions on the long-term outcome but not on the effect of those interventions on brain function in preterm populations. ...

In this thesis, the power of Machine Learning (ML) algorithms is combined with brain connectivity patterns, using Magnetic Resonance Imaging (MRI), for classification and prediction of Multiple Sclerosis (MS). White Matter (WM) as well as Grey Matter (GM) graphs are studied as connectome data types. The thesis addresses three main research objectives. The first objective aims to generate realistic brain connectomes data for improving the classification of MS clinical profiles in cases of data scarcity and class imbalance. To solve the problem of limited and imbalanced data, a Generative Adversarial Network (GAN) was developed for the generation of realistic and biologically meaningful connec- tomes. This network achieved a 10% better MS classification performance compared to classical approaches. As second research objective, we aim to improve classification of MS clinical profiles us- ing morphological features only extracted from GM brain tissue. ...

A key issue in understanding how the brain functions is the ability to correlate functional information with anatomical localisation. Functional information can be provided by a variety of techniques like positron emission tomography (PET), functional MRI (fMRI), electroencephalography (EEG), magnetoencephalography (MEG) or transcranial magnetic stimulation (TMS). All these methods provide different, but complementary, information about the functional areas of the brain. PET and fMRI provide spatially accurate picture of brain regions involved in a given task. TMS permits to infer the contribution of the stimulated brain area to the task under investigation. EEG and MEG, which reflects brain activity directly, have temporal accuracy of the order of a millisecond. TMS, EEG and MEG are offset by their low spatial resolution. In this thesis, we propose two methods to improve the spatial accuracy of method based on TMS and EEG. The ...

Diffusion magnetic resonance imaging (dMRI) is currently the method of choice for the in vivo and non-invasive quantification of water diffusion in biological tissue. Several diffusion models have been proposed to obtain quantitative diffusion parameters, which have shown to provide novel information on the structural and organizational features of biological tissue, the brain white matter in particular. The goal of this dissertation is to improve the accuracy of the diffusion parameter estimation, given the non-Gaussian nature of the diffusion-weighted MR data. In part I of this manuscript, the necessary basics of dMRI are provided. Next, Part II deals with diffusion parameter estimation and includes the main contributions of the research. Finally, Part III covers the construction of a population-based dMRI atlas of the rat brain.

All human actions involve motor control. Even the simplest movement requires the coordinated recruitment of many muscles, orchestrated by neuronal circuits in the brain and the spinal cord. As a consequence, lesions affecting the central nervous system, such as stroke, can lead to a wide range of motor impairments. While a certain degree of recovery can often be achieved by harnessing the plasticity of the motor hierarchy, patients typically struggle to regain full motor control. In this context, technology-assisted interventions offer the prospect of intense, controllable and quantifiable motor training. Yet, clinical outcomes remain comparable to conventional approaches, suggesting the need for a paradigm shift towards customized knowledge-driven treatments to fully exploit their potential. In this thesis, we argue that a detailed understanding of healthy and impaired motor pathways can foster the development of therapies optimally engaging plasticity. To this ...

Most cognitive processes in the brain are reflected through several aspects simultaneously, allowing us to observe the same process from different biological phenomena. The diverse nature of these biological processes suggests that a better understanding of cerebral activity may be achieved through multimodal measurements. One of the possible multimodal brain recording settings is the combination of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), which is one of the main topics of this thesis. Two groups of EEG-fMRI integration approaches are possible. The first group, commonly called model-based techniques, are very popular due to the fact that the results from such analyses confirm or disprove a specific hypothesis. However, such hypotheses are not always available, requiring a more explorative approach to analyze the data. This exploration is possible with the second group of approaches, the so-called data-driven methods. The data-driven ...

Preterm birth is a major risk factor for neurodevelopment impairments often only appearing later in life. The brain is still at a high rate of development during adolescence, making this a promising window for intervention. It is thus crucial to understand the mechanisms of altered brain function in this population. The aim of this thesis is to investigate how the brain dynamically reconfigures its own organisation over time in preterm-born young adolescents. Research to date has mainly focused on structural disturbances or in static features of brain function in this population. However, recent studies have shown that brain activity is highly dynamic, both spontaneously and during performance of a task, and that small disruptions in its complex architecture may interfere with normal behaviour and cognitive abilities. This thesis explores the dynamic nature of brain function in preterm-born adolescents in three ...

The abundance of large and heterogeneous systems is rendering contemporary data more pervasive, intricate, and with a non-regular structure. With classical techniques facing troubles to deal with the irregular (non-Euclidean) domain where the signals are defined, a popular approach at the heart of graph signal processing (GSP) is to: (i) represent the underlying support via a graph and (ii) exploit the topology of this graph to process the signals at hand. In addition to the irregular structure of the signals, another critical limitation is that the observed data is prone to the presence of perturbations, which, in the context of GSP, may affect not only the observed signals but also the topology of the supporting graph. Ignoring the presence of perturbations, along with the couplings between the errors in the signal and the errors in their support, can drastically hinder ...

The brain is the substrate of a complex dynamic system providing a remarkably varied range of functionalities, going from simple perception to higher-level cognition. Disturbances in its complex dynamics can cause an equally vast variety of mental disorders. One such brain disorder is schizophrenia, a neurodevelopmental disease characterized by abnormal perception of reality that manifests in symptoms like hallucinations or delusions. Even though the brain is known to be affected in schizophrenia, the exact pathophysiology underlying its developmental course is still mostly unknown. In this thesis, we develop and apply methods to look into ongoing brain function measured through magnetic resonance imaging (MRI) and evaluate the potential of these approaches for improving our understanding of psychosis vulnerability and schizophrenia. We focus on patients with chromosome 22q11.2 deletion syndrome (22q11DS), a genetic disorder that comes with a 30fold increased risk for ...

To the surprise of most of us, complexity in nature spawns from simplicity. No matter how simple a basic unit is, when many of them work together, the interactions among these units lead to complexity. This complexity is present in the spreading of diseases, where slightly different policies, or conditions,might lead to very different results; or in biological systems where the interactions between elements maintain the delicate balance that keep life running. Fortunately, despite their complexity, current advances in technology have allowed us to have more than just a sneak-peak at these systems. With new views on how to observe such systems and gather data, we aimto understand the complexity within. One of these new views comes from the field of graph signal processing which provides models and tools to understand and process data coming from such complex systems. With ...