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 ...

Worldwide approximately 11% of the babies are born before 37 weeks of gestation. The survival rates of these prematurely born infants have steadily increased during the last decades as a result of the technical and medical progress in the neonatal intensive care units (NICUs). The focus of the NICUs has therefore gradually evolved from increasing life chances to improving quality of life. In this respect, promoting and supporting optimal brain development is crucial. Because these neonates are born during a period of rapid growth and development of the brain, they are susceptible to brain damage and therefore vulnerable to adverse neurodevelopmental outcome. In order to identify patients at risk of long-term disabilities, close monitoring of the neurological function during the first critical weeks is a primary concern in the current NICUs. Electroencephalography (EEG) is a valuable tool for continuous noninvasive ...

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 ...

Every year, an estimated 15 million babies are born preterm, that is, before 37 weeks of gestation. This number is rising in all countries and currently represents more than 1 in 10 babies, affecting families all over the world. During the last decades, the survival rate of prematurely born neonates has steadily increased, mainly as a result of medical and technical progress in neonatal intensive care. The very preterm infants, which represent up to 10% of the preterm infants in the EU, remain at risk for adverse outcome and neurodevelopmental disability. These maladaptive outcomes have a severe effect on the children’s quality of life and a huge economic impact on society. In order to reduce this burden and improve neonatal care in general, appropriate tools need to be developed to identify the neonates with a higher risk of adverse outcomes. ...

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. ...

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 ...

This work has, as its objective, the development of non-invasive and low-cost systems for monitoring and automatic diagnosing specific neonatal diseases by means of the analysis of suitable video signals. We focus on monitoring infants potentially at risk of diseases characterized by the presence or absence of rhythmic movements of one or more body parts. Seizures and respiratory diseases are specifically considered, but the approach is general. Seizures are defined as sudden neurological and behavioural alterations. They are age-dependent phenomena and the most common sign of central nervous system dysfunction. Neonatal seizures have onset within the 28th day of life in newborns at term and within the 44th week of conceptional age in preterm infants. Their main causes are hypoxic-ischaemic encephalopathy, intracranial haemorrhage, and sepsis. Studies indicate an incidence rate of neonatal seizures of 2‰ live births, 11‰ for preterm ...

This thesis focuses on the design of various automatic signal processing algorithms to extract information from physiological signals of preterm infants. Overall, the aim was to improve the neurodevelopmental outcome of the neonate. More specifically, three main research objectives were carried out. The first objective was to describe the maturation of neonates during their stay in the neonatal intensive care unit. The second objective was to assess the stress and pain in premature infants and their impact on the development of neonates. The third objective was to predict developmental disabilities, such as autism. The first part of this thesis presents an extensive overview of various developmental models to describe the maturation of premature infants. Three main strategies were proposed. The first strategy proposed an investigation of EEG connectivity networks. A variety of functional and effective connectivity methods were combined with ...

Around 10 percent of all human births is premature, which means that annually about 15 million babies are born before 37 completed weeks of gestation. About one third of the admissions to the Neonatal Intensive Care Unit (NICU) consists of this patient group. Due to complications, 1 million babies die from premature delivery, and it is therefore the most important cause of neonatal death. In general, premature and immature babies have a high risk for neurological abnormalities by maturation in extra-uterine life. Even though improved health care has increased the survival changes of these neonates, they are sensitive to brain damage and consequently, neurocognitive disabilities. Nowadays, critical information about the brain development can be extracted from the electroencephalography (EEG). Clinical experts visually assess evolving EEG characteristics over both short and long periods to evaluate maturation of patients at risk and, ...

Disturbances in cerebral hemodynamics are one of the principal causes of cerebral damage in premature infants. Specifically, changes in cerebral blood flow might cause ischemia or hemorrhage that can lead to motor and developmental disabilities. Under normal circumstances, there are several mechanisms that act jointly to preserve cerebral hemodynamics homeostasis. However, in case that one of these mechanisms is disrupted the brain is exposed to damage. Premature infants are susceptible to variations in cerebral circulation due to their fragility. Therefore, monitoring cerebral hemodynamics is of vital importance in order to prevent brain damage in this population and avoid subsequent sequelae. This thesis is oriented to the development of signal processing techniques that can be of help in monitoring cerebral hemodynamics in neonates. There are several problems that hinder the use in clinical practice of monitoring cerebral hemodynamics. On one hand, ...

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 ...

Cardiovascular diseases are a growing problem in today’s society. The World Health Organization (WHO) reported that these diseases make up about 30% of total global deaths and that heart diseases have no geographic, gender or socioeconomic boundaries. Therefore, detecting cardiac irregularities early-stage and a correct treatment are very important. However, this requires a good physiological understanding of the cardiovascular system. The heart is stimulated electrically by the brain via the autonomic nervous system, where sympathetic and vagal pathways are always interacting and modulating heart rate. Continuous monitoring of the heart activity is obtained by means of an ElectroCardioGram (ECG). Studying the fluctuations of heart beat intervals over time reveals a lot of information and is called heart rate variability (HRV) analysis. A reduction of HRV has been reported in several cardiological and noncardiological diseases. Moreover, HRV also has a prognostic ...

Diffusion Magnetic Resonance Imaging (dMRI) is a meaningful technique for white matter (WM) fiber-tracking and microstructural characterization of axonal/neuronal integrity and connectivity. By measuring water molecules motion in the three directions of space, numerous parametric maps can be reconstructed. Among these, fractional anisotropy (FA), mean diffusivity (MD), and axial (λa) and radial (λr) diffusivities have extensively been used to investigate brain diseases. Overall, these findings demonstrated that WM and grey matter (GM) tissues are subjected to numerous microstructural alterations in multiple sclerosis (MS). However, it remains unclear whether these tissue alterations result from global processes, such as inflammatory cascades and/or neurodegenerative mechanisms, or local inflammatory and/or demyelinating lesions. Furthermore, these pathological events may occur along afferent or afferent WM fiber pathways, leading to antero- or retrograde degeneration. Thus, for a better understanding of MS pathological processes like its spatial and ...

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 ...

Obstructive sleep apnea (OSA) is among the most prevalent sleep disorders, which is estimated to affect 6 %−19 % of women and 13 %−33 % of men. Besides daytime sleepiness, impaired cognitive functioning and an increased risk for accidents, OSA may lead to obesity, diabetes and cardiovascular diseases (CVD) on the long term. Its prevalence is only expected to rise, as it is linked to aging and excessive body fat. Nevertheless, many patients remain undiagnosed and untreated due to the cumbersome clinical diagnostic procedures. For this, the patient is required to sleep with an extensive set of body attached sensors. In addition, the recordings only provide a single night perspective on the patient in an uncomfortable, and often unknown, environment. Thus, large scale monitoring at home is desired with comfortable sensors, which can stay in place for several nights. To ...