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. ...

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 ...

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, ...

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 ...

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 ...

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. ...

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 ...

Work-related musculoskeletal disorders are a growing problem in todays society. These musculoskeletal disorders are caused by, amongst others, repetitive movements and mental stress. Stress is defined as the mismatch between a perceived demand and the perceived capacities to meet this demand. Although stress has a subjective origin, several physiological manifestations (e.g. cardiovascular and muscular) occur during periods of perceived stress. New insight and algorithms to extract information, related to stress are beneficial. Therefore, two series of stress experiments are executed in a laboratory environment, where subjects underwent different tasks inducing physical strain, mental stress and a combination of both. In this manuscript, new and modified algorithms for electromyography signals are presented that improve the individual analysis of electromyography signals. A first algorithm removes the interference of the electrical activity of the heart on singlechannel electromyography measurements. This interference signal is ...

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 ...

Localizing the bioelectric phenomena originating from the cerebral cortex and evoked by auditory and somatosensory stimuli are clear objectives to both understand how the brain works and to recognize different pathologies. Diseases such as Parkinson's, Alzheimer's, schizophrenia and epilepsy are intensively studied to find a cure or accurate diagnosis. Epilepsy is considered the disease with major prevalence within disorders with neurological origin. The recurrent and sudden incidence of seizures can lead to dangerous and possibly life-threatening situations. Since disturbance of consciousness and sudden loss of motor control often occur without any warning, the ability to predict epileptic seizures would reduce patients' anxiety, thus considerably improving quality of life and safety. The common procedure for epilepsy seizure detection is based on brain activity monitorization via electroencephalogram (EEG) data. This process consumes a lot of time, especially in the case of long ...

The electrocardiogram or ECG is a relatively easy-to-record signal that contains an enormous amount of potentially useful information. It is currently mostly being used for screening purposes. For example, pre-participation cardiovascular screening of young athletes has been endorsed by both scientific organisations and sporting governing bodies. A typical cardiac examination is taken in a hospital environment and lasts 10 seconds. This is often sufficient to detect major pathologies, yet this small sample size of the heart’s functioning can be deceptive when used to evaluate one’s general condition. A solution for this problem is to monitor the patient outside of the hospital, during a longer period of time. Due to the extension of the analysis period, the detection rate of cardiac events can be highly increased, compared to the cardiac exam in the hospital. However, it also increases the likelihood of ...

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 ...

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, ...

This thesis contributes to motion characterization through inertial and physiological signals captured by wearable devices and analyzed using signal processing and deep learning techniques. This research leverages the possibilities of motion analysis for three main applications: to know what physical activity a person is performing (Human Activity Recognition), to identify who is performing that motion (user identification) or know how the movement is being performed (motor anomaly detection). Most previous research has addressed human motion modeling using invasive sensors in contact with the user or intrusive sensors that modify the user’s behavior while performing an action (cameras or microphones). In this sense, wearable devices such as smartphones and smartwatches can collect motion signals from users during their daily lives in a less invasive or intrusive way. Recently, there has been an exponential increase in research focused on inertial-signal processing to ...

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 ...