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 ...

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. ...

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, ...

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 ...

Brain function requires a continuous flow of oxygen and glucose. An insufficient supply for a few minutes during the first period of life may have severe consequences or even result in death. This happens in one to six infants per 1000 live term births. Therefore, there is a high need for a method which can enable bedside brain monitoring to identify those neonates at risk and be able to start the treatment in time. The most important currently available technology to continuously monitor brain function is electroEncephaloGraphy (or EEG). Unfortunately, visual EEG analysis requires particular skills which are not always present round the clock in the Neonatal Intensive Care Unit (NICU). Even if those skills are available it is laborsome to manually analyse many hours of EEG. The lack of time and skill are the main reasons why EEG is ...

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. ...

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 ...

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, ...

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 ...

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 ...

Epilepsy is one of the most common neurological diseases, especially in children. And although the majority of patients can be treated through medication or surgery (70%-75%), a significant group of patients cannot be treated. For this latter group of patients it is advisable to follow the evolution of the disease. This can be done through a long-term automatic monitoring, which gives an objective measure of the number of seizures that the patient has, for example during the night. On the other hand, there is a reduced social control overnight and the parents or caregivers can miss some seizures. In severe seizures, it is sometimes necessary, however, to avoid dangerous situations during or after the seizure (e.g. the danger of suffocation caused by vomiting or a position that obstructs breathing, or the risk of injury during violent movements), and to comfort ...

Cochlear implants (CIs) aim to restore hearing in severely to profoundly deaf adults, children and infants. Electrically evoked auditory steady-state responses (EASSRs) are neural responses to continuous modulated pulse trains, and can be objectively detected at the modulation frequency in the electro-encephalogram (EEG). EASSRs provide a number of advantages over other objective measures, because frequency-specific stimuli are used, because targeted brain areas can be studied, depending on the chosen stimulation parameters, and because they can objectively be detected using statistical methods. EASSRs can potentially be used to determine appropriate stimulation levels during CI fitting, without behavioral input from the subjects. Furthermore, speech understanding in noise varies greatly between CI subjects. EASSRs lend themselves well to study the underlying causes of this variability, such as the integrity of the electrode-neuron interface or changes in the auditory cortex following deafness and following ...

Current Human-Machine Interfaces (HMI) lack of “emotional intelligence”, i.e. they are not able to identify human emotional states and take this information into account to decide on the proper actions to execute. The goal of affective computing is to fill this lack by detecting emotional cues occurring during Human-Computer Interaction (HCI) and synthesizing emotional responses. In the last decades, most of the studies on emotion assessment have focused on the analysis of facial expressions and speech to determine the emotional state of a person. Physiological activity also includes emotional information that can be used for emotion assessment but has received less attention despite of its advantages (for instance it can be less easily faked than facial expressions). This thesis reports on the use of two types of physiological activities to assess emotions in the context of affective computing: the activity ...

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 ...

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 ...