Plagiarism penalties

Research in all areas of sciences and humanities has led to the creation of a highly competitive environment which necessitates reporting of ideas, and discoveries at rapid pace. The emergence of new technologies of communication has significantly enhanced the capabilities of individuals to record and transcribe data at high speed. Even though, one can accumulate information in a fraction of time, but quite often the creative skills and ability to write one‘s own original thoughts do not match the required level of output. Writing ideas in one’s own words is not always easy and at times it becomes quite challenging particularly for those with limited command over the language. These situations often tempt a writer to look around easily available resources

Quantitative analysis of hypoglycemia-induced EEG alterations in type 1 diabetes

The main risk for patients affected by type 1 diabetes (T1D) is to fall in hypoglycemia, an event which leads to both short and long-terms automatic failure and can be life-threatening especially when occurs at night without subject awareness. Moreover, T1D patients can develop asymptomatic hypoglycemia, reducing the prompt response of the counterregulatory system triggered by the fall in blood glucose. Avoiding hypoglycemia is important in children and adolescents because hypoglycemia episodes may have clinically relevant effects on cognition. Also in adults, cognitive tests assessed that hypoglycemia results in altered cerebral activity, most likely due to the complete dependence of the brain for glucose supply. The first organ influenced by this fall of glucose in the blood is the brain. Indeed, a lot of studies proved the mirroring of cognitive dysfunction due to hypoglycemia in the spectral power of the electroencephalogram (EEG) signal. In particular, the increase of the power in low frequency EEG bands is a well-known effect during hypoglycemia that seems more pronounced in the EEG recording in the posterior areas of the brain. Pilot studies about the real-time processing of the EEG signal to detect hypoglycemia have indicated that it might be possible to alert the patients by means of EEG analysis. The main advantages in exploiting EEG analysis is that the blood glucose threshold to enter in hypoglycemia has large inter-subjects variations, on the contrary the EEG onset in general occurs before the state of hypoglycemia is critical, i.e., the brain starts to experience neuroglycopoenia and its functions completely fail. The main aim of this work is to broaden out the quantitative analysis on the altered EEG activity due to hypoglycemia in T1D patients to identify potential margins of improvement in EEG processing and further features sensitive to hypoglycemia. In particular, the analyses are extended to different domains, i.e., time and frequency domains, to deepen the knowledge on the effects of hypoglycemia in the brain. So far, studies in the literature have mainly evaluated these changes only on a single EEG channel level on the frequency domain, but limited information is available on the hypoglycemia influence on brain network dynamics and on connection between different brain areas. To do so, this dissertation is structured in 7 chapters, briefly presented below. Chapter 1 will start with a brief overview about the impact of T1D and its main effects on daily life. Moreover, the main consequences of hypoglycemia in human brain will be described by reporting the main findings in the literature. Chapter 2 will present the database where EEG data and blood glucose samples were collected in parallel for about 8 h in 31 T1D hospitalized patients during an hyperinsulinemic - hypoglycemic clamp experiment. Chapter 3 will address on the main effects of hypoglycemia in the frequency domain. After testing the well-known changes in the spectral power of the EEG signal during hypoglycemia, a multivariate analysis based on the concept of Information Partial Directed Coherence will be presented. In particular, we will confirm the general slowing in the frequency domain and we will show how hypoglycemia affects the EEG functional connectivity. Chapter 4 will consider the effects of hypoglycemia on EEG complexity. Fractal dimension features, describing both amplitude and frequency properties, will be computed and compared with the results based on Sample Entropy. We will reveal a decrease of EEG signal complexity in the hypoglycemic condition. Chapter 5 will focus on the consequences of hypoglycemia in the so-called microstates or "athoms of thought". We will hypothesize that the changes in the frequency domain and the decrease of the EEG signal complexity in hypoglycemia have in common the same resting EEG electric potential amplitude map. Chapter 6 will describe how hypoglycemia influences the results of cognitive tests, and the relationship between the drop in the tests performance and the EEG quantitative measures presented in the previous chapters. We will find a direct correlation among the changes in the power spectra, the cognitive tests performance and the changes of one resting EEG electric potential amplitude map. Eventually, Chapter 7 will close the dissertation by interpreting the ensemble of the results from both the medical and engineering point of view, and presenting the possible future developments of this work

Moving into the wide clinical spectrum of consciousness disorders: Pearls, perils and pitfalls

The last few years have been characterized by a growing interest of the medical and scientific world for the field of consciousness and its related disorders. Medically speaking, conscious- ness can be defined as the state of awareness of self and environment and the alertness to external stimulation, besides responsiveness to inner need. Transient loss of consciousness can be due to alterations in cerebral blood flow leading to fainting or syncope, migraine, metabolic dysfunctions, unexpected intracranial pressure increases, epileptic seizures, and sleep disorders. Chronic disorders of consciousness are a tragic success of high-technology treatment, in an attempt to maintain or reestablish brain function, which is to be considered as the main goal of therapeutics. Management of vegetative or a minimally conscious state individuals involves charily getting the right diagnosis with an evidence-based prognosis, also taking into account the medical, ethical, and legal key factors of the ideal treatment. This paper is aimed at exploring the wide spectrum of consciousness disorders and their clinical differential diagnosis, with particular regards to those with a negative impact on patient and their caregiver quality of life, including epilepsy, sleep disorders, and vegetative/minimally conscious state

ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions

The International League Against Epilepsy (ILAE) Task Force on Nosology andDefinitions proposes a classification and definition of epilepsy syndromes in theneonate and infant with seizure onset up to 2 years of age. The incidence of epi-lepsy is high in this age group and epilepsy is frequently associated with significantcomorbidities and mortality. The licensing of syndrome specific antiseizure medi-cations following randomized controlled trials and the development of precision,gene- related therapies are two of the drivers defining the electroclinical pheno-types of syndromes with onset in infancy. The principal aim of this proposal, con-sistent with the 2017 ILAE Classification of the Epilepsies, is to support epilepsydiagnosis and emphasize the importance of classifying epilepsy in an individualboth by syndrome and etiology. For each syndrome, we report epidemiology, clini-cal course, seizure types, electroencephalography (EEG), neuroimaging, genetics,and differential diagnosis. Syndromes are separated into self- limited syndromes,where there is likely to be spontaneous remission and developmental and epilep-tic encephalopathies, diseases where there is developmental impairment related toboth the underlying etiology independent of epileptiform activity and the epilep-tic encephalopathy. The emerging class of etiology- specific epilepsy syndromes,where there is a specific etiology for the epilepsy that is associated with a clearlydefined, relatively uniform, and distinct clinical phenotype in most affected in-dividuals as well as consistent EEG, neuroimaging, and/or genetic correlates, ispresented. The number of etiology- defined syndromes will continue to increase,and these newly described syndromes will in time be incorporated into this clas-sification. The tables summarize mandatory features, cautionary alerts, and exclu-sionary features for the common syndromes. Guidance is given on the criteria forsyndrome diagnosis in resource- limited regions where laboratory confirmation,including EEG, MRI, and genetic testing, might not be available

L'épilepsie bénigne à pointes centrotemporales : investigation cognitive et études en imagerie fonctionnelle et structurelle

L’épilepsie bénigne à pointes centrotemporales (EPCT) est la forme la plus fréquente des épilepsies idiopathiques chez l’enfant (Fastenau et al., 2009). Le pronostic de ces patients est bon, notamment en raison de la rémission spontanée de cette épilepsie à l’adolescence; toutefois plusieurs études suggèrent la présence de troubles cognitifs et de spécificités neuroanatomiques. Il n’existe pas actuellement de consensus sur les liens entre leurs troubles cognitifs et leurs particularités neuroanatomiques et neurofonctionnelles. Dans cette thèse, notre but est de préciser le profil des enfants ayant une épilepsie bénigne à pointes centro-temporales, en investiguant les caractéristiques des patients à plusieurs niveaux: cognitif, fonctionnel, structurel. La thèse est composée de quatre articles, dont deux articles empiriques. Notre premier article a pour objectif de recenser les difficultés cognitives et affectives rapportées par les études s’intéressant aux caractéristiques des enfants ayant une épilepsie bénigne. Bien qu’une certaine variabilité soit retrouvée dans la littérature, cette revue démontre qu’une histoire d’épilepsie, même bénigne, peut être un facteur de risque pour le développement cognitif et socio-affectif des enfants. Notre revue de littérature a indiqué des troubles particuliers du langage chez ces enfants, mais aucune étude n’avait auparavant investigué spécifiquement la compréhension de lecture chez les enfants ayant une EPCT, une compétence essentielle dans le cheminement scolaire des enfants. Ainsi, nous avons développé une tâche novatrice de compréhension de lecture de phrases en imagerie par résonnance magnétique fonctionnelle (IRMf), adaptée à la population pédiatrique. Dans notre second article, nous avons validé cette tâche auprès d’enfants sains et nous avons mis en évidence une mobilisation des régions cérébrales généralement engagées dans des tâches langagières chez l’enfant sain, y compris les régions impliquées dans le traitement sémantique (Berl et al., 2010; Blumenfeld, Booth et Burman, 2006). Le troisième article de cette thèse rapporte notre investigation du réseau cérébral activé durant cette nouvelle tâche de compréhension de lecture de phrases en IRMf chez les enfants ayant une EPCT. Nos résultats suggèrent que ces derniers ont recours à l’activation d’un réseau cérébral plus large, présentant des similarités avec celui retrouvé chez les enfants dyslexiques. Par ailleurs, l’activation du striatum gauche, structure généralement associée à la réalisation de processus cognitifs complexes est uniquement retrouvée chez les enfants épileptiques. Étant donné que les enfants ayant une EPCT obtiennent des performances à la tâche d’IRMf équivalentes à celles des enfants sains, il est possible d’émettre l’hypothèse que ces différences d’activations cérébrales soient adaptatives. L’étude des relations entre les résultats neuropsychologiques, la performance à la tâche et les activations cérébrales a mis en évidence des prédicteurs différents entre les deux groupes d’enfants, suggérant qu’ils ne s’appuient pas exactement sur les mêmes processus cognitifs pour réussir la tâche. De plus, nous avons réalisé un travail d’intégration des diverses méthodologies utilisées dans les études en imagerie pondérée en diffusion chez l’enfant épileptique, ce qui constitue le quatrième article de cette thèse. Nous rapportons les diverses applications de cette méthode dans la caractérisation des anomalies structurelles subtiles de la matière blanche chez les enfants épileptiques en général. Les différentes méthodologies employées, les enjeux, et les biais potentiels relatifs aux traitements des données de diffusion y sont discutés. Enfin, pour mieux comprendre l’origine et les marqueurs de cette épilepsie, nous avons étudié les spécificités structurelles des cerveaux des enfants ayant une EPCT à l’aide d’analyses sur les données d’imagerie par résonnance magnétique. Aucune différence n’a été mise en évidence au niveau de la matière grise entre les cerveaux d’enfants sains et ceux ayant une EPCT. À l’inverse, nous rapportons des différences subtiles au niveau de la matière blanche dans notre population d’enfants épileptiques, avec une diminution de l’anisotropie fractionnelle (FA) au niveau temporal inférieur/moyen de l’hémisphère gauche, ainsi que dans l’hémisphère droit dans les régions frontales moyennes et occipitales inférieures. Ces résultats suggèrent la présence d’altérations de la matière blanche subtiles et diffuses dans le cerveau des enfants ayant une EPCT et concordent avec ceux d’autres études récentes (Ciumas et al., 2014).Benign epilepsy with centrotemporal spikes (BECTS) is the most common idiopathic epilepsy in children. Owing to its spontaneous remission during adolescence, prognosis is usually good. However, studies have recently demonstrated cognitive deficits and neuroanatomical abnormalities in BECTS. To date, the relationship between cognitive impairment and brain function and structure in BECTS is unclear owing to a lack of consensus in the literature. The aim of the present thesis was to establish a multidimensional profile of children with BECTS, investigating impairments on a cognitive, functional and structural level as compared to healthy controls. The present thesis is composed of four articles, including two review articles and two empirical articles. Our first review article summarizes the cognitive and behavioural impairments reported by studies investigating the characteristics of children with BECTS. Although some variability was found in the literature, our review demonstrates that a history of childhood epilepsy, even if benign, can be considered as a risk factor for both cognitive and socio-affective development in children. More precisely, our review showed that children with BECTS present specific language impairments. However, none of the studies reviewed investigated reading comprehension in these children, which represent an essential academic skill. Thus, we developed an innovative functional magnetic resonance imaging (fMRI) sentence reading comprehension task, adapted to a pediatric population. In our first empirical article, we validated this task in healthy children. Our results were concordant with those of other studies investigating semantic processing in children (Berl et al., 2010; Blumenfeld et al., 2006). The second empirical article aimed at investigating cerebral reading networks activated in BECTS children during our fMRI sentence-reading comprehension task. Our results suggest that these children activate a larger cerebral reading network as compared to healthy controls, showing similar activation patterns to children with dyslexia while performing a similar task. Moreover, activations in the left striatum, a region generally associated with complex cognitive processes, were found in BECTS children. Given that the performance of these children on the fMRI task was similar to that of healthy controls, we hypothesize that these differences in brain reading network activations are adaptive. We further studied relationships between neuropsychological results, task performance and brain activations. Our results suggest that BECTS children rely on slightly different cognitive processes during task performance as compared to healthy controls. In addition, we performed an integrated review of various methodologies used in diffusion magnetic resonance imaging (dMRI) studies of epileptic children, which constitutes the second review article in the present thesis. We reported various applications of this method in the characterisation of subtle white matter abnormalities in epileptic children in general. The different methodologies utilized, the challenges and the potential biases associated with data processing were discussed. Finally, we investigated structural abnormalities in children with BECTS using MRI data in order to better understand the origin and markers of this epilepsy. No grey matter differences were found between BECTS children and healthy controls. However, we reported subtle white matter differences between groups, such that children with BECTS demonstrated a decreased fractional anisotropy (FA) in the middle/superior temporal region of the left hemisphere as well as in the middle frontal and inferior occipital regions of the right hemisphere. These results suggest subtle and diffuse white matter alterations in BECTS, supporting recently reported results (Ciumas et al., 2014)