Dissertations / Theses on the topic 'Child neurodevelopment'

Background: Migraine headache is a chronic pain condition that affects 20% of women of reproductive age, and is often treated with triptans. Triptans are serotonin 1B, 1D, and 1F receptor agonists that act as vasoconstrictors and inhibitors of the trigeminal cervical complex as well as peripheral neurons; they cross the blood brain barrier and placenta, and as such are plausible neurodevelopmental teratogens. No studies have examined risk of neurodevelopmental problems in children with prenatal triptan exposure. This dissertation had three aims: (1) to examine risk of behavioral problems in children using in the presence of time-varying confounding by concomitant medication use; (2) to examine risk of temperamental, motor, and communication disturbances associated with prenatal triptans exposure, adjusting for unmeasured confounding by migraine type and severity; and (3) to examine changes in neurodevelopment over time associated with prenatal triptan exposure. Methods: This dissertation used data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort including more than 100,000 women recruited during their first prenatal ultrasound visit. Aims 1 and 3 used marginal structural models to assess the risk of (1) neurodevelopmental problems at age 36 months (Aim 1), or (2) change in risk of neurodevelopmental problems from 18 to 36 months (Aim 3) associated with prenatal triptan exposure. Aim 2 used propensity matching and calibration to adjust for unmeasured confounding by migraine type, severity, and attitudes towards medication use in pregnancy. Neurodevelopmental outcome measures included the Child Behavior Checklist (CBCL), the Emotionality, Activity, and Temperament Scale (EAS), and the Ages and Stages Questionnaire (ASQ). Exposure to triptans was ascertained by self-report. Results: Prenatal triptan exposure was associated with greater externalizing behavior problems at 18 and 36 months, as well as greater increases in emotionality and activity from 18 to 36 months. We observed no association between triptan exposure and motor skills or communication problems; triptan use during pregnancy was associated with migraine severity but not migraine type, and adjustment for unmeasured migraine characteristics moved effect estimates towards the null. Conclusions: Prenatal triptan exposure is associated with externalizing-type behaviors and temperament in children, while migraine itself is associated with internalizing-type behaviors and temperament. The use of concomitant medications and the severity of the underlying condition both exerted substantial influence on observed effect estimates, and should be considered in any future studies of triptan medication use in pregnancy.

With the recent evolution of mobile communication, there is a lack of understanding of increased radiofrequency (RF) exposure from these new technologies, especially among children. Little is known about the amount of RF exposure children experience day-to-day and its main sources. Furthermore, there is little understanding of RF dose during fetal life or RF dose to the brain during childhood. This thesis assessed environmental RF exposure and RF brain and body dose in children in several large, population-based cohort studies through personal exposure measurement studies and integrated exposure models. This thesis also evaluated whether maternal mobile phone use during pregnancy or RF dose to the brain in childhood was associated with neurodevelopmental outcomes, specifically, behavioral problems. In Europe, measured environmental RF in children and estimated dose to children’s brains was found to be far below recommended limits. Maternal mobile phone use during pregnancy was associated with hyperactivity/inattention problems in young children (ages 5-7) while RF dose to the brain during childhood was associated with behavioral problems, particularly in older children (ages 14-18). Uncontrolled confounding, reverse causality, and effects of mobile device use, apart from RF dose to the brain, could not be entirely excluded as possible explanations for these results. In the meantime, pregnant women could reduce RF exposure to the fetus by keeping mobile devices away from the belly, while children can reduce RF dose by limiting calls, limiting high resolution video streaming, or keeping mobile devices away from the body.
Con la reciente evolución de la comunicación, existe una falta de comprensión del aumento de la exposición a la radiofrecuencia (RF) de estas nuevas tecnologías, especialmente entre los niños. Se sabe poco sobre la cantidad de exposición a RF que experimentan los niños día a día y sus principales fuentes. Además, hay poca comprensión de la cantidad de RF durante la vida fetal o la cantidad de RF en el cerebro durante la infancia. Esta tesis ha evaluado la exposición ambiental a RFs y la cantidad de RF en el cerebro y cuerpo en niños en varios estudios de cohorte de gran tamaño a través de estudios de medición de exposición personal y modelos de exposición integrados. Esta tesis también evaluó si el uso del teléfono móvil materno durante el embarazo o la cantidad de RF al cerebro en la infancia se asoció con problemas del desarrollo neurológico, específicamente, problemas de comportamiento. En Europa, la RF ambiental medida en niños y la cantidad estimada en el cerebro de los niños se encontraron muy por debajo de los límites recomendados. El uso del teléfono móvil materno durante el embarazo se asoció con problemas de hiperactividad/falta de atención en niños pequeños (entre 5 y 7 años) mientras que la cantidad de RF al cerebro durante la infancia se asoció con problemas de conducta, particularmente en niños mayores (14-18 años). Los factores de confusión no controlados, la causalidad inversa y los efectos del uso de dispositivos móviles, aparte de la cantidad de RF al cerebro, no podrían excluirse como posibles explicaciones para estos resultados. Además, las mujeres embarazadas podrían reducir la exposición a RF al feto manteniendo los dispositivos móviles alejados del estómago, mientras que los niños pueden reducir la cantidad de RF limitando las llamadas, limitando la transmisión de video de alta resolución o manteniendo los dispositivos móviles alejados del cuerpo.

Abstract Understanding how modern technology plays a role in our children’s early development is especially crucial in this era of technological advancement. Never in human history have we seen such an exponential shift in the human experience than we have with the rise of the internet and the subsequent mass integration of technology into our daily lives. Put simply, times have changed, and our understanding of early childhood development must follow suit. This thesis explores the impact digital technologies have on the neurodevelopment of children, with regard to different critical periods in early childhood development. The apparent impacts on attention, memory, and focus, as well as the behavioral manifestations that result from these childhood interactions depend greatly on the critical period of neurodevelopment they occur. This thesis provides evidence and recommendations for parents and caretakers alike, advising parents on the perils associated with overexposure to sensory stimuli in infants, while demanding a more tailored approach technology mediation in adolescents, as the advent of social media presents its own unique perils and potentials for early neurodevelopment. Keywords: neurodevelopment, technology, infancy, adolescence

The main aims of this thesis can be divided into three focuses. First: to review the literature on the effect of the intake of seafood during early life on neurodevelopment. Secondly: to evaluate the impact of maternal use of acetaminophen during pregnancy on the neuropsychological development of the offspring and to explore potential epigenetic mechanisms that could contribute to this effect. Third: to examine the relationship between the mental health of the mother and wheezing in the child. Main results: 1) Seafood intake appears to be beneficial for neurodevelopment. 2) Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and to hyperactivity/impulsivity behaviors and changes in attention function in all children. 4) Exposure to acetaminophen during pregnancy was associated with a significant difference in the DNA methylation of a CpG site that corresponds to the OTOP3 gene. 5) Maternal distress at child ages 1-1.5 or 4-5 years could increase the risk of wheezing in the child, especially for wheezing types associated with a greater risk of asthma.
Los objetivos principales de esta tesis se pueden dividir en tres puntos. Primero: revisar la literatura sobre el efecto del consumo de comida de mar durante etapas tempranas de la vida sobre el neurodesarrollo. Segundo: evaluar el impacto del uso materno de paracetamol durante el embarazo sobre el desarrollo neuropsicológico de la progenie y explorar potenciales mecanismos epigenéticos que pudieran contribuir a este efecto. Tercero: examinar la relación entre la salud mental de la madre y las sibilancias en el niño. Resultados principales: 1) El consumo de comida de mar parece ser beneficioso para el neurodesarrollo. 2) La exposición prenatal a paracetamol estaba asociada con un mayor número de síntomas del espectro autista en varones y con conductas de hiperactividad/impulsividad y alteraciones de la función atencional de la progenie. 4) La exposición a paracetamol durante el embarazo estaba asociada a una diferencia significativa de la metilación del ADN a nivel de un sitio CpG correspondiente al gen OTOP3. 5) La presencia de distress materno a la edad de 1-1.5 o 4-5 años del niño puede incrementar el riesgo de sibilancias en el niño, especialmente para tipos de sibilancias que se han asociado a mayor riesgo de asma.

Profiles of sleep disturbance and sleep quality of children with the specific neurodevelopmental disorders of Smith-Magenis syndrome (SMS), Angelman syndrome (AS), autism spectrum disorder (ASD) and tuberous sclerosis complex (TSC) and the relationships between behavioural and health characteristics, age and sleep were described in these groups. Interview data demonstrated that children with AS's sleep disturbance had a negative impact on both parents and children. A homogeneous sleep disturbance profile of severe night waking and early morning waking affected over 70% of children with SMS but more heterogeneous profiles were found for children with AS, TSC and ASD using cross-group questionnaire data comparisons and when compared to typically developing (TD) children. A heightened risk of sleep-related breathing disorders was identified for children with AS and SMS. Compared to TD children, children with SMS had significantly earlier morning wake times and children with AS and SMS had significantly earlier bedtimes according to actigraphy and sleep diary data. Increased daytime sleepiness in children with SMS was associated with increased overactivity and impulsivity. This thesis includes the largest samples of actigraphy data for children with SMS and AS to date. The importance of aetiology of intellectual disability in the profiling of sleep disturbance was evidenced. Areas for further assessment and intervention include sleep-related breathing disorders for children with AS and SMS and individualized assessment of circadian rhythm disorders for both groups.

L'hexaclorobenzè (HCB) és un compost organoclorat àmpliament distribuït per tot el planeta, altament lipofílic que s'acumula als sistemes biològics. Els nounats s'exposen a aquests compostos organoclorats (OCs) a través de la placenta i de la lactància materna. Tot i que l'HCB és un dels OCs més comuns, la seva transferència a través de la placenta de la mare al fetus durant la gestació i a través de l'alletament matern està poc documentada. El coneixement sobre els seus possibles efectes sobre la salut infantil és també bastant limitat. A Flix, un poble de la Ribera d'Ebre, es van detectar nivells molt elevats d'HCB a l'atmosfera degut a la seva proximitat a una empresa electroquímica. Els objectius del present treball són els d'avaluar l'exposició a OCs a través de la placenta i de la lactància materna i els seus efectes sobre la salut infantil durant el primer any de vida en el conjunt de nounats d'aquesta població.
Hexachlorobenzene (HCB) is an organochlorine compound widely spread in the environment, highly lipophyilic which accumulates in all biological systems. Newborns are exposed to organochlorine compounds (OCs) through placenta and via breastfeeding. Although HCB is one of the most common OCs, its transference from the mother to the child through placenta and via breastfeeding is poorly documented. The knowledgement of the possible adverse effects on infant's health is also limited. In Flix, a small village in the Ribera d'Ebre area, high levels of HCB were detected in the atmosphere of the village due to the vicinity of an electrochemical factory. The objectives of the present study are to evaluate OCS exposition through placenta and breastfeeding and its effects on infant's health during the first year of life.

Includes bibliographical references.
Although various measures, such as the Prevention of Mother to Child Transmission (PMTCT) programme, have been put in place to combat the spread of HIV/AIDS, there are still many cases of children, in Zimbabwe, being born infected with HIV. Children born to HIV parents are reported to be at risk of having neurodevelopmental disorders (NDDs), which can reduce independence in activities of daily living by imposing varying limitations on these children. Technological advances in the field of HIV/AIDS have resulted in prolonged life for people infected with HIV/AIDS and therefore there is a growing population of mothers caring for their biologic al children who are infected with HIV. The aim of this study is focused on exploring the experiences of being a mother and caring for a child with HIV-related NDDs in Zimbabwe. Specific objectives were to describe the mothers’ experiences of engaging in the daily occupations of caring for a child with NDDs; to explore and describe factors that the mothers’ perceived to impact on their experiences while caring for their children and how these experiences of caring shape the mothers ’ own occupational identities and engagement. A descriptive phenomenological approach was designed to uncover their lived experience s of caring for a child with HIV - related NDDs. In-depth data was generated from phenomenological interviews conducted with five biological mothers who have been caring for their own children who have been diagnosed with HIV - related NDDs. A thematic analysis, guided by a simplified version of the Stevick - Colaizz - Keen method, was employed. The findings revealed the transactional nature of the mothers ’ experiences of the occupation of caring for a child with HIV - related NDD. Personal factors interacted with contextual factors such as stigma, culture and socioeconomics to shape their caring experiences, making caring for their child, a difficult and demanding role that they could not easily entrust to another. Although the mothers voiced that this caring was comprised of many burdensome tasks, the mothers reframe d the concept of the caregiver burden because they placed high value on and drew meaning from being a good mother to their child, thus making it an occupation that they would not readily entrust to another. The findings of this study encourage occupational therapists to consider carefully the resilience of these mothers and how their role as carers positively shape s their identities in the design of interventions for the mothers.

Includes bibliographical references.
Methamphetamine, part of the amphetamine group of drugs, was first discovered in Japan in 1919. It has been clandestinely manufactured in the United States since the 1960s, and is still legally produced there as a nasal inhalant, as treatment for Attention Deficit Disorder and exogenous obesity, as well as off-label treatment for narcolepsy. (1) It is a cheap (about R15- 30 per 'straw'), easily obtainable, odourless, white powder, which has a bitter, taste, but dissolves easily in water or alcohol. Known as, amongst others, ' speed', 'ice', 'crystal', 'chalk', 'glass', 'crank', and locally, 'tik', it can be smoked, snorted, orally ingested, injected intravenously or even administered anally. In South Africa the preferred method consists of placing the powder or crystal in a light bulb (from which the metal threading has been removed) and inhaling the fumes produced while heating the bulb from below with a lighter.(2). The use of methamphetamine has risen sharply globally over the last decade, used by 26 million people worldwide by 2007, more than heroin and cocaine combined, according to the United Nations Office on Drugs and Crime. This has been ascribed to many interlocking reasons: it is cheap, easily obtainable, easy to use without the need for needles or other special 'equipment', and it produces in the user a characteristic 'rush'. This feeling of confidence, power and heightened sexual levels, of feeling 'on top of the world' has made it especially popular amongst teenagers and young adults. (3)

Background: Oruro is a mining city in the Bolivian highlands. Most of its citizens are exposed to polymetalic cocktails. This study aims to determine whether the neuropsychological development of one year-old children can be associated with 1) polymetalic exposures and/or 2) growth patterns. Methods: The thesis builds from data collected by the ToxBol multidisciplinary project. The health task was centred on the follow-up of a birth-cohort that set to evaluate child development. Children were examined at 11 and 12 months of age using the Bayley Scale of Infant Development (BSID). Results: 1) Analyses revealed no high concentrations of metals in the blood of pregnant women. 2) No neuropsychological anomalies were observed in association with metal concentrations or growth patterns. 3) A positive association was observed between low lead values in blood and the neuropsychological development of children. 4) During the first 6 months of life, growth rate was negatively associated with weight at birth and positively associated with the BMI at 12 months of age. Conclusion: Although heavy metallic pollution was demonstrated by environmental studies, unexpected low levels of exposure were registered from pregnant women. Neither the level of exposure to metals nor the growth patterns appear to have an impact on child neuropsychological development. We argue that the positive effect that was observed in association to lead might be caused by factors such as diet.
Antecedentes: Oruro es una ciudad minera del altiplano boliviano. Muchos de sus habitantes están expuestos a un cóctel polimetálico. El objetivo principal es el de determinar si existe una asociación entre desarrollo neuropsicológico de los niños de un año y 1) la exposición polimetálica y/o 2) los patrones de crecimiento. Métodos: Esta tesis está basada en los datos recogidos del Proyecto multidisciplinario ToxBol. Se realizó el seguimiento de una cohorte de niños para evaluar su desarrollo. Para evaluar el desarrollo neuropsicológico de los niños se utilizaron las escalas de Bayley de desarrollo infantil (BSID). Resultados: 1) No se observaron altas concentraciones de metales en sangre de las mujeres embarazadas. 2) No se observaron anormalidades neuropsicológicas en relación con concentraciones de metales o patrones de crecimiento. 3) Se observó una asociación positiva entre exposiciones bajas de plomo y el desarrollo neuropsicológico del niño al año de vida. 4) La velocidad de crecimiento, desde el nacimiento hasta los 6 meses, se asoció negativamente con el peso al nacer y positivamente con el BMI a los 12 meses. Conclusión: A diferencia de lo demostrado en otros estudios epidemiológicos, se observó una inesperada baja exposición. No se observó una relación entre el grado de exposición a metales- o los patrones de crecimiento -y el desarrollo neuropsicológico del niño. El efecto positivo del plomo creemos que se debe a otros factores como la dieta.
Antecedents: Oruro es una ciutat minera del altiplà Bolivià. La població es troba es contacte amb fonts de contaminación polimetàlica. L’objectiu principal es el de determinar si existeix una associació entre el desenvolupament neuropsicològic dels nens d’un any i 1) la exposició polimetálica i/o 2) patrons de creixement. Mètodes: Esta tesi està basada en dades del Projecte multidisciplinari ToxBol. La tasca de salut es va centrar en el seguiment del desenvolupament d’una cohort de nens. El desenvolupament neuropsicològic infantil es va avaluar amb les escales de Baley de Desenvolupament infantil (BSID). Resultats: 1) No es van observar concentracions altes de metalls en sang de les dones embarassades. 2) No es va observar anormalitats neuropsicològiques en realció amb les concentracions de metalls o patrons de creixement. 3) Es va observar una associació positiva entre concentracions baixes de plom en sang i el desenvolupament neuropsicològic dels nens d’un any. 4) La velocitat de creixement, des del naixement fins els 6 mesos, es va associar negativament amb el pes al néixer i positivament amb el BMI als 12 mesos. Conclusió: A diferencia del que esperàvem, es van registrar baixes concentracions de metalls a les dones embarassades. Tampoc s’observa una relació entre el grau d’exposició a metalls, o patrons de creixement, i el desenvolupament neuropsicològic del nens. El efecte positiu que observem del plom, pensem que es deu a altres factors com la dieta.

Thesis (Ph. D.)--School of Nursing. University of Missouri--Kansas City, 2008.
"A dissertation in nursing." Advisor: Peggy Ward-Smith. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed Sept. 12, 2008. Includes bibliographical references (leaves 84-96). Online version of the print edition.

Contexte: L'augmentation rapide de la prévalence de certains troubles du neurodéveloppement nécessite une meilleure compréhension des facteurs de risque modifiables de ces troubles. Les femmes enceinte sont constamment exposés à plusieurs des phénols et les phtalates qui sont des perturbateurs endocriniens liés à divers effets neurotoxiques dans les études toxicologiques. L'un des mécanismes sous-jacents à ces effets pourrait être une action de ces composés sur l’axe thyroïdien.Objectifs: 1) De documenter si l'utilisation de produits de soin personnel pourrait influencer les concentrations urinaires de biomarqueurs d’exposition aux phénols chez les femmes enceintes; 2) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et le neurodéveloppement des enfants; et 3) d’évaluer les associations entre l'exposition prénatale aux phénols et aux phtalates et les concentrations d'hormones thyroïdiennes chez la femme enceinte et le nouveau-né.Méthodes: Ce travail s’appuie sur trois cohortes françaises complémentaires; l’étude SEPAGES-faisabilité pour lesquelles nous disposions de multiples échantillons d'urine et d'informations détaillées sur leurs utilisations de produits de soin, la cohorte EDEN avec les concentrations urinaires maternelles de phénols et phtalates et, l’information sur la neurodéveloppement des enfants et la cohorte SEPAGES avec les concentrations urinaires maternelles de phénols et phtalates et le taux d'hormones thyroïdiennes pendant la grossesse et à la naissance.Résultats: Le nombre total d'utilisation de produits de soin était associé à une augmentation des concentrations urinaires de bisphénol S et des parabènes mais pas des autres phénols.Aucun des composés étudiés n’était associé négativement aux scores de quotient intellectuel. Les concentrations urinaires maternelles de bisphénol A étaient associées à plus de symptômes de type troubles relationnels à 3 ans et de comportements de type hyperactif à 5 ans. Le MnBP était associé à une augmentation des scores liés aux troubles émotionnels et relationnels à 3 ans, tandis que le MBzP était lui associé à une augmentation des scores liés aux troubles internalisés et les troubles relationnels. Enfin lorsque les scores de comportement étaient étudiés en tant que variables binaires, une association entre le triclosan et les scores liés aux troubles émotionnels était observée à 3 et 5 ans.Les concentrations urinaires de bisphénol A étaient négativement associées aux concentrations de thyréostimuline (TSH) maternelles tandis que le MBzP, était lui positivement associé aux Z-scores de thyroxine totale et le triclosan négativement associé au ratio TT3/TT4. Lorsque les expositions étaient étudiées en terciles, des relations non linéaires ont aussi été observées entre le triclosan et la TSH (relation en U) et le MnBP et la TSH (U inversé). Pour les nouveau-nés, après stratification sur le sexe, les concentrations urinaires maternelles de bisphénol A étaient positivement associées au niveau de TT4 chez les garçons tandis que le triclosan était négativement associé à cette hormone chez les filles.Conclusion: Les associations positives entre l’utilisation de produits de soin et les concentrations urinaires de parabènes étaient en accord avec les études précédentes sur le sujet. Notre étude était la première à mettre en évidence de telles associations avec le bisphénol S. Les associations observées entre les expositions prénatales au bisphénol A et au DBP et le comportement avaient déjà été mis en évidence dans des études précédentes chez de jeunes garçons. Pour ce qui est du triclosan notre étude était la première à s’intéresser aux associations avec le comportement. Les composés associés au comportement dans la cohorte EDEN ont tous été associés à au moins une hormone thyroidienne dans la cohorte SEPAGES, suggérant une possible perturbation de l'homéostasie des hormones thyroïdiennes
Context: The increase in the prevalence of neurodevelopmental disorders warrants identification of the possible underlying modifiable risk factors. Pregnant women are constantly exposed to several phenols and phthalates that are endocrine disrupting chemicals and have been linked to various adverse neurodevelopmental outcomes in toxicological studies. One of the suggested mechanisms of neurotoxicity of these compounds is by disruption of the thyroid hormone pathway.Aims: 1) To document if the use of personal care products (PCP) could influence phenols biomarkers concentrations during pregnancy; 2) to assess associations between prenatal exposure to phenols and phthalates and child neurodevelopment; and 3) to assess associations between prenatal exposure to phenols and phthalates on the thyroid hormone levels of pregnant women and their newborns.Methods: We relied on three complementary cohorts; the SEPAGES-feasibility study with multiple urine samples and detailed, time-resolved information on PCP use, the EDEN cohort with maternal urinary concentrations of phenols, phthalates and information on child neurodevelopment and the SEPAGES cohort with information on gestational exposure to phenols and phthalates (assessed in 2 pools of 21 urine sample per participant) and levels of thyroid hormones levels during pregnancy and at birth.Results: The total number of PCP applications (without distinction) was positively associated with the parabens’ and bisphenol S urinary concentrations during pregnancy but not with other phenols assessed (benzophenone-3, triclosan and bisphenol A).No phenol or phthalate metabolite pregnancy concentration was negatively associated with IQ of boys at 5 years. Some associations with child behavior were observed at 3 and 5 years: Bisphenol A was positively associated with the relationship problems subscale at 3 years and the hyperactivity–inattention subscale scores at 5 years. Mono-n-butyl phthalate (MnBP) was positively associated with internalizing behavior, relationship problems, and emotional symptom scores at 3 years. Monobenzyl phthalate (MBzP) was positively associated with internalizing behavior and relationship problems scores at 3 years. After dichotomizing behavioral scores, triclosan tended to be positively associated with emotional symptom subscales at both 3 and 5 years.Regarding the associations with maternal hormones, bisphenol A was negatively associated with the Ln (TSH) z-score; MBzP, a metabolite of benzylbutyl phthalate (BBP), was positively associated with the TT4 z-score and triclosan was negatively associated with the TT3/TT4 ratio z-score. When biomarker concentrations were categorized in tertiles, we observed non-monotonic associations between TSH and triclosan (U-shape) and MnBP, a metabolite of di-n-butyl phthalate (DBP) (inverse U-shape). In newborns, only sex-specific effects were observed: bisphenol A was positively associated with the TT4 z-score in male newborns while triclosan was negatively associated with the TT4 z-score in females.Conclusion: Findings in this study concur with previous literature that PCPs use may contribute to exposure to parabens. Our study was the first to report associations between PCP use and bisphenol S, a substitute of bisphenol A. In line with previous studies, bisphenol A and various phthalates, including DBP and BBP exposure during pregnancy, were associated adverse behavioral symptoms among boys. Our study was the first to report adverse neurobehavioral effects in relation to triclosan exposure. The four compounds associated with adverse behavioral effects in EDEN were also associated with one or more thyroid hormone levels of mothers or newborns in the SEPAGES cohort, suggesting possible disruption of thyroid hormones homeostasis

Thesis (MA)--Stellenbosch University, 2015
ENGLISH ABSTRACT : It has been suggested that the complex needs of children with neurodevelopmental disorders are best addressed with a family-centred approach. As this approach has been increasingly incorporated into healthcare systems over recent years, most children with disabilities are now able to remain at home as opposed to living in institutions or group homes. Many parents have thus been forced to adopt the role of a primary caregiver for their child that has been diagnosed with a disability or chronic condition. This study aimed to investigate the experiences of caregivers for children with cerebral palsy in rural communities of the Western Cape, with a specific focus on the barriers and facilitators that they encounter. An exploratory qualitative design was employed and 15 individuals (aged 27-62), who were identified as caregivers for a child with cerebral palsy through purposive sampling were interviewed. Thematic analysis was used to analyse and generate themes from the semi-structured interviews that were conducted with participants. A number of barriers to caring emerged including the personal consequences of caregiving, difficulty adjusting to caregiving duties, environmental conditions, lack of access to healthcare services, lack of respite services, and negative perceptions towards disability. Various facilitators to caring were also identified, namely personal coping methods, personal transformation, social support, relationship with one’s child, community resources, child’s crèche, and financial assistance. The five levels of the Social Ecological Model were used to conceptualise the discussion of these findings and links were made to the existing literature on the caregiver experience in the developing context. In this process it was found that participants often encountered similar barriers and facilitators to caregivers for individuals with other types of conditions, such as HIV/AIDS, autism, mental illness, cancer, and neurological disorders. This could suggest that caregivers residing in developing countries share similar experiences, regardless of the condition of the care receiver. Although participants received support from a number of sources that aided them with their caregiving duties, it is evident that they still encountered gaps in the provision of a number of important services, including lack of information from healthcare professionals, lack of community programs to reduce stress and promote empowerment, and lack of disability-friendly facilities. It is vital that caregivers have access to these services to ensure their child’s well-being as well as their own. There is thus a need to explore how these services can be made more accessible to caregivers in rural communities.
AFRIKAANSE OPSOMMING : Daar word voorgestel dat die komplekse behoeftes van kinders met neuro-ontwikkelingsversteurings die beste aangespreek word deur ‘n familie-gefokusde benadering. Aangesien hierdie benadering meer geredelik geïnkorporeer is in die gesondheidsorg sisteem oor die afgelope paar jaar is meeste kinders met gestremdhede nou in staat om by die huis te kan bly in plaas daarvan om in inrigtings of groepshuise te woon. Baie ouers is dus geforseer om die rol as primêre versorger aan te neem vir hulle kind wat gediagnoseer is met ‘n gestremdheid of kroniese toestand. Hierdie studie se doel was om die ervarings van versorgers van kinders met serebrale gestremdheid in landelike gemeenskappe van die Wes-Kaap, te ondersoek, met ‘n spesifieke fokus op die hindernisse en fasiliteerders wat hulle ondervind. ‘n Ondersoekende kwalitatiewe ontwerp is gebruik en onderhoude is gevoer met 15 individue (ouderdomme 27-62) wat deur doelgerigte steekproefneming geïdentifiseer is as versorgers van ‘n kind met serebrale gestremdheid. Tematiese analise is gebruik om die semi-gestruktureerde onderhoude wat met die deelnemers gevoer is te analiseer en temas te genereer. ‘n Aantal van die hindernisse tot versorging het na vore gekom en sluit die persoonlike gevolge van versorging, probleme om aan te pas by die versorgingspligte, omgewingstoestande, tekort aan toegang tot gesondheidsorg dienste, tekort aan verligting dienste en negatiewe persepsies teenoor gestremdhede in. Verskeie fasiliteerders tot versorging is ook geïdentifiseer, naamlik persoonlike hanteringsmetodes, persoonlike transformasie, sosiale ondersteuning, verhouding met hulle kind, gemeenskapsfasiliteerders, kind se speelskool en finansiële hulp. Die vyf vlakke van die Sosiale Ekologiese Model is gebruik om die bespreking van hierdie bevindinge te konseptualiseer en verbintenisse is gemaak met bestaande literatuur wat handel oor die versorger se ervaring in die ontwikkellende konteks. In hierdie proses is gevind dat deelnemers dikwels dieselfde hindernisse en fasiliteerders ondervind as versorgers van individue met ander tipe toestande, soos MIV/VIGS, outisme, geestesiektes, kanker en neurologiese versteurings. Dit kan moontlik beteken dat versorgers wat in ontwikkellende lande woord dieselfde ervarings deel, ten spyte van die toestand van die persoon wat die versorging ontvang. Alhoewel deelnemers ondersteuning van ʼn aantal bronne ontvang het wat hulle help met hulle versorgingspligte, is dit duidelik dat hulle steeds gapings ervaar in die voorsiening van ʼn aantal belangrike dienste, insluitende ʼn tekort aan inligting van gesondheidsorg werkers, ʼn tekort aan gemeenskapsprogramme om stres verligting en bemagtiging te bevorder en ʼn tekort aan gestremdheid-vriendelike fasiliteite. Dit is baie belangrik dat versorgers toegang het tot hierdie dienste om die welstand van hulle kind en hulself te verseker. Daar is dus ʼn behoefte om te ondersoek hoe hierdie dienste meer toegangklik gemaak kan word vir versorgers in landelike gemeenskappe.

Contexte : De la conception à l'âge adulte, de nombreux déterminants environnementaux influencent le neurodéveloppement. Des études montrent que durant la fin de la grossesse et les premiers mois de vie, une grande quantité d'acides gras polyinsaturés (AGPI), notamment à longue chaîne (AGPI-LC), se fixe dans le tissu cérébral. Un apport optimal durant ces périodes critiques pourrait soutenir précocement le bon développement du cerveau et de ses fonctions.Objectifs : Étudier les relations entre les expositions pré- et postnatales précoces aux AGPI, et le neurodéveloppement d'enfants de 2 et 3 ans.Population : Les données utilisées étaient celles de l'étude EDEN, une cohorte mère enfant ayant recruté 2002 femmes enceintes dans les maternités de Nancy et Poitiers entre 2003 et 2006. L'alimentation maternelle pendant la grossesse a été évaluée par un questionnaire de fréquence alimentaire et une table de composition nutritionnelle. Quatre questionnaires postnatals ont permis d'évaluer la durée d'allaitement maternel, et la composition lipidique du colostrum des mères allaitantes a été analysée par chromatographie en phase gazeuse. Des questionnaires parentaux (2 et 3 ans) et un examen neuropsychologique (3 ans) ont permis d'évaluer plusieurs aspects du neurodéveloppement. Les analyses statistiques ont été réalisées par régressions linéaires multivariées, après ajustement sur de nombreux facteurs de confusion potentiels.Résultats : Les scores de neurodéveloppement à 2 et 3 ans des enfants allaités étaient plus élevés que ceux des enfants non allaités. Chez les enfants allaités, la durée d'allaitement maternel était associée positivement au neurodéveloppement. Le rapport n 6/n 3 dans l'alimentation maternelle en acides gras en fin de grossesse était négativement associé à plusieurs mesures du neurodéveloppement, et cette association était renforcée chez les enfants non allaités. La composition du colostrum en AGPI et en AGPI-LC reflétait amplement les apports nutritionnels en AGPI et en AGPI-LC en fin de grossesse. L'utilisation de matières grasses alimentaires était aussi associée à la composition du colostrum. Les différences de neurodéveloppement des enfants allaités ne semblait pas être expliquées par la composition du colostrum en AGPI ni en AGPI-LC, à l'exception de la teneur en acide linoléique qui était négativement associée à certaines mesures du neurodéveloppement. Dans l'ensemble, les associations avec le neurodéveloppement étaient plus fréquemment retrouvées avec les questionnaires parentaux, mais certaines évaluations par les psychologues venaient parfois conforter ces résultats.Conclusion : Associés à ceux de la littérature, ces résultats soulignent le rôle notable des AGPI durant les périodes pré- et postnatale précoce pour le neurodéveloppement de l'enfant. Le suivi des enfants de l'étude EDEN jusqu'à leur 5 ans permettra d'étudier la persistance de ces résultats. Dans une perspective de santé publique, ces travaux rappellent la nécessité de promouvoir l'allaitement maternel dans la durée et de surveiller l'équilibre des apports nutritionnels en AGPI pendant la grossesse et la période de lactation.

La schizophrénie précoce (SP) est une forme rare, sévère et neurodéveloppementale de schizophrénie débutant avant l’âge de 18 ans. Afin de mieux comprendre les bases génétiques complexes de ce trouble nous avons développé un projet pilote avec pour objectif principal de caractériser sur le plan clinique et génétique les patients atteints de SP. Compte tenu du chevauchement clinique et génétique de la SP avec les autres troubles neurodéveloppementaux, dont le Trouble du Spectre de l’Autisme (TSA) et le Trouble Déficit de l’Attention Hyperactivité (TDAH), nous avons porté une attention particulière aux gènes impliqués dans le neurodéveloppement.Il s'agit d'une étude multicentrique conduite d’avril 2014 à mai 2023. Les critères d'inclusion sont: âge de 7 à 22 ans, un diagnostic de SP (K-SADS-PL DSM-5) avec des symptômes autistiques prémorbides (ADI-R 0-5 ans) et un QI> 40; les parents et les frères et sœurs sont inclus. L’exploration du profil clinique a été effectuée à l’aide d’outils standardisés (KSADS-PL, PANSS) et a compris des évaluations neurocognitives (WISC-V/WAIS-IV). L’exploration génétique (approche hiérarchisée) a compris une recherche de l’X-Fragile, la réalisation d’un CGH-array puis, en cas de négativité des examens précédents, la réalisation d’un séquençage de l’ADN (exome) en trio. Nous avons procédé à la priorisation des gènes en combinant de multiples outils bio-informatiques.20 sujets ont été inclus: 15 Garçons et 5 filles. L’âge moyen de début du trouble était de 8,90 ans (+/-2,30). Les comorbidités psychiatriques étaient le TDAH (15/20 patients), les troubles anxieux (14/20) et le TSA (13/20). Le QI moyen était de 70,26 (+/-18,09). Un retard de langage et une rupture scolaire étaient notés chez 18/20 patients. L’affection somatique principale était l’asthme (15/20 patients). Sur le plan génétique, nous rapportons chez une patiente (ségrégation familiale) une duplication 10q26.3 (324 Kb) comprenant une partie du gène INPP5A. Nous avons montré que son homologue de la drosophile 5PtaseI est spécifiquement exprimée dans le système nerveux central. Enfin, grâce aux séquençages de l’ADN (9 exomes en trio ; mère, père, enfant soit 27 sujets) et aux outils bio-informatiques, nous avons identifié la présence de variants dans les gènes appartenant aux voies de signalisation Wnt, cadhérine et cholécystokinine.Ainsi, nous avons mis en évidence chez nos patients atteints de SP une grande hétérogénéité clinique avec des comorbidités psychiatriques et des atteintes neurodéveloppementales systématiquement associées. INPP5A est un gène exprimé dans le cerveau (humain, souris et drosophile), très conservé entre espèces et qui code une InsP3 5-phosphatase dont les produits d’hydrolyse mobilisent le calcium intracellulaire, essentiel pour la morphogenèse des épines dendritiques dans les neurones. L’altération de ce processus, par dysrégulation de la voie de signalisation InsP3/Ca2+, est retrouvée à la fois dans la schizophrénie et le TSA, renforçant le lien entre ces troubles. De plus, nous avons effectué la première description de l’implication potentielle de voies de signalisation Wnt, Cadhérine et Cholécystokinine dans la SP. L’implication de ces différentes voies de signalisation décrite de manière variable dans d’autres troubles neurodéveloppementaux et/ou psychiatriques souligne l’hétérogénéité génétique de ce trouble. Élucider les mécanismes moléculaires de la SP et ouvrir la voie à une intervention thérapeutique spécifique nécessitera d’effectuer systématiquement et à grande échelle : 1) le diagnostic syndromique précis de SP avec un âge exact de début de la maladie et le phénotype neurodéveloppemental associé ; 2) une évaluation génétique hiérarchisée allant jusqu’au séquençage du génome et 3) le partage des données à l’échelle internationale avec la constitution de bases de données spécifiques, comparables, génétiques et moléculaires corrélées aux phénotypes de précision des différentes formes de SP
Early-onset schizophrenia (EOS) is a rare, severe and neurodevelopmental form of schizophrenia beginning before the age of 18. In order to better understand the complex genetic basis of this disorder, we have developed a pilot project with the main objective of clinically and genetically characterize EOS patients presenting additional neurodevelopmental disabilities. Given the clinical and genetic overlap of EOS with other neurodevelopmental disorders, including Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), we paid particular attention to the genes involved in neurodevelopment.This is a multi-center study carried out from April 2014 to May 2023 in a paediatric population. Inclusion criteria are: age 7-22 years, a diagnosis of EOS (K-SADS-PL DSM-5) with premorbid autistic symptoms (ADI-R 0-5 years) and IQ > 40; parents and siblings are included. Clinical profile explorations are performed using standardized tools (KSADS-PL and PANSS) and included neurocognitive assessments (WISC-V/WAIS-IV), the search for psychiatric co-morbidities, neurodevelopmental disorders and associated extracerebral somatic pathologies. The exploration of the genetic profile consists in identifying genetic mutations by a hierarchical approach searching for Fragile-X Syndrome (PCR), CGH-array and, in case of negativity of the previous examinations, DNA sequencing (exome) in trio (mother, father, child). Finally; we proceed to the prioritization of genes by combining multiple bioinformatics tools.20 subjects were included: 15 boys and 5 girls. The mean age of onset of the disorder was 8.90 years (+/-2.30). Psychiatric comorbidities (DSM-5) were ADHD (15/20 patients), anxiety disorders (14/20) and ASD (13/20). The mean IQ was 70.26 (+/-18.09). Language delay and school disruption were noticed in 18/20 patients. The main associated somatic condition was asthma (15/20 patients). Genetically, we report a 10q26.3 324 kb microduplication in one patient (with familial segregation), encompassing part of the INPP5A gene. We have shown that its homologue 5PtaseI is specifically expressed in the Drosophila central nervous system. Furthermore, we have identified, through DNA sequencing of 9 exomes of patients in trio (27 subjects with mother, father and child) and bioinformatics tools, the presence of variants in genes belonging to the Wnt, cadherin and cholecystokinin signaling pathways.In our EOS patients, we have shown a large clinical heterogeneity with psychiatric co-morbidities and neurodevelopmental disorders systematically associated. INPP5A is expressed in the brain (human, mouse and Drosophila), is highly conserved between species and encodes a InsP3 5-phosphatase whose hydrolysis products mobilize intracellular calcium, essential for the morphogenesis of dendritic spines in neurons. The alteration of this process, by the InsP3/Ca2+ signaling pathway, is found in both schizophrenia and ASD, strengthening the link between these disorders. In addition, we have made the first description of the potential involvement of the Wnt, Cadherin and Cholecystokinin signaling pathways in EOS. The already described involvement of these different pathways in other neurodevelopmental and/or psychiatric disorders underlines the genetic heterogeneity of this disorder. Therefore, elucidating the molecular mechanisms of EOS and paving the way for specific therapeutic interventions will require systematic and large-scale: 1) definition of the precise syndromic diagnosis of EOS with an exact age of onset and determination of the premorbid neurodevelopmental phenotype, psychiatric comorbidities and associated extracerebral somatic pathologies; 2) genetic evaluation using a hierarchical approach up to whole genome sequencing; 3) data sharing between teams on an international scale with the constitution of specific, comparable, genetic, and molecular databases correlated to the precise phenotypes of the different forms of EOS

BACKGROUND: Many women of reproductive age are employed in industries involving exposure to organic solvents. Animal toxicological studies and human case reports demonstrate that exposure to organic solvents can cause neuropsychological deficits in exposed offspring; however, there is limited data from prospective controlled human studies. OBJECTIVE: To compare neuropsychological functioning between children whose mothers were occupationally exposed to organic solvents during pregnancy with a non-exposed matched comparison group. METHODS: Participants were 48 women who had previously contacted the Motherisk Program in Toronto, Canada during pregnancy regarding occupational exposure to organic solvents and a matched comparison group of women with no known exposure to teratogens during pregnancy. Children (18 months to 8 years 11 months at time of study) were compared in areas of cognitive, language, motor, and behavioral functioning. RESULTS: Children whose mothers were exposed to organic solvents during pregnancy displayed a lower level of functioning when compared with their matched peers in areas of cognitive, language, motor, and behavioral domains. Although the scores on measures of behavioral functioning were not in the clinical range, the mothers of exposed children reported more challenging behavioral problems. In order to determine whether exposure predicted neuropsychological outcomes above and beyond maternal intellectual functioning, hierarchical regressions were run with maternal IQ and maternal education at Step 1and exposure status added at Step 2. In utero exposure to organic solvents predicted lower sores on global measures of Verbal IQ, receptive and expressive language scales above and beyond maternal intellectual functioning. Factors associated with higher levels of exposure (detecting odor, longer duration and total number of toxicity symptoms) was associated with poorer outcome on behavioral and motor functioning tests. CONCLUSION: Despite the fact that the exposed mothers experienced minimal symptoms of toxicity, detrimental effects were still evident in their offspring. Current safety standards for exposure were designed for adults and need to be reevaluated. Further studies addressing exposure to specific organic solvents, dose, and gestational timing of exposure are warranted.

Background: The prenatal period is a critical window for neurodevelopment and is particularly sensitive to toxicant exposure. Traffic-related air pollution and per- and polyfluoroalkyl substances (PFASs) are two classes of potential developmental toxicants to which pregnant women are ubiquitously exposed. Objectives: In a cohort of children, characterize in utero exposure to traffic-related air pollution and PFASs and examine the effects of these exposures on childhood assessments of neurodevelopment. Methods: Analyses were conducted in Project Viva, a longitudinal Boston-area birth cohort enrolled during 1999‒2002. In mid-childhood (at age 6‒10), children completed assessments of cognitive function and mothers and classroom teachers assessed executive function and behavior problems in children using validated questionnaires. Estimates of traffic-related pollutant exposures, residential proximity to major roadways, and near-residence traffic density were generated for periods in pregnancy and childhood. Stored maternal plasma from pregnancy was analyzed for concentrations of four common PFASs: perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA). We modeled associations of exposures with neurodevelopmental assessment scores, adjusted for potential confounders. Results: Living within 50 meters of a major roadway at birth predicted lower non-verbal intelligence, verbal intelligence, and visual motor abilities in mid-childhood. Children with higher black carbon exposure during childhood had greater teacher-assessed problems with behavior regulation, but prenatal traffic exposures were not associated with greater problems. Children with higher prenatal exposure to PFOA scored lower on assessments of verbal IQ and visual motor abilities, but children with the highest levels of PFOS and PFNA exposure appeared to have better scores on some cognitive assessments (verbal IQ, non-verbal IQ and design memory for PFOS and verbal IQ, design memory and picture memory for PFNA). Conclusions: The influence of exposure to traffic-related pollution and PFASs on neurodevelopment varied across pollutants, exposure windows, and neurobehavioral domains. Results suggested that residential proximity to major roadways during gestation adversely affected cognitive development. Prenatal exposure to traffic-related pollution did not predict greater neurobehavioral problems, but childhood exposure appeared to influence behavioral regulation. Observed associations of prenatal PFAS exposure with childhood cognition differed across studied compounds and cognitive assessments, suggesting both deleterious and protective effects.

Craniosynostosis is a common developmental disorder characterised by premature, pathological fusion of one or more of the fibrous connections, or sutures, that normally separate the bony plates of the skull during early development. Premature sutural fusion, typically occurring in utero, results in anomalous skull growth, and may have consequences for the developing brain. Most cases of single-suture craniosynostosis (SSC) require surgery, preferentially performed within the first year of life, to release the fused suture and reshape the deformed skull and improve brain growth potential. The exact mechanisms by which brain development is disrupted in SSC are uncertain. Research suggests that children with all forms of SSC are at heightened risk for neuropsychological problems; however, the nature, extent and risk factors (e.g., genetic, environmental, severity of skull deformity) for these disturbances, are yet to be established. The aim of this study was to examine the impact that SSC may have on neurodevelopmental skills during infancy and to use a theory-driven approach to explore the possible contributory factors to developmental progression during infancy.
Participants included 30 infants with SSC (16 metopic, 14 sagittal). Participants were assessed on the Bayley Scales of Infant and Toddler Development – Third Edition (BSID-III) during early infancy when they were between 5 and 15 months of age. Fifty-three percent (n=16) of these infants were also assessed in late infancy when they were between 17 and 33 months of age and at least six months post-surgical intervention. During both early and late infancy, children with craniosynostosis demonstrated significantly poorer gross motor skills compared to the normative sample, but other skills were in line with normal population expectations. Factors including subtype of craniosynostosis, severity of deformity, social risk and age at surgery, were not shown to be significantly associated with developmental level during early or late infancy. The impact of genetic variables on early development was unclear in the current sample.
This study has provided important insights into the functional significance of disruption to typical brain growth in infants with SSC. Findings indicate that SSC is a condition associated with developmental delay during early infancy prior to surgical intervention, with developmental concerns remaining evident post-surgically in late infancy. Findings support recommendations for the close monitoring of the development of these children during early life.

Thesis (M.Sc.(Med.))--University of the Witwatersrand, Faculty of Health Sciences, 2012.
Neurodevelopmental delay has been documented in up to 97.5% ofHIV-infected childfen in Soweto who were not yet on ART. With growing numbers of children in South Africa being successfully treated with antiretroviral treatment (ART), the effects of ART on neurocognitive functioning in children require investigation. The objective of this study was to determine the extent of neurodevelopmental delay in stable HIV -infected preschool children (aged) 5-6 years) receiving ART and compare it to an apparently healthy . (unconfirmed HIV-status) group of preschool children. Thirty HIV-infected preschool children (virologically and immunologically stable on ART for> 1 year) were conveniently sampled from 350 eligible children on ART at the Harriet Shezi Children's Clinic in Soweto, Johannesburg. The comparison group comprised thirty well-nourished preschool children attending the Lilian Ngoyi Primary Health Care Clinic in Soweto for routine immunisations. Each child was assessed using the Griffiths Mental Development Scales-Extended Revised Version (GMDS-ER), at a single point in time. The overall developmental z-scores on GMDS-ER were <-2 (indicating severe delay) in 27 (90%) children in the HIV-infected group compared to 23 (76%) in the comparison group (p=0.166). Mental handicap (overall GQ<70) was evident in 46.7% of children in the HIV -infected group compared to 10% in the comparison group (p= 0.002). There was a 7.88-fold increased likelihood of severe delay in the HIV infected group. The HIV -infected group and comparison group had significantly different (p=0.001) mean overall GQ scores of70 (95% CI: 66.0-74.0) and 78 (95% CI: 75.6- 80.5), respectively, with lower mean scores in the HIV -infected group in all individual domains. Early initiation of ART in HIV-infected infants may improve cognitive functioning among this group, however, intervention strategies which optimize early cognitive development for all children in the area, need to be urgently considered.

Trabalho de revisão do 6º ano médico com vista à atribuição do grau de mestre (área científica de pediatria) no âmbito do ciclo de estudos de Mestrado Integrado em Medicina.
Although prognosis of Congenital Hypothyroidism (CH) has been greatly modified since the introduction of newborn screening programs, persistent cognitive deficits are still reported. The aim of this study was to evaluate neurodevelopmental outcomes of children with CH and to determine whether severity of CH, age of start of L-thyroxine supplementation and control of CH play an important role. We analyzed a sample of children with CH (N=44) using neurodevelopmental assessment tests according to child’s age and level of functioning: Griffiths Scale of Mental Development (GSMD), Portuguese version of Wechsler Intelligence Scale for Children – Third Edition (WISC-III), and Vineland Adaptive Behaviour Scale (VABS) and early developmental milestones. We further compared this data with screening TSH values and follow-up mean values of TSH, fT4 and L-thyroxine dosage. Communication Disorders and Attention-Deficit/Hyperactivity Disorder were the most common diagnosis, 25% and 15.9% respectively, found among children with neurodevelopmental problems (59.1%). Average scores in Practical Reasoning Quotient in the Griffiths subscale and Adaptive Behaviour Composite, Daily Living Skills and Socialization (VABS domains) in children with CH were significantly lower than in normal population. A correlation was found between mean L-thyroxine dosage and Full Scale Intelligence Quotient (WISC-III). No correlation was found between screening level of TSH, age of treatment initiation, follow-up mean TSH, mean fT4 values and results in the three global scales of neurodevelopmental tests. Even though prognosis of CH has been greatly modified since early detection through screening programs, careful monitoring of these children is crucial to guarantee an early intervention and to assure optimal neuro- and sociodevelopmental outcomes.

Le trouble du spectre de l’autisme (TSA) est défini par l’atteinte de deux domaines: une diminution de la réciprocité sociale et une inflexibilité comportementale. Il n'existe pas de test diagnostique ni de mesure des mécanismes impliqués. En population adulte TSA, l’utilisation d’un jeu d’interaction dynamique, dyadique et intégratif présentant alternativement un contexte social ou non social, a permis d’obtenir un phénotype computationnel de la réciprocité sociale révélant une insensibilité au type de contexte, une utilisation de stratégie spécifique à ce groupe et une variation de performance dépendante de la sophistication de l’adversaire. Cette étude vise à étendre cette compréhension de la réciprocité sociale en population TSA pédiatrique et de la distinguer d'éléments psychopathologiques comme l'anxiété ou les symptômes de TDAH, parfois associés ou confondus avec des symptômes autistiques. L’analyse des données de performance des participants au jeu a permis de valider son utilisation en population pédiatrique, en répliquant l’impact du type d’algorithme sur la performance des participants. Une approche dimensionnelle utilisant des outils standardisés et permettant la quantification de la sévérité des symptômes autistiques, TDAH et troubles anxieux, a permis de spécifier l’impact des symptômes autistiques et anxieux sur la performance des participants contre un algorithme de type ToM d’ordre 0. Cette étude est une étape dans la compréhension des mécanismes impliqués dans l'interaction sociale au cours du développement, et dans la capacité à les mesurer. Des analyses computationnelles complémentaires permettront d’affiner ce phénotype computationnel en apportant des précisions quant aux stratégies utilisées pendant le jeu et à la flexibilité des participants à varier dans leur utilisation.
Autism Spectrum Disorder (ASD) is defined by two main domains of impairment: decreased social reciprocity and behavioural inflexibility. There is no diagnostic test or measurement of the mechanisms involved. A study with ASD adults used a dynamic, dyadic and integrative interaction game which alternately presents a social or non-social context, it resulted in a computational phenotype of social reciprocity revealing insensitivity to the type of context, a use of strategy specific to this group and a variation in performance depending on the opponent’s sophistication. This study aims to extend this understanding of social reciprocity in the pediatric ASD population and to distinguish psychopathological symptoms such as anxiety or ADHD symptoms, which are sometimes associated or confused with autistic symptoms. Analysis of the participants’ performance data validated its use in the pediatric population by replicating the impact of the algorithm on the participants’ performance. A dimensional approach using standardized tools and allowing the quantification of the autistic, ADHD and anxiety disorders symptoms’ severity, permits the emphasis of the impact of autistic and anxious symptoms on participants’ performance against a ToM-0 agent. This study is a step in the understanding of the mechanisms developed in social interaction during development and in the ability to measure them. Complementary computational analyzes will help refine this computational phenotype by giving more details about the strategies used during the game and the participants' flexibility to vary in their use.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Occupational Therapy. 2012
This study investigated the effects of a five-day “block” of intensive NDT on the gross motor function and occupational performance of 34 children with CP from an under resourced rural area of South Africa, functioning at GMFCS Levels I-V. The repeated measures research design used two preintervention (baseline of change) and two post-intervention (immediate and sustained change) assessments. The GMFM–66 and PEDI–Modified Functional Skills Scale (MFSS) were used to assess change in motor skills and occupational performance in self-care, mobility and social function over a 21 week period. The intervention included individual NDT therapy, caregiver training and provision of adapted equipment. Participants showed significant positive improvement in scores postintervention compared with the pre-intervention period, in: GMFM-66 total score (p=0.050); PEDI-MFSS: self-care skills (p=0.001), mobility (p=0.002) and social (p=0.000). The greatest gains were made in the self-care domain. In this sample, positive change was effected by a five-day intensive NDT programme.

A research report submitted to the Faculty of Health Sciences, the University of the Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the degree of Master of Science in Medicine in Child Health Neurodevelopment Johannesburg, 2013
Human Immunodeficiency Virus (HIV) infection in infancy may influence the developing brain and lead to adverse neurodevelopmental consequences. We aim to describe the neurodevelopmental characteristics of a cohort of young children infected with HIV prior to antiretroviral therapy (ART) initiation and after achieving viral suppression. A retrospective analysis of data collected as part of a randomised equivalence trial between April 2005 and May 2009, at a hospital in Johannesburg, South Africa. 195 HIV-infected children under 2 years of age were assessed. A simple, inexpensive screening questionnaire (Ages and Stages Questionnaire - ASQ) was used to identify neurodevelopmental delays. The ASQ was administered prior to ART initiation, and again after viral suppression on a protease inhibitor-based regimen had been achieved. Median age pre-ART was 8.8 months (range 2.2 - 24.9), 53.9% were male. Mean time to viral suppression was 9.4 months (range 5.9 - 14.5) and the ASQ was administered to 108 caregivers at this time. Compared to pre-ART, at viral suppression, there was significant reduction in the proportion of children failing the gross motor (31.5% vs. 13%, p<0.01), fine motor (21.3% vs. 10.2%, p=0.02), problem solving (26.9% vs. 9.3%, p<0.001) and personal social (17.6% vs. 7.4%, p=0.02) domains. The proportion of children failing the communication domain was similar at each time point (14.8% vs. 12%, p=0.61). At time of viral suppression 10.2% failed at least one of the five domains. Achieving viral suppression on ART resulted in significant improvements in the neurodevelopmental function of young HIV-infected children, however, neurodevelopmental problems still persisted in a large proportion. Appropriate screening for neurodevelopmental delay and timely referral could help improve outcomes.

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina
Introdução: As perturbações do neurodesenvolvimento são um conjunto de patologias que se manifestam precocemente na criança, afetando o seu funcionamento a todos os níveis. A sua prevalência é de 15.0% na população em geral entre os 3 e os 17 anos. A Perturbação do Espectro do Autismo (PEA) é uma destas patologias, caracterizada por défices persistentes na comunicação e interação social, assim como por padrões restritivos de comportamento, interesses ou atividades. Apresenta vários fatores de risco conhecidos, genéticos e ambientais. Pensa-se que alguns destes fatores de risco sejam comuns a outras perturbações do neurodesenvolvimento e, portanto, os irmãos destas crianças com PEA, ao partilharem fatores de risco comuns, terão maior probabilidade de apresentar também patologia do neurodesenvolvimento. Este estudo pretende avaliar a frequência das perturbações do neurodesenvolvimento nos irmãos de crianças com PEA, assim como encontrar uma relação entre possíveis fatores de risco comuns aos irmãos.População e métodos: Foram colhidos dados relativos a 453 crianças diagnosticadas com PEA, das quais 249 tinham irmãos em que havia informações acerca da existência de perturbações do neurodesenvolvimento. Destes foram obtidas informações, tanto relativas à caracterização da amostra como a eventuais fatores de risco identificados. Dos irmãos obtiveram-se informações acerca da idade, género, ordem de nascimento e idade paterna e materna ao nascimento. Foram definidas diversas hipóteses, na tentativa de relacionar estas perturbações do neurodesenvolvimento com fatores encontrados ou relacionados com o irmão com PEA. Resultados: Das 249 crianças com PEA, 60 têm irmãos com perturbações, havendo um total de 332 irmãos, 66 (19.9%) dos quais com perturbações do neurodesenvolvimento. Observou-se uma relação estatisticamente significativa entre a ordem de nascimento dos irmãos e a frequência de perturbações do neurodesenvolvimento: nos irmãos mais velhos dos indivíduos com PEA, há maior frequência de perturbações do neurodesenvolvimento, relativamente aos mais novos e aos gémeos. Apesar do género dos irmãos não apresentar uma relação estatística, há mais indivíduos com PEA do género feminino a ter irmãos com perturbações do neurodesenvolvimento, do que do género masculino.Discussão: Nos irmãos de indivíduos com PEA foi observado um aumento da frequência das perturbações do neurodesenvolvimento relativamente à população em geral. A única relação com significância estatística encontrada foi o aumento desta frequência com a ordem de nascimento dos irmãos (superior nos irmãos mais velhos de crianças com PEA). Mais nenhuma das hipóteses apresentou resultados com significância estatística.
Introduction: Neurodevelopmental disorders are a set of pathologies that manifest early in the child and interfere with normal development, prejudicing their function at all levels. They present a prevalence of 15.0% in the general population between the ages of 3 and 17. One of those is Autism Spectrum Disorder (ASD) which is a pathology characterized by persistent deficits in communication and social interaction, as well as by restrictive patterns of behavior, interests or activities. It presents several known genetic, environmental and risk factors. It is thought that some of this risk factors are common to the other neurodevelopmental disorders and therefore, the siblings of these children with ASD, when sharing common risk factors, would be more likely to develop these disorders. This study aims to evaluate the frequency of neurodevelopmental disorders in siblings of children with ASD, as well as to find a relationship between possible risk factors common to two siblings.Methods and population: Data were collected from 453 children diagnosed with ASD, of wich 249 had siblings who had information about the existence of neurodevelopmental disorders. From the siblings, information about age, gender, birth order, and paternal and maternal age at birth was obtained. Several hypotheses were defined in an attempt to relate these neurodevelopmental disorders with factors found or related to the sibling with ASD.Results: Of the 249 children with ASD, 60 had siblings with neurodevelopmental disorders, with a total of 332 siblings, 66 (19.9%) of whom had alterations. A statistically significant relationship was observed between the order of birth of the siblings and the frequency of neurodevelopmental disorders: in older siblings of the children with ASD, there is a higher frequency of neurodevelopmental disorders, in relation to the younger ones and the twins. Although the gender of the siblings does not show a statistical relationship with the neurodevelopmental disorders, there are more children with ASD of the female gender to have siblings with these disorders, than the male gender.Discussion: In the siblings of children with ASD, an increased frequency of neurodevelopmental disorders was observed in relation to the general population. The only relation with statistical significance was the increase in this frequency with the siblings' birth order (higher in the older siblings of children with ASD). None of the others hypotheses presented results with statistical significance.

This study aimed to develop a framework for improved legislation, methods of practice and services used to meet the best interest of child offenders with psychiatric disorders within the South African child justice system. This aim was achieved via a qualitative study, which evaluated child justice and mental health legislation, methods of practice, role-players, and services in South Africa, and compared same to those in Namibia, Botswana, and Nigeria; to establish if the best interest of child offenders with psychiatric disorders are currently met from a South African perspective. Data collection occurred in two phases: a document analysis of legislation, policies, and procedures in the selected comparative jurisdictions; followed by semi-structured interviews with child justice and mental health experts. During phase one the researcher analysed child justice and mental health legislation, human rights protections, and policy related to child justice in Nigeria, Botswana, Namibia, and South Africa. In addition, she interrogated literature relating to child justice and mental health, in comparative jurisdictions. This phase formed the foundation for the semi-structured interview schedule. Purposive and theoretical sampling was used to conduct 24 semi-structured interviews. Data was analysed and interpreted using pure qualitative document and thematic analysis. The overarching findings indicate that the best interest of child offenders with psychiatric disorders, in the South African child justice system, are unprotected. This vulnerable group is not dealt with from an individualised, case-specific, multi-disciplinary perspective; informed by legislation, practice-policy, and a service-orientated approach. Further, certain domestic legislation and methods of practice are inadequate in holistically assessing a child who comes into conflict with the law in the jurisdictions of comparison. Further findings identified that biological, psychological, environmental, cultural, and social factors influence the development of psychiatric disorders in children, which may bring them into conflict with the law. This study further confirmed that Attention Deficit Hyperactivity Disorder, Intellectual Development Disorder, Learning Disorder, Oppositional Defiant Disorder, and Conduct Disorder are prevalent in children who iv come into conflict with the law. Further, substance abuse disorder, depression and attachment disorder were identified as predominant factors affecting children who come into conflict with the law. The influence of these factors, in conjunction with biological, psychological, environmental, cultural, and social factors, were found to predispose children to psychiatric disorders linked to criminal behaviour. Thus, to meet the best interest standard; children in conflict with the law must be dealt with using a multi-factorial approach which considers biological, environmental, social, cultural, and psychological factors. In this way, the behaviour of child offenders with psychiatric disorders will be addressed holistically in a manner that considers all factors influencing behaviour. The empirical data supported the recommendations used to develop a trans-disciplinary framework for child offenders with psychiatric disorders.
Olu phononongo lwesi sifundo lujolise ekuphuhliseni isakhelo somthetho ophuculiweyo, iindlela zokusebenza kunye neenkonzo ukwenzela ukunikezela ezona zilungileyo iimfuno zabantwana abangabaphuli-mthetho benengulo yesifo sengqondo kwinkqubo yobulungisa yabantwana eMzantsi Afrika. Le njongo yaphunyezwa ngokwenziwa kwezifundo ezisemgangathweni ezahlola umthetho wobulungisa kubantwana kunye nomthetho olawula ezempilo ngokwengqondo, iindlela zokusebenza, abathathi-nxaxheba kunye neenkonzo eMzantsi Afrika. Ezi zathi ngoko zathelekiswa nomthetho, umsebenzi abathathi-nxaxheba kunye neenkonzo eNamibia, eBotswana, kunye naseNigeria ukufumanisa ukuba iimfanelo ezizizo zabantwana abangabaphuli-mthetho abaneengxaki zengqondo bayanakekelwa ngoku eMzantsi Afrika. Ukuqokelelwa kweenkcukacha kwenzeka kumanqanaba amabini: uhlalutyo lwemiqulu yomthetho, umgaqo-nkqubo kunye nenkqubo; Ukucazululwa kwamaxwebhu/kwemiqulu omthetho, umgaqo-nkqubo kunye neenkqubo ezikhethiweyo zothelekiso kulawulo lwezobulungisa, lilandelwe ludliwano-ndlebe olungahlelwanga ngokupheleleyo neengcaphephe/neengcali zezobulungisa lwabantwana kunye nemilo yezengqondo. Kwinqanaba lokuqala umphandi ucazulule umthetho wobulungisa kubantwana kunye nempilo yezengqondo, ukhuseleko lwamalungelo oluntu.kunye nemigaqo-nkqubo ehambelana/ enxulumene nobulungisa kubantwana eNigeria, eBotswana, eNamibia naseMzantsi Afrika. Ukongezelela walugocagoca uncwadi olubhekisele kubulungisa babantwana nezempilo yezengqondo kulawulo lwezobulungisa Eli nqanaba libe sisiseko soludwe lwenkqubo yodliwano-ndlebe olungamiselwanga ngokupheleleyo. Isampulu enenjongo neyingcingane yasetyenziswa ukuze kuqhutywe udliwano-ndlebe olungama-24 olungahlelwanga ngokupheleleyo. Ulwazi (idata) lwacalulwa lwacaciswa kusetyenziswa uxwebhu olusemgangathweni kunye nocalulo (analysis) olusemxholweni. Iziphumo ezicacileyo/eziqaqambileyo eziluphahla zibonisa ukuba okukokona kulungele abantwana abangabaphuli-mthetho abaneengxaki zezengqondo, abakhuselekanga kwinkqubo yezobulungisa babantwana eMzantsi Afrika. Eli qela lingakhuselekanga alivelelwa ngokomntu neengxaki zakhe yedwa, ngokwengxaki yakhe ngokuthe ngqo kusetyenziswe indlela ezahlukileyo ezilawulwa ngumthetho, ngumgaqo-nkqubo osebenzayo nokuvelela ngendlela yokuziqhelanisa nemeko. Ukuya phambili, eminye yemithetho yasekhaya neendlela zokusebenza azonelanga ekuhloleni ngokupheleleyo kumntwana ohlangabezana nokuphikisana nomthetho kummandla wothelekiso. Kuphinde kwafunyaniswa ukuba iimeko zozalo, zengqondo, zendawo, zenkcubeko nezentlalo ziyaziphembelela iingxaki zezengqondo ezivelayo ebantwaneni, ezinokwenza baphikisane nomthetho. Olu phononongo luqhubeka lungqina ukuba ukunganiki ngqalelo kwingxaki yokuphaphazela, ingxaki yokukhula kwengqiqo, ingxaki yokufunda, ingxaki yenkcaso yokulungileyo/ ukudelela kunye nengxaki yokuziphatha zixhaphakile kubantwana (abonayo) abaphikisana nomthetho. Ingxaki yokusebenzisa iziyobisi, ingcinezelo kunye nokuxhomekeka ziye zaphawulwa njengeemeko ezixhaphakileyo ezikhathaza abantwana abalwa nomthetho (abonayo). Iimpembelelo zezi meko, zidibene neemeko zozalo, zezengqondo, zendawo, zenkcubeko nezentlalo, zifunyenwe zilungiselela kwangaphambili abantwana kwezi ngxaki zezengqondo zithungelene ekuziphatheni ngokolwaphulo-mthetho. Ngoko ke ukuhlangabezana nomgangatho ofanelekileyo nobalulekileyo, ebhekelela abantwana abaphikisana nomthetho (abonayo) makusetyenzwe ngabo kusetyenziswe indlela ejongene neemeko ezininzi ezibandakanya iimeko zozalo, zendawo, zentlalo, zenkcubeko kunye nezengqondo. Ngale ndlela abantwana abaphula umthetho abanengxaki yezengqondo baya kuncedwa ngokupheleleyo ngendlela ebandakanya zonke iimeko eziphembelela ukuziphatha. Idatha ekholose ngamava avela kumava nokuboniweyo ixhasa izindululo ezenziweyo zokumisa isakhelo esisebenza kulo lonke uqeqesho lomntwana ophikisana nomthetho (owonayo) onengxaki yezengqondo.
Patlisiso ena e reretswe ho hlahisa moralo wa molao o ntlafetseng, mekgwa ya tshebetso le ditshebeletso bakeng sa molemo wa batlodi ba molao bao e leng bana ba nang le mathata a kelello tshebeletsong ya toka ya bana Afrika Borwa. Morero ona o fihletswe ka boithuto ba boleng, bo lekantseng melao ya toka ya bana le ya bophelo bo botle ba kelello, mekgwa ya tshebetso, baamehi le ditshebeletso Afrika Borwa. Tsona di ile tsa bapiswa le melao, tshebetso, baamehi le ditshebeletso dinaheng tsa Namibia, Botswana le Nigeria ho fumana hore na melemo e loketseng ya batlodi ba molao bao e leng bana ba nang le mathata a kelello e ya fumaneha hajwale Afrika Borwa. Pokeletso ya dintlha e etsahetse ka mekgahlelo e mmedi: manollo ya ditokomane tsa molao, melawana le mekgwatshebetso dibakeng tse kgethilweng tsa papiso tsa semolao; ho latetswe ke di-inthavu tse sa hlophiswang le ditsebi tsa toka ya bana le tsa molao wa bophelo bo botle ba kelello. Mokgahlelong wa pele mofuputsi o ile a manolla molao wa toka ya bana le wa bophelo bo botle ba kelello, ditshireletso tsa ditokelo tsa botho le melawana e amanang le toka ya bana dinaheng tsa Nigeria, Botswana, Namibia le South Africa. Ho feta moo, o ile a batlisisa dingolwa tse mabapi le toka ya bana le bophelo bo botle ba kelello dibakeng tse ka bapiswang tsa semolao. Mokgahlelo ona o bile motheo wa lenane la di-inthavu tse sa hlophiswang. Ho sebedisitswe mokgwa wa disampole wa kgetho le wa theho ya thiori ho etsa di-inthavu tse 24 tse sa hlophiswang. Dintlha di manollotswe le ho tolokwa ka manollo e sa tswakwang ya boleng ba ditokomane le ditema. Diphetho tse akaretsang di supa hore melemo e nepahetseng ya batlodi ba molao bao e leng bana ba nang le mathata a kelello ha e ya sireletswa moralong wa toka ya bana wa Afrika Borwa. Sehlopha sena se kotsing ha se sebetswe ka tjhebo ya bo-motho ka mong, ya kgetsi e kgethehileng, ya mafapha a mangata e tshehedistsweng ke molao, molawana wa tshebetso le tjhebo ya tshebetso. Ho feta moo, melao e meng ya lehae le mekgwa ya tshebetso e ne e fokola bakeng sa ho lekola ngwana ka tsela e felletseng, ya iphumanang a le kgahlano le molao dibakeng tsa semolao tse neng di bapiswa. ix Ho boetse ha fumanwa hore dintlha tsa tlhaho, kelello, tikoloho, setso le botjhaba di susumetso tlhaho ya bokudi ba kelello baneng, e leng ho etsang hore ba iphumane ba le kgahlano le molao. Boithuto bona hape bo tiisitse hore bokudi ba tlholeho ya tsepamiso le ketso e fetang tekano, bokudi ba kgolo ya bohlale, bokudi ba ho ithuta, bokudi ba ho ba kgahlano le ba bang le bokudi ba boitshwaro bo bongata bakeng ba iphumanang ba le kgahlano le molao. Bokudi ba tshebediso e mpe ya tahi kapa dithethefatsi, tshithabelo ya maikutlo le bokudi ba kgokahano di fumanwe e le mabaka a mantlha a amang bana ba qwaketsanang le molao. Tshusumetso ya dintlha tsena, hammoho le dintlha tsa tlhaho, kelello, tikoloho, setso le botjhaba, di fumanwe e le hore di pepesa bana ho bokudi ba mafu a kelello a amanngwang le botlokotsebe. Kahoo, e le ho ka fihlella maemo a melemo e nepahetseng, bana ba kgahlano le molao ba lokela ho sebetswa ka mokgwa wa ditsela tse fapaneng tse ngata, o kenyeletsang dintlha tsa tlhaho, tikoloho, setso, botjhaba le kelello. Ka mokgwa ona, batlodi ba molao bao e leng bana ba nang le bokudi ba kelello ba tla shejwa le ho sebetswa ka mokgwa o phethahetseng o kenyelletsang dintlha tsohle tse susumetsang boitshwaro. Dintlha tse bokelleditsweng di tsheheditse ditlhahiso tse sebedisitsweng ho hlahisa moralo wa makala a fapaneng bakeng sa batlodi ba molao bao e leng bana ba nang le bokudi ba kelello.
Criminology and Security Science
D. Phil. (Criminal Justice)

Este documento relata o percurso final no âmbito do Mestrado em Reabilitação Psicomotora. Decorreu no Hospital de Santo Espírito da Ilha Terceira, EPER, incindindo essencialmente na Saúde Mental Infantil e Juvenil. A Psicomotricidade tem uma visão holística do desenvolvimento humano. Passa por um descobrir ou redescobrir a alegria do movimento, o prazer do corpo, de ser ele mesmo (Audrey, 2013). A Saúde Mental é a adaptação do sentimento, pensamento e comportamento aos agentes stressores do ambiente externo ou interno apropriados à idade e acordantes com as normas locais e culturais (Townsend, 2011). Este estágio teve dois grandes objetivos: primeiramente, introduzir a Psicomotricidade numa equipa que dá resposta à Pedopsiquiatria em contexto hospitalar, apercebendo dos desafios a encontrar e como os ultrapassar; e, o segundo objetivo, averiguar o impacto que a Intervenção Psicomotora tem nas problemáticas de saúde mental infantil e juvenil. Ultrapassados os desafios que surgiram inicialmente, verificou-se uma maior consolidação da Equipa Multidisciplinar de Apoio à Pedopsiquiatria e, consequentemente, da sua resposta à comunidade infantil e juvenil. Conclui-se, que a Intervenção Psicomotora em contexto clínico tem como principal finalidade promover a evolução da personalidade do sujeito e a sua inserção social, onde a autenticidade e o respeito sejam os princípios para o projeto de vida.
This document reports my final course for master degree in psychomotor rehabilitation. It took place at the Hospital de Santo Espirito da Ilha Teceira, EPER, in children and young Mental Health. The Psychomotricity has a holistic view of human development. Passes by a discover or rediscover the joy of movement, the pleasure of the body, of being himself (Audrey, 2013). Mental health is the adaptation of feeling, thought and behavior to the stress agents to the external or internal environment suitable for age and accordant with local and cultural norms (Townsend, 2011). This stage had two major goals: first, introduce the Psycomotricity in a multidisciplinary team that support Child Psychiatry in the hospital, realizing the challenges and how to overcome them; the second objective, investigate the impact that the Psychomotor Intervention has on children and youth mental health problems. Overcome the challenges that arose initially, it became a greater consolidation of the team to support Child Psychiatry and, as a result of their responding to community children and youth. It was concluded that the Psychomotor Intervention in clinical context as its more purpose promote the development of the personality of the person and his social inclusion, where the authenticity and respect are principles for the design of life.

Il est maintenant bien établi que le cerveau humain est doté d’un système de neurones qui s’active tant à la perception qu’à l’exécution d’une action. Les neurones miroirs, ainsi que le système qu’ils forment avec des structures adjacentes appelées système neurones miroirs (SNM), ont été relié à la compréhension d’action et pourrait être impliqué dans les fonctions sociales de haut niveau tel que l’empathie et l’imitation. Dans la foulée spéculative reliant le SNM à la sphère sociale, le dysfonctionnement de ce système a rapidement gagné intérêt dans la genèse des anomalies du domaine social chez les personnes présentant le Trouble du spectre de l’autisme (TSA). Néanmoins, l’hypothèse voulant que le dysfonctionnement social des TSA repose sur une atteinte du SNM est controversée. En effet, les études soutenant cette hypothèse nécessitent des fonctions cognitives et sociales qui peuvent contribuer à l’obtention de résultats atypiques, telles que la compréhension des consignes, l’attention sur des stimuli sociaux ou la réalisation d’acte moteur. Récemment, un protocole auditif de négativité de discordance (MMN) utilisant des stimuli reliés à l’action humaine a été utilisé pour mesurer l’activité du SNM. Cette technique semble prometteuse dans la mesure où elle ne nécessite pas de capacités attentionnelles ou langagières, elle est brève et demande un montage minimal d’électrodes. Le premier article avait comme objectif principal de mesurer la validité de convergence du protocole MMN relié à l’action avec celui du rythme mu, le protocole le plus utilisé pour enregistrer l’activité miroir à l’aide de l’électroencéphalographie (EEG). Les modes de stimulation ont été délivrées en bloc successif à un groupe de 12 adultes en santé. Alors que les deux techniques ont modulé efficacement les régions fronto-centrales et centrales respectivement, mais ne sont pas corrélées, nous avons conclu qu’il est possible 2 qu’elles mesurent des aspects différents du SNM. Le deuxième article avait comme objectif principal de mesurer l’activité du SNM à l’aide du protocole MMN relié à l’action chez 10 enfants présentant un TSA ainsi que chez 12 enfants neurotypiques dans la même tranche d’âge (5-7ans). Chez les enfants TSA, nous avons montré un patron de latence inversée, comparativement aux enfants du groupe contrôle; ils traitaient plus rapidement les sons contrôles que les sons reliés à l’action humaine, alors que la tendance inverse était observée chez les contrôles. De plus, bien que les deux groupes différaient quant aux sons d’action, ils ne différaient pas quant aux sons contrôles. Quant à l’amplitude, les enfants TSA se distinguaient du groupe contrôle par une amplitude restreinte du son d’action provenant de la bouche. Par ailleurs, les mesures neurophysiologiques et neuropsychologiques n’étaient pas corrélées. En sommes, basé sur la prémisse que ce protocole MMN pourrait mesurer l’activité du SNM, cette thèse a comme but d’améliorer les connaissances quant à son utilisation chez l’adulte et l’enfant neurotypique ainsi que chez l’enfant TSA. Celui-ci pourrait ultimement être utilisé comme un biomarqueur potentiel du TSA.
Mirror-neuron system (NMS) has been suggested to underlie action understanding, which is believed to be involved in higher social functions such as empathy and imitation. Numerous studies have also provided indirect evidence supporting the existence of a MNS in the human brain using functional magnetic resonance imaging, transcranial magnetic stimulation, magnetoenceophalography and electroencephalography (EEG). As evidence relating MNS function with social cognition accumulated, its dysfunction was proposed to underlie social impairments in Autism Spectrum Disorder (ASD). Although some studies have reported structural and/or functional data supporting this hypothesis, it remains controversial. Indeed, the techniques used to probe MNS activity often require the participant to understand the task, display sustained attention and present spared visual cognitive functions, which could be altered in ASD population. This, in turn, could partly explain differences in MNS activity found between invididuals with ASD and neurotypical participants. The auditory mismatch negativity (MMN) protocol has recently been proposed as a viable tool to assess MNS activity using action-related sounds. This relatively short oddball paradigm does not require visual, attentional or language skills and can be performed with minimal electrode installation (minimal use of 4 electrodes). This action-related MMN may therefore be well-suited to investigate MNS function in very young children or populations with mental disabilities, such as ASD. The first article of this thesis assessed the convergent validity of the action-related MMN protocol with a mu rhythm suppression paradigm, which is the most commonly used EEG measure of MNS activity. To do so, both protocols were consecutively administered in healthy adults in the same experimental session. While both techniques successfully 4 modulated the fronto-central and central brain regions using action-related stimuli, they did not correlate significantly. This suggests that the two techniques may not probe the same aspects of MNS function. The second article aimed at investigating MNS activity in children with ASD using the action-related MMN protocol. Data were compared to age-matched typically developing children. We show that children with ASD present an opposite pattern to that of control children : whereas MMN latencies are shorter for action-related sounds compared to control sounds in neurotypical children, the opposite pattern is observed in children with ASD. Furthermore, although the two groups present different response patterns with regards to action-related sounds, they repond similarly to control sounds. For amplitude measurements, children with ASD display reduced amplitude to action-related sounds produced by the mouth compared to neurotypical children. In summary, this thesis aimed at determining whether and action-related MMN protocol could be used to measure MNS activity in neurotypical adults and children, as well as in ASD children. The action-related MMN could potentially be used as a biological biomarker of ASD pending further studies.