Thesis (MSc)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Although the neurodevelopmental therapy (NDT) treatment approach is used extensively in the management of children with cerebral palsy, there is currently very little documented research to support its efficacy. The purpose of this study was to evaluate the efficacy of NDT in terms of its effect on motor function in a group of 10 cerebral palsy children. A multiple simple single-subject design was used in which the children each acted as their own controls. A 5 week baseline period, during which no intervention was received by the children, was followed by a 5 week intervention phase during which the children received twice weekly NDT treatment. The children were assessed at the beginning and end of each phase using the Gross Motor Function Measure (GMFM), and an assessment tool, which allowed the establishment of individualised outcome measures, called TELER. The group of children demonstrated no statistically significant gains in motor function on either of the outcome measures during the baseline phase of the study. However during the intervention phase the overall improvements demonstrated by the group on both the GMFM and TELER were statistically significant. Nine out of the ten children achieved greater improvements in their goal total GMFM scores during the intervention phase than during the baseline phase. Similarly all of the children achieved a greater number of clinically significant improvements on the TELER outcome measures. NDT was beneficial and useful in promoting motor function in this group of cerebral palsy children. / AFRIKAANSE OPSOMMING: Alhoewel die Neuro-ontwikkelingsterapie (NOT) behandelingsbenadering wydeverspreid gebraik word in die behandeling van kinders met serebrale verlamming, is daar huidiglik baie min gedokumenteerde navorsing om die effektiwiteit daarvan te staaf. Die doel van hierdie studie was om die effektitiwiteit van NOT te evalueer met betrekking tot die impak daarvan op die motoriese funksie van ‘n groep van 10 kinders met serebrale verlamming. ‘n Veelvuldige eenvoudige enkeling -subjek raamwerk is gebruik waarvolgens die kinders elk as hul eie kontrolegoep ageer het. ‘n 5-weke basislyn fase, waartydens die kinders aan geen intervensies onderwerp is nie, is gevolg deur ‘n 5-weke intervensie fase waartydens die kinders twee keer per week NOT behandeling ontvang het. Die kinders is geevalueer aan die begin en einde van elke fase met die Oorhoofse Motoriese Funksie Maatstaf (OMFM)/Gross Motor Function Measure (GMFM), asook ‘n evalueringsmaatstaf genaamd TELER, wat die bepaling van geindivualiseerde resultate moontlik gemaak het. Die groep kinders het geen statistics bewese vordering in motoriese fiinksies getoon volgens beide die evalueringsmaatstawwe tydens die basislyn fase van die studie nie. Daarteenoor het die groep tydens die intervensie fase oorhoofs gesproke statistics bewese vordering getoon met betrekking tot beide die OMFM en die TELER. Nege uit die 10 kinders het groter vordering getoon met hul totale OMFM resultate tydens die intervensie fase as gedurende die basislyn fase. A1 die kinders het tegelykertyd ‘n groter hoeveelheid substantiewe kliniese verbeterings getoon met betrekking tot hul TELER uitkomste. NOT was voordelig en nuttig in terme van die verbetering van motoriese funksie in die groep van serebraal verlamde kinders.

Bakgrund: Aktivitetsbalans är en subjektiv upplevelse som innefattar rätt mängd och rätt variation mellan aktiviteter. Att ha ett barn med NPF kan ha effekter på hur familjens vardagsrutiner utformas samt påverka föräldrarnas val och planering av aktiviteter. Syfte: Undersöka aktivitetsbalans hos föräldrar till barn med neuropsykiatrisk funktionsnedsättning, NPF, i åldrarna 6–12 år. Metod: En kvantitativ enkätstudie genomfördes. Webbenkäten utformades enligt Occupational Balance Questionnaire (OBQ) och varje fråga på ordinalskalenivå kompletterades med ett fritextsvar. Vid analys av data tillämpades en kvantitativ bearbetning och en kvalitativ innehållsanalys. I studien deltog 194 föräldrar. Resultat: Föräldrarna skattade sin aktivitetsbalans övervägande lågt. Resultatet visade även att det fanns en signifikant skillnad mellan föräldrarnas arbetssituation och antal barn med NPF. Däremot visade resultatet ingen signifikant skillnad om föräldrarna var sammanboende/gifta eller ensamstående. I studiens innehållsanalys identifierades tre kategorier: Omstrukturering av vardagen, Förälderns kontakt med samhällsinsatser och Den förändrade rollen som förälder. Slutsats: Föräldrarna har en genomgående låg aktivitetsbalans. För att bemöta föräldrarnas behov av stöd bör arbetsterapeuter utgå från ett helhetsperspektiv på familjen i arbetet med barn med NPF. / Background: Occupational balance is a subjective experience that includes the right amount and the right variation between activities. Having a child with NDD can have effects on how the family's everyday routines are organized and affect the parents' choice and planning of activities. Aim: Exploring occupational balance in parents to children with neurodevelopmental disorder, NDD, ages 6-12 years. Method: A quantitative survey was conducted. The web survey was designed according to the Occupational Balance Questionnaire (OBQ) and each question at the ordinal scale level was supplemented with a free text response. When analyzing data, a quantitative processing and a qualitative content analysis were applied. The study had 194 parents participating. Result: Parents estimated their occupational balance predominantly low. The result also showed that there was a significant difference between the parents' work situation and the number of children with NDD. However, the result showed no significant difference if the parents were cohabiting / married or single. In the study's content analysis three categories were identified: Restructuring of everyday life, Parent's contact with social support and The changed role as a parent. Conclusion: The parents have a consistently low occupational balance. To address the parents' need for support, occupational therapists should proceed a holistic perspective on the family in the work with children with NDD.

The attempt to identify risk factors or correlates of intraventricular hemorrhage (IVH) has been constrained by conflicting research findings, changing hypotheses about the etiology of IVH, and by the exceedingly complex nature of this neurological disorder. In addition, few studies have investigated the possibility that antenatal factors might predispose the infant to IVH. Thus, research aimed at identifying IVH correlates from all time periods in which stress could occur to the neonate needs to be undertaken. This study was conducted for the purpose of identifying and quantifying correlates of IVH by constructing an interactive statistical model to predict the occurrence, severity, and onset of IVH. The study sample was composed of inborn neonates admitted to the University of Utah Medical Center's Neonatal Intensive Care Unit from July 1985 to June 1987. Ultrasound brain scans were used to assigned 150 infants into two groups of equal numbers: an IVH group and a nonIVH group. Forty-three maternal, 17 obstetric, and 35 neonatal variables were collected from the infants' and infants' mothers' medical records and included demographic, medical, and behavioral data. The mean birthweights and gestational ages for the IVH and non-IVH groups were 1413 g, 29.9 weeks, and 1573 g 31.3 weeks, respectively. Factors found to be associated with IVH were neonatal hypotension, bronchopulmonary dysplasia, lower hematocrit percent, pulmonary interstitial emphysema, severe respiratory distress syndrome, shorter gestational ages, lower 5-minute Apgar score, pneumothorax, shorter umbilical cord lengths, and lower maternal hemoglobin concentrations. No obstetric factors were found to be related to IVH. A second-order, interactive model used to predict IVH occurrence and severity explained 90.9% of the total variability. The attempt to predict the onset time of IVH was unsuccessful. While the condition of the neonate immediately following birth is the best predictor of IVH, maternal or antenatal factors may interact to contribute to the development of this neurological disorder.

Children with alcohol-related neurodevelopmental disorder or attention deficit/hyperactivity disorder differ on neuropsychological tasks and measures of eye movement control. M.Sc. Thesis, Queen’s University, Kingston, Ontario, Canada, January 2010. Background: Alcohol-related neurodevelopmental disorder (ARND) accounts for the majority of diagnoses associated with prenatal alcohol exposure. Unfortunately, ARND frequently poses a significant clinical challenge as these patients lack the visible physical characteristics associated with alcohol teratogenicity. Moreover, the cognitive and behavioural disabilities are complex and overlap with those of attention deficit/hyperactivity disorder (ADHD). Furthermore, co-morbid ADHD is prevalent in children with prenatal alcohol exposure. While early and accurate diagnosis provides the best prognosis for those affected, there is a lack of tools for differential diagnosis between these two disorders. The goal of this study was to test the hypothesis that children with ARND exhibit different performance from children with ADHD on computer-based neuropsychological tests and eye movement tasks. Methods: Our study group was composed of 42 children with ARND and 31 children with ADHD aged 8-15 years, male and female. Children completed four tasks selected from the Cambridge Neuropsychological Test Automated Battery (CANTAB®) that provided measures of attention, planning, strategy and spatial working memory. Subjects also performed pro- and anti-saccade tasks, and eye movements were recorded using a mobile eye-tracking system. Results: Children with ARND demonstrated elevated decision times on a visual matching test of attention and longer response times on a task of spatial working memory, although the two groups had similar errors scores. Also, compared to children with ADHD, children with ARND had greater anticipatory errors in both the pro- and anti-saccade tasks. Conclusion: This study demonstrates that there are measurable differences in executive function and eye movement control between children with ARND or ADHD. Greater deficits in visuospatial processing in ARND may underlie these differences. These findings demonstrate that the neurobehavioural phenotypes of children with ARND or ADHD have distinct features, which may be accounted for by differences in the patterns of brain injury underlying these two disorders. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2010-01-15 15:15:47.738

Being hearing impaired does not only affect a child’s academic performance, but can also influence a child’s overall development and ability to succeed academically. Evidence suggests that the outlay in early childhood has a large impact on a child’s readiness to learn. Neurodevelopmental movement programmes are generally not accepted as evidenced-based practice and their effect on academic performance is often underrated. Movement, however, is regarded by many as essential to learning and there seems to be a positive interchange between the brain and the body. This study reports on the influence of a neurodevelopmental movement programme on the development, behaviour and performance on a neurodevelopmental evaluation scale of four to eight year-old children with hearing impairment children. The study furthermore provides a report of the results of the psychometric assessment in the form of a neurodevelopmental profile for this specific sample. Children were selected from a special needs school in the rural QwaQwa Free State area of South Africa. Two groups of children (an experimental and comparison group) were used in this study, with both groups undergoing a pretest and posttest phase using three test batteries (Griffiths Mental Developmental Scales- Extended Revised, Child Behaviour Checklist, and a neurodevelopmental evaluation scale). The experimental group was subjected to a fourteen-week neurodevelopmental movement programme. The comparison group underwent a placebo intervention. The results indicate that the children in the experimental group showed an improvement in some aspects of specific development following the intervention (locomotor functioning, performance related abilities, and practical reasoning skills). General developmental age showed significant improvement in both the experimental group and the comparison group. No behavioural aspects showed significant improvements following the intervention, whereas some neurodevelopmental aspects, such as the vestibular system (Tandem Walk and One Leg Stand) and the reflex system (TLR – reflex) showed significant improvements. The results of this empirical investigation aid in understanding the impact of movement programmes on a child with hearing disability’s general development and neurodevelopmental development. / Thesis (PhD (Psychology))--North-West University, Potchefstroom Campus, 2013.

Being hearing impaired does not only affect a child’s academic performance, but can also influence a child’s overall development and ability to succeed academically. Evidence suggests that the outlay in early childhood has a large impact on a child’s readiness to learn. Neurodevelopmental movement programmes are generally not accepted as evidenced-based practice and their effect on academic performance is often underrated. Movement, however, is regarded by many as essential to learning and there seems to be a positive interchange between the brain and the body. This study reports on the influence of a neurodevelopmental movement programme on the development, behaviour and performance on a neurodevelopmental evaluation scale of four to eight year-old children with hearing impairment children. The study furthermore provides a report of the results of the psychometric assessment in the form of a neurodevelopmental profile for this specific sample. Children were selected from a special needs school in the rural QwaQwa Free State area of South Africa. Two groups of children (an experimental and comparison group) were used in this study, with both groups undergoing a pretest and posttest phase using three test batteries (Griffiths Mental Developmental Scales- Extended Revised, Child Behaviour Checklist, and a neurodevelopmental evaluation scale). The experimental group was subjected to a fourteen-week neurodevelopmental movement programme. The comparison group underwent a placebo intervention. The results indicate that the children in the experimental group showed an improvement in some aspects of specific development following the intervention (locomotor functioning, performance related abilities, and practical reasoning skills). General developmental age showed significant improvement in both the experimental group and the comparison group. No behavioural aspects showed significant improvements following the intervention, whereas some neurodevelopmental aspects, such as the vestibular system (Tandem Walk and One Leg Stand) and the reflex system (TLR – reflex) showed significant improvements. The results of this empirical investigation aid in understanding the impact of movement programmes on a child with hearing disability’s general development and neurodevelopmental development. / Thesis (PhD (Psychology))--North-West University, Potchefstroom Campus, 2013.

The present study examined social information processing in a sample of teenagers with various comorbid neurodevelopmental disabilities and typically developing controls. Crick and Dodge’s (1996) model of social information processing was used as the theoretical framework for the current study. Specifically, emotion recognition of self and others, attribution biases, and outcome expectations were measured in adolescents with and without a neurodevelopmental disability. Performance on these social measures was compared to caregiver ratings of social skills, and was also compared across diagnostic groups. 52 adolescents with a diagnosis of autism spectrum disorder, attention-deficit/hyperactivity disorder, and/or learning disability participated in the current study, as well as 51 typically developing control participants. Analyses showed that individuals with any neurodevelopmental disability were less accurate at recognizing sadness in others and at identifying their own feelings and emotions. An interaction between participant group and sex was found, such that females with a neurodevelopmental disability were most likely to report feeling badly after acting aggressively and reported that acting aggressively would be difficult, but that they believed aggression would result in a successful social outcome. Males with a neurodevelopmental disability believed the opposite, that acting aggressively would be socially unsuccessful, but that they would feel good about themselves and that acting aggressively would be easy. Additionally, caregiver ratings of social skills were positively related to participants’ abilities to identify their own feelings, and negatively related to participants’ ratings of the ease of aggressive social encounters. Interestingly, although diagnostic group differences were predicted on these measures, few were found. This research has implications for clinical and educational work with individuals with neurodevelopmental disabilities. First, individuals with any neurodevelopmental disability appeared to have similar social impairments, suggesting that deficits may be related to the presence of any diagnosis, rather than one in particular. Analysis of the steps of social information processing in this population is useful for teachers and clinicians when trying to plan social skills interventions.

Chromatin remodeling complexes modulate DNA accessibility permitting neuronal progenitor cells to proliferate and differentiate to form the mammalian neocortex. In the case of BPTF (Bromodomain PHD transcription Factor), the major subunit of a chromatin remodelling complex called NURF (Nucleosome Remodelling Factor), mutations leading to its haploinsufficiency have been linked to cause a recently annotated human neurodevelopmental disorder called NEDDFL (Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies). Patients with this syndrome are mainly characterized with microcephaly and intellectual disability. We conditionally knockout (cKO) the Bptf gene during neocortical neurogenesis to analyze its role during embryonic and postnatal brain development. The Bptf cKO animals reveal significant forebrain hypoplasia. During cortical neurogenesis, the Bptf cKO mice show a reduction in intermediate neuronal progenitor (INP) cells, an increase in apoptosis as well as a prolonged cell cycle within proliferating progenitors. Similarly, the postmitotic pyramidal neurons of the Bptf cKO mice contained lower levels of Ctip2 and Foxp1. Lastly, our RNA-seq analysis delineated gene pathways deregulated by Bptf removal, which are involved in neurogenesis and neuronal differentiation. Our results indicate that Bptf is critical for murine telencephalon neurogenesis. The hypoplasia demonstrated in the mouse model can resemble the microcephaly displayed by the human NEDDFL patients, highlighting the relevance of chromatin remodelling complexes during intricate neural developmental processes.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22690号 / 医博第4634号 / 新制||医||1045(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 古川 壽亮, 教授 滝田 順子, 教授 万代 昌紀 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

BACKGROUND: It has long been accepted that the environment we experience can impact our well-being; throughout recorded history, the greatest prevalence and severity of disease has been experienced by marginalized and underserved populations. However, the translation of such nontangible influences into biological changes in our health has been elusive until the recent advent of epigenetic studies. Modifications outside of the genome play a critical role in regulating transcription as well as subsequent gene expression without altering DNA sequencing by controlling the accessibility of the DNA for interaction with key initiation proteins and enzymes. These modifications, which include DNA methylation, histone acetylation, and small noncoding microRNA regulation, have increasingly been found to have a fluid, adaptive response to experiences throughout life. Based on the literature supporting societal stressors negatively impacting neurologic outcome, as well as elucidating an association between epigenetic changes and adverse neurologic outcome, we hypothesize that alterations in CpG methylation sites associated with socioeconomic adversity will also be correlated with the incidence of Neurodevelopmental Disorders. METHODS: 889 of the 1,506 neonates initially recruited from 14 medical centers throughout the United States at their time of birth qualified to participate in this study. Placental samples were taken immediately following delivery and neonatal blood samples were taken within the first month of life. Children that survived were followed at 2 years old and 10 years old to evaluate for the presence of four possible Neurodevelopmental Disorders: cognitive impairment, Cerebral Palsy, Autism Spectrum Disorder, and epilepsy. Taking this data as well as demographic information into consideration, the entire cohort included in this study was first evaluated for aberrant methylation levels at 33 CpG sites previously associated with socioeconomic adversity to analyze the degree of significant correlation between altered methylation status and Neurodevelopmental Disorder prevalence. A secondary Epigenome-Wide Association Study was conducted for each of our 889 participants to pinpoint significant changes in CpG methylation in order to evaluate the relationship between altered methylation of particular genes and incidence of Neurodevelopmental Disorders. Taking the previous finding that cognitive impairment imposes a greater burden on both the individual and society than non-cognitive impairment into consideration, both analyses were categorized based on this measure of impairment severity: No Impairment, Non-Cognitive Impairment (diagnosed with Cerebral Palsy, Autism Spectrum Disorder, and/or epilepsy without cognitive deficit), and Cognitive Impairment (cognitive deficit with or without other neurodevelopmental disorders present). RESULTS: Primary analysis of the 33 CpG sites previously associated with socioeconomic adversity did not reveal any significant associations with Non-Cognitive or Cognitive Impairment. However, cg15519318 and cg10613063 (located in the PCCB gene) were marginally associated with Non-Cognitive Impairment while cg02765535 (located in the NTN4 gene) was marginally associated with Cognitive Impairment. Secondary analysis of the entire epigenome found 4 CpG sites significantly associated with Non-Cognitive Impairment (cg07322235, cg13592565, cg13723879, and cg24387818) as well as 4 CpG sites significantly associated with Cognitive Impairment (cg23081580, cg14134658, cg00762003, and cg08546514). DISCUSSION: We were not able to define a significant relationship between the CpG methylation sites related to socioeconomic adversity and adverse neurodevelopmental outcomes. This could stem from several causes, including insufficient power as well as limiting our evaluation of the extensive list of environmental influences to the four measures of societal stress focused on in this study (low educational attainment, single relationship status, public health insurance, and receiving supplemental nutrition assistance). Investigating the epigenome for differential methylation that was significantly associated with the incidence of Neurodevelopmental Disorders identified CpGs associated with several important genes, including genes coding for Neuregulin-3 (NRG3) and Premature Ovarian Failure Actin Binding Protein 1B (POF1B) region with Non-Cognitive Impairment as well as genes coding for Six-Transmembrane Epithelial Antigen of Prostate 2 Metalloreductase (STEAP2), Ly1 Antibody Reactive (LYAR), 1-Acylglycerol-3-Phosphate O-Acyltransferase 3 (AGPAT3), and Ninein-like protein (NINL) with Cognitive Impairment.