A criança com transtorno do espectro autista (TEA) e o professor: uma proposta de intervenção baseada na experiência de aprendizagem mediada (EAM)

The presence of students with Autism Spectrum Disorder (ASD) in regular schools has increased and with it, the need to develop interventional strategies that enhance their learning. One of the tools that can facilitate this process is Mediated Learning, defined as an interaction style where the teacher selects, modifies, enhances, and interprets environmental stimuli in order to promote student learning. In recent years several studies have used the Mediated Learning Experience Scale (MLE; Lidz, 1991) as a tool to assess the mediator behavior. These studies have suggested that the EAM Scale can provide important guidelines for planning educational interventions, particularly those involving students with special needs. In order to extend these findings, this study aimed to evaluate the effects of an intervention based on the Mediated Learning Experience on social / academic skills of a child with ASD, enrolled in the 4th grade of a regular elementary school. This collaborative study was held in the city of Parnamirim, state of Rio Grande do Norte, in 2014. A 9-year old boy with ASD and his teacher participated in the study. The research used a quasi-experimental A-B design (baseline and treatment) to evaluate the teacher's behavior. Qualitative procedures were also used to analyze the dyad´s responses. Teacher and student behaviors were observed in three school routines during baseline. Based on the results of this phase, a training program was designed for the teacher. Dyad behavior was analyzed again after training in the same routines. The results of this phase showed qualitative and quantitative changes in levels of teacher mediation. Additionally, data indicated that the child enhanced his social and academic skills during the intervention.

Caring for the autistic child: a resource manual for health care providers

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that affects approximately 1 in 68 children (CDC, 2014). Comorbid medical conditions and psychiatric disorders increase the likelihood that these children will require acute care services more often than their neurotypical peers (McDermott, Zhou, & Mann, 2008; Simonoff et al., 2008). The evidence suggests that most health care providers are unprepared for the complexity of the interactions with these children during an acute care episode (McGongile, Migyanka, et al., 2014; McGongile, Venkat, et al., 2014; Muskat et al., 2015). Currently, there are no formalized training programs for acute health care workers in Regina Qu’Appelle Health Region (RQHR). Purpose: The purpose of this practicum project was to use the best available evidence on the care needs of children with Autism Spectrum Disorder (ASD) and effective interaction strategies to guide development of a resource manual for acute care health workers, especially registered nurses (RNs), working in the RQHR. Methods: Initial steps involved planning for and conducting a needs assessment. The resulting database emerged from a critical review of relevant literature, an environmental scan of resources within RQHR, and informal consultations with parents and caregivers of children with ASD, acute care nurses and nurse managers and experts in the field of ASD. Following analysis and collation of all data into major themes, a draft blueprint guided development of a resource manual for health care providers interacting with and providing care to children with ASD. Results: The needs assessment data informed development of an educational resource manual appropriate for all health care providers who encounter children with ASD and their parents and/or caregivers within acute care environments. The Caring for the Autistic Child: A Guide for Health Care Providers in Acute Care provides insightful information on the disorder and associated comorbid conditions, as well as effective approaches to care delivery with this priority population. Implementation and evaluation plans will guide distribution of the resource manual within the RQHR. Conclusion: The sequential and interdependent steps taken in this practicum project led to the development of a resource manual comprised of simple, easy to implement strategies capable of assisting nurses and all healthcare providers in providing care tailored to the autistic child’s unique needs and challenges.

Pediatric CNS pathophysiology

Research in pediatric central nervous system pathophysiology is focused around three primary goals: identification of neurodevelopmental disorders, understanding the differences in brain development which underlie these disorders, and improving treatment for these young children. Autism spectrum disorders (ASDs) are a complex set of disorders which are characterized by difficulties in language and social interactions. These behavioral measures are highly variable and a number of underlying causes can generate similar behavioral effects. Therefore, it is important to identify neurophysiological markers to better identify and characterize these disorders. Recent ASD findings using MEG show atypical latency and amplitude responses and poor cortical connectivity in children with ASDs across the cognitive spectrum from basic auditory processing, multisensory integration, to face and semantic processing. These results further support the view that ASDs are a complex neurologically-based disorder. On the other hand, the cause of Down syndrome is well understood as originating from a partial or full replication of chromosome 21. However, the cognitive and neurological consequences of this chromosomal abnormality are not yet well understood. Using a simple observation and motor execution task, poor functional connectivity in sensory-motor areas, particularly in the gamma band range, has been identified in children with Down syndrome and is consistent with behavioral deficits in the sensory-motor realm. Additional studies are needed to better understand whether targeted identification of these abnormalities can facilitate treatment in this disorder. Finally, while epilepsy can be reliably diagnosed, seizure control is still limited in many cases where the seizure onset zone is not readily apparent. Advances in pre-surgical evaluation and intra-operative co-registration will be described. These studies describing pediatric CNS pathophysiology will be discussed. © Springer-Verlag 2010.

A Qualitative Study of Contextual Factors’ Impact on the Adaptation of a Caregiver-mediated Early Autism Intervention in South Africa

Background: Autism Spectrum Disorder (ASD) is a major global health challenge as the majority of individuals with ASD live in low- and middle-income countries (LMICs) and receive little to no services or support from health or social care systems. Despite this global crisis, the development and validation of ASD interventions has almost exclusively occurred in high-income countries, leaving many unanswered questions regarding what contextual factors would need to be considered to ensure the effectiveness of interventions in LMICs. This study sought to conduct explorative research on the contextual adaptation of a caregiver-mediated early ASD intervention for use in a low-resource setting in South Africa.

Methods: Participants included 22 caregivers of children with autism, including mothers (n=16), fathers (n=4), and grandmothers (n=2). Four focus groups discussions were conducted in Cape Town, South Africa with caregivers and lasted between 1.5-3.5 hours in length. Data was recorded, translated, and transcribed by research personnel. Data was then coded for emerging themes and analyzed using the NVivo qualitative data analysis software package.

Results: Nine contextual factors were reported to be important for the adaptation process including culture, language, location of treatment, cost of treatment, type of service provider, familial needs, length of treatment, support, and parenting practices. One contextual factor, evidence-based treatment, was reported to be both important and not important for adaptation by caregivers. The contextual factor of stigma was identified as an emerging theme and a specifically relevant challenge when developing an ASD intervention for use in a South African context.

Conclusions: Eleven contextual factors were discussed in detail by caregivers and examples were given regarding the challenges, sources, and preferences related to the contextual adaptation of a parent-mediated early ASD intervention in South Africa. Caregivers reported a preference for an affordable, in-home, individualized early ASD intervention, where they have an active voice in shaping treatment goals. Distrust of community-based nurses and health workers to deliver an early ASD intervention and challenges associated with ASD-based stigma were two unanticipated findings from this data set. Implications for practice and further research are discussed.

The effects of aging on the BTBR mouse model of autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental disorder characterized by alterations in social functioning, communicative abilities, and engagement in repetitive or restrictive behaviors. The process of aging in individuals with autism and related neurodevelopmental disorders is not well understood, despite the fact that the number of individuals with ASD aged 65 and older is projected to increase by over half a million individuals in the next 20 years. To elucidate the effects of aging in the context of a modified central nervous system, we investigated the effects of age on the BTBR T + tf/j mouse, a well characterized and widely used mouse model that displays an ASD-like phenotype. We found that a reduction in social behavior persists into old age in male BTBR T + tf/j mice. We employed quantitative proteomics to discover potential alterations in signaling systems that could regulate aging in the BTBR mice. Unbiased proteomic analysis of hippocampal and cortical tissue of BTBR mice compared to age-matched wild-type controls revealed a significant decrease in brain derived neurotrophic factor and significant increases in multiple synaptic markers (spinophilin, Synapsin I, PSD 95, NeuN), as well as distinct changes in functional pathways related to these proteins, including "Neural synaptic plasticity regulation" and "Neurotransmitter secretion regulation." Taken together, these results contribute to our understanding of the effects of aging on an ASD-like mouse model in regards to both behavior and protein alterations, though additional studies are needed to fully understand the complex interplay underlying aging in mouse models displaying an ASD-like phenotype.

Hippocampal Transcriptomic and Proteomic Alterations in the BTBR Mouse Model of Autism Spectrum Disorder.

Autism spectrum disorders (ASD) are complex heterogeneous neurodevelopmental disorders of an unclear etiology, and no cure currently exists. Prior studies have demonstrated that the black and tan, brachyury (BTBR) T+ Itpr3tf/J mouse strain displays a behavioral phenotype with ASD-like features. BTBR T+ Itpr3tf/J mice (referred to simply as BTBR) display deficits in social functioning, lack of communication ability, and engagement in stereotyped behavior. Despite extensive behavioral phenotypic characterization, little is known about the genes and proteins responsible for the presentation of the ASD-like phenotype in the BTBR mouse model. In this study, we employed bioinformatics techniques to gain a wide-scale understanding of the transcriptomic and proteomic changes associated with the ASD-like phenotype in BTBR mice. We found a number of genes and proteins to be significantly altered in BTBR mice compared to C57BL/6J (B6) control mice controls such as BDNF, Shank3, and ERK1, which are highly relevant to prior investigations of ASD. Furthermore, we identified distinct functional pathways altered in BTBR mice compared to B6 controls that have been previously shown to be altered in both mouse models of ASD, some human clinical populations, and have been suggested as a possible etiological mechanism of ASD, including "axon guidance" and "regulation of actin cytoskeleton." In addition, our wide-scale bioinformatics approach also discovered several previously unidentified genes and proteins associated with the ASD phenotype in BTBR mice, such as Caskin1, suggesting that bioinformatics could be an avenue by which novel therapeutic targets for ASD are uncovered. As a result, we believe that informed use of synergistic bioinformatics applications represents an invaluable tool for elucidating the etiology of complex disorders like ASD.

Investigating the developmental and behavioral consequences of maternal immune activation on affected offspring

Maternal infection during pregnancy increases the risk of several neuropsychiatric disorders later in life, many of which have a component of dopaminergic (DA) dysfunction, including schizophrenia, autism spectrum disorders (ASD), and attention deficit hyperactivity disorder (ADHD). The majority of DA neurons are found in the adult midbrain; as such the midbrain is a key region of interest regarding these disorders. The literature is conflicting regarding the behavioral alterations following maternal immune activation (MIA) exposure, and the cellular and molecular consequences of MIA on the developing midbrain remain to be fully elucidated. Thus, this thesis aimed to establish the consequences of acute and mild MIA on offspring dopamine-related behaviors, as well as the associated cellular and molecular disturbances of MIA on offspring midbrains. We utilized a rat model of MIA using low dose (50μg/kg, I.P.) of LPS administered at different gestational ages. Our first study indicated that MIA at later gestational ages significantly increased pro-inflammatory IL-1β expression, and reduced HSD11B2 expression in the placenta, which is an important regulator of fetal development. In utero LPS exposure at later gestational ages also impaired the growth of neurons from affected offspring. This study identified key gestational stages during which MIA resulted in differential effects. We utilized these time points in subsequent studies, the next of which investigated neurobehavioral outcomes following MIA. Our results from that study showed that motor differences occurred in juvenile offspring following MIA at E16 only, and these differences were compensated for in adolescence. Then, there was a decline in motor behavior capabilities in adulthood, again only for animals exposed to MIA on E16 (and not E12). Furthermore, our results also demonstrated adolescent and adult offspring that were exposed to MIA at E12 had diminished responses to amphetamine in reward seeking behaviors. In our final study, we aimed to investigate the molecular and cellular changes following MIA which might explain these behavioral alterations. This final study showed a differential inflammatory response in fetal midbrains depending on gestational age of exposure as well as differential developmental alterations. For example, LPS exposure at E16 resulted in decreased VM neurosphere size after 7DIV and this was associated with an increased susceptibility to neurotoxic effects of pro-inflammatory cytokines for VM neurospheres and VM DA neurons treated in culture. In utero LPS exposure at E16 also reduced DA neuron count of fetal VM, measured by TH staining. However, there were no differences in DA neuron number in juvenile, adolescent, or adult offspring. Similarly, LPS exposure did not alter cell number or morphology of glial cells in the midbrains of affected offspring. In conclusion, this thesis indicated later rat pregnancy (E16) as vulnerable time for MIA to affect the development of the nigrostriatal pathway and subsequent behavioral outcomes, possibly implicating a role for MIA in increased risk for disorders associated with motor behavior, like PD. These effects may be mediated through alterations in the placenta and altered inflammatory mediators in the offspring brain. This thesis has also shown that MIA in earlier rat pregnancy (E12) results in altered mesocorticolimbic function, and in particular MIA on E12 resulted in a differential response to amphetamine in affected offspring, which may implicate a role for MIA in increasing the risk for disorders associated with this pathway, including drug tolerance and addiction.

Neural mechanisms of negative reinforcement in children and adolescents with autism spectrum disorders.

BACKGROUND: Previous research has found accumulating evidence for atypical reward processing in autism spectrum disorders (ASD), particularly in the context of social rewards. Yet, this line of research has focused largely on positive social reinforcement, while little is known about the processing of negative reinforcement in individuals with ASD. METHODS: The present study examined neural responses to social negative reinforcement (a face displaying negative affect) and non-social negative reinforcement (monetary loss) in children with ASD relative to typically developing children, using functional magnetic resonance imaging (fMRI). RESULTS: We found that children with ASD demonstrated hypoactivation of the right caudate nucleus while anticipating non-social negative reinforcement and hypoactivation of a network of frontostriatal regions (including the nucleus accumbens, caudate nucleus, and putamen) while anticipating social negative reinforcement. In addition, activation of the right caudate nucleus during non-social negative reinforcement was associated with individual differences in social motivation. CONCLUSIONS: These results suggest that atypical responding to negative reinforcement in children with ASD may contribute to social motivational deficits in this population.

Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards.

BACKGROUND: There has been significant progress in identifying genes that confer risk for autism spectrum disorders (ASDs). However, the heterogeneity of symptom presentation in ASDs impedes the detection of ASD risk genes. One approach to understanding genetic influences on ASD symptom expression is to evaluate relations between variants of ASD candidate genes and neural endophenotypes in unaffected samples. Allelic variations in the oxytocin receptor (OXTR) gene confer small but significant risk for ASDs for which the underlying mechanisms may involve associations between variability in oxytocin signaling pathways and neural response to rewards. The purpose of this preliminary study was to investigate the influence of allelic variability in the OXTR gene on neural responses to monetary rewards in healthy adults using functional magnetic resonance imaging (fMRI). METHODS: The moderating effects of three single nucleotide polymorphisms (SNPs) (rs1042778, rs2268493 and rs237887) of the OXTR gene on mesolimbic responses to rewards were evaluated using a monetary incentive delay fMRI task. RESULTS: T homozygotes of the rs2268493 SNP demonstrated relatively decreased activation in mesolimbic reward circuitry (including the nucleus accumbens, amygdala, insula, thalamus and prefrontal cortical regions) during the anticipation of rewards but not during the outcome phase of the task. Allelic variation of the rs1042778 and rs237887 SNPs did not moderate mesolimbic activation during either reward anticipation or outcomes. CONCLUSIONS: This preliminary study suggests that the OXTR SNP rs2268493, which has been previously identified as an ASD risk gene, moderates mesolimbic responses during reward anticipation. Given previous findings of decreased mesolimbic activation during reward anticipation in ASD, the present results suggest that OXTR may confer ASD risk via influences on the neural systems that support reward anticipation.

Adults with autism spectrum disorders exhibit decreased sensitivity to reward parameters when making effort-based decisions.

BACKGROUND: Efficient effort expenditure to obtain rewards is critical for optimal goal-directed behavior and learning. Clinical observation suggests that individuals with autism spectrum disorders (ASD) may show dysregulated reward-based effort expenditure, but no behavioral study to date has assessed effort-based decision-making in ASD. METHODS: The current study compared a group of adults with ASD to a group of typically developing adults on the Effort Expenditure for Rewards Task (EEfRT), a behavioral measure of effort-based decision-making. In this task, participants were provided with the probability of receiving a monetary reward on a particular trial and asked to choose between either an "easy task" (less motoric effort) for a small, stable reward or a "hard task" (greater motoric effort) for a variable but consistently larger reward. RESULTS: Participants with ASD chose the hard task more frequently than did the control group, yet were less influenced by differences in reward value and probability than the control group. Additionally, effort-based decision-making was related to repetitive behavior symptoms across both groups. CONCLUSIONS: These results suggest that individuals with ASD may be more willing to expend effort to obtain a monetary reward regardless of the reward contingencies. More broadly, results suggest that behavioral choices may be less influenced by information about reward contingencies in individuals with ASD. This atypical pattern of effort-based decision-making may be relevant for understanding the heightened reward motivation for circumscribed interests in ASD.

Obstetric mode of delivery and child psychological development

Background/aims: Objective of the current thesis is to investigate the potential impact of birth by Caesarean section (CS) on child psychological development, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), behavioural difficulties and school performance. Structure/methods: Published literature to date on birth by CS, ASD and ADHD was reviewed (Chapter 2). Data from the UK Millennium Cohort Study (MCS) were analysed to determine the association between CS and ASD, ADHD and parent-reported behavioural difficulties (Chapter 3). The Swedish National Registers were used to further assess the association with ASD, ADHD and school performance (Chapters 4-6). Results: In the review, children born by CS were 23% more likely to be diagnosed with ASD after controlling for potential confounders. Only two studies reported adjusted estimates on the association between birth by CS and ADHD, results were conflicting and limited. CS was not associated with ASD, ADHD or behavioural difficulties in the UK MCS. In the Swedish National Registers, children born by CS were more likely to be diagnosed with ASD or ADHD. The association with elective CS did not persist when compared amongst siblings. There was little evidence of an association between birth by elective CS and poor school performance. Children born by elective CS had slight reduction in school performance. Conclusions: The lack of association with the elective CS in the sibling design studies indicates that the association in the population is most probably due to confounding. A small but significant association was found between birth by CS and school performance. However, the effect may have been due to residual confounding or confounding by indication and should be interpreted with caution. The overall conclusion is that birth by CS does not appear to have a causal relationship with the aspects of child psychological development investigated.

Le décours temporel de l'utilisation des fréquences spatiales dans les troubles du spectre autistique

Notre système visuel extrait d'ordinaire l'information en basses fréquences spatiales (FS) avant celles en hautes FS. L'information globale extraite tôt peut ainsi activer des hypothèses sur l'identité de l'objet et guider l'extraction d'information plus fine spécifique par la suite. Dans les troubles du spectre autistique (TSA), toutefois, la perception des FS est atypique. De plus, la perception des individus atteints de TSA semble être moins influencée par leurs a priori et connaissances antérieures. Dans l'étude décrite dans le corps de ce mémoire, nous avions pour but de vérifier si l'a priori de traiter l'information des basses aux hautes FS était présent chez les individus atteints de TSA. Nous avons comparé le décours temporel de l'utilisation des FS chez des sujets neurotypiques et atteints de TSA en échantillonnant aléatoirement et exhaustivement l'espace temps x FS. Les sujets neurotypiques extrayaient les basses FS avant les plus hautes: nous avons ainsi pu répliquer le résultat de plusieurs études antérieures, tout en le caractérisant avec plus de précision que jamais auparavant. Les sujets atteints de TSA, quant à eux, extrayaient toutes les FS utiles, basses et hautes, dès le début, indiquant qu'ils ne possédaient pas l'a priori présent chez les neurotypiques. Il semblerait ainsi que les individus atteints de TSA extraient les FS de manière purement ascendante, l'extraction n'étant pas guidée par l'activation d'hypothèses.

L’environnement intérieur et l’autisme : un Centre de jour pour adultes

Ce mémoire présente et discute d’une problématique importante qui s’inscrit dans un contexte actuel, autant sur le plan international que local, puisqu’elle touche 1 enfant sur 68 (CDC, 2010). On parle ici du trouble du spectre de l’autisme (TSA). Plus spécifiquement, cette recherche se concentre sur les jeunes adultes autistes, qui du jour au lendemain, se retrouvent face à une interruption de services. Elle suggère qu’une adaptation adéquate de l’environnement soit davantage explorée en vue d’offrir des centres de jour adaptés à cette clientèle. La question de recherche est la suivante : Quels sont les éléments du design intérieur qui peuvent améliorer la qualité de vie des adultes autistes? Il est essentiel de s’y attarder, puisque les personnes TSA sont entre autres caractérisées par leur hypersensibilité et leur hyposensibilité face à l’environnement. Bien que le sujet de l’autisme soit richement documenté par le domaine des sciences médicales, il est apparu qu’il l’est moins par celui de l’aménagement. La stratégie méthodologique de cette recherche repose sur des analyses de précédents, des observations participantes ainsi que la tenue d’entretiens semi-dirigés auprès de parents d’enfants autistes. Cette étude vise simultanément l’amélioration de la compréhension de la pratique émergente du design comme moyen d’intervention ainsi que l’identification des facteurs (éclairages, couleurs, matériaux, division de l’espace, etc.) pouvant améliorer le bien-être des adultes autistes. Sur la base des données collectées, il a été remarqué qu’effectivement, plusieurs moyens peuvent être entrepris pour concevoir des environnements améliorant le bien-être de ces adultes. Les résultats extraits du terrain mènent à des propositions d’aménagement claires : rendre l’abstrait le plus concret possible, aménager des zones de retrait social, offrir une variété d’ambiances, et finalement, offrir un encadrement sécuritaire.