Effects of Training and E-Mail Feedback on Behavior Therapists' Use of Instructive Feedback

Thesis (Ph.D.)--University of Washington, 2016-06

Singing About Expected Behaviors for Group Instruction

The proposed study will be displayed on a poster board that contains the research methods and results due to the use of music intervention with students with ASD.

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.

The Role of TET Proteins in the Epigenetic Regulation of Neural Gene Expression and Behavior

Understanding how genes affect behavior is critical to develop precise therapies for human behavioral disorders. The ability to investigate the relationship between genes and behavior has been greatly advanced over the last few decades due to progress in gene-targeting technology. Recently, the Tet gene family was discovered and implicated in epigenetic modification of DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). 5hmC and its catalysts, the TET proteins, are highly abundant in the postnatal brain but with unclear functions. To investigate their neural functions, we generated new lines of Tet1 and Tet3 mutant mice using a gene targeting approach. We designed both mutations to cause a frameshift by deleting the largest coding exon of Tet1 (Tet1Δe4) and the catalytic domain of Tet3 (Tet3Δe7-9). As Tet1 is also highly expressed in embryonic stem cells (ESCs), we generated Tet1 homozygous deleted ESCs through sequential targeting to compare the function of Tet1 in the brain to its role in ESCs. To test our hypothesis that TET proteins epigenetically regulate transcription of key neural genes important for normal brain function, we examined transcriptional and epigenetic differences in the Tet1Δe4 mouse brain. The oxytocin receptor (OXTR), a neural gene implicated in social behaviors, is suggested to be epigenetically regulated by an unknown mechanism. Interestingly, several human studies have found associations between OXTR DNA hypermethylation and a wide spectrum of behavioral traits and neuropsychiatric disorders including autism spectrum disorders. Here we report the first evidence for an epigenetic mechanism of Oxtr transcription as expression of Oxtr is reduced in the brains of Tet1Δe4-/- mice. Likewise, the CpG island overlapping the promoter of Oxtr is hypermethylated during early embryonic development and persists into adulthood. We also discovered altered histone modifications at the hypermethylated regions, indicating the loss of TET1 has broad effects on the chromatin structure at Oxtr. Unexpectedly, we discovered an array of novel mRNA isoforms of Oxtr that are selectively reduced in Tet1Δe4-/- mice. Additionally, Tet1Δe4-/- mice display increased agonistic behaviors and impaired maternal care and short-term memory. Our findings support a novel role for TET1 in regulating Oxtr expression by preventing DNA hypermethylation and implicate TET1 in social behaviors, offering novel insight into Oxtr epigenetic regulation and its role in neuropsychiatric disorders.

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.

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.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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.

Executief Functioneren en Copingstijl van Normaal- en Hogerbegaafde Volwassenen met een Autismespectrumstoornis

Ten eerste wordt nagegaan of volwassenen met ASS beperkt zijn in hun executieve functies Cognitieve Flexibiliteit, Zelfevaluatie, Initiatief nemen, Werkgeheugen en Plannen en Organiseren. Ten tweede wordt onderzocht of beperkingen in het executief functioneren (EF) negatief samenhangen met het gebruik van een probleemgerichte copingstijl (H.1), positief met het gebruik van een emotiegerichte copingstijl (H.2) en positief met gebruik van een passief reactiepatroon (H.3). Daarnaast wordt exploratief onderzocht of leeftijd een modererende invloed heeft op bovengenoemde drie relaties. Volwassenen met een gemiddeld of hoger intelligentieniveau bij wie ASS is vastgesteld hebben een zelfrapportagevragenlijst ingevuld (survey met één meetmoment). Circa 27% van de data is afkomstig uit GGZ-cliëntendossiers, de overige data zijn afkomstig via respondentenwerving (53% non-respons op 182 uitgezette vragenlijsten). Naast enkele biografische gegevens werd gebruik gemaakt van de Brief-A, die beperkingen in het executief functioneren meet en van de Utrechtse Copinglijst (UCL), die het gebruik van zeven copingmechanismen in kaart brengt. Conform H.1 blijken beperkingen in het EF (met name Cognitieve Flexibiliteit) gerelateerd te zijn aan een geringer gebruik van probleemgerichte coping. H.2 wordt niet ondersteund door de bevindingen, aangezien resultaten erop wijzen dat EF geen variantie verklaart in het gebruik van emotiegerichte coping. EF doet dit wel ten aanzien van een passieve reactie, conform H.3. Met name Cognitieve Flexibiliteit en Werkgeheugen spelen hier een betekenisvolle rol. Er is geen significante ondersteuning voor een modererende rol van leeftijd in de drie verbanden.

Characteristics of change triggered temper outbursts in children with PWS and ASD and how these may impact on the efficacy of behavioural intervention strategies.

Background
Temper outbursts are prevalent in individuals with PWS and are often triggered by unexpected changes to routines or plans. However, such outbursts are also common in individuals with several other neurodevelopmental disorders, including those with a diagnosis of autism spectrum disorder (ASD). We compared the profile of temper outbursts in children with PWS to that in children with ASD. We examined whether differences in the temper outburst profile predicted differences in the outcomes of two caregiver led intervention strategies aiming to reduce change triggered outbursts.
Methods and results
Thirteen 7-15 year olds with PWS – taking part in a larger study involving 60 children evidencing temper outbursts following changes – were individually matched for age to children with ASD (mean ages: 10.70; 10.76 yrs). Caregivers participated in a structured/semi-structured interview on children's outbursts; completed a web-based outburst diary over a 6 month baseline; and are currently using either a change signalling intervention to reliably warn children of forthcoming changes; or a planning ahead intervention to reduce children's exposure to unexpected changes.
As reported at interview, on average, children with PWS showed more frequent temper outbursts than those with ASD (closer to daily vs. weekly). For seven children with PWS and six with ASD, 60% or more of their temper outbursts were reported to be triggered by changes. Whilst outbursts had similar durations when triggered by changes or by other events in children with PWS; change triggered outbursts in children with ASD were generally shorter. The most commonly reported outburst components in children with PWS included indicators of heightened emotional arousal but this was not the case for children with ASD. Data on behavioural change associated with each of the intervention strategies will be discussed.
Conclusions
Change triggered temper outbursts can be a problem for children PWS and ASD, however subtle differences appear to exist in the profile of these outbursts. Some of these differences may be relevant for the expected efficacy of different behavioural intervention strategies that target outbursts.
Summary
Temper outbursts (tantrums) were compared in children with PWS or autism spectrum disorder before and during use of one of two helping strategies. Helping strategies were led by caregivers and aimed to reduce outbursts that follow changes to routines or plans by making such changes more predictable, or by reducing the quantity of changes. Characteristics of outbursts may be important to help us predict which helping strategies may be most effective.

Planning for the Unseen and Unheard: the child with ASD

“Children are a kind of indicator species.
If we can build a successful city for children,
we will have a successful city for all people.”

Enrique Peñalosa (former mayor of Bogotá)

Should society be judged by how they treat their weakest members, the concept of the Child Friendly City offers more than ample scope for critiquing the genuine health and inclusivity of our urban environments. If we accept childhood as a crucial human development phase that demands inclusive and welcoming places for play, exploration and growth, many cities today are becoming increasingly barren habitats, arguably full of nothing but empty childhoods. (Raven-Ellison 2015) With children today less able to roam and explore our streets than those of yesteryear, (Bird 2007) the situation is now developing where our young are becoming increasingly socially and spatially excluded from our supposedly shared Built Environment. That progressively restrictive urban realm is particularly pronounced for those with Autism Spectrum Disorder, for whom our cities can be disorientating, difficult and even frightening places.

As a profession we have a responsibility to provide inclusive built environments that do not preclude the presence of the most vulnerable in society, among them those with ASD. Accordingly this paper seeks to introduce emerging research into the current challenges facing these young urban stakeholders before discussing how planning processes and design interventions might make our cities more accessible to those with ASD.

References:

Bird, W. (2007) Natural Thinking, Sandy, Bedfordshire: RSPB.

Raven-Ellison, D. (2015) “London’s Empty Childhoods” in London Essays – Green Spaces, Issue 3 – found at: http://essays.centreforlondon.org/issues/green/londons-empty-childhoods/ accessed 9th May 2016.