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Item Aberrant Neural Activity in Cortico-Striatal-Limbic Circuitry Underlies Behavioral Deficits in a Mouse Model of Neurofibromatosis Type 1(2022-05) Drozd, Hayley Paulina; McKinzie, David L.; Clapp, D. Wade; Shekhar, Anantha; Lukkes, Jodi L.; Lapish, Christopher L.; Block, Michelle L.Nearly 18% of children are diagnosed with developmental disabilities. Autism spectrum disorders (ASDs) and attention deficit hyperactivity disorder (ADHD) are increasingly common developmental disabilities, but neither is well understood. ADHD and ASD are both prevalent in the genetic disorder Neurofibromatosis type 1 (NF1) which impairs the Ras-MAPK/ERK pathway through mutation of the neurofibromin gene (NF1+/−). More broadly, syndromic forms of developmental disorders are often caused by mutations of proteins in pathways interconnected with Ras including TSC1/2, FMR1, and SynGAP. Of NF1 patients, around 30-50% are diagnosed with ASDs and more than 60% with ADHD. These studies are the first to show that male mice haploinsufficient for the Nf1 gene (Nf1+/−) exhibit deficits in behavioral inhibition in multiple contexts, a key feature of ADHD. They exhibit hyperactivity and impulsivity in an open field, delay discounting task, and cliff avoidance reaction test, rescuable through treatment with the clinically effective ADHD drug, guanfacine (α2A adrenergic receptor agonist). Previous experiments in our lab identified social deficits including deficits in consolidation of social memory. Using optogenetics and awake behaving electrode recordings, we explored the role of the cortico-striatal-limbic circuitry in impulsivity and in social deficits in male Nf1+/− mice. Manipulation of the prefrontal cortex, nucleus accumbens, or basolateral amygdala through optogenetics rescued social deficits. These studies are the first to record brain activity in a preclinical model of NF1 during impulsive behavior, finding broad spectrum changes across slow, delta, theta, and gamma oscillatory frequencies and decreased synchrony of the prefrontal cortex and nucleus accumbens during a delay discounting task. Overall, Nf1+/− male mice with deletion of a single NF1 gene recapitulate cognitive phenotypes of NF1 patients and are a useful model system to identify alterations in neural circuitry associated with ASD and ADHD.Item Educators’ and caregivers’ perceptions on the implementation of social narratives with individuals with autisim spectrum disorder(2016-09) Jordan, Kristi Ann; Crabtree, Jeffrey L.; Solas Allen, Martina; Fisher, ThomasSocial narratives are considered by the National Professional Development Center on Autism Spectrum Disorders (NPDC) to be effective in reducing challenging behaviors, improving expected behaviors, and preparing for change. This study is addressing the gap in literature about educators’ and caregivers’ perceptions of the implementation of and the differences in implementation of social narratives with individuals with Autism Spectrum Disorder (ASD).Item Evidence for the Effectiveness of Occupation-Based Interventions to Improve Social Participation for School-Aged Autistic Children: A Rapid Systematic Review(2021-05-05) Hernandez, Jocelyne; Belkiewitz, Johnna; Feldman, Anna; Payne, Chafin; Smith, Cassie; Taylor, Abigail; Chase, Anthony; Department of Occupational Therapy, School of Health and Human SciencesA rapid systematic review of the literature was conducted to review effective occupational therapy interventions for promoting social participation in children with autism spectrum disorder (ASD) was conducted as part of the Evidence-Based Literature Review Project of the American Occupational Therapy Association. This review provides a comprehensive overview and analysis of 30 studies that addressed many of the occupation-based interventions commonly used for children with ASD. Findings reveal that the use of occupation-based activities has reasonable, yet limited evidence to support its effectiveness in increasing social participation within this population. This review supports the premise that many client factors can be positively affected through the use of several commonly used occupational therapy–related modalities and methods. Further research should be conducted assessing the implementation of these interventions by occupational therapy practitioners to ensure generalizability. The implications for occupational therapy practice, research, and education and limitations of reviewed articles are presented within this systematic review.Item An Exploratory Analysis of Current Autism Terminology Usage, Including Its Implications for Public Health and Special Education in the State of Indiana(2013-07-12) Brown, Stephen Lawrence; Jones, Josette F.; Gamache, Roland E.; Dixon, Brian E.Consistent under-reporting of autism cases by Indiana physicians to the Indiana Birth Defects and Problems Registry (IBDPR) has made quality autism-related data very difficult to obtain (Indiana Birth Defects and Problems Registry [IBDPR], 2011). As a result, the Indiana State Department of Health (ISDH) currently also utilizes data from billing information that it receives from hospital discharges. However, such cases must be investigated further because autism is often merely suspected as a possibility in the discharge data. A chart auditor must therefore review the child’s chart to determine if the condition is confirmed. Meanwhile, the Indiana Department of Education (IDOE) has a different diagnostic procedure from physicians for determining whether a student has an Autism Spectrum Disorder (ASD), which qualifies him or her for special education. A physician diagnosis of autism does not guarantee that a child will receive special education from public schools. With all of these current complications surrounding autism, announced changes in the definition of autism by the American Psychiatric Association (APA) will likely have effects on both the special education field and the public health field. There is a possibility that children who had previously received special education could cease to maintain their eligibility and may find it difficult to obtain benefits. The IDOE may find it necessary to reevaluate their criteria for determining special education eligibility. Additionally, public health officials may see the definition changes affect the number of autism cases they perceive their populations to have, thus impacting community and policy decisions. This study was performed as an attempt to investigate and compare the sources used by the IBDPR to obtain autism data, and determine whether or not the resulting data creates an accurate depiction of the autistic population of Indiana. It was also performed to speculate whether a stricter definition of autism will result in a higher quality of data for the IBDPR and a more consistent view on the disorder between the ISDH and the IDOE. Perhaps from such consistency and simpler definitions, future recorded data will more closely resemble that of reality, enabling the ISDH to utilize the IBDPR to its full extent. Using current definitions for an exploratory analysis of data from the past five years, a discrepancy clearly exists between the IBDPR and the reality of the population of Indiana.Item Learning of Skilled Movements via Imitation in ASD(Wiley, 2020-05) McAuliffe, Danielle; Zhao, Yi; Pillai, Ajay S.; Ament, Katarina; Adamek, Jack; Caffo, Brian S.; Mostofsky, Stewart H.; Ewen, Joshua B.; Biostatistics, School of Public HealthAutism spectrum disorder (ASD) consists of altered performance of a range of skills, including social/communicative and motor skills. It is unclear whether this altered performance results from atypical acquisition or learning of the skills or from atypical “online” performance of the skills. Atypicalities of skilled actions that require both motor and cognitive resources, such as abnormal gesturing, are highly prevalent in ASD and are easier to study in a laboratory context than are social/communicative skills. Imitation has long been known to be impaired in ASD; because learning via imitation is a prime method by which humans acquire skills, we tested the hypothesis that children with ASD show alterations in learning novel gestures via imitation. Eighteen participants with ASD and IQ > 80, ages 8–12.9 years, and 19 typically developing peers performed a task in which they watched a video of a model performing a novel, meaningless arm/hand gesture and copied the gesture. Each gesture video/copy sequence was repeated 4–6 times. Eight gestures were analyzed. Examination of learning trajectories revealed that while children with ASD made nearly as much progress in learning from repetition 1 to repetition 4, the shape of the learning curves differed. Causal modeling demonstrated the shape of the learning curve influenced both the performance of overlearned gestures and autism severity, suggesting that it is in the index of learning mechanisms relevant both to motor skills and to autism core features.Item Occupation-Based Group Interventions Impacting Social Participation For Autistic Children and Adolescents: A Rapid Systematic Review(2022-05) Oleshchuk, Oksana; Legue, Anna; Gibbons, Molly; Banks, Riley; Chase, Tony; Department of Occupational Therapy, School of Health and Human SciencesThis rapid systematic review examines the literature on effective group interventions targeting social participation in autistic children and adolescents. Autistic youth often receive occupational therapy with social participation being a distinct targeted outcome. However, recent advocacy has introduced a need for reducing social skills training in favor of client-centered social participation, which can be done through the lens of occupational therapy’s unique core values. This review provides an overview and analysis of 20 studies that addressed a wide range of occupation-based group interventions in the areas of art, play, physical activity, school-based, and social skills group training (SSGT). Findings reveal moderate strength of evidence for the use of occupation-based group interventions in enhancing social participation in autistic children and adolescents, limited mostly by lack of blinding in studies. This review supports the use of group occupation-based interventions which can widen, inform, and guide the intervention approaches for occupational therapy practitioners working with this population.Item Pharmacological Inhibition of ERK Signaling Rescues Pathophysiology and Behavioral Phenotype Associated with 16p11.2 Chromosomal Deletion in Mice(Society for Neuroscience, 2018-07-25) Pucilowska, Joanna; Vithayathil, Joseph; Pagani, Marco; Kelly, Caitlin; Karlo, J. Colleen; Robol, Camilla; Morella, Ilaria; Gozzi, Alessandro; Brambilla, Riccardo; Landreth, Gary E.; Anatomy and Cell Biology, School of MedicineThe human 16p11.2 microdeletion is one of the most common gene copy number variations linked to autism, but the pathophysiology associated with this chromosomal abnormality is largely unknown. The 593 kb deletion contains the ERK1 gene and other genes that converge onto the ERK/MAP kinase pathway. Perturbations in ERK signaling are linked to a group of related neurodevelopmental disorders hallmarked by intellectual disability, including autism. We report that mice harboring the 16p11.2 deletion exhibit a paradoxical elevation of ERK activity, cortical cytoarchitecture abnormalities and behavioral deficits. Importantly, we show that treatment with a novel ERK pathway inhibitor during a critical period of brain development rescues the molecular, anatomical and behavioral deficits in the 16p11.2 deletion mice. The ERK inhibitor treatment administered to adult mice ameliorates a subset of these behavioral deficits. Our findings provide evidence for potential targeted therapeutic intervention in 16p11.2 deletion carriers. SIGNIFICANCE STATEMENT The ERK/MAPK pathway is genetically linked to autism spectrum disorders and other syndromes typified by intellectual disability. We provide direct evidence connecting the ERK/MAP kinases to the developmental abnormalities in neurogenesis and cortical cytoarchitecture associated with the 16p11.2 chromosomal deletion. Most importantly, we demonstrate that treatment with a novel ERK-specific inhibitor during development rescues aberrant cortical cytoarchitecture and restores normal levels of cell-cycle regulators during cortical neurogenesis. These treatments partially reverse the behavioral deficits observed in the 16p11.2del mouse model, including hyperactivity, memory as well as olfaction, and maternal behavior. We also report a rescue of a subset of these deficits upon treatment of adult 16p11.2del mice. These data provide a strong rationale for therapeutic approaches to this disorder.Item Randomized Control Trial of COMPASS for Improving Transition Outcomes of Students with Autism Spectrum Disorder(Springer, 2018-10) Ruble, Lisa; McGrew, John H.; Toland, Michael; Dalrymple, Nancy; Adams, Medina; Snell-Rood, Claire; Psychology, School of ScienceThe postsecondary outcomes of individuals with autism spectrum disorder (ASD) are significantly worse than peers with other disabilities. One problem is the lack of empirically-supported transition planning interventions to guide services and help produce better outcomes. We applied an implementation science approach to adapt and modify an evidence-based consultation intervention originally tested with young children called the Collaborative Model for Promoting Competence and Success (COMPASS; Ruble et al., The collaborative model for promoting competence and success for students with ASD. Springer, New York, 2012a) and evaluate it for efficacy in a randomized controlled trial for transition-age youth. Results replicated findings with younger students with ASD that IEP outcomes were higher for COMPASS compared to the placebo control group (d = 2.1). Consultant fidelity was high and teacher adherence improved over time, replicating the importance of ongoing teacher coaching.Item Rapid Systematic Review of Occupational Therapy-Adaptable Interventions to Improve Social Engagement in Children and Adolescents with Autism Spectrum Disorder(2020-08-27) Alexander, Joelyn; Gordon, Madeline; Heydon, Mallory; Klukken, Angela; Moring, Kelly; Nguyen, Elizabeth; Chase, Anthony; Petrenchik, Terry; Department of Occupational Therapy, School of Health and Human SciencesIn this rapid systematic review, we describe how evidence-based interventions aiming to improve social engagement in children and adolescents with Autism Spectrum Disorder (ASD) can be potentially adapted to be included within the scope of occupational therapy. Children and adolescents with ASD often experience difficulty with social engagement, impacting overall social participation and other aspects of daily life. It is important to address this issue within this population to ensure engagement in the occupation of social participation, which is vital to optimal health and well-being. We discovered several themes including communication, joint attention, peer engagement, social skills, and play as outcomes addressed within the interventions included in this review. There is limited research available regarding social engagement interventions for children and adolescents with ASD directly including an occupational therapist within the intervention. This review demonstrates that there is a large variety of social engagement interventions that could be implemented by occupational therapists; however, therapists must be mindful of choosing an intervention that is specific to the client's condition. There is strong evidence to suggest that interventions targeting social engagement in children and adolescents with ASD result in increased social abilities. Further research should be conducted assessing the implementation of these interventions by occupational therapists to ensure generalizability.Item "Will I always be not social?": Re-Conceptualizing Sociality in the Context of a Minecraft Community for Autism(ACM, 2016-05) Ringland, Kathryn E.; Wolf, Christine T.; Faucett, Heather; Dombrowski, Lynn; Hayes, Gillian R.; Human-Centered Computing, School of Informatics and ComputingTraditional face-to-face social interactions can be challenging for individuals with autism, leading some to perceive and categorize them as less social than their typically-developing peers. Individuals with autism may even see themselves as less social relative to their peers. Online communities can provide an alternative venue for social expression, enabling different types of communication beyond face-to-face, oral interaction. Using ethnographic methods, we studied the communication ecology that has emerged around a Minecraft server for children with autism and their allies. Our analysis shows how members of this community search for, practice, and define sociality through a variety of communication channels. These findings suggest an expansion in how sociality has traditionally been conceptualized for individuals with autism.