Medicine and Health Sciences Commons^™

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2^-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2^-/- littermates at three postnatal age ranges (P8-12, P18-21, and …

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …

Auditory Sensory Filtering And Development In Children With Autism Spectrum Disorder, Hiruthika Ravi, Ala Seif, Ryan A. Stevenson

Undergraduate Student Research Internships Conference

Sensory filtering is the process of separating and distilling relevant sensory information from irrelevant, which in turn greatly reduces the quantity of sensory information that is fully processed and leads to significant increases in efficiency. Atypical sensory filtering can result in sensory hypo- or hypersensitivity — atypical sensory filtering and hypo/hypersensitivity have been observed in people with autism. Atypical sensory filtering contributes to canonical symptoms in Autism.

Sensory filtering can be measured in a few different ways, one of which is the Acoustic Startle Response (ASR). ASR is a reflexively produced muscular reaction to sudden auditory stimuli.

Our study aims …

Exploring Sensory Phenotypes In Autistic Children And Children With Adhd, Anahid Pourtousi

Undergraduate Student Research Internships Conference

Autistic children and children with attention-deficit/hyperactivity disorder (ADHD) often experience sensory processing difficulties, which are highly heterogeneous. Researchers have identified sensory phenotypes that co-occur within autistic individuals. However, sensory phenotypes have not been examined in children with ADHD. The aim of this research is to identify whether these sensory phenotypes exist in children with ADHD, and whether these phenotypes are similar to those observed in autism. A secondary aim of this study is to determine whether these sensory phenotypes are related to autism, ADHD, and obsessive-compulsive (OCD) traits. Short Sensory Profile data from 495 autistic children and 461 children with …

Defining The Genotypic And Phenotypic Spectrum Of X-Linked Msl3-Related Disorder, Theresa Brunet, Kirsty Mcwalter, Katharina Mayerhanser, Grace M Anbouba, Amy Armstrong-Javors, Ingrid Bader, Evan Baugh, Amber Begtrup, Caleb P Bupp, Bert L Callewaert, Anna Cereda, Margot A Cousin, Juan C Del Rey Jimenez, Laurie Demmer, Nikita R Dsouza, Nicole Fleischer, Ralitza H Gavrilova, Sumedha Ghate, Elisabeth Graf, Andrew Green, Sarah R Green, Maria Iascone, Ameni Kdissa, Dirk Klee, Eric W Klee, Emily Lancaster, Kristin Lindstrom, Johannes A Mayr, Meriel Mcentagart, Naomi J L Meeks, Dana Mittag, Harrison Moore, Anne K Olsen, Damara Ortiz, Gretchen Parsons, Loren D M Pena, Richard E Person, Sumit Punj, Gonzalo Alonso Ramos-Rivera, Maria J Guillen Sacoto, G Bradley Schaefer, Rhonda E Schnur, Tiana M Scott, Daryl A Scott, Carolyn R Serbinski, Vandana Shashi, Victoria Mok Siu, Barbro Fossøy Stadheim, Jennifer A Sullivan, Jana Švantnerová, Lea Velsher, David S Wargowski, Ingrid M Wentzensen, Dagmar Wieczorek, Juliane Winkelmann, Patrick Yap, Michael Zech, Michael T Zimmermann, Thomas Meitinger, Felix Distelmaier, Matias Wagner

Paediatrics Publications

PURPOSE: We sought to delineate the genotypic and phenotypic spectrum of female and male individuals with X-linked, MSL3-related disorder (Basilicata-Akhtar syndrome).

METHODS: Twenty-five individuals (15 males, 10 females) with causative variants in MSL3 were ascertained through exome or genome sequencing at ten different sequencing centers.

RESULTS: We identified multiple variant types in MSL3 (ten nonsense, six frameshift, four splice site, three missense, one in-frame-deletion, one multi-exon deletion), most proven to be de novo, and clustering in the terminal eight exons suggesting that truncating variants in the first five exons might be compensated by an alternative MSL3 transcript. Three-dimensional modeling of …

Sensory Filtering Disruption Caused By Poly I:C - Timing Of Exposure And Other Experimental Considerations., Faraj L Haddad, Lu Lu, Kelly J Baines, Susanne Schmid

Anatomy and Cell Biology Publications

Maternal immune activation (MIA) in response to infection during pregnancy has been linked through various epidemiological and preclinical studies to an increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia in exposed offspring. Sensory filtering disruptions occur in both of these disorders and are typically measured using the acoustic startle response in both humans and rodents. Our study focuses on characterizing the baseline reactivity, habituation and prepulse inhibition (PPI) of the acoustic startle response following exposure to MIA. We induced MIA using polyinosinic: polycytidylic acid (poly I:C) at gestational day (GD) 9.5 or 14.5, and we …

What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that are caused by genetic and/or environmental impacts, often probably by the interaction of both. They are characterised by deficits in social communication and interaction and by restricted and repetitive behaviours and interests from early childhood on, causing significant impairment. While it is clear that no animal model captures the full complexity of ASD in humans, genetic models are extremely useful for studying specific symptoms associated with ASD and the underlying cellular and molecular mechanisms. In this review we summarize the behavioral paradigms used in rodents to model ASD symptoms as they …

Sensory Processing In Autism Spectrum Disorders And Fragile X Syndrome-From The Clinic To Animal Models., D Sinclair, B Oranje, K A Razak, S J Siegel, S Schmid

Brain and Mind Institute Researchers' Publications

Brains are constantly flooded with sensory information that needs to be filtered at the pre-attentional level and integrated into endogenous activity in order to allow for detection of salient information and an appropriate behavioral response. People with Autism Spectrum Disorder (ASD) or Fragile X Syndrome (FXS) are often over- or under-reactive to stimulation, leading to a wide range of behavioral symptoms. This altered sensitivity may be caused by disrupted sensory processing, signal integration and/or gating, and is often being neglected. Here, we review translational experimental approaches that are used to investigate sensory processing in humans with ASD and FXS, and …

Behavioral, Perceptual, And Neural Alterations In Sensory And Multisensory Function In Autism Spectrum Disorder., Sarah H Baum, Ryan A Stevenson, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Although sensory processing challenges have been noted since the first clinical descriptions of autism, it has taken until the release of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013 for sensory problems to be included as part of the core symptoms of autism spectrum disorder (ASD) in the diagnostic profile. Because sensory information forms the building blocks for higher-order social and cognitive functions, we argue that sensory processing is not only an additional piece of the puzzle, but rather a critical cornerstone for characterizing and understanding ASD. In this review we discuss what …

An Exploration Of Parental Experiences With Interventions For Children And Adolescents With Autism Spectrum Disorder, Kaity Gain

Electronic Thesis and Dissertation Repository

Autism Spectrum Disorder (ASD) is defined as a group of pervasive developmental disorders that cause clinically significant impairments in social, occupational and overall functioning. The current body of research highlights the importance of community based interventions, programs and services for this population across their lifespan. This dissertation explores parental experiences with interventions, programs and services for their children and adolescents with ASD.

This dissertation contains three manuscripts in addition to the introductory and concluding chapters. The first manuscript explores the current literature on occupational therapy based interventions for school aged children with ASD. Manuscript two presents the findings of an …

The Impact Of Multisensory Integration Deficits On Speech Perception In Children With Autism Spectrum Disorders., Ryan A Stevenson, Magali Segers, Susanne Ferber, Morgan D Barense, Mark T Wallace

Brain and Mind Institute Researchers' Publications

Speech perception is an inherently multisensory process. When having a face-to-face conversation, a listener not only hears what a speaker is saying, but also sees the articulatory gestures that accompany those sounds. Speech signals in visual and auditory modalities provide complementary information to the listener (Kavanagh and Mattingly, 1974), and when both are perceived in unison, behavioral gains in in speech perception are observed (Sumby and Pollack, 1954). Notably, this benefit is accentuated when speech is perceived in a noisy environment (Sumby and Pollack, 1954). To achieve a behavioral gain from multisensory processing of speech, however, the auditory and visual …