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Impaired sensory processing in Autism Spectrum Disorder: Towards better phenotyping and cellular models

Projectomschrijving

Mensen met autisme zijn vaak overgevoelig voor zintuigelijke prikkels zoals harde geluiden of fel licht. Een mogelijke verklaring voor deze gevoeligheid is dat bij mensen met autisme de communicatie tussen zenuwcellen in de hersenen anders verloopt. Ons onderzoek zal voor het eerst in mensen met autisme deze mogelijk verstoorde communicatie gaan onderzoeken. Bij proefpersonen zal een heel klein stukje huid worden afgenomen waarna de huidcellen met een nieuwe techniek worden getransformeerd naar hersencellen. Deze kunnen buiten het lichaam, in een kweekbakje, in leven worden gehouden en onderzocht op allerlei kenmerken. De onderzoekers werken hiervoor samen met het Nederlands Autisme Register om proefpersonen met een uitzonderlijk sterke zintuigelijke gevoeligheid te vragen voor dit onderzoek. Het doel is om meer inzicht te krijgen in de oorzaken van autisme, om betere diagnoses te kunnen stellen en om interventies te bedenken die de overgevoeligheid voor prikkels kunnen verminderen.

Producten

Titel: Sensory sensitivity in Autism
Auteur: Matthijs Verhage
Link: https://bonnbrain.de
Titel: Sensory sensitivity in Autism spectrum disorder
Auteur: Matthijs Verhage
Link: http://www.autismeurope.org/event
Titel: Autisme en extreme prikkelgevoeligheid: een kijkje in de hersencellen
Auteur: L. Niels Cornelisse, Sander Begeer, Tinca J. Polderman, Bernadette Wijnker-Holmes, Matthijs Verhage
Magazine: Autisme Magazine
Link: https://www.autisme.nl/activiteiten/autisme-magazine.aspx
Titel: 5 vragen over AUTISME | Psychologie Magazine
Auteur: Sander Begeer
Link: https://www.youtube.com/watch?v=ZGjGnX6jLks

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Samenvatting van de aanvraag

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with a >1% prevalence characterized by impairments in social skills and flexibility and by a complex aetiological heterogeneity. The neurobiological mechanisms underlying ASD are still poorly understood and the aetiological heterogeneity complicates their elucidation. Recently, sensory processing sensitivities, such as extreme sensitivity to light, sound, or touch, were added to the ASD diagnostic criteria (DSM5) as negative and prevalent symptoms (reported up to 87%). These symptoms are now considered “a critical cornerstone for characterizing and understanding ASD”. A new network theory explains ASD by a disturbed excitation/inhibition (E/I) balance in synaptic networks in the brain. We aim to test this theory using behavioral, neuropsychological, neurophysiological and synaptic analyses of sensory processing deficits in ASD. We will first exploit our Netherlands Autism Register to pre-select extreme cases of high and low sensory sensitivity among ASD participants (currently 683) and control subjects and examine the relationship between sensory sensitivity and other clinical characteristics and daily functioning skills. Secondly, we will assess 80 pre-selected participants further, using customized sensory processing tasks and EEG, which we have previously optimized to analyze sensory sensitivity and E/I balance. Thirdly, we will utilize our unique expertise to generate small, standardized neuronal networks in vitro, made of human neurons derived from induced pluripotent stem cells (iPSCs) and to record differences in synaptic and network properties. The sensory sensitivity and E/I balance tests will be exploited to generate these standardized in vitro networks of the most extreme cases. Finally, it has been proposed that the (unknown) neurobiological mechanisms underlying sensory processing deficits are similar to those underlying higher order social function deficits. Therefore, we will test whether the outcomes of our neuropsychological and neurophysiological tests are predictive for the reported higher order function deficits. This project brings together unique expertise to bridge across behavioral, neuropsychological, neurophysiological and cellular research domains of ASD, focusing on a symptom that is only recently recognized as a central symptom, also in relation to other indicators of ASD, but for which integrated studies across research domains are still lacking. Whereas higher order social functions are difficult to measure quantitatively, sensory processing can be easily quantified in a manner that is less biased for age, gender, or cultural background. This quantification is expected to lead to a more objective, unbiased and homogeneous ASD subtyping which is again expected to improve ASD diagnosis and facilitate cellular studies with neurons derived from ASD participants. Such iPSC-derived neuronal models, in contrast to current (monogenic) animal- or cell-models, present the full polygenic complexity of ASD. Given the expected subtle cellular effects and the heterogeneity in ASD, current IPSCs-studies are often underpowered. We will exploit the precise classification of the disease subtypes to overcome this problem and arrive at homogenously phenotyped ASD subgroups. Together, this project provides a unique opportunity to bring together information from these different research domains, enhance our understanding of the complexity of ASD, and provide intervention targets to alleviate the burden of ASD.

Onderwerpen

Kenmerken

Projectnummer:
91216064
Looptijd: 100%
Looptijd: 100 %
2017
2023
Onderdeel van programma:
Gerelateerde subsidieronde:
Projectleider en penvoerder:
dr. L.N. Cornelisse
Verantwoordelijke organisatie:
Amsterdam UMC Locatie VUmc