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The Because Project: Impaired Sensory Processing in ASD: From Clinical Profiles to Synaptic Mechanisms
The neurobiological mechanisms underlying ASD are still poorly understood. Recently, sensory sensitivities, such as extreme sensitivity to light, sound, or touch, were added to the ASD diagnostic criteria (DSM5) as negative and prevalent symptoms. A new network theory explains the sensory sensitivity problems in ASD by a disturbed excitation/inhibition (E/I) balance in synaptic networks in the brain.The current project aims to test this theory using behavioral, neuropsychological, neurophysiological and cellular analyses of sensory processing deficits in ASD.
Objectives:
In this presentation, I will highlight the progress of BECAUSE: From Behavior to Cell in AUtism SEnsory processing, a Dutch national project to test this theory using behavioral, neuropsychological, neurophysiological and synaptic analyses of sensory processing deficits in ASD.
Methods:
BECAUSE has exploited 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. Eighty pre-selected participants have been assessing further, using customized sensory processing tasks and EEG, which we have previously optimized to analyze sensory sensitivity and E/I balance. We have previously optimied 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 is used 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 (Baum et al., 2015). Therefore, we are testing whether the outcomes of our neuropsychological and neurophysiological tests are predictive for the reported higher order function deficits.
Results:
This presentation will be the first presentation of the BECAUSE screenings data. In addition, the completed pilot studies on EEG-analysis of excitation/inhibition balance and synapse physiology in patient-derived neurons will be discussed.
Conclusions:
BECAUSE brings together unique expertise to bridge across behavioral, neuropsychological, neurophysiological and cellular research domains of ASD, focusing on a symptom that is recently recognized as a central mechanism, 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. BECAUSE 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. Together, BECAUSE 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.