Electrophysiological alterations in early auditory predictive processing as potential markers for autistic symptomatology

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that has been linked to a range of perceptual processing alterations, including hypo- and hyperresponsiveness to auditory stimulation. A recently proposed theory that attempts to account for these symptoms suggest that autistic individuals have a decreased ability to anticipate upcoming sensory stimulation. In a series of ERP experiments, we show that autistic individuals have alterations in the early processing of both highly predictable self-initiated auditory stimulation (van Laarhoven, Stekelenburg, Eussen, & Vroomen, 2019), and unexpected omissions of auditory stimulation that is predictable by visual motion (van Laarhoven, Stekelenburg, Eussen, & Vroomen, 2020). In addition, deviancy detection of auditory speech is reduced in autistic individuals, while deviancy detection of visual speech and incongruent audiovisual speech seems to be intact (van Laarhoven et al., in prep). Our findings suggest that autistic individuals may indeed experience difficulties in anticipating upcoming auditory stimulation. Importantly, these difficulties might be due to domain-specific alterations, rather than general impairments in predictive coding. This notion provides potential avenues for future research on electrophysiological markers for autistic symptomatology

Neural correlates of impaired motor-auditory prediction in Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) have difficulties with the unexpected and unpredictable nature of external events. Prior knowledge of the statistics of the environment (i.e. priors, in terms of Bayesian statistical framework) can aid resolving these uncertainties. In individuals with ASD, these priors may either be ill-constructed or not appropriately combined with the actual sensory information, resulting in less-precise or attenuated priors (Pellicano and Burr, 2012). These ‘hypo-priors’ may cause a greater reliance on bottom-up incoming sensory signals, which in turn leads to every stimulus being experienced afresh. Here, we tested the hypo-priors hypothesis by examining the neural underpinnings of prediction of sensory consequences of motor actions in individuals with ASD and individuals with typical development (TD). In this experiment, subjects pressed a button at a steady pace, which generated a sound. In another condition, the sounds were replayed at the same pace. In individuals with TD, the auditory N1 potential induced by the sound was attenuated in the motor-auditory condition compared to the auditory-only condition, indicating that - as expected - the motor action predicted the sound and dampened the sensation (Bäss et al., 2008). In individuals with ASD, there was no auditory N1 attenuation, indicating that they relied more strongly on bottom-up auditory cues. These results show that individuals with ASD make less use of their priors to interpret the sensory environment and support the notion of hypo-priors as the underlying cause of atypical multisensory processing in ASD

Atypical visual-auditory predictive coding in Autism Spectrum Disorder:Electrophysiological evidence from stimulus omissions

Autism spectrum disorder is a pervasive neurodevelopmental disorder that has been linked to a range of perceptual processing alterations, including hypo- and hyperresponsiveness to sensory stimulation. A recently proposed theory that attempts to account for these symptoms, states that autistic individuals have a decreased ability to anticipate upcoming sensory stimulation due to overly precise internal prediction models. Here, we tested this hypothesis by comparing the electrophysiological markers of prediction errors in auditory prediction by vision between a group of autistic individuals and a group of age-matched individuals with typical development. Between-group differences in prediction error signaling were assessed by comparing event-related potentials evoked by unexpected auditory omissions in a sequence of audiovisual recordings of a handclap in which the visual motion reliably predicted the onset and content of the sound. Unexpected auditory omissions induced an increased early negative omission response in the autism spectrum disorder group, indicating that violations of the prediction model produced larger prediction errors in the autism spectrum disorder group compared to the typical development group. The current results show that autistic individuals have alterations in visual-auditory predictive coding, and support the notion of impaired predictive coding as a core deficit underlying atypical sensory perception in autism spectrum disorder.  Lay abstract:  Many autistic individuals experience difficulties in processing sensory information (e.g. increased sensitivity to sound). Here we show that these difficulties may be related to an inability to process unexpected sensory stimulation. In this study, 29 older adolescents and young adults with autism and 29 age-matched individuals with typical development participated in an electroencephalography study. The electroencephalography study measured the participants’ brain activity during unexpected silences in a sequence of videos of a handclap. The results showed that the brain activity of autistic individuals during these silences was increased compared to individuals with typical development. This increased activity indicates that autistic individuals may have difficulties in processing unexpected incoming sensory information, and might explain why autistic individuals are often overwhelmed by sensory stimulation. Our findings contribute to a better understanding of the neural mechanisms underlying the different sensory perception experienced by autistic individuals

Predictive coding in autism spectrum disorder:Electrophysiological alterations in early auditory predictive processing as potential markers for autistic symptomatology

Background :  Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder that has been linked to a range of perceptual processing alterations, including hypo- and hyperresponsiveness to auditory stimulation. A recently proposed theory that attempts to account for these symptoms suggest that autistic individuals have a decreased ability to anticipate upcoming sensory stimulation. Objectives :  If the ability to anticipate upcoming sensory stimulation is indeed decreased in ASD, perception in ASD could be less affected by prior expectations and more driven by sensory input. Here, we tested this hypothesis with a series of event-related potential (ERP) studies in which we examined the neural correlates of motor-auditory prediction (N1 attenuation), visual-auditory prediction error (omission N1) and deviancy detection of auditory, visual and audiovisual speech (MMN). Methods :  In a series of ERP studies, we first compared the electrophysiological brain response to self- versus externally-initiated tones between a group of individuals with ASD and a group of age matched individuals with typical development. Next, we assessed between-group differences in prediction error signaling by comparing ERPs evoked by unexpected auditory omissions in a sequence of audiovisual recordings of a handclap in which the visual motion reliably predicted the onset and content of the sound. Finally, we examined between group differences in deviancy detection of auditory, visual and audiovisual speech by applying a MMN paradigm. Results :  The results of our first ERP study showed that, unlike in age-matched participants with typical development, self-initiation of tones through a button press did not attenuate the auditory N1 in autistic individuals, indicating that the ability to anticipate the auditory sensory consequences of self-initiated motor actions might be decreased in ASD (van Laarhoven, Stekelenburg, Eussen, & Vroomen, 2019, https://doi.org/10.1002/aur.2087). The results of our second study showed that unexpected omissions of a sound of which the timing and content could be predicted by preceding visual anticipatory motion elicited an increased early auditory omission response (oN1) in the ASD group, indicating that violations of the prediction model produced larger prediction errors in autistic individuals when compared to their peers with typical development (van Laarhoven, Stekelenburg, Eussen, & Vroomen, 2020, https://doi.org/10.1177%2F1362361320926061). Finally, the results of our third study showed that deviancy detection of auditory speech is reduced in autistic individuals, while deviancy detection of visual speech and incongruent audiovisual speech seems to be intact (van Laarhoven et al., in prep). Conclusions :  Taken together, our findings suggest that individuals with ASD may indeed experience difficulties in anticipating upcoming auditory stimulation. Importantly, these difficulties might be due to domain-specific alterations, rather than general impairments in predictive coding. This notion provides potential avenues for future research on electrophysiological markers for autistic symptomatology

The GLOBE-Consortium: The Next-Generation Genome Viewer

The GLOBE 3D Genome Viewer is the novel system-biology oriented genome browser necessary to access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning of this tremendous evolutionary information grail – genomes. This has required completely new approaches to represent the genome architecture realistically in combination with the various types of informational annotation including experimental data or instant analysis capabilities. This creates unrivalled new opportunities for scientific researchers, diagnostic users, educators and publishers as well as PR and commercial applicants. Potential BETA-TESTERS of the GLOBE 3D Genome Viewer are asked to sign up now

Electrophysiological alterations in motor‐auditory predictive coding in autism spectrum disorder

The amplitude of the auditory N1 component of the event‐related potential (ERP) is typically attenuated for self‐initiated sounds, compared to sounds with identical acoustic and temporal features that are triggered externally. This effect has been ascribed to internal forward models predicting the sensory consequences of one's own motor actions. The predictive coding account of autistic symptomatology states that individuals with autism spectrum disorder (ASD) have difficulties anticipating upcoming sensory stimulation due to a decreased ability to infer the probabilistic structure of their environment. Without precise internal forward prediction models to rely on, perception in ASD could be less affected by prior expectations and more driven by sensory input. Following this reasoning, one would expect diminished attenuation of the auditory N1 due to self‐initiation in individuals with ASD. Here, we tested this hypothesis by comparing the neural response to self‐ versus externally‐initiated tones between a group of individuals with ASD and a group of age matched neurotypical controls. ERPs evoked by tones initiated via button‐presses were compared with ERPs evoked by the same tones replayed at identical pace. Significant N1 attenuation effects were only found in the TD group. Self‐initiation of the tones did not attenuate the auditory N1 in the ASD group, indicating that they may be unable to anticipate the auditory sensory consequences of their own motor actions. These results show that individuals with ASD have alterations in sensory attenuation of self‐initiated sounds, and support the notion of impaired predictive coding as a core deficit underlying autistic symptomatology

The system-biological GLOBE 3D Genome Platform.

Genomes are tremendous co-evolutionary holistic systems for molecular storage, processing and fabrication of information. Their system-biological complexity remains, however, still largely mysterious, despite immense sequencing achievements and huge advances in the understanding of the general sequential, three-dimensional and regulatory organization. Here, we present the GLOBE 3D Genome Platform a completely novel grid based virtual “paper” tool and in fact the first system-biological genome browser integrating the holistic complexity of genomes in a single easy comprehensible platform: Based on a detailed study of biophysical and IT requirements, every architectural level from sequence to morphology of one or several genomes can be approached in a real and in a symbolic representation simultaneously and navigated by continuous scale-free zooming within a unique three-dimensional OpenGL and grid driven environment. In principle an unlimited number of multi-dimensional data sets can be visualized, customized in terms of arrangement, shape, colour, and texture etc. as well as accessed and annotated individually or in groups using internal or external data bases/facilities. Any information can be searched and correlated by importing or calculating simple relations in real-time using grid resources. A general correlation and application platform for more complex correlative analysis and a front-end for system-biological simulations both using again the huge capabilities of grid infrastructures is currently under development. Hence, the GLOBE 3D Genome Platform is an example of a grid based approach towards a virtual desktop for genomic work combining the three fundamental distributed resources: i) visual data representation, ii) data access and management, and iii) data analysis and creation. Thus, the GLOBE 3D Genome Platform is the novel system-biology oriented information system urgently needed to access, present, annotate, and to simulate the holistic genome complexity in a unique gateway towards a real understanding, educative presentation and curative manipulation planning of this tremendous evolutionary information grail – genomes