European Autism GEnomics Registry (EAGER): protocol for a multicentre cohort study and registry.

INTRODUCTION: Autism is a common neurodevelopmental condition with a complex genetic aetiology that includes contributions from monogenic and polygenic factors. Many autistic people have unmet healthcare needs that could be served by genomics-informed research and clinical trials. The primary aim of the European Autism GEnomics Registry (EAGER) is to establish a registry of participants with a diagnosis of autism or an associated rare genetic condition who have undergone whole-genome sequencing. The registry can facilitate recruitment for future clinical trials and research studies, based on genetic, clinical and phenotypic profiles, as well as participant preferences. The secondary aim of EAGER is to investigate the association between mental and physical health characteristics and participants' genetic profiles. METHODS AND ANALYSIS: EAGER is a European multisite cohort study and registry and is part of the AIMS-2-TRIALS consortium. EAGER was developed with input from the AIMS-2-TRIALS Autism Representatives and representatives from the rare genetic conditions community. 1500 participants with a diagnosis of autism or an associated rare genetic condition will be recruited at 13 sites across 8 countries. Participants will be given a blood or saliva sample for whole-genome sequencing and answer a series of online questionnaires. Participants may also consent to the study to access pre-existing clinical data. Participants will be added to the EAGER registry and data will be shared externally through established AIMS-2-TRIALS mechanisms. ETHICS AND DISSEMINATION: To date, EAGER has received full ethical approval for 11 out of the 13 sites in the UK (REC 23/SC/0022), Germany (S-375/2023), Portugal (CE-085/2023), Spain (HCB/2023/0038, PIC-164-22), Sweden (Dnr 2023-06737-01), Ireland (230907) and Italy (CET_62/2023, CEL-IRCCS OASI/24-01-2024/EM01, EM 2024-13/1032 EAGER). Findings will be disseminated via scientific publications and conferences but also beyond to participants and the wider community (eg, the AIMS-2-TRIALS website, stakeholder meetings, newsletters).

Disrupted Spatial Organization of Cued Exogenous Attention Persists Into Adulthood in Developmental Dyslexia.

Purpose: Abnormal exogenous attention orienting and diffused spatial distribution of attention have been associated with reading impairment in children with developmental dyslexia. However, studies in adults have failed to replicate such relationships. The goal of the present study was to address this issue by assessing exogenous visual attention and its peripheral spatial distribution in adults with developmental dyslexia. Methods: We measured response times, accuracy and eye movements of 18 dyslexics and 19 typical readers in a cued discrimination paradigm, in which stimuli were presented at different peripheral eccentricities. Results: Results showed that adults with developmental dyslexia were slower that controls in using their mechanisms of exogenous attention orienting. Moreover, we found that while controls became slower with the increase of eccentricity, dyslexics showed an abnormal inflection at 10° as well as similar response times at the most distant eccentricities. Finally, dyslexics show attentional facilitation deficits above 12° of eccentricity, suggesting an attentional engagement deficit at far periphery. Conclusion: Taken together, our findings indicate that, in dyslexia, the temporal deficits in orientation of attention and its abnormal peripheral spatial distribution are not restricted to childhood and persist into adulthood. Our results are, therefore, consistent with the hypothesis that the neural network underlying selective spatial attention is disrupted in dyslexia.

Parametric fMRI analysis of videos of variable arousal levels reveals different dorsal vs ventral activation preferences between autism and controls.

Atypical sensory processing is now considered a ubiquitous feature of autism spectrum disorder (ASD) and is responsible for the atypical sensory-based behaviours seen in these individuals. Specifically, emotional arousal is a critical ASD target since it comprises emotion regulation and sensory processing, two core aspects of autism. So, in this project, we used task-based fMRI and a well-catalogued dataset of videos with variable arousal levels to characterize the sensory processing of emotional arousal content in ASD and typically developed controls. Our analysis revealed a difference in the secondary attention network where ASD individuals showed a clear yet lateralized preference to the dorsal attention network, whereas the neurotypical individuals preferred the ventral attention network.

Neural Responses of the Anterior Ventral Occipitotemporal Cortex in Developmental Dyslexia: Beyond the Visual Word Form Area.

Purpose: For the past 2 decades, neuroimaging studies in dyslexia have pointed toward a hypoactivation of the ventral occipitotemporal cortex (VOTC), a region that has been closely associated to reading through the extraction of a representation of words which is invariant to position, size, font or case. However, most of the studies are confined to the visual word form area (VWFA), while recent studies have demonstrated a posterior-to-anterior gradient of print specificity along the VOTC. In our study, the whole VOTC, partitioned into three main patches of cortex, is assessed in dyslexic and control adults. Methods: A total of 30 participants were included in this study (14 developmental dyslexics and 16 age- and education-matched controls). The design consisted of alternately viewed blocks of stimuli from a given class (words, consonant strings, phase-scrambled words, phase-scrambled consonant strings, small checkerboards, large checkerboards). The analyzed contrast was print stimuli (words and consonants) versus scrambled stimuli and checkerboards. Results: Corroborating previous findings, our results showed underactivation to print stimuli in the VWFA of dyslexics. Additionally, differences between dyslexics and controls were also found, particularly in an area of the anterior partition of the VOTC, suggesting a relevant role of this area in word processing. Conclusions: In sum, our study goes beyond the underactivation hypothesis in the VWFA of dyslexics and indicates that a particular area on the anterior fusiform region might be particularly involved in the reading deficits in dyslexia, demonstrating the involvement of multiple areas within VOTC in reading processes.

Evidence for a differential interference of noise in sub-lexical and lexical reading routes in healthy participants and dyslexics.

The ineffective exclusion of surrounding noise has been proposed to underlie the reading deficits in developmental dyslexia. However, previous studies supporting this hypothesis focused on low-level visual tasks, providing only an indirect link of noise interference on reading processes. In this study, we investigated the effect of noise on regular, irregular, and pseudoword reading in 23 dyslexic children and 26 age- and IQ-matched controls, by applying the white noise displays typically used to validate this theory to a lexical decision task. Reading performance and eye movements were measured. Results showed that white noise did not consistently affect dyslexic readers more than typical readers. Noise affected more dyslexic than typical readers in terms of reading accuracy, but it affected more typical than dyslexic readers in terms of response time and eye movements (number of fixations and regressions). Furthermore, in typical readers, noise affected more the speed of reading of pseudowords than real words. These results suggest a particular impact of noise on the sub-lexical reading route where attention has to be deployed to individual letters. The use of a lexical route would reduce the effect of noise. A differential impact of noise between words and pseudowords may therefore not be evident in dyslexic children if they are not yet proficient in using the lexical route. These findings indicate that the type of reading stimuli and consequent reading strategies play an important role in determining the effects of noise interference in reading processing and should be taken into account by further studies.

Visual Perception and Reading: New Clues to Patterns of Dysfunction Across Multiple Visual Channels in Developmental Dyslexia.

Purpose: The specificity of visual channel impairment in dyslexia has been the subject of much controversy. The purpose of this study was to determine if a differential pattern of impairment can be verified between visual channels in children with developmental dyslexia, and in particular, if the pattern of deficits is more conspicuous in tasks where the magnocellular-dorsal system recruitment prevails. Additionally, we also aimed at investigating the association between visual perception thresholds and reading. Methods: In the present case-control study, we compared perception thresholds of 33 children diagnosed with developmental dyslexia and 34 controls in a speed discrimination task, an achromatic contrast sensitivity task, and a chromatic contrast sensitivity task. Moreover, we addressed the correlation between the different perception thresholds and reading performance, as assessed by means of a standardized reading test (accuracy and fluency). Group comparisons were performed by the Mann-Whitney U test, and Spearman's rho was used as a measure of correlation. Results: Results showed that, when compared to controls, children with dyslexia were more impaired in the speed discrimination task, followed by the achromatic contrast sensitivity task, with no impairment in the chromatic contrast sensitivity task. These results are also consistent with the magnocellular theory since the impairment profile of children with dyslexia in the visual threshold tasks reflected the amount of magnocellular-dorsal stream involvement. Moreover, both speed and achromatic thresholds were significantly correlated with reading performance, in terms of accuracy and fluency. Notably, chromatic contrast sensitivity thresholds did not correlate with any of the reading measures. Conclusions: Our evidence stands in favor of a differential visual channel deficit in children with developmental dyslexia and contributes to the debate on the pathophysiology of reading impairments.