Lien Van Eylen

Precise minds in uncertain worlds: predictive coding in autism.

There have been numerous attempts to explain the enigma of autism, but existing neurocognitive theories often provide merely a refined description of 1 cluster of symptoms. Here we argue that deficits in executive functioning, theory of mind, and central coherence can all be understood as the consequence of a core deficit in the flexibility with which people with autism spectrum disorder can process violations to their expectations. More formally we argue that the human mind processes information by making and testing predictions and that the errors resulting from violations to these predictions are given a uniform, inflexibly high weight in autism spectrum disorder. The complex, fluctuating nature of regularities in the world and the stochastic and noisy biological system through which people experience it require that, in the real world, people not only learn from their errors but also need to (meta-)learn to sometimes ignore errors. Especially when situations (e.g., social) or stimuli (e.g., faces) become too complex or dynamic, people need to tolerate a certain degree of error in order to develop a more abstract level of representation. Starting from an inability to flexibly process prediction errors, a number of seemingly core deficits become logically secondary symptoms. Moreover, an insistence on sameness or the acting out of stereotyped and repetitive behaviors can be understood as attempts to provide a reassuring sense of predictive success in a world otherwise filled with error. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Distorted Symptom Perception in Patients With Medically Unexplained Symptoms

The present study investigated differences in symptom perception between a clinical sample with medically unexplained symptoms (MUS) and a matched healthy control group. Participants (N = 58, 29 patients) were told that they would inhale different gas mixtures that might induce symptoms. Next, they went through 2 subsequent rebreathing trials consisting of a baseline (60 s room air breathing), a rebreathing phase (150 s, which gradually increased ventilation, PCO2 in the blood, and perceived dyspnea), and a recovery phase (150 s, returning to room air breathing). Breathing behavior was continuously monitored, and dyspnea was rated every 10 s. The within-subject correlations between dyspnea on the one hand and end-tidal CO2 and minute ventilation on the other were used to index the degree to which perceived dyspnea was related to specific relevant respiratory changes. The results showed that perceived symptoms were less strongly related to relevant physiological parameters in MUS patients than in healthy persons, specifically when afferent physiological input was relatively weak. This suggests a stronger role for top-down psychological processes in the symptom perception of patients with MUS.

Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic condition. While considerable work has focused on cognitive functioning, several research groups also observed difficulties in social functioning as a prominent feature of NF1. These problems and the possible link between NF1 and Autism Spectrum Disorder (ASD) have become increasingly important in recent NF1 literature. The aim of the current study was to assess ASD characteristics in a hospital‐based NF1 pediatric population (n = 82) using the standardized Children Social Behavior Questionnaire (CSBQ) and Social Responsiveness Scale (SRS) to account for the prevalence, severity, and nature of social problems. In a parallel study, comprehensive ASD assessment was performed in a subgroup of NF1 children with a strong suspicion of ASD (n = 31). Results indicate that NF1 children have more social problems than typical controls, more frequently reported above 8 years. The SRS shows that 63% is at risk of ASD symptoms. According to item analyses, most problems were observed on items measuring orientation in, understanding of and being tuned onto a social situation (CSBQ) and social cognition and communication (SRS). In the parallel study, 27 NF1 children were diagnosed with ASD. These children have a distinct phenotype compared to a heterogeneous ASD group, with pronounced social–communicative impairments and fewer restrictive/repetitive behaviors. This study provides a better understanding of social problems in NF1 and the phenotypical overlap with ASD symptomatology. Despite their willingness to engage with others, NF1 children with or without ASD encounter various difficulties in their social–communicative life.

Haploinsufficiency of the autism candidate gene Neurobeachin induces autism-like behaviors and affects cellular and molecular processes of synaptic plasticity in mice

Neurobeachin (NBEA), a brain-enriched multidomain scaffolding protein involved in neurotransmitter release and synaptic functioning, has been identified as a candidate gene for autism spectrum disorder (ASD) in four unrelated patients haploinsufficient for NBEA. The aim of this study was to map the behavioral phenotype of Nbea(+/-) mice in order to understand its contribution to the pathogenesis of ASD. ASD-like behavioral variables of Nbea(+/-) mice were related to basal neuronal activity in different brain regions by in situ hybridizations and extracellular field recordings of synaptic plasticity in hippocampal cornu ammonis 1 (CA1) region. Levels of BDNF and phosphorylated cAMP response element-binding protein (CREB) were measured in an attempt to investigate putatively underlying changes in these neuromolecules. Nbea(+/-) mice exhibit several ASD-like features, including changes in self-grooming behavior, social behaviors, conditioned fear responses, and spatial learning and memory, which coincided with enhanced long-term potentiation (LTP) in their CA1 region. The observed alterations in learning and memory and hippocampal LTP are concomitant with decreased expression of the immediate early gene zif268 in dorsomedial striatum and hippocampal CA1 region, increased CREB phosphorylation, and increased hippocampal BDNF expression. These findings indicate that Nbea haploinsufficiency leads to various molecular and cellular changes that affect neuroplasticity and behavioral functions in mice, and could thus underlie the ASD symptomatology in NBEA deficient humans.

Executive functioning in autism spectrum disorders: influence of task and sample characteristics and relation to symptom severity

Impaired executive functioning (EF) has been proposed to underlie symptoms of autism spectrum disorders (ASD). However, insight in the EF profile of ASD individuals is hampered due to task impurity and inconsistent findings. To elucidate these inconsistencies, we investigated the influence of task and sample characteristics on EF in ASD, with an extended test battery designed to reduce task impurity. Additionally, we studied the relation between EF and ASD symptoms. EF (inhibition, cognitive flexibility, generativity, working memory and planning) was measured in open-ended versus structured assessment situations, while controlling for possible confounding EF and non-EF variables. The performance of 50 individuals with ASD was compared with that of 50 age, gender and IQ matched typically developing (TD) individuals. The effects of group (ASD versus TD), age (children versus adolescents) and gender were examined, as well as the correlation between age, IQ, ASD symptoms and EF. Individuals with ASD showed impairments in all EF domains, but deficits were more pronounced in open-ended compared to structured settings. Group differences did not depend on gender and only occasionally on participants’ age. This suggests that inconsistencies between studies largely result from differences in task characteristics and less from differences in the investigated sample features. However, age and IQ strongly correlated with EF, indicating that group differences in these factors should be controlled for when studying EF. Finally, EF correlated with both social and non-social ASD symptoms, but further research is needed to clarify the nature of this relationship.

Local and Global Visual Processing in Autism Spectrum Disorders: Influence of Task and Sample Characteristics and Relation to Symptom Severity

Local and global visual processing abilities and processing style were investigated in individuals with autism spectrum disorder (ASD) versus typically developing individuals, children versus adolescents and boys versus girls. Individuals with ASD displayed more attention to detail in daily life, while laboratory tasks showed slightly reduced global processing abilities, intact local processing abilities, and a more locally oriented processing style. However, the presence of these group differences depended on particular task and sample (i.e., age and gender) characteristics. Most measures of local and global processing did not correlate with each other and were not associated with processing style. Significant associations between local–global processing and ASD symptom severity were observed, but the causality of these associations remains unclear.

Executive functioning deficits in children with neurofibromatosis type 1: The influence of intellectual and social functioning

The aim of this study was to provide a broad picture of Executive Functioning (EF) in NF1 children, while taking into account their lower average IQ and increased Autism Spectrum Disorder (ASD) symptoms. This was done by administering an extended battery of tasks and questionnaires, designed to reduce task impurity, that measures five EF domains (inhibition, cognitive flexibility, working memory, generativity and planning) in a laboratory setting and in daily life. Data are presented for 42 age‐ and gender‐matched NF1, 52 typically developing, and 52 ASD children (8–18 years). Our results indicated that although EF is highly influenced by IQ and severity of ASD symptoms, EF deficits seem to be a core feature of NF1 and not merely a secondary effect of a lower IQ and/or increased ASD symptoms. However, additional research is needed to confirm these findings.

Alterations in the inferior longitudinal fasciculus in autism and associations with visual processing: a diffusion-weighted MRI study

BackgroundOne of the most reported neural features of autism spectrum disorder (ASD) is the alteration of multiple long-range white matter fiber tracts, as assessed by diffusion-weighted imaging and indexed by reduced fractional anisotropy (FA). Recent methodological advances, however, have shown that this same pattern of reduced FA may be an artifact resulting from excessive head motion and poorer data quality and that aberrant structural connectivity in children with ASD is confined to the right inferior longitudinal fasciculus (ILF). This study aimed at replicating the observation of reduced FA along the right ILF in ASD, while controlling for group differences in head motion and data quality. In addition, we explored associations between reduced FA in the right ILF and quantitative ASD characteristics, and the involvement of the right ILF in visual processing, which is known to be altered in ASD.MethodGlobal probabilistic tractography was performed on diffusion-weighted imaging data of 17 adolescent boys with ASD and 17 typically developing boys, matched for age, performance IQ, handedness, and data quality. Four tasks were administered to measure various aspects of visual information processing, together with questionnaires assessing ASD characteristics. Group differences were examined and the neural data were integrated with previously published findings using Bayesian statistics to quantify evidence for replication and to pool data and thus increase statistical power. (Partial) correlations were calculated to investigate associations between measures.ResultsThe ASD group showed consistently reduced FA only in the right ILF and slower performance on the visual search task. Bayesian statistics pooling data across studies confirmed that group differences in FA were confined to the right ILF only, with the evidence for altered FA in the left ILF being indecisive. Lower FA in the right ILF tended to covary with slower visual search and a more fragmented part-oriented processing style. Individual differences in FA of the right ILF were not reliably associated with the severity of ASD traits after controlling for clinical status.ConclusionOur findings support the growing evidence for reduced FA along a specific fiber tract in ASD, the right ILF.

Visuoperceptual processing in children with neurofibromatosis type 1: True deficit or artefact?

Impairments in visuoperceptual processing have long been considered a hallmark deficit of individuals with Neurofibromatosis type 1 (NF1). However, it is unclear which specific visuoperceptual subprocesses are impaired and whether impairments on these tasks really result from visuoperceptual impairments or rather from confounding factors like Executive Functioning (EF) impairments, lower intelligence (IQ) and/or co‐occurring symptoms of Autism Spectrum Disorder (ASD). To answer these questions, we administered four visuoperceptual tasks and two control tasks in 39 children with NF1, 52 typically developing children and 52 children with ASD (8–18 years), all matched for age and gender. Furthermore, EF, IQ, and symptoms of ASD were assessed. Children with NF1 displayed intact visual form discrimination and intact information integration along the dorsal visual pathway. Moreover, their reduced performance on a task requiring integration of information along the ventral visual stream and their more detail‐oriented processing style appeared to result from confounding EF impairments and not from visuoperceptual impairments per se. The co‐occurring ASD symptoms and lower IQ of the children with NF1 did not impact substantially upon their visuoperceptual performance. These findings point to the large impact of EF impairments on the performance of visuoperceptual task and suggest that individuals with NF1 show intact visual form discrimination, intact visual integration, and typical visual processing style when potential confounding factors are controlled for. This may have large repercussions for the interpretation of other findings on visuoperceptual processing in individuals with NF1.