Event-Related Potentials and Executive Function in Adolescents with Autism Spectrum Disorders; a Case-Control Study
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- Institutt for psykisk helse 
Autism Spectrum Disorder (ASD) is now regarded a neurobiological disorder (NDD) with perturbations of brain development. Even so, the diagnosis is still defined based on behavioral criteria, including developmental history and observations of present behavior. The wide range of ability and disability in ASD creates a need for tools that parse the phenotypic heterogeneity into meaningful subtypes with respect to both understanding disease mechanisms and managing symptoms. A steadily increasing number of genes are found to be associated with ASD, and the connections between genotype and phenotype is complex. Performance in neuropsychological tests show considerable variations within the group, and is not necessarily associated with symptom severity or core disease features. The aim of the current study is to identify electrophysiological correlates of core features at a biological level between genetics and behavior and by this elucidate neuropathological mechanisms. The focus is on performance and electrophysiological parameters related to executive function (EF), the effect of emotional content in the stimuli and age related changes. Electrophysiological data during a cognitive task performance were recorded to capture real time neurobiological activity. The participants included 49 adolescents 12 – 21 years with ASD and 49 typical developing (TD) adolescents in the same age range. Electrophysiological responses in the electroencephalogram (EEG) were registered while the participants completed a visual cued Go-Nogo task with either neutral (part one) or emotional (part two) pictures as stimuli. All data were registered in the two parts of the test separately. Social function was assessed by parent-rated Social Responsiveness Scale (SRS), EF by performance in the task and parent-rated Behavior Rating Inventory of Executive Function (BRIEF). The SRS and BRIEF scores were markedly enhanced in the ASD group (Cohens d correspondingly 3.7/ 3.1). The effect of age was investigated either with age as a continuous variable or by splitting the participants at the age of 16 years. Performance data; reaction time (RT), reaction time variability (RTV), omissions and commissions, were registered. The following Event Related Potentials (ERPs) were computed: cue P3, CNV, N2 Go/ Nogo and P3 Go/ Nogo. The first paper focuses on the performance data. In the part with emotional pictures, a positive correlation between reaction time (RT)/ reaction time variability (RTV) and social function (SRS) (p = 0.044/ 0.037) was found in the young age group, suggesting increasing difficulties in emotion recognition with increasing social problems. The results did not support the same in the old group or in part one of the task. In the last quartile of the test, RTV in participants over 16 years was negatively correlated with SRS (p = 0.011), suggesting enhanced sustained attention with increasing social problems. In the second paper, ERPs elicited by the cued Go-Nogo task are discussed. The P3s, components related to target identification and response selection, were similar between ASD and TD. The CNV, associated with response preparation, was enhanced in the old group of ASD participants (p = 0.015). When excluding participants with comorbid ADHD this CNV enhancement increased (p = 0.008). In the ASD-group without comorbid ADHD, enhancement in the N2, a component supposed to represent conflict monitoring, was found. The ERPs related to emotional pictures were equally attenuated in all participants, suggesting a similar effect of stimulus content on neurophysiological responses in ASD and TD. Thus, performance in our task did not indicate executive dysfunction in ASD, despite markedly increased deficits in everyday EF as reported by scores on the BRIEF. On the contrary, the study supports enhanced response preparation and conflict monitoring in ASD. This may be related to the clinical core feature Insistence of Sameness (IOS). The third paper aimed to evaluate the ERPs in the passive parts of the test, when no action was required. The peak amplitude and latency of the occipital N1, an early ERP related to visual perception, and the P3a amplitude, a component related to switching of attention, were calculated. The N1 peak was markedly delayed in ASD subjects, (p < 0.001, Cohens d = 0.75) and the P3a amplitude was increased (p = 0.002, Cohens d = 0.64). N1 latency and P3a amplitude correlated positively with the BRIEF (r = 0.35/ 0.35, p = 0.003). This study supports delayed emotion recognition in young adolescents with ASD. No executive dysfunction in task performance was found, on the contrary, enhanced sustained attention measured as reduced RTV was found with increasing social problems. ERP components suggesting enhanced response preparation and conflict monitoring were registered in ASD. The ASD participants also showed delayed components related to perception and increased components related to attention orienting in the passive parts of the test, suggesting “hyper-awareness” and abnormal attention allocation. Our findings underscore the importance of controlling for comorbidity when interpreting results of studies on ASD. Describing meaningful subtypes of ASD has proven difficult. ERP alterations may be useful biomarkers contributing to stratification of the disorder to better understand underlying pathology and guide effective interventions.
Has partsPaper 1: Høyland, Anne Lise; Nærland, Terje; Engstrøm, Morten; Lydersen, Stian; Andreassen, Ole Andreas. The relation between face-emotion recognition and social function in adolescents with autism spectrum disorders: A case control study. PLoS ONE 2017 ;Volum 12.(10) s. 1-16 - This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://doi.org/10.1371/journal.pone.0186124
Paper 2: Høyland, Anne Lise; Øgrim, Kjell Geir; Lydersen, Stian; Hope, Sigrun; Engstrøm, Morten; Torske, Tonje; Nærland, Terje; Andreassen, Ole Andreas. Event-related potentials in a cued Go-NoGo task associated with executive functions in adolescents with autism spectrum disorder; A case-control study. Frontiers in Neuroscience 2017 ;Volum 11:393. s. 1-13 - This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) https://doi.org/10.3389/fnins.2017.00393
Paper 3: Høyland, A. L., Nærland, T., Lydersen, S., Engstrøm, M., Torske, T. & Andreassen, O. A. Atypical Event Related Potentials revealed during the passive parts of a Go- Nogo task in Autism Spectrum Disorder. A case-control study.