Evidence of executive dysfunction in autism spectrum disorders (ASD) across development remains mixed and establishing its role is critical for guiding diagnosis and intervention. The primary objectives of this meta-analysis is to analyse executive function (EF) performance in ASD, the fractionation across EF subdomains, the clinical utility of EF measures and the influence of multiple moderators (for example, age, gender, diagnosis, measure characteristics). The Embase, Medline and PsychINFO databases were searched to identify peer-reviewed studies published since the inclusion of Autism in DSM-III (1980) up to end of June 2016 that compared EF in ASD with neurotypical controls. A random-effects model was used and moderators were tested using subgroup analysis. The primary outcome measure was Hedges’ g effect size for EF and moderator factors. Clinical sensitivity was determined by the overlap percentage statistic (OL%). Results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081 participants were included (N, ASD=6816, Control=7265). A moderate overall effect size for reduced EF (Hedges’ g=0.48, 95% confidence interval (CI) 0.43–0.53) was found with similar effect sizes across each domain. The majority of moderator comparisons were not significant although the overall effect of executive dysfunction has gradually reduced since the introduction of ASD. Only a small number of EF measures achieved clinical sensitivity. This study confirms a broad executive dysfunction in ASD that is relatively stable across development. The fractionation of executive dysfunction into individual subdomains was not supported, nor was diagnostic sensitivity. Development of feasible EF measures focussing on clinical sensitivity for diagnosis and treatment studies should be a priority.
The refined formulas yield improved exchange rate estimation. General convergence intervals of the methods that would apply for smaller shift agents are also discussed. Magn Reson Med 79:1708-1721, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
This review presents an outline of executive function (EF) and its application to autism spectrum disorder (ASD). The development of the EF construct, theoretical models of EF, and limitations in the study of EF are outlined. The potential of EF as a cognitive endophenotype for ASD is reviewed, and the Research Domain Criteria (RDoC) framework is discussed for researching EF in ASD given the multifaceted factors that influence EF performance. A number of executive-focused cognitive models have been proposed to explain the symptom clusters observed in ASD. Empirical studies suggest a broad impairment in EF, although there is significant inter-individual variability in EF performance. The observed heterogeneity of EF performance is considered a limiting factor in establishing EF as a cognitive endophenotype in ASD. We propose, however, that this variability in EF performance presents an opportunity for subtyping within the spectrum that can contribute to targeted diagnostic and intervention strategies. Enhanced understanding of the neurobiological basis that underpins EF performance, such as the excitation/inhibition hypothesis, will likely be important. Application of the RDoC framework could provide clarity on the nature of EF impairment in ASD with potential for greater understanding of, and improved interventions for, this disorder.
The ability to walk is critical for functional independence and wellbeing. The pre-frontal cortex (PFC) plays a key role in cognitive control of locomotion, notably under attention-demanding conditions. Factors that influence brain responses to cognitive demands of locomotion, however, are poorly understood. Herein we evaluated the individual and combined effects of gender and perceived stress on stride velocity and PFC Oxygenated Hemoglobin (HbO2) assessed during single and dual-task walking conditions. The experimental paradigm included three tasks: a) Normal-Walk (NW); b) Cognitive Interference (Alpha); c) Walk-While-Talk (WWT). An instrumented walkway was used to assess stride velocity in NW and WWT conditions. Functional Near-Infrared-Spectroscopy (fNIRS) was used to quantify PFC HbO2 levels during NW, Alpha and WWT. Perceived task-related stress was evaluated with a single 11-point scale item. Participants were community residing older adults (age=76.8±6.7ys; %female=56). Results revealed that higher perceived stress was associated with greater decline in stride velocity from single to dual-task conditions among men. Three-way interactions revealed that gender moderated the effect of perceived stress on changes in HbO2 levels comparing WWT to NW and Alpha. Attenuation in the increase in HbO2 levels, in high compared to low perceived stress levels, from the two single task conditions to WWT was observed only in men. Conclusion Older men maybe more vulnerable to the effect of perceived stress on the change in PFC oxygenation levels across walking conditions that vary in terms of cognitive demands. These findings confer important implications for assessment and treatment of individuals at risk of mobility impairments.
In this study, we consecutively recruited treatment-seeking young autistic adults without intellectual impairment aged 16–30 years who presented to a mental health service and evaluated general health (distress, quality of life, and disability), functioning (work loss days and social functioning), and mood symptoms (depression, anxiety, and stress) in those diagnosed with autism spectrum disorder ( n = 96). This group was compared to young adults presenting to the same service with primary mental health disorders (depression, n = 343; bipolar, n = 132; psychosis, n = 166; and anxiety, n = 303). This study also investigated the influence of mood symptoms on general health and functioning in the autism spectrum disorder group. Young autistic adults reported significant general health and functioning impairments that were of similar degree to those presenting with primary mental health disorders. Interestingly, the autistic group also reported similarly high levels of mood symptoms to those with primary depressive and anxiety disorders. In the autistic group, depressive symptoms were strongly associated with distress, quality of life, and work loss days, while stress symptoms were strongly associated with disability. This study highlights further research, and mental health services are required specifically targeting young autistic adults to address their significant unmet needs.
Background: The aim of this study was to translate dynamic glucose enhancement (DGE) body magnetic resonance imaging (MRI) based on the glucose chemical exchange saturation transfer (glucoCEST) signal to a 3 T clinical field strength. Methods: An infusion protocol for intravenous (i.v.) glucose was optimised using a hyperglycaemic clamp to maximise the chances of detecting exchange-sensitive MRI signal. Numerical simulations were performed to define the optimum parameters for glucoCEST measurements with consideration to physiological conditions. DGE images were acquired for patients with lymphomas and prostate cancer injected i.v. with 20% glucose. Results: The optimised hyperglycaemic clamp infusion based on the DeFronzo method demonstrated higher efficiency and stability of glucose delivery as compared to manual determination of glucose infusion rates. DGE signal sensitivity was found to be dependent on T 2 , B 1 saturation power and integration range. Our results show that motion correction and B 0 field inhomogeneity correction are crucial to avoid mistaking signal changes for a glucose response while field drift is a substantial contributor. However, after B 0 field drift correction, no significant glucoCEST signal enhancement was observed in tumour regions of all patients in vivo. Conclusions: Based on our simulated and experimental results, we conclude that glucose-related signal remains elusive at 3 T in body regions, where physiological movements and strong effects of B 1 + and B 0 render the originally small glucoCEST signal difficult to detect.
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