Increasing Extrinsic Motivation Improves Time-Based Prospective Memory in Adults with Autism: Relations with Executive Functioning and Mentalizing

Time-based prospective memory (PM) is diminished under various task demands in individuals with autism spectrum disorder (ASD). However, it is still unclear what underpins their impairment or how it could be remediated. This study explored whether instructions to prioritise one element of a PM task over another improved performance in adults with ASD (compared to a group of matched neurotypical adults), and how that is related to cognitive abilities. Results indicated that importance instructions significantly improved the PM performance of participants with ASD. Moreover, the extent of the benefit was associated significantly with objectively-measured executive set-shifting ability and self-reported inhibitory control ability (the poorer the set-shifting/inhibitory control, the greater the benefit). Implications for future research and clinical practice are discussed

Prospective memory in children and adults with autism spectrum disorder

Prospective memory (PM) or memory for delayed intentions refers to the ability to remember to carry out a planned intention at an appropriate moment in the future. Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by a cognitive profile of strengths and weaknesses, which suggest that PM may be a challenge for individuals with this condition. A small group of studies investigating PM in ASD have produced heterogeneous evidence. Thus, the aim of this thesis was to advance our understanding of PM abilities in ASD. Based on a meta-analysis as well as a thorough review of the existing literature, the experiments in this thesis targeted two main questions. (1) What underpins time-based PM problems in ASD and how could they be addressed? (2) Is event-based PM in ASD impaired or spared? The findings in this thesis indicate that ASD is characterised by time-based PM impairments, which were related to executive functioning, on the one hand, whereas on the other hand event-based PM abilities remain spared. The theoretical and practical implications of these results, as well as directions for future research are discussed

The role of motion in the neural representation of social interactions in the posterior temporal cortex

Humans are an inherently social species, with multiple focal brain regions sensitive to various visual social cues such as faces, bodies, and biological motion. More recently, research has begun to investigate how the brain responds to more complex, naturalistic social scenes, identifying a region in the posterior superior temporal sulcus (SI-pSTS; i.e., social interaction pSTS), among others, as an important region for processing social interaction. This research, however, has presented images or videos, and thus the contribution of motion to social interaction perception in these brain regions is not yet understood. In the current study, 22 participants viewed videos, image sequences, scrambled image sequences and static images of either social interactions or non-social independent actions. Combining univariate and multivariate analyses, we confirm that bilateral SI-pSTS plays a central role in dynamic social interaction perception but is much less involved when ‘interactiveness’ is conveyed solely with static cues. Regions in the social brain, including SI-pSTS and extrastriate body area (EBA), showed sensitivity to both motion and interactive content. While SI-pSTS is somewhat more tuned to video interactions than is EBA, both bilateral SI-pSTS and EBA showed a greater response to social interactions compared to non-interactions and both regions responded more strongly to videos than static images. Indeed, both regions showed higher responses to interactions than independent actions in videos and intact sequences, but not in other conditions. Exploratory multivariate regression analyses suggest that selectivity for simple visual motion does not in itself drive interactive sensitivity in either SI-pSTS or EBA. Rather, selectivity for interactions expressed in point-light animations, and selectivity for static images of bodies, make positive and independent contributions to this effect across the LOTC region. Our results strongly suggest that EBA and SI-pSTS work together during dynamic interaction perception, at least when interactive information is conveyed primarily via body information. As such, our results are also in line with proposals of a third visual stream supporting dynamic social scene perception

The effect of body posture on cognitive performance: a question of sleep quality

Nearly all functional magnetic resonance imaging (fMRI) studies are conducted in the supine body posture, which has been discussed as a potential confounder of such examinations. The literature suggests that cognitive functions, such as problem solving or perception, differ between supine and upright postures. However, the effect of posture on many cognitive functions is still unknown. Therefore, the aim of the present study was to investigate the effects of body posture (supine vs. sitting) on one of the most frequently used paradigms in the cognitive sciences: the N-back working memory paradigm. Twenty-two subjects were investigated in a randomized within-subject design. Subjects performed the N-back task on two consecutive days in either the supine or the upright posture. Subjective sleep quality and chronic stress were recorded as covariates. Furthermore, changes in mood dimensions and heart rate variability (HRV) were assessed during the experiment. Results indicate that the quality of sleep strongly affects reaction times when subjects performed a working memory task in a supine posture. These effects, however, could not be observed in the sitting position. The findings can be explained by HRV parameters that indicated differences in autonomic regulation in the upright vs. the supine posture. The finding is of particular relevance for fMRI group comparisons when group differences in sleep quality cannot be ruled out

Molecular signatures of angiogenesis inhibitors: a single-embryo untargeted metabolomics approach in zebrafish

Angiogenesis is a key process in embryonic development, a disruption of this process can lead to severe developmental defects, such as limb malformations. The identification of molecular perturbations representative of antiangiogenesis in zebrafish embryo (ZFE) may guide the assessment of developmental toxicity from an endpoint- to a mechanism-based approach, thereby improving the extrapolation of findings to humans. Thus, the aim of the study was to discover molecular changes characteristic of antiangiogenesis and developmental toxicity. We exposed ZFEs to two antiangiogenic drugs (SU4312, sorafenib) and two developmental toxicants (methotrexate, rotenone) with putative antiangiogenic action. Molecular changes were measured by performing untargeted metabolomics in single embryos. The metabolome response was accompanied by the occurrence of morphological alterations. Two distinct metabolic effect patterns were observed. The first pattern comprised common effects of two specific angiogenesis inhibitors and the known teratogen methotrexate, strongly suggesting a shared mode of action of antiangiogenesis and developmental toxicity. The second pattern involved joint effects of methotrexate and rotenone, likely related to disturbances in energy metabolism. The metabolites of the first pattern, such as phosphatidylserines, pterines, retinol, or coenzyme Q precursors, represented potential links to antiangiogenesis and related developmental toxicity. The metabolic effect pattern can contribute to biomarker identification for a mechanism-based toxicological testing

A meta-analysis and critical review of prospective memory in autism spectrum disorder

Prospective memory (PM) is the ability to remember to carry out a planned intention at an appropriate moment in the future. Research on PM in ASD has produced mixed results. We aimed to establish the extent to which two types of PM (event-based/time-based) are impaired in ASD. In part 1, a meta-analysis of all existing studies indicates a large impairment of time-based, but only a small impairment of event-based, PM in ASD. In Part 2, a critical review concludes that time-based PM appears diminished in ASD, in line with the meta-analysis, but that caution should be taken when interpreting event-based PM findings, given potential methodological limitations of several studies. Clinical implications and directions for future research are discussed

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Extension of an open Machine Learning teaching resource by classification model material

This thesis aims to extend an existing Open Educational Resource (OER), which is available as a GitHub repository, and provide an organized introduction to basic machine learning (ML) concepts and algorithms. Further models, followed by structured metadata for each object, will be included while adhering to the contribution guidelines of the OER and following the CC license. The Machine-Learning-OER Basics repository intends to provide a wide range of benefits by enabling diverse users to apply and distribute machine learning algorithms. The goal of this digital collection is to fill the existing gap for instructional material on using machine learning in OER as well as make it easier to learn ML concepts effectively. These ML models are developed using the programming language Python and the library scikit-learn, among other standard libraries. Jupyter Notebook will make it straightforward for the user to explore the code. In order to apply the models to various practical scenarios, a non-specific data set is selected. This work is considered a solution approach in that it includes adding classification models. A performance comparison of the models is conducted. This comparative analysis evaluates the efficiency of each model. The examination includes various metrics for measurement. This work serves as a written extension, providing comprehensive background information on the algorithms utilized within the repositories and the performance comparison