Autistic adolescents show atypical activation of the brain′s mentalizing system even without a prior history of mentalizing problems

AbstractSome autistic children pass classic Theory of Mind (ToM) tasks that others fail, but the significance of this finding is at present unclear. We identified two such groups of primary school age (labelled ToM+ and ToM−) and a matched comparison group of typically developing children (TD). Five years later we tested these participants again on a ToM test battery appropriate for adolescents and conducted an fMRI study with a story based ToM task. We also assessed autistic core symptoms at these two time points. At both times the ToM− group showed more severe social communication impairments than the ToM+ group, and while showing an improvement in mentalizing performance, they continued to show a significant impairment compared to the NT group. Two independent ROI analyses of the BOLD signal showed activation of the mentalizing network including medial prefrontal cortex, posterior cingulate and lateral temporal cortices. Strikingly, both ToM+ and ToM− groups showed very similar patterns of heightened activation in comparison with the NT group. No differences in other brain regions were apparent. Thus, autistic adolescents who do not have a history of mentalizing problems according to our ToM battery showed the same atypical neurophysiological response during mentalizing as children who did have such a history. This finding indicates that heterogeneity at the behavioural level may nevertheless map onto a similar phenotype at the neuro-cognitive level

Examining patient preferences in the treatment of rheumatoid arthritis using a discrete-choice approach

Background: Biological disease-modifying antirheumatic drugs (bDMARDs) used in second-line treatment of rheumatoid arthritis (RA) are administered parenterally. However, so-called targeted synthetic DMARDs (tsDMARDs) – developed more recently – offer alternative (ie, oral) administration forms in second-line treatment. Since bDMARDs and tsDMARDs can be regarded as equal in terms of efficacy, the present study examines whether such characteristics as route of administration drive RA patients’ treatment choice. This may ultimately suggest superiority of some second-line DMARDs over equally effective options, at least according to RA-patient preferences. Objective: The current study assessed the importance of oral administration among other treatment characteristics differing between available second-line DMARDs for RA patients’ preferences using a discrete-choice experiment (DCE). Materials and methods: The DCE involved scenarios of three hypothetical treatment options in a d-efficient design with varying levels of key attributes (route and frequency of administration, time till onset of drug effect, combination therapy, possible side effects), as defined by focus groups. Further patient characteristics were recorded by an accompanying questionnaire. In the DCE, patients were asked to choose best and worst options (best–worst scaling). Results were analyzed by count analysis and adjusted regression analysis. Results: A total of 1,588 subjects completed the DCE and were eligible for final analyses. Across all characteristics included in the DCE, “oral administration” was most desired and “intravenous infusion” was most strongly rejected. This was followed by “no combination with methotrexate” being strongly preferred and “intake every 1–2 weeks” being strongly rejected. On average, levels of route of administration showed strongest influences on patients’ decisions in post hoc bootstrapping analysis. Conclusion: According to the results, an oral DMARD that does not have to be combined with methotrexate and is not administered (only) every 1–2 weeks appears a highly favorable treatment option for patients with RA. DMARDs meeting these preferences may increase compliance and adherence in RA treatment

Automaticity in affective face processing

Emotionale Gesichtsausdrücke sind hochrelevante Reize für den Menschen. Es wurde daher angenommen, dass sie von evolutionär bedingten Mechanismen automatisch verarbeitet werden. Bis zu welchem Maße diese Verarbeitung tatsächlich automatisch verläuft ist noch immer kontrovers. Die vorliegende Arbeit schließt an diese Debatte an, indem sie eine spontane Tendenz aufzeigt vor allem bedrohlichen Gesichtsaudrücken vermehrt Verarbeitungsressourcen zuzuweisen, auch dann, wenn sie nur oberflächlich enkodiert werden und Emotionalität irrelevant für die gegebene Aufgabe ist (Studie 1 und 2). Diese Tendenz wurde bezüglich zweier Schlüsselkriterien von Automatizität untersucht, nämlich dem Intentionalitäts- (Studie 3) und dem Auslastungskriterium (Studie 4 und 5); diese nehmen an, dass automatische Verarbeitung unabhängig von der gegebenen Intention des Individuums, beziehungsweise konkurrierender Aufgabenanforderungen verläuft. Anhand ereigniskorrelierter Potenziale (EKPs) konnte gezeigt werden, dass verstärkte perzeptuelle Enkodierung emotionaler Gesichtsausdrücke weitgehend unabhängig von Intention auftrat, wohingegen verstärkte höhere kognitive Verarbeitung davon abhing, ob Reize vertieft verarbeitet wurden (Studie 3). Wurde die Kontrolle über die Gesichtsverarbeitung durch eine konkurrierende Aufgabe beeinträchtigt, während Emotionalität relevant war, so verstärkte dies emotionale Effekte auf der perzeptuellen und frühen, höheren kognitiven Ebene (Studie 4). Ähnliches konnte auch für die perzeptuelle Verarbeitung attraktiver Gesichter beobachtet werden (Studie 5). Hingegen war bei verminderter Kontrolle die verstärkte Enkodierung bedrohlicher Ausdrücke in späten kognitiven Verarbeitungsstufen unterdrückt. Die vorliegenden Befunde sprechen gegen eine Automatisierung affektiver Gesichtsverarbeitung und legen stattdessen nahe, dass biologisch vorbereitete Verarbeitungstendenzen durch aufgabenorientierte Kontrollmechanismen und ihr Zusammenspiel mit Intention moduliert werden.Emotional facial expressions are highly relevant stimuli in humans. It has thus been suggested that they are processed automatically by evolutionarily in-built mechanisms. However, to which extent such processing in fact arises automatically is still controversial. The current work feeds into this debate by showing a tendency to spontaneously allocate increased processing capacity to emotional, especially threat-related expressions, even when processed merely superficially and emotionality is irrelevant to the task at hand (Study 1 and 2). This bias was further tested with regard to key criteria of automaticity; that is the intentionality (Study 3) and the load-insensitivity criterion (Study 4 and 5) assuming automatic processing to arise irrespective of intention of the individual, and concurrent task demands, respectively. Event-related brain potentials (ERPs) revealed enhanced perceptual encoding of threat-related expressions to remain largely unaffected by intention. In contrast, at the higher cognitive level, enhanced encoding depended on whether stimuli were voluntarily processed more deeply (Study 3). However, when control over face processing was impaired by a concurrent task, while emotionality was deemed relevant, emotion effects were enhanced at both, the perceptual and early higher cognitive level (Study 4). Similar was observed for perceptual encoding of attractive faces (Study 5). In contrast, during late higher cognitive stages of in-depth face processing, enhanced encoding of threat was eliminated when control was reduced (Study 4). The present results speak against full automaticity in affective face processing but suggest that biologically prepared processing biases are modulated by task-oriented control mechanisms and their interplay with intention