Specificity of the short-story task for autism diagnosis when controlling for depression.

Securing an accurate autism-spectrum-condition diagnosis, particularly among women, remains challenging for autistic adults. Building upon previous research highlighting the short-story task (SST) as a promising tool for detecting fiction-based mentalizing difficulties in autistic adults, this study expands its scope. We investigated the SST's discriminative capacity across three distinct groups: autistic individuals (n = 32), nonautistic individuals without mental health problems (n = 32), and nonautistic individuals with clinical depression (n = 30). All three groups differed significantly from each other in their SST mentalizing score with the nonautistic group having the highest scores, the nonautistic but depressed group having medium scores and the autistic group showing the lowest scores. Receiver operator curve (ROC) analysis reaffirmed the SST's efficacy as a discriminator. Moreover, a linear regression analysis identified the SST mentalizing score, the SST comprehension score, and the number of books read per month as significant predictors of autism-spectrum-condition diagnosis. These findings bolster the SST's potential as a valuable adjunct in autism diagnostics, highlighting its discriminatory ability across diverse samples.

"Why do they do it?": The short-story task for measuring fiction-based mentalizing in autistic and non-autistic individuals.

This study aimed to validate the short-story-task (SST) based on Dodell-Feder et al. as an instrument to quantify the ability of mentalizing and to differentiate between non-autistic adults and autistic adults, who may have acquired rules to interpret the actions of non-autistic individuals. Autistic (N = 32) and non-autistic (N = 32) adult participants were asked to read "The End of Something" by Ernest Hemingway and to answer implicit and explicit mentalizing questions, and comprehension questions. Furthermore, verbal and nonverbal IQ was measured and participants were asked how much fiction they read each month. Mentalizing performance was normally distributed for autistic and non-autistic participants with autistic participants scoring in the lower third of the distribution. ROC (receiver operator curve) analysis revealed the task to be an excellent discriminator between autistic and non-autistic participants. A linear regression analysis identified number of books read, years of education and group as significant predictors. Overall, the SST is a promising measure of mentalizing. On the one hand, it differentiates among non-autistic individuals and on the other hand it is sensitive towards performance differences in mentalizing among autistic adults. Implications for interventions are discussed.

False Belief Reasoning in Adults with and without Autistic Spectrum Disorder: Similarities and Differences.

A central diagnostic criteria for autism spectrum disorder (ASD) is the qualitative impairment in reciprocal social interaction and a prominent hypotheses that tried to explain this impairment is the Theory of Mind (ToM) deficit hypotheses. On a behavioral level the critical test for having a ToM, the understanding of false beliefs (FB), is often used for testing ToM abilities in individuals with ASD. Investigating the neural underpinnings several neuroimaging studies revealed a network of areas involved in FB reasoning in neurotypical individuals. For ASD individuals the neural correlates of false belief processing are largely unknown. Using functional magnetic resonance imaging and an adapted unexpected transfer task, that makes it possible to distinguish between the computation of diverging beliefs and the selection of a belief-associated response, we investigated a group of adult high-functioning individuals with ASD (N = 15) and an age and IQ matched group of neurotypical adults (NT; N = 15). On the behavioral level we found no group differences. On the neural level, results were two-fold: In the story phase, in which participants had to compute whether the character's belief is congruent or incongruent to their own belief, there were no differences between neurotypical participants and those diagnosed with ASD. But, in the subsequent question phase, participants with ASD showed increased activity in the bilateral anterior prefrontal cortex, the left posterior frontal cortex, the left superior temporal gyrus, and the left temporoparietal area. These results suggest that during the story phase in which the participants processed observable actions the neural correlates do not differ between adult individuals with ASD and NT individuals. But in the question phase in which participants had to infer an unobservable mental state results revealed neural differences between the two groups. Possibly, these subtle neural processing differences may contribute to the fact that adult ASD individuals are able to master explicit false belief tasks but fail to apply their strategies during everyday social interaction.

Acute psychosocial stress and everyday moral decision-making in young healthy men: The impact of cortisol.

In everyday life, moral decisions must frequently be made under acute stress. Although there is increasing evidence that both stress and cortisol affect moral judgment and behavior as well as decision-making in various domains unrelated to morality, surprisingly few attempts have been made to explore the effects of stress on everyday moral decision-making. Therefore, in the present study, we exposed 50 young healthy men to the Trier Social Stress Test (TSST) or its non-stressful placebo version (PTSST). We investigated the impact of acute stress exposure and stress-related cortisol levels on decision-making, decision certainty, and emotions in 28 everyday moral conflict situations with altruistic versus egoistic response alternatives. Results showed that the TSST-exposed group made more altruistic decisions than the non-stress control group, while groups did not differ in decision certainty and emotion ratings. Moreover, in correlational as well as regression analyses, additionally controlling for confounding variables, we observed significant positive associations between cortisol levels and altruistic decision-making. Further analyses revealed that altruistic decisions came along with significantly higher decision certainty and significantly more positive emotion ratings than egoistic decisions. Notably, our data also raise the idea that the personality trait agreeableness plays an important role in everyday moral decision-making. In sum, our findings provide initial evidence that both acute stress exposure and cortisol levels have prosocial effects on everyday moral decision-making in young healthy men.

An fMRI study on the comparison of different types of false belief reasoning: False belief-based emotion and behavior attribution.

False belief (FB) reasoning is a key Theory of Mind (ToM) competence. By 4 years of age, children understand that a person's behavior can be based on a FB about reality. Children cannot understand that a person's emotion can also be based on a FB before the age of six. In order to generate hypothesis on basic processes distinguishing these two types of belief reasoning, the present functional magnetic resonance imaging study in adults directly compares functional activity associated with these two FB tasks. Both tasks were associated with activity in the ToM network including the medial prefrontal cortex and the left temporo-parietal junction. Differential activity was observed in the anterior dorsolateral prefrontal cortex for FB-based emotion relative to behavior attribution. Contrary to FB behavior attribution, FB-based emotion attribution requires the processing of two different mental states: a belief and an emotion and their relation to each other. The activity pattern may reflect the differential demands on cognitive processes associated with the two different belief-based attribution processes. These results shed new light on the still ongoing debate about the nature of the developmental lag between the two FB tasks.

Inhibiting the posterior medial prefrontal cortex by rTMS decreases the discrepancy between self and other in Theory of Mind reasoning.

Switching between one's own and another person's perspective is a cognitive component of Theory of Mind (ToM) reasoning that is essential for successful social interaction. Computing another's divergent belief independently from one's own perspective poses a particular challenge. Neuroimaging has demonstrated the involvement of the posterior medial prefrontal cortex (pMPFC) in establishing this perspective difference. Here, we transiently interfered with pMPFC activity by repetitive transcranial magnetic stimulation (rTMS) in a sample of young healthy adults. Reaction times of belief judgments in an adapted false belief task were measured after 1Hz rTMS applied via a double-cone coil. This procedure decreased the discrepancy in reaction times between judging another's and one's own belief, irrespective of whether they were incongruent or congruent. The current results suggest that pMPFC inhibition impaired the ability to distinguish the other's from one's own perspective and support the pMPFC's causal role in establishing perspective differences, an essential component of ToM reasoning.

Me or you? Neural correlates of moral reasoning in everyday conflict situations in adolescents and adults.

Throughout adolescence, progress in the understanding of the moral domain as well as changes in moral behavior is observable. We tested 16 adolescents (14-16 years of age) and 16 healthy adults (22-31 years of age) on the developmental changes in everyday moral decision making using functional magnetic resonance imaging (fMRI). Using verbal stories describing everyday moral conflict situations, subjects had to decide between a moral standard or a personal desire. In the moral conflict situations, adolescents not only chose significantly more often the hedonistic alternative than adults, but they also reported higher certainty ratings. Contrasted with everyday social conflict situations that required a decision between a social-oriented behavior and a personal need, moral conflict situations induced an activity increase in frontal areas, the middle temporal gyrus, the thalamus, and the parahippocampal gyrus in adolescents compared to adults. Moreover, a closer look at the moral conflict situations revealed that adolescents showed more activity than adults in brain areas that are also centrally involved in theory of mind (ToM) during morally oriented decisions in contrast to personal-oriented decisions. This indicated that the development of moral reasoning may be strongly correlated with the development of ToM reasoning.

Ongoing neural development of affective theory of mind in adolescence.

Affective Theory of Mind (ToM), an important aspect of ToM, involves the understanding of affective mental states. This ability is critical in the developmental phase of adolescence, which is often related with socio-emotional problems. Using a developmentally sensitive behavioral task in combination with functional magnetic resonance imaging, the present study investigated the neural development of affective ToM throughout adolescence. Eighteen adolescent (ages 12-14 years) and 18 young adult women (aged 19-25 years) were scanned while evaluating complex affective mental states depicted by actors in video clips. The ventromedial prefrontal cortex (vmPFC) showed significantly stronger activation in adolescents in comparison to adults in the affective ToM condition. Current results indicate that the vmPFC might be involved in the development of affective ToM processing in adolescence.

Functional activity and effective connectivity of the posterior medial prefrontal cortex during processing of incongruent mental states.

The neurocognitive components of Theory of Mind reasoning remain poorly understood. In particular the role of the posterior medial prefrontal cortex in the processing of other's mental states such as beliefs that are incongruent with one's own knowledge of reality is not clear-cut. It is unknown whether this region is involved in computing discrepant mental states or in subsequently resolving a response conflict between the discrepant others' and one's own beliefs. To test this, we adapted a false belief paradigm for the separate inspection of functional brain activity related to (1) the computation of diverging beliefs and (2) the subsequent consideration and selection of another's or one's own belief. Based on statistical parametric findings from functional neuroimaging, we employed dynamic causal modelling combined with Bayesian model selection to further characterize the interplay of resulting brain regions. In the initial computation of diverging beliefs, the posterior medial prefrontal cortex (pMPFC) and the bilateral temporoparietal cortex were crucially involved. The findings suggest that the bilateral temporal cortex engages in the construction and adjustment of diverging mental states by encoding relevant environmental information. The pMPFC inhibits this stimulus-bound processing which helps to compute discrepant mental states and process another's false belief decoupled from one's own perception of reality. In the subsequent question phase the right temporoparietal cortex showed increased activity related to switching to and reconsidering another's beliefs in order to select the correct response.

Functional activity of the right temporo-parietal junction and of the medial prefrontal cortex associated with true and false belief reasoning.

Since false belief reasoning requires mental state representation independently of the state of reality, it is seen as a key ability in Theory of Mind (ToM). Although true beliefs do not have to be processed independently of the state of reality, growing behavioural evidence indicates that true belief reasoning is different from just reasoning about the state of reality. So far, neural studies on true and false belief reasoning revealed inconsistent findings in the medial prefrontal cortex (MPFC) and in the right temporo-parietal junction (R-TPJ), brain regions that are hypothesized to play an important role in ToM. To further explore true and false belief reasoning, the present functional magnetic resonance imaging (fMRI) study in eighteen adult subjects used methodological refinements such as ensuring that the true belief trials did not elicit false belief reasoning, as well as including paralleled control conditions requiring reasoning about the state of reality. When compared to its control condition, common R-TPJ activity was observed for true and false belief reasoning, supporting its role in belief reasoning in general, and indicating that, at least in adults, also true belief reasoning appears to be different from reasoning about the state of reality. Differential activity was observed in a broad network of brain regions such as the MPFC, the inferior frontal cortex, and the precuneus. False over true belief reasoning induced activation in the posterior MPFC (pMPFC), supporting its role in the decoupling mechanisms, which is defined as processing a mental state independently of the state of reality.

Common and distinct neural networks for false-belief reasoning and inhibitory control.

Ample behavioral evidence has shown that the ability to attribute false beliefs as part of a Theory of Mind (ToM) and the ability to inhibit a prepotent response are strongly correlated in both children and adults. Frequently reported areas associated with both processes are the right temporo-parietal junction (TPJ) and the medial prefrontal cortex (MPFC). Nevertheless, the exact nature of the relationship between belief-reasoning and inhibitory control at the neural level remains unclear. A functional magnetic resonance imaging (fMRI) study was conducted to investigate the neural correlates of belief-reasoning and inhibitory control in a within-subjects design using virtually identical visual stimuli. A false-belief task was used to investigate belief-attribution. The neural correlates of response inhibition were measured using a Go/No-Go task. Besides distinct activation for belief-reasoning and inhibitory control, the results also showed a substantial overlap for both processes in the right superior dorsal MPFC, the right TPJ, the dorsal part of the left TPJ, and lateral prefrontal areas. These findings suggest that the previously described behavioral link between belief attribution and inhibitory control may be explained by a common recruitment of brain areas related to domain-general cognitive processes. Also, the results indicate that neither the right TPJ nor MPFC is specific to the attribution of false beliefs.

True- and false-belief reasoning in children and adults: an event-related potential study of theory of mind.

The understanding that another person's belief can differ from reality and that behaviour is guided by beliefs and not by reality reflects an important cornerstone in the development of a Theory of Mind. The present event-related potential (ERP) study had two aims: first, to reveal ERPs that distinguish between false- and true-belief reasoning and second, to investigate the neural changes in the development of false- and true-belief reasoning from childhood to adulthood. True- and false-belief cartoon stories were presented to adults and 6-8-year-old children. Results revealed two waveforms that differentiated between the two conditions: a late positive complex (LPC) associated with the reorientation from external stimuli to internal mental representations and a late anterior slow wave (LSW) associated with stimulus-independent processing of internal mental representations, a process that might be centrally involved in the decoupling mechanism. Additionally, we found developmental effects at an ERP level. Children showed a more posterior localization of the LPC and a broader frontal distribution of the LSW. The results may reflect developmental progress in conceptualizing the mental domain and support the idea that the cortical mentalizing network continues to develop even after children are able to master false beliefs.

Modulation of the cortical false belief network during development.

The ability to represent false beliefs is commonly considered as to be the critical test for having a Theory of Mind (ToM). For correct predictions or explanations of other peoples' behavior it is necessary to understand that mental states are sometimes independent of reality and misrepresent the real state of the world. In contrast, when people hold true beliefs, predictions and explanations about behavior can simply be derived from reality. Previous neuroimaging studies with adults suggest that the dorsal medial prefrontal cortex (dmPFC) and the right temporo-parietal junction (rTPJ) are engaged in false belief reasoning. However, studies investigating the neural correlates of belief reasoning in children are rare. Using cartoon stories that depicted an unexpected transfer, we compared false belief reasoning with true belief reasoning in children of a narrow age range between 10 and 12years and in adults. In both groups, the dorsal medial frontal cortex was activated during false versus true belief reasoning. In contrast to adults, children did not selectively recruit the rTPJ during false belief reasoning. We found a group by belief interaction in the right rostral PFC and the posterior cingulate cortex. In these areas, children compared to adults showed increased activity associated with false belief reasoning in contrast to true belief reasoning. These results implicate modulation of the cortical network that underlies false belief reasoning during development and far beyond the time children successfully master false belief tasks.

In psychopathic patients emotion attribution modulates activity in outcome-related brain areas.

The understanding that other people's emotional states depend on the fulfilment of their intention is fundamentally important for responding adequately to others. Psychopathic patients show severe deficits in responding adequately to other people's emotion. The present study explored whether these impairments are associated with deficits in the ability to infer others' emotional states. Using functional magnetic resonance imaging (fMRI), identical cartoon stories, depicting a subject whose intention was fulfilled or not fulfilled, were presented to 14 psychopathic patients and 14 non-psychopathic patients. The participants should indicate the protagonist's emotional state. Additionally, a non-mentalizing control condition was presented. The two groups showed no behavioural differences. But in non-psychopathic patients emotion attribution was associated with increased activity of the mirror neuron system, the bilateral supramarginal gyrus and the superior frontal gyrus. In contrast psychopathic patients showed increased activation of regions associated with outcome monitoring and attention, such as the orbitofrontal cortex, the medial frontal cortex and temporo-parietal areas. The results emphasize that although psychopathic patients show no deficits in reasoning about other people's emotion if an explicit evaluation is demanded, they use divergent neural processing strategies that are related to more rational, outcome-oriented processes.

How should I decide? The neural correlates of everyday moral reasoning.

The present fMRI study is the first that investigates everyday moral conflict situations in which a moral standard clashes with a personal desire. In such situations people have to decide between a morally guided and a hedonistic behaviour. Twelve healthy subjects were presented with verbal stories describing conflicts with either moral or neutral content. The moral stories described conflicts requiring a decision between a personal desire and a conflicting moral standard, whereas the neutral conflicts required a decision between two conflicting personal desires. When compared to neutral conflicts, moral conflicts elicited higher activity in a wide spread neural network including the medial frontal cortex, the temporal cortex and the temporo-parietal junction and the posterior cingulate cortex. Further analyses of the moral conflicts revealed that hedonistic decisions in contrast to morally guided decisions were associated with significantly higher rankings of uncertainty and unpleasant emotions and induced significant more activation in the amygdala/parahippocampal region. The present results generalise findings on the neuroscience of moral understanding by extending it to everyday moral decisions. Furthermore, the results show that the amydala region plays a central role in the processing of negative emotional consequences associated with immoral decisions.

Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry.

"Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCL<10). We found significant gray matter reductions in frontal and temporal brain regions in psychopaths compared with controls. In particular, we found a highly significant volume loss in the right superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

Decoding of affective facial expressions in the context of emotional situations.

The ability to recognize other persons' affective states and to link these with aspects of the current situation arises early in development and is precursor functions of a Theory of Mind (ToM). Until now, studies investigated either the processing of affective faces or affective pictures. In the present study, we tried to realize a scenario more similar to every day situations. We employed fMRI and used a picture matching task to explore the neural correlates associated with the integration and decoding of facial affective expressions in the context of affective situations. In the emotion condition, the participants judged an emotional facial expression with respect to the content of an emotional picture. In the two other conditions, participants indicated colour matches on the background of either affective or scrambled pictures. In contrast to colour matching on scrambled pictures, colour matching on emotional pictures resulted in longer reaction times and increased activation of the bilateral fusiform and occipital gyrus. These results indicated that, although task irrelevant, participants may attend to the emotional background of the pictures. The emotion task was associated with higher reaction times and with activation of the bilateral fusiform and occipital gyrus. Additionally, emotion attribution induced left amygdala activity. Possibly, attention processes and amygdala projections modulated the activation found in the occipital and fusiform areas. Furthermore, the involvement of the amygdala in the ToM precursor ability to link facial expressions with an emotional situation may indicate that the amygdala is involved in the development of stable ToM abilities.

Emotion-dependent modulation of interference processes: an fMRI study.

We studied the effects of experimentally induced emotions on inhibitory control using functional magnetic resonance tomography (fMRI). The Simon task used involves two conditions with different attentional demands and is a well established paradigm for studying inhibitory control. Incompatible trials demand cognitive control for resolving interference. Compatible trials need no inhibitory control. Twelve participants viewed a series of affective pictures inducing positive, negative or neutral affects. Between the picture blocks, participants performed either incompatible or compatible trials. Behavioral and fMRI data revealed an impact of negative emotions only on the processing of ncompatible trials. Subjects made more errors and showed less activation of brain areas associated with task performance. There was no effect of positive emotions neither on compatible nor incompatible trials. The results first showed that especially the processing of negative emotions is resource competing and secondly that the competition concerns only the controlled route of cognitive processing.

Disturbed prefrontal and temporal brain function during emotion and cognition interaction in criminal psychopathy.

Impaired emotional responsiveness has been revealed as a hallmark of psychopathy. In spite of an increasing database on emotion processing, studies on cognitive function and in particular on the impact of emotion on cognition in psychopathy are rare. We used pictures from the International Affective Picture Set (IAPS) and a Simon Paradigm to address emotion-cognition interaction while functional and structural imaging data were obtained in 12 healthy controls and 10 psychopaths. We found an impaired emotion-cognition interaction in psychopaths that correlated with a changed prefrontal and temporal brain activation. With regard to the temporal cortex, it is shown that structure and function of the right superior temporal gyrus is disturbed in psychopathy, supporting a neurobiological approach to psychopathy, in which structure and function of the right STG may be important.

Neural correlates of emotional working memory in patients with mild cognitive impairment.

Emotional stimuli can have beneficial effects on memory in healthy aged subjects and partly on patients with dementia. So far, no experimental study has explored the effects of memory for emotional stimuli in patients with mild cognitive impairment (MCI), a concept that describes a transitional state between normal aging and dementia. The present fMRI study explored working memory for emotional stimuli in 16 patients with amnestic MCI (aMCI) and 16 healthy aged participants. Subjects performed an n-back task (2-back) with neutral, positive, and negative emotional pictures. The analysis focused on target processing. Results showed that groups did not differ in working memory performance. In healthy aged participants emotional targets had no significant impact on working memory. In patients with aMCI a negativity bias was observed, indicating that negative targets were better remembered compared to neutral and positive targets. Regarding fMRI results, both groups showed an increase in functional activity in prefrontal and lateral parietal brain regions associated with target processing. As a key result, we observed significant group by emotion interaction effects in the precuneus. Healthy aged participants showed a signal decrease in the left precuneus for positive compared to neutral targets. The precuneus deactivation in healthy aged participants may indicate a disengagement of self-referential processes towards task-related processes. Patients with aMCI revealed a signal increase in the right precuneus for negative compared to neutral targets. This increase in precuneus activity, combined with a behavioural facilitation effect, may indicate a mechanism to compensate disease related processes in aMCI.