Self-Conscious Emotion Processing in Autistic Adolescents: Over-Reliance on Learned Social Rules During Tasks with Heightened Perspective-Taking Demands May Serve as Compensatory Strategy for Less Reflexive Mentalizing.

Autistic adolescents experience a secondary wave of social cognitive challenges which impact interpersonal success. We investigated self-conscious emotion (SCE) processing in autistic and neurotypical adolescents. Participants watched videos of peers acting embarrassed and proud and rated inferred and empathic SCEs. We compared intensity ratings across groups and conducted correlations with social cognitive abilities and autistic features. Autistic adolescents recognized SCEs and felt empathic SCEs; however, they made atypical emotion attributions when perspective-taking demands were high, which more strongly reflected the situational context. Atypical attributions were associated with perspective-taking difficulties and autistic feature intensity. An over-reliance on contextual cues may reflect a strict adherence to learned social rules, possibly compensating for less reflexive mentalizing, which may underlie interpersonal challenges in ASD.

Brain and behavioral alterations in subjects with social anxiety dominated by empathic embarrassment.

Social-anxiety disorder involves a fear of embarrassing oneself in the presence of others. Taijin-kyofusho (TKS), a subtype common in East Asia, additionally includes a fear of embarrassing others. TKS individuals are hypersensitive to others' feelings and worry that their physical or behavioral defects humiliate others. To explore the underlying neurocognitive mechanisms, we compared TKS ratings with questionnaire-based empathic disposition, cognitive flexibility (set-shifting), and empathy-associated brain activity in 23 Japanese adults. During 3-tesla functional MRI, subjects watched video clips of badly singing people who expressed either authentic embarrassment (EMBAR) or hubristic pride (PRIDE). We expected the EMBAR singers to embarrass the viewers via emotion-sharing involving affective empathy (affEMP), and the PRIDE singers to embarrass via perspective-taking involving cognitive empathy (cogEMP). During affEMP (EMBAR > PRIDE), TKS scores correlated positively with dispositional affEMP (personal-distress dimension) and with amygdala activity. During cogEMP (EMBAR < PRIDE), TKS scores correlated negatively with cognitive flexibility and with activity of the posterior superior temporal sulcus/temporoparietal junction (pSTS/TPJ). Intersubject correlation analysis implied stronger involvement of the anterior insula, inferior frontal gyrus, and premotor cortex during affEMP than cogEMP and stronger involvement of the medial prefrontal cortex, posterior cingulate cortex, and pSTS/TPJ during cogEMP than affEMP. During cogEMP, the whole-brain functional connectivity was weaker the higher the TKS scores. The observed imbalance between affEMP and cogEMP, and the disruption of functional brain connectivity, likely deteriorate cognitive processing during embarrassing situations in persons who suffer from other-oriented social anxiety dominated by empathic embarrassment.

Inter-subject correlation of temporoparietal junction activity is associated with conflict patterns during flexible decision-making.

Although behavioral flexibility and conflict regulation may rely on executive function, the mechanism underlying these relationships remains obscure. We studied whether subjects' conflict ratings were associated with right dorsolateral prefrontal cortex (rDLPFC) and temporoparietal junction (rTPJ) activity during flexible decision-making in a moral dilemma task using inter-subject correlation (ISC)-based approach (i.e., brain-behavior correlation matrices analysis). We observed a statistically significant positive correlation between the ISC matrix of rTPJ and conflict-scores. This implies that similar rTPJ activity patterns across subjects were associated with similar conflict-rating patterns across subjects. Our findings suggest that rTPJ activity may be also related to conflicting experience.

Feeling left out: depressed adolescents may atypically recruit emotional salience and regulation networks during social exclusion.

Depression is associated with negative attention and attribution biases and maladaptive emotion responsivity and regulation, which adversely impact self-evaluations and interpersonal relationships. Using functional magnetic resonance imaging, we investigated the neural substrates of these impairments. We compared neural activity recruited by 126 clinically depressed and healthy adolescents (ages 11-17 years) during social exclusion (Exclusion > Inclusion) using Cyberball. Results revealed significant interaction effects within left anterior insula (AI)/inferior frontal gyrus and left middle temporal gyrus. Insula hyperresponsivity was associated with peer exclusion for depressed adolescents but peer inclusion for healthy adolescents. In additional, healthy adolescents recruited greater lateral temporal activity during peer exclusion. Complementary effect size analyses within independent parcellations offered converging evidence, as well as highlighted medium-to-large effects within subgenual/ventral anterior cingulate cortex and lateral prefrontal, lateral temporal and lateral parietal regions implicated in emotion regulation. Depressogenic neural patterns were associated with negative self-perceptions and negative information processing biases. These findings suggest a neural mechanism underlying cognitive biases in depression, as reflected by emotional hyperresponsivity and maladaptive regulation/reappraisal of negative social evaluative information. This study lends further support for salience and central executive network dysfunction underlying social threat processing, and in particular, highlights the anterior insula as a key region of disturbance in adolescent depression.

Role of Spontaneous Brain Activity in Explicit and Implicit Aspects of Cognitive Flexibility under Socially Conflicting Situations: A Resting-state fMRI Study using Fractional Amplitude of Low-frequency Fluctuations.

We are constantly exposed to socially conflicting situations in everyday life, and cognitive flexibility is essential for adaptively coping with such difficulties. Flexible goal choice and pursuit are not exclusively conscious, and therefore cognitive flexibility involves both explicit and implicit forms of processing. However, it is unclear how individual differences in explicit and implicit aspects of flexibility are associated with neural activity in a resting state. Here, we measured intrinsic fractional amplitude of low-frequency fluctuations (fALFF) by resting-state functional magnetic resonance imaging (RS-fMRI) as an indicator of regional brain spontaneous activity, together with explicit and implicit aspects of cognitive flexibility using the Cognitive Flexibility Scale (CFS) and Implicit Association Test (IAT). Consistent with the dual processing theory, there was a strong association between explicit aspects of flexibility (CFS score) and "rationalism" thinking style and between implicit aspects (IAT effect) and "experientialism." The level of explicit flexibility was also correlated with fALFF values in the left lateral prefrontal cortex, whereas the level of implicit flexibility was correlated with fALFF values in the right cerebellum. Furthermore, the fALFF values in both regions predicted individual preference for flexible decision-making strategy in a vignettes simulation task. These results add to our understanding of the neural mechanisms underlying flexible decision-making for solving social conflicts. More generally, our findings highlight the utility of RS-fMRI combined with both explicit and implicit psychometric measures for better understanding individual differences in social cognition.

Collaborative roles of Temporoparietal Junction and Dorsolateral Prefrontal Cortex in Different Types of Behavioural Flexibility.

Behavioural flexibility is essential for everyday life. This involves shifting attention between different perspectives. Previous studies suggest that flexibility is mainly subserved by the dorsolateral prefrontal cortex (DLPFC). However, although rarely emphasized, the temporoparietal junction (TPJ) is frequently recruited during flexible behaviour. A crucial question is whether TPJ plays a role in different types of flexibility, compared to its limited role in perceptual flexibility. We hypothesized that TPJ activity during diverse flexibility tasks plays a common role in stimulus-driven attention-shifting, thereby contributing to different types of flexibility, and thus the collaboration between DLPFC and TPJ might serve as a more appropriate mechanism than DLPFC alone. We used fMRI to measure DLPFC/TPJ activity recruited during moral flexibility, and examined its effect on other domains of flexibility (economic/perceptual). Here, we show the additional, yet crucial role of TPJ: a combined DLPFC/TPJ activity predicted flexibility, regardless of domain. Different types of flexibility might rely on more basic attention-shifting, which highlights the behavioural significance of alternatives.

Preliminary evidence of the impact of early childhood maltreatment and a preventive intervention on neural patterns of response inhibition in early adolescence.

Maltreated youths in foster care often experience negative developmental and psychological outcomes, which have been linked with poor response inhibition. Recent evidence suggests that childhood maltreatment is also associated with alterations in the neural circuitry underlying response inhibition. However, a burgeoning line of research has begun to explore the mitigating effects of preventive interventions on neural functioning. The current study used event-related functional magnetic resonance imaging to explore the impact of early childhood maltreatment and a preventive intervention on response inhibition in early adolescence. Thirty-six demographically similar adolescents (ages 9-14 years) completed a Go/NoGo task. The sample included nonmaltreated adolescents (n = 14) and maltreated adolescents who were in foster care as preschoolers and randomly assigned to receive services as usual (n = 11) or a preventive intervention, Multidimensional Treatment Foster Care for Preschoolers (n = 11). The groups demonstrated similar behavioral performance but significantly different neural patterns. The maltreated adolescents who received services as usual demonstrated subcortical hypoactivity during successful response inhibition and subcortical hyperactivity during unsuccessful response inhibition. In contrast, the nonmaltreated adolescents and maltreated adolescents who received the intervention exhibited strikingly similar neural patterns during successful response inhibition, but the maltreated adolescents who received the intervention demonstrated prefrontal hypoactivity during unsuccessful response inhibition. These findings offer preliminary evidence that early childhood maltreatment alters the neural patterns underlying response inhibition in early adolescence and that participating in a preventive intervention could mitigate maltreatment-related effects on these neural systems.

Default mode network segregation and social deficits in autism spectrum disorder: Evidence from non-medicated children.

Functional pathology of the default mode network is posited to be central to social-cognitive impairment in autism spectrum disorders (ASD). Altered functional connectivity of the default mode network's midline core may be a potential endophenotype for social deficits in ASD. Generalizability from prior studies is limited by inclusion of medicated participants and by methods favoring restricted examination of network function. This study measured resting-state functional connectivity in 22 8-13 year-old non-medicated children with ASD and 22 typically developing controls using seed-based and network segregation functional connectivity methods. Relative to controls the ASD group showed both under- and over-functional connectivity within default mode and non-default mode regions, respectively. ASD symptoms correlated negatively with the connection strength of the default mode midline core-medial prefrontal cortex-posterior cingulate cortex. Network segregation analysis with the participation coefficient showed a higher area under the curve for the ASD group. Our findings demonstrate that the default mode network in ASD shows a pattern of poor segregation with both functional connectivity metrics. This study confirms the potential for the functional connection of the midline core as an endophenotype for social deficits. Poor segregation of the default mode network is consistent with an excitation/inhibition imbalance model of ASD.

Neural Correlates of Set-Shifting in Children With Autism.

Autism spectrum disorder (ASD) is often associated with high levels of inflexible thinking and rigid behavior. The neural correlates of these behaviors have been investigated in adults and older adolescents, but not children. Prior studies utilized set-shifting tasks that engaged multiple levels of shifting, and depended on learning abstract rules and establishing a strong prepotent bias. These additional demands complicate simple interpretations of the results. We used functional magnetic resonance imaging (fMRI) to investigate the neural correlates of set-shifting in 20 children (ages 7-14) with ASD and 19 typically developing, matched, control children. Participants completed a set-shifting task that minimized nonshifting task demands through the use of concrete instructions that provide spatial mapping of stimuli-responses. The shift/stay sets were given an equal number of trials to limit the prepotent bias. Both groups showed an equivalent "switch cost," responding less accurately and slower to Switch stimuli than Stay stimuli, although the ASD group was less accurate overall. Both groups showed activation in prefrontal, striatal, parietal, and cerebellum regions known to govern effective set-shifts. Compared to controls, children with ASD demonstrated decreased activation of the right middle temporal gyrus across all trials, but increased activation in the mid-dorsal cingulate cortex/superior frontal gyrus, left middle frontal, and right inferior frontal gyri during the Switch vs. Stay contrast. The successful behavioral switching performance of children with ASD comes at the cost of requiring greater engagement of frontal regions, suggesting less efficiency at this lowest level of shifting.

Cognitive neuroscience of social emotions and implications for psychopathology: examining embarrassment, guilt, envy, and schadenfreude.

Social emotions are affective states elicited during social interactions and integral for promoting socially appropriate behaviors and discouraging socially inappropriate ones. Social emotion-processing deficits significantly impair interpersonal relationships, and play distinct roles in the manifestation and maintenance of clinical symptomatology. Elucidating the neural correlates of discrete social emotions can serve as a window to better understanding and treating neuropsychiatric disorders. Moral cognition and social emotion-processing broadly recruit a fronto-temporo-subcortical network, supporting empathy, perspective-taking, self-processing, and reward-processing. The present review specifically examines the neural correlates of embarrassment, guilt, envy, and schadenfreude. Embarrassment and guilt are self-conscious emotions, evoked during negative evaluation following norm violations and supported by a fronto-temporo-posterior network. Embarrassment is evoked by social transgressions and recruits greater anterior temporal regions, representing conceptual social knowledge. Guilt is evoked by moral transgressions and recruits greater prefrontal regions, representing perspective-taking and behavioral change demands. Envy and schadenfreude are fortune-of-other emotions, evoked during social comparison and supported by a prefronto-striatal network. Envy represents displeasure in others' fortunes, and recruits increased dorsal anterior cingulate cortex, representing cognitive dissonance, and decreased reward-related striatal regions. Schadenfreude represents pleasure in others' misfortunes, and recruits reduced empathy-related insular regions and increased reward-related striatal regions. Implications for psychopathology and treatment design are discussed.

But do you think I'm cool? Developmental differences in striatal recruitment during direct and reflected social self-evaluations.

The current fMRI study investigates the neural foundations of evaluating oneself and others during early adolescence and young adulthood. Eighteen early adolescents (ages 11-14, M=12.6) and 19 young adults (ages 22-31, M=25.6) evaluated whether academic, physical, and social traits described themselves directly (direct self-evaluations), described their best friend directly (direct other-evaluations), described themselves from their best friend's perspective (reflected self-evaluations), or in general could change over time (control malleability-evaluations). Compared to control evaluations, both adolescents and adults recruited cortical midline structures during direct and reflected self-evaluations, as well as during direct other-evaluations, converging with previous research. However, unique to this study was a significant three-way interaction between age group, evaluative perspective, and domain within bilateral ventral striatum. Region of interest analyses demonstrated a significant evaluative perspective by domain interaction within the adolescent sample only. Adolescents recruited greatest bilateral ventral striatum during reflected social self-evaluations, which was positively correlated with age and pubertal development. These findings suggest that reflected social self-evaluations, made from the inferred perspective of a close peer, may be especially self-relevant, salient, or rewarding to adolescent self-processing--particularly during the progression through adolescence - and this feature persists into adulthood.

Separate components of emotional go/no-go performance relate to autism versus attention symptoms in children with autism.

OBJECTIVE: The present investigation examined whether higher functioning children with autism would demonstrate impaired response inhibition performance in an emotional go/no-go task, and whether severity of attention-deficit/hyperactivity disorder (ADHD) or autism symptoms correlated with performance. METHOD: Forty-four children (21 meeting criteria for autism; 23 typically developing controls [TDCs]) completed an emotional go/no-go task in which an emotional facial expression (angry, fearful, happy, or sad) was the go stimulus and a neutral facial expression was the no-go stimulus, and vice versa. RESULTS: The autism group was faster than the TDC group on all emotional go trials. Moreover, the children in the autism group who had the fastest reaction times on emotional go trials were rated as having the greatest number of symptoms (Autism Diagnostic Observation Schedule Social + Communication score), even after accounting for the association with ADHD symptoms. The autism group also made more impulsive responses (i.e., lower d', more false alarms) than the TDC group on all trials. As d' decreased or false alarms increased, so did ADHD symptoms. Hyperactivity/impulsivity symptoms were significantly correlated with false alarms, but inattention symptoms were not. There was not a significant relationship between no-go false alarms and autism symptoms; even after partialing out associations with autism symptoms, the significant correlation between ADHD symptoms and no-go false alarms remained. CONCLUSION: The present findings support a comorbidity model that argues for shared and independent risk factors, because ADHD and autism symptoms related to independent aspects of emotional go/no-go performance.

Interests in high-functioning autism are more intense, interfering, and idiosyncratic than those in neurotypical development.

Although circumscribed interests are pathognomonic with autism, much about these interests remains unknown. Using the Interests Scale (IS), this study compares interests between 76 neurotypical (NT) individuals and 109 individuals with high-functioning autism spectrum disorder (HF-ASD) matched groupwise on age, IQ, and gender ratio. Participants and their parents/caregivers completed diagnostic measures (the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule; HF-ASD only), cognitive tests (Wechsler IQ Scales), and questionnaires (the Repetitive Behavior Scale-Revised, the Behavior Rating Inventory of Executive Function, and the Social Responsiveness Scale), in addition to the IS. Consistent with previous research, HF-ASD and NT individuals did not differ in number of interest areas, but the types of interests and intensity of those interests differed considerably. Using only the IS intensity score, 81% of individuals were correctly classified (NT or HF-ASD) in a logistic regression analysis. Among individuals with HF-ASD, Interests Scale scores were significantly related to Autism Diagnostic Observation Schedule, Behavior Rating Inventory of Executive Function, Repetitive Behavior Scale-Revised, and Social Responsiveness Scale scores, but they were not related to Autism Diagnostic Interview-Revised scores, IQ, gender, age, or psychotropic medication use. The type and intensity, but not the number, of interests distinguish high-functioning individuals with ASD from NT individuals.

Impaired Consonant Trigrams Test (CTT) performance relates to everyday working memory difficulties in children with autism spectrum disorders.

Individuals with Autism Spectrum Disorders (ASD) often struggle with complex tasks, such as those requiring divided attention (simultaneously completing two independent tasks) that also place high demands on working memory. Prior research shows that divided attention is impaired in adults and children with ASD and is related to ASD and comorbid attention deficit/hyperactivity disorder (ADHD) symptoms, but the impact on everyday functioning is unclear. Because ADHD symptoms are associated with poor divided attention and working memory performance in children with ASD, we also examined ADHD symptoms as moderators of divided attention performance. We examined performance on the Consonant Trigrams Test (CTT) between high-functioning 8- to 13-year-olds with ASD (n = 28) and typically developing controls (n = 18) matched on age and IQ. In the ASD group, we also correlated performance with ADHD symptoms and behavior ratings of everyday working memory. CTT performance in children with ASD was significantly worse than in matched controls. A significant correlation between CTT performance and everyday working memory was observed, but CTT performance was not related to comorbid ADHD symptoms in the ASD group. Divided attention with high working-memory demands is a relative weakness in children with high-functioning ASD; this weakness relates to everyday functioning, and it is independent from ADHD symptoms. That ADHD symptoms are not associated with divided attention performance is inconsistent with one prior investigation, which likely results from using different divided attention tasks in the two studies.

The fMRI success rate of children and adolescents: typical development, epilepsy, attention deficit/hyperactivity disorder, and autism spectrum disorders.

Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18-year-old had a significantly greater scan success rate than 4- to 6-year-old; adolescents (13- to 18-year-old) demonstrated greater scan success rates than 7- to 9-year-old. Success rate for completing an entire battery of experimental runs (n = 2-6), varied between 50-59% for patient populations and 69% for TYP (79% when excluding 4- to 6-year-old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4- to 6-year-olds may require 20-40% additional participants; studies with 10- to 18-year-olds may require 10-15% additional participants.