Differences in neural activity when processing emotional arousal and valence in autism spectrum disorders

Individuals with autism spectrum disorders (ASD) often have difficulty recognizing and interpreting facial expressions of emotion, which may impair their ability to navigate and communicate successfully in their social, interpersonal environments. Characterizing specific differences between individuals with ASD and their typically developing (TD) counterparts in the neural activity subserving their experience of emotional faces may provide distinct targets for ASD interventions. Thus we used functional magnetic resonance imaging (fMRI) and a parametric experimental design to identify brain regions in which neural activity correlated with ratings of arousal and valence for a broad range of emotional faces. Participants (51 ASD, 84 TD) were group‐matched by age, sex, IQ, race, and socioeconomic status. Using task‐related change in blood‐oxygen‐level‐dependent (BOLD) fMRI signal as a measure, and covarying for age, sex, FSIQ, and ADOS scores, we detected significant differences across diagnostic groups in the neural activity subserving the dimension of arousal but not valence. BOLD‐signal in TD participants correlated inversely with ratings of arousal in regions associated primarily with attentional functions, whereas BOLD‐signal in ASD participants correlated positively with arousal ratings in regions commonly associated with impulse control and default‐mode activity. Only minor differences were detected between groups in the BOLD signal correlates of valence ratings. Our findings provide unique insight into the emotional experiences of individuals with ASD. Although behavioral responses to face‐stimuli were comparable across diagnostic groups, the corresponding neural activity for our ASD and TD groups differed dramatically. The near absence of group differences for valence correlates and the presence of strong group differences for arousal correlates suggest that individuals with ASD are not atypical in all aspects of emotion‐processing. Studying these similarities and differences may help us to understand the origins of divergent interpersonal emotional experience in persons with ASD. Hum Brain Mapp 37:443–461, 2016. © 2015 Wiley Periodicals, Inc.     

Dissociation in performance of children with ADHD and high-functioning autism on a task of sustained attention

Attention deficit hyperactivity disorder (ADHD) and autism are two neurodevelopmental disorders associated with prominent executive dysfunction, which may be underpinned by disruption within fronto-striatal and fronto-parietal circuits. We probed executive function in these disorders using a sustained attention task with a validated brain-behaviour basis. Twenty-three children with ADHD, 21 children with high-functioning autism (HFA) and 18 control children were tested on the Sustained Attention to Response Task (SART). In a fixed sequence version of the task, children were required to withhold their response to a predictably occurring no-go target (3) in a 1-9 digit sequence; in the random version the sequence was unpredictable. The ADHD group showed clear deficits in response inhibition and sustained attention, through higher errors of commission and omission on both SART versions. The HFA group showed no sustained attention deficits, through a normal number of omission errors on both SART versions. The HFA group showed dissociation in response inhibition performance, as indexed by commission errors. On the Fixed SART, a normal number of errors was made, however when the stimuli were randomised, the HFA group made as many commission errors as the ADHD group. Greater slow-frequency variability in response time and a slowing in mean response time by the ADHD group suggested impaired arousal processes. The ADHD group showed greater fast-frequency variability in response time, indicative of impaired top-down control, relative to the HFA and control groups. These data imply involvement of fronto-parietal attentional networks and sub-cortical arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in children with HFA.     

Social and non-social deficits in children with high-functioning autism and their cooperative behaviors

The persistent deficits in social communication and social interactions of individuals with high-functioning autism (HFA) may impair their cooperative behaviors. This study investigated the relationship between social and non-social deficits in children with HFA and the cooperative behaviors of such children. Theory of mind (ToM), executive function, and central coherence of children with HFA and typically developing (TD) children, aged 6–12 years, were investigated, and the effects of these social and non-social deficits on children's cooperativeness were examined. The classical prisoner's dilemma game (PDG) and cooperative implemental tasks were used to assess children's cooperativeness. ToM was measured using a series of classical false belief tasks and the face test. The Wisconsin Card Sorting Task (WCST) and the Embedded Figures Test (EFT) were administered to assess executive function and central coherence, respectively. The results showed that there was no significant difference in cooperation in PDG between HFA and TD children, while cooperation in children with HFA in the interruption period of the implemental tasks was significantly lower than that of TD children. Children with HFA had social deficits and had more poorly developed ToM than TD children, and executive function in children with HFA was poorer than that in TD children. Different types of deficits were predictive of HFA children's degree of cooperation on different tasks: the social perceptual component of ToM and executive function predicted children's cooperativeness in the PDG, and executive function predicted HFA children's cooperativeness during the interruption period of an implemental task. By contrast, central coherence did not predict either of the two types of cooperation. It might indicate that the two different types of cooperative tasks may require different mental abilities.     

Emotional prosody perception and its association with pragmatic language in school-aged children with high-function autism

Emotional prosody perception is essential for social communication, but it is still an open issue whether children with high-function autism (HFA) exhibit any prosodic perception deficits or experience selective impairments in recognizing the prosody of positive emotions. Moreover, the associations between prosody perception, pragmatic language, and social adaptation in children with HFA have not been fully explored. This study investigated whether emotional prosody perception for words and sentences in children with HFA (n = 25, 6–11 years of age) differed from age-matched, typically developing children (TD, n = 25) when presented with an emotional prosody identification task. The Children's Communication Checklist and Vineland Adaptive Behavior Scale were used to assess pragmatic and social adaption abilities. Results show that children with HFA performed poorer than TD children in identifying happy prosody in both emotionally neutral and relevant utterances. In contrast, children with HFA did not exhibit any deficits in identifying sad and angry prosody. Results of correlation analyses revealed a positive association between happy prosody identification and pragmatic function. The findings indicate that school-aged children with HFA experience difficulties in recognizing happy prosody, and that this limitation in prosody perception is associated with their pragmatic and social adaption performances.     

Neural and cortisol responses during play with human and computer partners in children with autism

Children with autism spectrum disorder (ASD) exhibit impairment in reciprocal social interactions, including play, which can manifest as failure to show social preference or discrimination between social and nonsocial stimuli. To explore mechanisms underlying these deficits, we collected salivary cortisol from 42 children 8–12 years with ASD or typical development during a playground interaction with a confederate child. Participants underwent functional MRI during a prisoner’s dilemma game requiring cooperation or defection with a human (confederate) or computer partner. Search region of interest analyses were based on previous research (e.g. insula, amygdala, temporal parietal junction—TPJ). There were significant group differences in neural activation based on partner and response pattern. When playing with a human partner, children with ASD showed limited engagement of a social salience brain circuit during defection. Reduced insula activation during defection in the ASD children relative to TD children, regardless of partner type, was also a prominent finding. Insula and TPJ BOLD during defection was also associated with stress responsivity and behavior in the ASD group under playground conditions. Children with ASD engage social salience networks less than TD children during conditions of social salience, supporting a fundamental disturbance of social engagement.     

Enhanced neural responses to rule violation in children with autism: a comparison to social exclusion

The present study aimed to explore the neural correlates of two characteristic deficits in autism spectrum disorders (ASD); social impairment and restricted, repetitive behavior patterns. To this end, we used comparable experiences of social exclusion and rule violation to probe potentially atypical neural networks in ASD. In children and adolescents with and without ASD, we used the interactive ball-toss game (Cyberball) to elicit social exclusion and a comparable game (Cybershape) to elicit a non-exclusive rule violation. Using functional magnetic resonance imaging (fMRI), we identified group differences in brain responses to social exclusion and rule violation. Though both groups reported equal distress following exclusion, the right insula and ventral anterior cingulate cortex were hypoactive during exclusion in children with ASD. In rule violation, right insula and dorsal prefrontal cortex were hyperactive in ASD. Right insula showed a dissociation in activation; it was hypoactive to social exclusion and hyperactive to rule violation in the ASD group. Further probed, different regions of right insula were modulated in each game, highlighting differences in regional specificity for which subsequent analyses revealed differences in patterns of functional connectivity. These results demonstrate neurobiological differences in processing social exclusion and rule violation in children with ASD.     

An investigation of upper limb motor function in high functioning autism and Asperger's disorder using a repetitive Fitts’ aiming task

There is now a growing body of research examining movement difficulties in children diagnosed with high functioning autism (HFA) and Asperger's disorder (AD). Despite this, few studies have investigated the kinematic components of movement that may be disrupted in children diagnosed with these disorders. The current study investigated rapid aiming movements in 19 individuals diagnosed with HFA, 20 individuals diagnosed with AD and 18 typically developing (TD) controls. A novel touchscreen version of a Fitts’ aiming task was administered that required participants to make 10 reciprocal aiming movements between targets. Task difficulty was manipulated by varying the size and distance between targets. Movement time in the HFA and AD groups was comparable to TD controls. Children with HFA displayed more constant and variable error across repeated aiming attempts compared to the TD group that may be attributed to deficits in feedforward online refinement of movement. These findings are in accordance with previous gait, ocular motor, upper limb and neuroimaging studies that suggest that the cerebellum may underlie movement disturbance in individuals diagnosed with HFA. Additionally, differences in the nature of upper limb motor disturbance in HFA may serve as a useful future adjunct to clinical measures.     

Evidence for Impairments in Using Static Line Drawings of Eye Gaze Cues to Orient Visual-Spatial Attention in Children with High Functioning Autism

We examined the ability to use static line drawings of eye gaze cues to orient visual-spatial attention in children with high functioning autism (HFA) compared to typically developing children (TD). The task was organized such that on valid trials, gaze cues were directed toward the same spatial location as the appearance of an upcoming target, while on invalid trials gaze cues were directed to an opposite location. Unlike TD children, children with HFA showed no advantage in reaction time (RT) on valid trials compared to invalid trials (i.e., no significant validity effect). The two stimulus onset asynchronies (200 ms, 700 ms) did not differentially affect these findings. The results suggest that children with HFA show impairments in utilizing static line drawings of gaze cues to orient visual-spatial attention.     

An Examination of Handedness and Footedness in Children with High Functioning Autism and Asperger Syndrome

Motor control deficits have been documented in children with high functioning autism and Asperger syndrome (HFA/AS), but the extent to which these disorders affect the children's footedness must be delineated. Twelve typically developing (TD) children and 12 children with HFA/AS, ages 6-9?years, were recruited. Motor control skills were assessed through a variety of footedness tasks to determine location and nature of impairment, regarding motor dominance. Overall, greater inconsistencies in dominance arose in children with HFA/AS, through disparities in measures of preference. Results will have broader implications for understanding motor impairments in children with HFA/AS as determined by comparing performance on footedness tasks, as well as for the design of interventions to account for these deficits.     

Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia

OBJECTIVE: People with schizophrenia have exhibited reduced functional activity in the anterior cingulate cortex during the performance of many types of cognitive tasks and during the commission of errors. According to conflict theory, the anterior cingulate cortex is involved in the monitoring of response conflict, acting as a signal for a need for greater cognitive control. This study examined whether impaired conflict monitoring in people with schizophrenia could underlie reduced anterior cingulate activity during both correct task performance and error-related activity. METHOD: Functional activity in the anterior cingulate of 13 schizophrenia patients and 13 healthy comparison subjects was investigated by using event-related fMRI and a Stroop task that allowed simultaneous examination of activity during both conflict (incongruent trials) and error (commission of error trials). RESULTS: In the presence of comparable reaction time measures for conflict as well as comparable error rates, the schizophrenia subjects showed both decreased conflict- and error-related activity in the same region of the anterior cingulate cortex. Moreover, those with schizophrenia did not exhibit significant post-conflict or post-error behavioral adjustments. CONCLUSIONS: Concurrently reduced conflict- and error-related activity in the anterior cingulate cortex along with reduced trial-to-trial adjustments in performance has not previously been reported in schizophrenia. The current results suggest that impaired conflict monitoring by the anterior cingulate cortex might play an important role in contributing to cognitive control deficits in patients with schizophrenia.     

Impaired Error Monitoring and Correction Function in Autism

Introduction. Error monitoring and correction is one of the executive functions and is important for effective goal-directed behavior. Deficient executive functioning, including reduced error monitoring ability, is one of the typical features of such neurodevelopmental disorders as autism, probably related to perseverative responding, stereotyped repetitive behaviors, and an inability to accurately monitor ongoing behavior. Our prior studies of behavioral and event-related potential measures during performance on visual oddball tasks in high-functioning autistic (HFA) children showed that despite only minor differences in reaction times (RTs) HFA children committed significantly more errors.

Method. This study investigated error monitoring in children with autism spectrum disorder (ASD) with response-locked event-related potentials—the error-related negativity (ERN) and error-related positivity (Pe) recorded at fronto-central sites. The ERN reflects early error detection processes, whereas the Pe has been associated with later conscious error evaluation and attention reallocation. RTs in correct trials and posterror slowing in RTs were measured. In this study 14 participants with ASD and 14 age- and IQ-matched controls received a three-category visual oddball task with novel distracters.

Results. ERN had a lower amplitude and longer latency in the ASD group but was localized in the caudal part of anterior cingulate cortex in both groups. The Pe component was significantly prolonged in the ASD group but did not reach significance in amplitude differences compared to controls. We found significant posterror slowing in RTs in controls and posterror acceleration in RTs in the ASD group.

Conclusion. The reduced ERN and altered Pe along with a lack of posterror RT slowing in autism might be interpreted as insensitivity in the detection and monitoring of response errors and a reduced ability of execute corrective actions. This might result in reduced error awareness and failure in adjustment when dealing with situations where erroneous responses may occur. This deficit might be manifested in the perseverative behaviors often seen in individuals with ASD. The results are discussed in terms of a general impairment in self-monitoring and other executive functions underlying behavioral and social disturbances in ASD.     

Basal ganglia-thalamocortical circuitry disruptions in schizophrenia during delayed response tasks.

BACKGROUND: Schizophrenia is characterized by executive functioning deficits, presumably mediated by prefrontal cortex dysfunction. For example, schizophrenia participants show performance deficits on ocular motor delayed response (ODR) tasks, which require both inhibition and spatial working memory for correct performance. METHODS: The present functional magnetic resonance imaging (fMRI) study compared neural activity of 14 schizophrenia and 14 normal participants while they performed ODR tasks. RESULTS: Schizophrenia participants generated: 1) more trials with anticipatory saccades (saccades made during the delay period), 2) memory saccades with longer latencies, and 3) memory saccades of decreased accuracy. Increased blood oxygenation level-dependent (BOLD) signal changes were observed in both groups in ocular motor circuitry (e.g., supplementary eye fields [SEF], lateral frontal eye fields [FEF], inferior parietal lobule [IPL], cuneus, and precuneus). The normal, but not the schizophrenia, group demonstrated BOLD signal changes in dorsolateral prefrontal regions (right Brodmann area [BA] 9 and bilateral BA 10), medial FEF, insula, thalamus, and basal ganglia. Correlations between percentage of anticipatory saccade trials and BOLD signal changes were more similar between groups for subcortical regions and less similar for cortical regions. CONCLUSIONS: These results suggest that executive functioning deficits in schizophrenia may be associated with dysfunction of the basal ganglia-thalamocortical circuitry, evidenced by decreased prefrontal cortex, basal ganglia, and thalamus activity in the schizophrenia group during ODR task performance.     

Event-related potential correlates of extradimensional and intradimensional set-shifts in a modified Wisconsin Card Sorting Test

Event-related potentials (ERPs) were recorded in healthy adult participants during the performance of a modified version of the Wisconsin Card Sorting Test that was designed to isolate the effects of extradimensional (ED) and intradimensional (ID) set-shifts. ERP averages were created for ED- and ID-Shift trials, as well as for the 5th trial in each block (Maintain-Rule). Differences in sensory and longer latency ERP components were found between the ED- and ID conditions, and between the two shift conditions and the Maintain-Rule trials. Consistent with the previous literature, these data indicated that ED- and ID-Shifts require different levels of neural resources. A secondary goal of this experiment was to use the excellent temporal resolution of ERPs to examine the neural correlates of various other aspects of the performance of a set-shift task, including differences between correct shifts and the commission of errors, and the differences between the reception of correct and error feedback. Comparisons were made between ERP averages to correct ED-Shift trials and ED-Error trials, and to feedback following a correct ED-Shift compared to feedback following an error. As expected, ERP differences were found between correct trials and error trials, and between the ERP correlates of receiving different types of feedback. Overall, these data further indicate the utility of using ERP methodology to study various aspects of complex neuropsychological paradigms.     

Questioning the role of amygdala and insula in an attentional capture by emotional stimuli task

Our senses are constantly monitoring the environment for emotionally salient stimuli that are potentially relevant for survival. Because of our limited cognitive resources, emotionally salient distractors prolong reaction times (RTs) as compared to neutral distractors. In addition, many studies have reported fMRI blood oxygen level‐dependent (BOLD) activation of both the amygdala and the anterior insula for similar valence contrasts. However, a direct correlation of trail‐by‐trial BOLD activity with RTs has not been shown, yet, which would be a crucial piece of evidence to relate the two observations. To investigate the role of the above two regions in the context of emotional distractor effects, we study here the correlation between BOLD activity and RTs for a simple attentional capture by emotional stimuli (ACES) choice reaction time task using a general linear subject‐level model with a parametric RT regressor. We found significant regression coefficients in the anterior insula, supplementary motor cortex, medial precentral regions, sensory‐motor areas and others, but not in the amygdala, despite activation of both insula and amygdala in the traditional valence contrast across trials (i.e., negative vs. neutral pictures). In addition, we found that subjects that exhibit a stronger RT distractor effect across trials also show a stronger BOLD valence contrast in the right anterior insula but not in the amygdala. Our results indicate that the current neuroimaging‐based evidence for the involvement of the amygdala in RT slowing is limited. We advocate that models of emotional capture should incorporate both the amygdala and the anterior insula as separate entities.     

Personality modulates the effects of emotional arousal and valence on brain activation

The influence of personality on the neural correlates of emotional processing is still not well characterized. We investigated the relationship between extraversion and neuroticism and emotional perception using functional magnetic resonance imaging (fMRI) in a group of 23 young, healthy women. Using a parametric modulation approach, we examined how the blood oxygenation level dependent (BOLD) signal varied with the participants' ratings of arousal and valence, and whether levels of extraversion and neuroticism were related to these modulations. In particular, we wished to test Eysenck's biological theory of personality, which links high extraversion to lower levels of reticulothalamic-cortical arousal, and neuroticism to increased reactivity of the limbic system and stronger reactions to emotional arousal. Individuals high in neuroticism demonstrated reduced sustained activation in the orbitofrontal cortex (OFC) and attenuated valence processing in the right temporal lobe while viewing emotional images, but an increased BOLD response to emotional arousal in the right medial prefrontal cortex (mPFC). These results support Eysenck's theory, as well as our hypothesis that high levels of neuroticism are associated with attenuated reward processing. Extraversion was inversely related to arousal processing in the right cerebellum, but positively associated with arousal processing in the right insula, indicating that the relationship between extraversion and arousal is not as simple as that proposed by Eysenck.     

White matter microstructure correlates of narrative production in typically developing children and children with high functioning autism

This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and more on alternative ventral pathways that possibly mediate visual elements of language.     

Atypical spatiotemporal signatures of working memory brain processes in autism

Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed.     

Overcontrol and neural response to errors in pediatric anxiety disorders

Multiple risk factors that may contribute to the development and severity of pediatric anxiety disorders, one of which is dimensional overcontrol. Overcontrol is a constellation of characteristics including heightened performance monitoring, inflexibility, perfectionism and aversion to making mistakes. In this study, we examined overcontrol in children with anxiety disorders and tested whether the underlying dimension of overcontrol specifically explains altered brain response to errors in pediatric anxiety disorders. Parent-reported scores of child overcontrol were collected in a sample of children (ages 8–12 years) with (n = 35) and without (n = 34) anxiety disorders and the relationship of overcontrol and anxiety symptoms to neural responding to errors during functional magnetic resonance imaging (fMRI) was examined. Results indicated childhood overcontrol was elevated in pediatric anxiety disorders and was significantly associated with anxiety severity, even when controlling for comorbid depression and ADHD. Additionally, overcontrol was associated with reduced neural response to errors versus correct responses in the bilateral dorsal anterior cingulate cortex (dACC) and insula, even when controlling for anxiety symptoms. Overcontrol may serve as an underlying mechanism associated with clinical pediatric anxiety that demonstrates significant associations with aberrant neural error responding. Overcontrol may be an underlying mechanism contributing to pediatric anxiety that could be targeted for early intervention.     

Probability effects in the stop-signal paradigm: the insula and the significance of failed inhibition

In the present randomized, mixed-trial event-related fMRI study, we examined the neural mechanisms underlying inhibitory control using a stop-signal paradigm in which stop-signal frequency was manipulated parametrically across blocks. As hypothesized, presenting stop signals less frequently was accompanied by a stronger set to respond to the go stimuli as subjects were faster in responding to go stimuli on no stop-signal trials and made more commission errors (i.e., were less successful in inhibiting the go response) on stop-signal trials. When response inhibition was successful, having to inhibit responses more frequently compared to less frequently was associated with greater activation in occipital areas. This presumably reflects enhanced visual attention to the stop signal. When response inhibition failed, greater activity was observed in bilateral insula when stop signals were presented less compared to more frequently. The insula may thus play a role in processing the significance of inhibitory failure.     

Brief Report: A Comparison of Statistical Learning in School-Aged Children with High Functioning Autism and Typically Developing Peers

Individuals with autism spectrum disorders have impairments in language acquisition, but the underlying mechanism of these deficits is poorly understood. Implicit learning is potentially relevant to language development, particularly in speech segmentation, which relies on sensitivity to transitional probabilities between speech sounds. This study investigated the relationship between implicit learning and current language abilities in school-aged children with high functioning autism and a history of language delay (n = 17) and in children with typical development (n = 24) using a well-studied artificial language learning task. Results suggest that high functioning children with autism (HFA) and TD groups were equally able to implicitly learn transitional probabilities from a lengthy stimulus stream. Furthermore, task performance was not strongly associated with current language abilities. Implications for implicit learning research in HFA are discussed.