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1.  Race modulates neural activity during imitation 
NeuroImage  2011;59(4):3594-3603.
Imitation plays a central role in the acquisition of culture. People preferentially imitate others who are self-similar, prestigious or successful. Because race can indicate a person's self-similarity or status, race influences whom people imitate. Prior studies of the neural underpinnings of imitation have not considered the effects of race. Here we measured neural activity with fMRI while European American participants imitated meaningless gestures performed by actors of their own race, and two racial outgroups, African American, and Chinese American. Participants also passively observed the actions of these actors and their portraits. Frontal, parietal and occipital areas were differentially activated while participants imitated actors of different races. More activity was present when imitating African Americans than the other racial groups, perhaps reflecting participants' reported lack of experience with and negative attitudes towards this group, or the group's lower perceived social status. This pattern of neural activity was not found when participants passively observed the gestures of the actors or simply looked at their faces. Instead, during face-viewing neural responses were overall greater for own-race individuals, consistent with prior race perception studies not involving imitation. Our findings represent a first step in elucidating neural mechanisms involved in cultural learning, a process that influences almost every aspect of our lives but has thus far received little neuroscientific study.
doi:10.1016/j.neuroimage.2011.10.074
PMCID: PMC3909702  PMID: 22062193
Race; Imitation; Mirror neuron system; Neuroimaging; Cultural learning
2.  Social status modulates neural activity in the mentalizing network 
NeuroImage  2012;60(3):1771-1777.
The current research explored the neural mechanisms linking social status to perceptions of the social world. Two fMRI studies provide converging evidence that individuals lower in social status are more likely to engage neural circuitry often involved in ‘mentalizing’ or thinking about others' thoughts and feelings. Study 1 found that college students' perception of their social status in the university community was related to neural activity in the mentalizing network (e.g., DMPFC, MPFC, precuneus/PCC) while encoding social information, with lower social status predicting greater neural activity in this network. Study 2 demonstrated that socioeconomic status, an objective indicator of global standing, predicted adolescents' neural activity during the processing of threatening faces, with individuals lower in social status displaying greater activity in the DMPFC, previously associated with mentalizing, and the amygdala, previously associated with emotion/salience processing. These studies demonstrate that social status is fundamentally and neurocognitively linked to how people process and navigate their social worlds.
doi:10.1016/j.neuroimage.2012.01.080
PMCID: PMC3909703  PMID: 22289808
Social status; SES; Mentalizing; fMRI
3.  Atypical Neural Processing of Ironic and Sincere Remarks in Children and Adolescents with Autism Spectrum Disorders 
Metaphor and symbol  2012;27(1):70-92.
Individuals with ASD show consistent impairment in processing pragmatic language when attention to multiple social cues (e.g., facial expression, tone of voice) is often needed to navigate social interactions. Building upon prior fMRI work examining how facial affect and prosodic cues are used to infer a speaker's communicative intent, the authors examined whether children and adolescents with ASD differ from typically developing (TD) controls in their processing of sincere versus ironic remarks. At the behavioral level, children and adolescents with ASD and matched TD controls were able to determine whether a speaker's remark was sincere or ironic equally well, with both groups showing longer response times for ironic remarks. At the neural level, for both sincere and ironic scenarios, an extended cortical network—including canonical language areas in the left hemisphere and their right hemisphere counterparts—was activated in both groups, albeit to a lesser degree in the ASD sample. Despite overall similar patterns of activity observed for the two conditions in both groups, significant modulation of activity was detected when directly comparing sincere and ironic scenarios within and between groups. While both TD and ASD groups showed significantly greater activity in several nodes of this extended network when processing ironic versus sincere remarks, increased activity was largely confined to left language areas in TD controls, whereas the ASD sample showed a more bilateral activation profile which included both language and “theory of mind” areas (i.e., ventromedial prefrontal cortex). These findings suggest that, for high-functioning individuals with ASD, increased activity in right hemisphere homologues of language areas in the left hemisphere, as well as regions involved in social cognition, may reflect compensatory mechanisms supporting normative behavioral task performance.
doi:10.1080/10926488.2012.638856
PMCID: PMC3909704  PMID: 24497750
4.  Neural and Behavioral Responses During Self-Evaluative Processes Differ in Youth With and Without Autism 
This fMRI study investigated neural responses while making appraisals of self and other, across the social and academic domains, in children and adolescents with and without autism spectrum disorders (ASD). Compared to neurotypical youth, those with ASD exhibited hypoactivation of ventromedial prefrontal cortex during self-appraisals. Responses in middle cingulate cortex (MCC) and anterior insula (AI) also distinguished between groups. Stronger activity in MCC and AI during self-appraisals was associated with better social functioning in the ASD group. Although self-appraisals were significantly more positive in the neurotypical group, positivity was unrelated to brain activity in these regions. Together, these results suggest that multiple brain regions support making self-appraisals in neurotypical development, and function atypically in youth with ASD.
doi:10.1007/s10803-012-1563-3
PMCID: PMC3507334  PMID: 22760337
Autism; Self; Ventral mPFC; Anterior insula; Middle cingulate cortex; Development
5.  Entering Adolescence: Resistance to Peer Influence, Risky Behavior, and Neural Changes in Emotion Reactivity 
Neuron  2011;69(5):10.1016/j.neuron.2011.02.019.
SUMMARY
Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.
doi:10.1016/j.neuron.2011.02.019
PMCID: PMC3840168  PMID: 21382560
6.  Mirroring others’ emotions relates to empathy and interpersonal competence in children 
NeuroImage  2007;39(4):10.1016/j.neuroimage.2007.10.032.
The mirror neuron system (MNS) has been proposed to play an important role in social cognition by providing a neural mechanism by which others’ actions, intentions, and emotions can be understood. Here functional magnetic resonance imaging was used to directly examine the relationship between MNS activity and two distinct indicators of social functioning in typically-developing children (aged 10.1 years±7 months): empathy and interpersonal competence. Reliable activity in pars opercularis, the frontal component of the MNS, was elicited by observation and imitation of emotional expressions. Importantly, activity in this region (as well as in the anterior insula and amygdala) was significantly and positively correlated with established behavioral measures indexing children’s empathic behavior (during both imitation and observation) and interpersonal skills (during imitation only). These findings suggest that simulation mechanisms and the MNS may indeed be relevant to social functioning in everyday life during typical human development.
doi:10.1016/j.neuroimage.2007.10.032
PMCID: PMC3840169  PMID: 18082427
7.  Longitudinal change in the neural bases of adolescent social self-evaluations: Effects of age and pubertal development 
Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers’ social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a “social reorientation” (Nelson, Leibenluft, McClure, and Pine, 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N = 27, M age = 10.1 and 13.1 years at timepoints one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.
doi:10.1523/JNEUROSCI.4074-12.2013
PMCID: PMC3809090  PMID: 23616547
8.  Own-gender imitation activates the brain's reward circuitry 
Imitation is an important component of human social learning throughout life. Theoretical models and empirical data from anthropology and psychology suggest that people tend to imitate self-similar individuals, and that such imitation biases increase the adaptive value (e.g., self-relevance) of learned information. It is unclear, however, what neural mechanisms underlie people's tendency to imitate those similar to themselves. We focused on the own-gender imitation bias, a pervasive bias thought to be important for gender identity development. While undergoing fMRI, participants imitated own- and other-gender actors performing novel, meaningless hand signs; as control conditions, they also simply observed such actions and viewed still portraits of the same actors. Only the ventral and dorsal striatum, orbitofrontal cortex and amygdala were more active when imitating own- compared to other-gender individuals. A Bayesian analysis of the BrainMap neuroimaging database demonstrated that the striatal region preferentially activated by own-gender imitation is selectively activated by classical reward tasks in the literature. Taken together, these findings reveal a neurobiological mechanism associated with the own-gender imitation bias and demonstrate a novel role of reward-processing neural structures in social behavior.
doi:10.1093/scan/nsr055
PMCID: PMC3475355  PMID: 22383803
imitation; neuroimaging; reward; gender; cultural learning
9.  Relationships between Cerebral Blood Flow and IQ in Typically Developing Children and Adolescents 
Journal of cognitive science  2011;12(2):151-170.
The objective of this study was to explore the relationships between IQ and cerebral blood flow (CBF) measured by arterial spin labeling (ASL) in children and adolescents. ASL was used to collect perfusion MRI data on 39 healthy participants aged 7 to 17. The Wechsler Abbreviated Intelligence Scale was administered to determine IQ scores. Multivariate regression was applied to reveal correlations between CBF and IQ scores, accounting for age, sex and global mean CBF. Voxel Based Morphometry (VBM) analysis, which measures regional cortical volume, was performed as a control. Regression analyses were further performed on CBF data with adjustment of regional gray matter density (GMD). A positive correlation between CBF and IQ scores was primarily seen in the subgenual/anterior cingulate, right orbitofrontal, superior temporal and right inferior parietal regions. An inverse relationship between CBF and IQ was mainly observed in bilateral posterior temporal regions. After adjusting for regional GMD, the correlations between CBF and IQ in the subgenual/anterior cingulate cortex, right orbitofrontal, superior temporal regions and left insula remained significant. These findings support the Parieto-Frontal Integration Theory of intelligence, especially the role of the subgenual/anterior cingulate cortex in the neural networks associated with intelligence. The present study also demonstrates the unique value of CBF in assessing brain-behavior relationships, in addition to structural morphometric measures.
PMCID: PMC3749787  PMID: 23976891
Arterial Spin Labeling (ASL); Perfusion; Voxel Based Morphometry (VBM); Cognitive Development; Intelligence quotient (IQ)
10.  Age and experience shape developmental changes in the neural basis of language-related learning 
Developmental science  2011;14(6):1261-1282.
Very little is known about the neural underpinnings of language learning across the lifespan and how these might be modified by maturational and experiential factors. Building on behavioral research highlighting the importance of early word segmentation (i.e. the detection of word boundaries in continuous speech) for subsequent language learning, here we characterize developmental changes in brain activity as this process occurs online, using data collected in a mixed cross-sectional and longitudinal design. One hundred and fifty-six participants, ranging from age 5 to adulthood, underwent functional magnetic resonance imaging (fMRI) while listening to three novel streams of continuous speech, which contained either strong statistical regularities, strong statistical regularities and speech cues, or weak statistical regularities providing minimal cues to word boundaries. All age groups displayed significant signal increases over time in temporal cortices for the streams with high statistical regularities; however, we observed a significant right-to-left shift in the laterality of these learning-related increases with age. Interestingly, only the 5- to 10-year-old children displayed significant signal increases for the stream with low statistical regularities, suggesting an age-related decrease in sensitivity to more subtle statistical cues. Further, in a sample of 78 10-year-olds, we examined the impact of proficiency in a second language and level of pubertal development on learning-related signal increases, showing that the brain regions involved in language learning are influenced by both experiential and maturational factors.
doi:10.1111/j.1467-7687.2011.01075.x
PMCID: PMC3717169  PMID: 22010887
11.  Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders 
Nature neuroscience  2005;9(1):28-30.
To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional ‘mirror neuron system’ may underlie the social deficits observed in autism.
doi:10.1038/nn1611
PMCID: PMC3713227  PMID: 16327784
12.  Cracking the Language Code: Neural Mechanisms Underlying Speech Parsing 
Word segmentation, detecting word boundaries in continuous speech, is a critical aspect of language learning. Previous research in infants and adults demonstrated that a stream of speech can be readily segmented based solely on the statistical and speech cues afforded by the input. Using functional magnetic resonance imaging (fMRI), the neural substrate of word segmentation was examined on-line as participants listened to three streams of concatenated syllables, containing either statistical regularities alone, statistical regularities and speech cues, or no cues. Despite the participants’ inability to explicitly detect differences between the speech streams, neural activity differed significantly across conditions, with left-lateralized signal increases in temporal cortices observed only when participants listened to streams containing statistical regularities, particularly the stream containing speech cues. In a second fMRI study, designed to verify that word segmentation had implicitly taken place, participants listened to trisyllabic combinations that occurred with different frequencies in the streams of speech they just heard (“words,” 45 times; “partwords,” 15 times; “nonwords,” once). Reliably greater activity in left inferior and middle frontal gyri was observed when comparing words with partwords and, to a lesser extent, when comparing partwords with nonwords. Activity in these regions, taken to index the implicit detection of word boundaries, was positively correlated with participants’ rapid auditory processing skills. These findings provide a neural signature of on-line word segmentation in the mature brain and an initial model with which to study developmental changes in the neural architecture involved in processing speech cues during language learning.
doi:10.1523/JNEUROSCI.5501-05.2006
PMCID: PMC3713232  PMID: 16855090
fMRI; language; speech perception; word segmentation; statistical learning; auditory cortex; inferior frontal gyrus
13.  Reading Affect in the Face and Voice 
Archives of general psychiatry  2007;64(6):698-708.
Context
Understanding a speaker’s communicative intent in everyday interactions is likely to draw on cues such as facial expression and tone of voice. Prior research has shown that individuals with autism spectrum disorders (ASD) show reduced activity in brain regions that respond selectively to the face and voice. However, there is also evidence that activity in key regions can be increased if task demands allow for explicit processing of emotion.
Objectives
To examine the neural circuitry underlying impairments in interpreting communicative intentions in ASD using irony comprehension as a test case, and to determine whether explicit instructions to attend to facial expression and tone of voice will elicit more normative patterns of brain activity.
Design, Setting, and Participants
Eighteen boys with ASD (aged 7–17 years, full-scale IQ >70) and 18 typically developing (TD) boys underwent functional magnetic resonance imaging at the Ahmanson-Lovelace Brain Mapping Center, University of California, Los Angeles.
Main Outcome Measures
Blood oxygenation level– dependent brain activity during the presentation of short scenarios involving irony. Behavioral performance (accuracy and response time) was also recorded.
Results
Reduced activity in the medial prefrontal cortex and right superior temporal gyrus was observed in children with ASD relative to TD children during the perception of potentially ironic vs control scenarios. Importantly, a significant group X condition interaction in the medial prefrontal cortex showed that activity was modulated by explicit instructions to attend to facial expression and tone of voice only in the ASD group. Finally, medial prefrontal cortex activity was inversely related to symptom severity in children with ASD such that children with greater social impairment showed less activity in this region.
Conclusions
Explicit instructions to attend to facial expression and tone of voice can elicit increased activity in the medial prefrontal cortex, part of a network important for understanding the intentions of others, in children with ASD. These findings suggest a strategy for future intervention research.
doi:10.1001/archpsyc.64.6.698
PMCID: PMC3713233  PMID: 17548751
14.  Neural basis of irony comprehension in children with autism: the role of prosody and context 
Brain : a journal of neurology  2006;129(0 4):932-943.
While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.
doi:10.1093/brain/awl032
PMCID: PMC3713234  PMID: 16481375
autism; brain development; fMRI; language pragmatics; social cognition
15.  Infants’ Pre-Empathic Behaviors are Associated with Language Skills 
Infant behavior & development  2012;35(3):561-569.
Infants’ responses to other people’s distress reflect efforts to make sense of affective information about another person and apply it to oneself. This study sought to determine whether 12-month olds’ responses to another person’s display of negative affect reflect characteristics that support social learning and predict social functioning and language skills at 36 months. Measures of infants’ responsiveness include congruent changes in affect and looking time to the person in distress. Attention to the examiner displaying positive affect, analyzed as a control condition, was not related to social functioning or language skills at 36 months. Neither attention nor affective response to the examiner’s distress at 12 months was related to social functioning at 36 months. However, longer time spent looking at the examiner feigning distress predicted higher language scores. Moreover, infants who demonstrated a congruent affective response to distress had higher receptive language scores at 36 months than children who did not respond affectively. Importantly, these relations were not mediated by maternal education, household income, or 12-month verbal skills. These findings are consistent with the notion that adaptation to changes in a social partner’s affective state supports an infants’ ability to glean useful information from interactions with more experienced social partners. Infants’ sensitivity to affective signals may thus be related to the ability to interpret other people’s behavior and to achieve interpersonal understanding through language.
doi:10.1016/j.infbeh.2012.05.007
PMCID: PMC3428260  PMID: 22728336
Empathy; Infancy; Social Interaction; Language Development; Social Development
16.  Reduced Functional Integration and Segregation of Distributed Neural Systems Underlying Social and Emotional Information Processing in Autism Spectrum Disorders 
Cerebral Cortex (New York, NY)  2011;22(5):1025-1037.
A growing body of evidence suggests that autism spectrum disorders (ASDs) are related to altered communication between brain regions. Here, we present findings showing that ASD is characterized by a pattern of reduced functional integration as well as reduced segregation of large-scale brain networks. Twenty-three children with ASD and 25 typically developing matched controls underwent functional magnetic resonance imaging while passively viewing emotional face expressions. We examined whole-brain functional connectivity of two brain structures previously implicated in emotional face processing in autism: the amygdala bilaterally and the right pars opercularis of the inferior frontal gyrus (rIFGpo). In the ASD group, we observed reduced functional integration (i.e., less long-range connectivity) between amygdala and secondary visual areas, as well as reduced segregation between amygdala and dorsolateral prefrontal cortex. For the rIFGpo seed, we observed reduced functional integration with parietal cortex and increased integration with right frontal cortex as well as right nucleus accumbens. Finally, we observed reduced segregation between rIFGpo and the ventromedial prefrontal cortex. We propose that a systems-level approach—whereby the integration and segregation of large-scale brain networks in ASD is examined in relation to typical development—may provide a more detailed characterization of the neural basis of ASD.
doi:10.1093/cercor/bhr171
PMCID: PMC3328339  PMID: 21784971
amygdala; connectivity; default mode network; face processing; mirror neuron system
17.  Facing puberty: associations between pubertal development and neural responses to affective facial displays 
Adolescence is marked by profound psychosocial and physiological changes. Although investigations into the interactions between these forces have begun to shed light on the neural correlates of affective processing during the transition to adolescence, relatively little is known about the relationship between pubertal development and emotion perception at the neural level. In the current longitudinal study, 45 neurotypical participants were shown affective facial displays while undergoing fMRI, at ages 10 and 13. Neural responses to emotional expressions at both time points were then correlated with a self-report measure of pubertal development, revealing positive associations with activity in amygdala, thalamus and visual cortical areas at age 10 that increased in magnitude and extent by age 13. At the latter time point, pubertal development was additionally correlated with enhanced responses to faces in temporal pole, ventrolateral prefrontal cortex (PFC) and dorsomedial PFC. Longitudinal comparisons revealed that the relationships between pubertal development and activity in the amygdala, hippocampus and temporal pole were significantly stronger during early adolescence than late childhood. These results suggest that pubertal development per se is linked to neural processing of socioemotional stimuli, particularly with respect to the integration of complex perceptual input and higher order cortical processing of affective content.
doi:10.1093/scan/nsr066
PMCID: PMC3252633  PMID: 22228752
adolescence; puberty; emotion; fMRI; amygdala; longitudinal
18.  Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2 
Brain Connectivity  2011;1(6):447-459.
Abstract
Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism.
doi:10.1089/brain.2011.0064
PMCID: PMC3420970  PMID: 22500773
autism; CNTNAP2; graph theory; HARDI; structural connectivity; twins
19.  Altered integration of speech and gesture in children with autism spectrum disorders 
Brain and Behavior  2012;2(5):606-619.
The presence of gesture during speech has been shown to impact perception, comprehension, learning, and memory in normal adults and typically developing children. In neurotypical individuals, the impact of viewing co-speech gestures representing an object and/or action (i.e., iconic gesture) or speech rhythm (i.e., beat gesture) has also been observed at the neural level. Yet, despite growing evidence of delayed gesture development in children with autism spectrum disorders (ASD), few studies have examined how the brain processes multimodal communicative cues occurring during everyday communication in individuals with ASD. Here, we used a previously validated functional magnetic resonance imaging (fMRI) paradigm to examine the neural processing of co-speech beat gesture in children with ASD and matched controls. Consistent with prior observations in adults, typically developing children showed increased responses in right superior temporal gyrus and sulcus while listening to speech accompanied by beat gesture. Children with ASD, however, exhibited no significant modulatory effects in secondary auditory cortices for the presence of co-speech beat gesture. Rather, relative to their typically developing counterparts, children with ASD showed significantly greater activity in visual cortex while listening to speech accompanied by beat gesture. Importantly, the severity of their socio-communicative impairments correlated with activity in this region, such that the more impaired children demonstrated the greatest activity in visual areas while viewing co-speech beat gesture. These findings suggest that although the typically developing brain recognizes beat gesture as communicative and successfully integrates it with co-occurring speech, information from multiple sensory modalities is not effectively integrated during social communication in the autistic brain.
doi:10.1002/brb3.81
PMCID: PMC3489813  PMID: 23139906
Autism spectrum disorders; fMRI; gesture; language; superior temporal gyrus
20.  Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2 
Brain connectivity  2011;1(6):447-459.
Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 females, 119 males, age: 23.4 +/−2.17 SD years) were scanned with 105-gradient high angular diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual’s co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole brain analyses, as well as greater eccentricity (maximum path length) in 60 of 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study to link graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of circuits implicated in risk for autism.
doi:10.1089/brain.2011.0064
PMCID: PMC3420970  PMID: 22500773
structural connectivity; HARDI; autism; CNTNAP2; graph theory; twins
21.  “I Know You Are But What Am I?!”: Neural Bases of Self- and Social Knowledge Retrieval in Children and Adults 
Journal of cognitive neuroscience  2007;19(8):1323-1337.
Previous neuroimaging research with adults suggests that the medial prefrontal cortex (MPFC) and the medial posterior parietal cortex (MPPC) are engaged during self-knowledge retrieval processes. However, this has yet to be assessed in a developmental sample. Twelve children and 12 adults (average age = 10.2 and 26.1 years, respectively) reported whether short phrases described themselves or a highly familiar other (Harry Potter) while undergoing functional magnetic resonance imaging. In both children and adults, the MPFC was relatively more active during self- than social knowledge retrieval, and the MPPC was relatively more active during social than self-knowledge retrieval. Direct comparisons between children and adults indicated that children activated the MPFC during self-knowledge retrieval to a much greater extent than adults. The particular regions of the MPPC involved varied between the two groups, with the posterior precuneus engaged by adults, but the anterior precuneus and posterior cingulate engaged by children. Only children activated the MPFC significantly above baseline during self-knowledge retrieval. Implications for social cognitive development and the processing functions performed by the MPFC are discussed.
doi:10.1162/jocn.2007.19.8.1323
PMCID: PMC3407805  PMID: 17651006
22.  fMRI of syntactic processing in typically developing children: structural correlates in the inferior frontal gyrus 
Development of syntactic processing was examined to evaluate maturational processes including left language lateralization functions and increased specialization of brain regions important for syntactic processing. We utilized multimodal methods, including indices of brain activity from fMRI during a syntactic processing task, cortical thickness measurements from structural MRI, and neuropsychological measures. To evaluate hypotheses about increasing lateralization and specialization with development, we examined relationships between cortical thickness and magnitude and spatial activation extent within the left inferior frontal gyrus (IFG) and its right hemisphere homologue. We predicted that increased activation in the left and decreased activation in the right IFG would be associated with increased syntactic proficiency. As predicted, a more mature pattern of increased thickness in the right pars triangularis was associated with decreased activation intensity and extent in the right IFG. These findings suggest a maturational shift towards decreased involvement of the right IFG for syntactic processing. Better syntactic skills were associated with increased activation in the left IFG independent from age, suggesting increased specialization of the left IFG with increased proficiency. Overall, our findings show relationships between structural and functional neurodevelopment that co-occur with improved syntactic processing in critical language regions of the IFG in typically developing children.
doi:10.1016/j.dcn.2011.02.004
PMCID: PMC3129989  PMID: 21743820
Syntax; language; typical development; lateralization; fMRI; multimodal
23.  Atypical Neural Networks for Social Orienting in Autism Spectrum Disorders 
NeuroImage  2011;56(1):354-362.
Autism spectrum disorders (ASD) are characterized by significant social impairments, including deficits in orienting attention following social cues. Behavioral studies investigating social orienting in ASD, however, have yielded mixed results, as the use of naturalistic paradigms typically reveals clear deficits whereas computerized laboratory experiments often report normative behavior. The present study is the first to examine the neural mechanisms underlying social orienting in ASD in order to provide new insight into the social attention impairments that characterize this disorder. Using fMRI, we examined the neural correlates of social orienting in children and adolescents with ASD and in a matched sample of typically developing (TD) controls while they performed a spatial cueing paradigm with social (eye gaze) and nonsocial (arrow) cues. Cues were either directional (indicating left or right) or neutral (indicating no direction), and directional cues were uninformative of the upcoming target location in order to engage automatic processes by minimizing expectations. Behavioral results demonstrated intact orienting effects for social and nonsocial cues, with no differences between groups. The imaging results, however, revealed clear group differences in brain activity. When attention was directed by social cues compared to nonsocial cues, the TD group showed increased activity in frontoparietal attention networks, visual processing regions, and the striatum, whereas the ASD group only showed increased activity in the superior parietal lobule. Significant group × cue type interactions confirmed greater responsivity in task-relevant networks for social cues than nonsocial cues in TD as compared to ASD, despite similar behavioral performance. These results indicate that, in the autistic brain, social cues are not assigned the same privileged status as they are in the typically developing brain. These findings provide the first empirical evidence that the neural circuitry involved in social orienting is disrupted in ASD and highlight that normative behavioral performance in a laboratory setting may reflect compensatory mechanisms rather than intact social attention.
doi:10.1016/j.neuroimage.2011.02.031
PMCID: PMC3091391  PMID: 21334443
autism; attention; functional magnetic resonance imaging; gaze; social cue
24.  An fMRI investigation of responses to peer rejection in adolescents with autism spectrum disorders 
Peer rejection is particularly pervasive among adolescents with autism spectrum disorders (ASD). However, how adolescents with ASD differ from typically developing adolescents in their responses to peer rejection is poorly understood. The goal of the current investigation was to examine neural responses to peer exclusion among adolescents with ASD compared to typically developing adolescents. Nineteen adolescents with ASD and 17 typically developing controls underwent fMRI as they were ostensibly excluded by peers during an online game called Cyberball. Afterwards, participants reported their distress about the exclusion. Compared to typically developing adolescents, those with ASD displayed less activity in regions previously linked with the distressing aspect of peer exclusion, including the subgenual anterior cingulate and anterior insula, as well as less activity in regions previously linked with the regulation of distress responses during peer exclusion, including the ventrolateral prefrontal cortex and ventral striatum. Interestingly, however, both groups self-reported equivalent levels of distress. This suggests that adolescents with ASD may engage in differential processing of social experiences at the neural level, but be equally aware of, and concerned about, peer rejection. Overall, these findings contribute new insights about how this population may differentially experience negative social events in their daily lives.
doi:10.1016/j.dcn.2011.01.004
PMCID: PMC3272329  PMID: 22318914
Autism spectrum disorders; Peer rejection; Social exclusion; Adolescence; Functional magnetic resonance imaging
25.  Abnormal social reward processing in autism as indexed by pupillary responses to happy faces 
Background
Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding.
Methods
We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects.
Results
Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group.
Conclusions
We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli.
doi:10.1186/1866-1955-4-17
PMCID: PMC3461481  PMID: 22958650
Autism; Pupillary response; Reward processing

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