- Psychology, Child and Adolescent
- Autism and Developmental Disabilities
Clinical Associate Professor, Psychiatry and Behavioral Sciences - Child and Adolescent Psychiatry
Co-Director, Autism and Developmental Disabilities Clinic, Stanford Child Psychiatry Clinic (2011 - Present)
PhD Training:University of Texas Southwestern Medical Center (1999) TX
Fellowship:Stanford University School of Medicine Registrar (2002) CA
Internship:University of Texas Southwestern Medical Center (1999) TX
Fellowship, Arizona State University, Autism and Developmental Disabilities (2001)
Fellowship:Arizona State University (2001) AR
Ph.D., UT Southwestern Medical Center, Clinical Psychology (1999)
BS, Texas A&M University, Psychology (1995)
Current Research and Scholarly Interests
Autism spectrum disorders, young child assessment, developmental disabilities
An Evaluation of a Developmentally-Based Parent Training Program for Children With Autism
The purpose of this study is to assess the efficacy of a parent training program in the treatment of social and communication deficits in children with autism. Specifically, this study will evaluate a developmentally based parent delivered intervention in the community developed by Pacific Autism Center for Education (PACE).
Stanford is currently not accepting patients for this trial. For more information, please contact Christina Ardel, MA, 650-736-1235.
Graduate and Fellowship Programs
Effects of a parent-implemented Developmental Reciprocity Treatment Program for children with autism spectrum disorder.
Autism : the international journal of research and practice
Developmental approaches to autism treatment aim to establish strong interpersonal relationships through joint play. These approaches have emerging empirical support; however, there is a need for further research documenting the procedures and demonstrating their effectiveness. This pilot study evaluated changes in parent behavior and child autism symptoms following a 12-week Developmental Reciprocity Treatment parent-training program. A total of 22 children with autism spectrum disorder between 2 and 6years (mean age=44.6months, standard deviation=12.7) and a primary caregiver participated in 12 weekly sessions of Developmental Reciprocity Treatment parent training, covering topics including introduction to developmental approaches, supporting attention and motivation, sensory regulation and sensory-social routines, imitation/building nonverbal communication, functional language development, and turn taking. Results indicated improvement in aspects of parent empowerment and social quality of life. Improvement in core autism symptoms was observed on the Social Responsiveness Scale total score (F(1,19): 5.550, p=0.029), MacArthur-Bates Communicative Development Inventories number of words produced out of 680 (F(1,18): 18.104, p=0.000), and two subscales of the Repetitive Behavior Scale, Revised (compulsive, p=0.046 and restricted, p=0.025). No differences in sensory sensitivity were observed on the Short Sensory Profile. Findings from this pilot study indicate that Developmental Reciprocity Treatment shows promise and suggest the need for future controlled trials of this developmentally based intervention.
View details for DOI 10.1177/1362361318775538
View details for PubMedID 29775078
Plasma anandamide concentrations are lower in children with autism spectrum disorder
2018; 9: 18
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by restricted, stereotyped behaviors and impairments in social communication. Although the underlying biological mechanisms of ASD remain poorly understood, recent preclinical research has implicated the endogenous cannabinoid (or endocannabinoid), anandamide, as a significant neuromodulator in rodent models of ASD. Despite this promising preclinical evidence, no clinical studies to date have tested whether endocannabinoids are dysregulated in individuals with ASD. Here, we addressed this critical gap in knowledge by optimizing liquid chromatography-tandem mass spectrometry methodology to quantitatively analyze anandamide concentrations in banked blood samples collected from a cohort of children with and without ASD (N = 112).Anandamide concentrations significantly differentiated ASD cases (N = 59) from controls (N = 53), such that children with lower anandamide concentrations were more likely to have ASD (p = 0.041). In keeping with this notion, anandamide concentrations were also significantly lower in ASD compared to control children (p = 0.034).These findings are the first empirical human data to translate preclinical rodent findings to confirm a link between plasma anandamide concentrations in children with ASD. Although preliminary, these data suggest that impaired anandamide signaling may be involved in the pathophysiology of ASD.
View details for DOI 10.1186/s13229-018-0203-y
View details for Web of Science ID 000427704800001
View details for PubMedID 29564080
View details for PubMedCentralID PMC5848550
Feasibility Testing of a Wearable Behavioral Aid for Social Learning in Children with Autism
APPLIED CLINICAL INFORMATICS
2018; 9 (1): 129–40
Recent advances in computer vision and wearable technology have created an opportunity to introduce mobile therapy systems for autism spectrum disorders (ASD) that can respond to the increasing demand for therapeutic interventions; however, feasibility questions must be answered first.We studied the feasibility of a prototype therapeutic tool for children with ASD using Google Glass, examining whether children with ASD would wear such a device, if providing the emotion classification will improve emotion recognition, and how emotion recognition differs between ASD participants and neurotypical controls (NC).We ran a controlled laboratory experiment with 43 children: 23 with ASD and 20 NC. Children identified static facial images on a computer screen with one of 7 emotions in 3 successive batches: the first with no information about emotion provided to the child, the second with the correct classification from the Glass labeling the emotion, and the third again without emotion information. We then trained a logistic regression classifier on the emotion confusion matrices generated by the two information-free batches to predict ASD versus NC.All 43 children were comfortable wearing the Glass. ASD and NC participants who completed the computer task with Glass providing audible emotion labeling (n = 33) showed increased accuracies in emotion labeling, and the logistic regression classifier achieved an accuracy of 72.7%. Further analysis suggests that the ability to recognize surprise, fear, and neutrality may distinguish ASD cases from NC.This feasibility study supports the utility of a wearable device for social affective learning in ASD children and demonstrates subtle differences in how ASD and NC children perform on an emotion recognition task.
View details for DOI 10.1055/s-0038-1626727
View details for Web of Science ID 000428690000006
View details for PubMedID 29466819
View details for PubMedCentralID PMC5821509
A proton MR spectroscopy study of the thalamus in twins with autism spectrum disorder.
Progress in neuro-psychopharmacology & biological psychiatry
Multiple lines of research have reported thalamic abnormalities in individuals with autism spectrum disorder (ASD) that are associated with social communication impairments (SCI), restricted and repetitive behaviors (RRB), or sensory processing abnormalities (SPA). Thus, the thalamus may represent a common neurobiological structure that is shared across symptom domains in ASD. Same-sex monozygotic (MZ) and dizygotic (DZ) twin pairs with and without ASD underwent cognitive/behavioral evaluation and magnetic resonance imaging to assess the thalamus. Neurometabolites were measured with (1)H magnetic resonance spectroscopy (MRS) utilizing a multi-voxel PRESS sequence and were referenced to creatine+phosphocreatine (tCr). N-acetyl aspartate (NAA), a marker of neuronal integrity, was reduced in twins with ASD (n=47) compared to typically-developing (TD) controls (n=33), and this finding was confirmed in a sub-sample of co-twins discordant for ASD (n=11). NAA in the thalamus was correlated to a similar extent with SCI, RRB, and SPA, such that reduced neuronal integrity was associated with greater symptom severity. Glutamate+glutamine (Glx) was also reduced in affected versus unaffected co-twins. Additionally, NAA and Glx appeared to be primarily genetically-mediated, based on comparisons between MZ and DZ twin pairs. Thus, thalamic abnormalities may be influenced by genetic susceptibility for ASD but are likely not domain-specific.
View details for DOI 10.1016/j.pnpbp.2017.09.016
View details for PubMedID 28941767
Biomarker discovery for disease status and symptom severity in children with autism.
2017; 89: 39–45
Autism spectrum disorder (ASD) is characterized by social impairments and repetitive behaviors, and affects 1 in 68 US children. Despite ASD's societal impact, its disease mechanisms remain poorly understood. Recent preclinical ASD biomarker discovery research has implicated the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP), and their receptors, OXTR and AVPR1A, in animal models. Efforts to translate these findings to individuals with ASD have typically involved evaluating single neuropeptide measures as biomarkers of ASD and/or behavioral functioning. Given that ASD is a heterogeneous disorder, and unidimensional ASD biomarker studies have been challenging to reproduce, here we employed a multidimensional neuropeptide biomarker analysis to more powerfully interrogate disease status and symptom severity in a well characterized child cohort comprised of ASD patients and neurotypical controls. These blood-based neuropeptide measures, considered as a whole, correctly predicted disease status for 57 out of 68 (i.e., 84%) participants. Further analysis revealed that a composite measure of OXTR and AVPR1A gene expression was the key driver of group classification, and that children with ASD had lower neuropeptide receptor mRNA levels compared to controls. Lower neuropeptide receptor mRNA levels also predicted greater symptom severity for core ASD features (i.e., social impairments and stereotyped behaviors), but were unrelated to intellectual impairment, an associated feature of ASD. Findings from this research highlight the value of assessing multiple related biological measures, and their relative contributions, in the same study, and suggest that low blood neuropeptide receptor availability may be a promising biomarker of disease presence and symptom severity in ASD.
View details for DOI 10.1016/j.psyneuen.2017.12.022
View details for PubMedID 29309996
White matter structure in the uncinate fasciculus: Implications for socio-affective deficits in Autism Spectrum Disorder.
2016; 255: 66-74
Individuals with Autism Spectrum Disorder (ASD) have social and communication deficits and difficulties regulating emotions. The brain bases of these socio-affective deficits are not yet clear, but one candidate is structural connectivity in the left uncinate fasciculus, which connects limbic temporal and frontal areas thought to be involved in socio-affective processing. In this study, we assessed white matter structure in the left and right uncinate fasciculus in 18 high-functioning individuals with ASD and 18 group-matched typically developing (TD) controls using Diffusion Tensor Imaging. To test specificity of the associations, we also examined the association between both uncinate fasciculi and restricted and repetitive behaviors. Compared to TD individuals, individuals with ASD had significantly lower fractional anisotropy (FA) in the left and right uncinate. Group status significantly moderated the association between left uncinate and socio-affective deficits, indicating that within the ASD group, FA was associated with socio-affective deficits: Individuals with ASD with lower FA in the left uncinate had significantly more social and emotion regulation deficits. There was no association with restricted and repetitive behaviors. This study provides evidence that the left uncinate may play a critical role in socio-affective skills in individuals with ASD.
View details for DOI 10.1016/j.pscychresns.2016.08.004
View details for PubMedID 27552717
- Brain State Differentiation and Behavioral Inflexibility in Autism†. Cerebral cortex 2015; 25 (12): 4740-4747
- Maladaptive Behavior in Autism Spectrum Disorder: The Role of Emotion Experience and Emotion Regulation. Journal of autism and developmental disorders 2015; 45 (11): 3424-3432
- Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS 2015; 45 (9): 2889-2898
Pivotal Response Treatment Parent Training for Autism: Findings from a 3-Month Follow-Up Evaluation.
Journal of autism and developmental disorders
2015; 45 (9): 2889-2898
This study's objective was to assess maintenance of treatment effects 3 months after completion of a 12-week Pivotal Response Treatment (PRT) parent education group. Families who completed the active treatment (N = 23) were followed for an additional 12 weeks to measure changes in language and cognitive skills. Results indicated a significant improvement in frequency of functional utterances, with maintenance at 3-month follow-up [F(2, 21): 5.9, p = .009]. Children also made significant gains on the Vineland Communication Domain Standard Score [F(2, 12):11.74, p = .001] and the Mullen Scales of Early Learning Composite score [F(1, 20) = 5.43, p = .03]. These results suggest that a brief PRT parent group intervention can lead to improvements in language and cognitive functioning that are maintained 12 weeks post treatment.
View details for DOI 10.1007/s10803-015-2452-3
View details for PubMedID 25911977
Emotion regulation in autism spectrum disorder: evidence from parent interviews and children's daily diaries.
Journal of child psychology and psychiatry, and allied disciplines
2015; 56 (8): 903-913
Although emotion dysregulation is not a defining feature of Autism Spectrum Disorder (ASD), there is a growing consensus that emotional problems play a prominent role in this disorder.The present study examined a wide range of emotion regulation (ER) strategies in 32 individuals with ASD compared to 31 group-matched typically developing (TD) participants in three emotional domains (anger, anxiety, and amusement). Parents of individuals with ASD and TD individuals were interviewed about their child's emotional experience and the use and efficacy of 10 ER strategies. In addition, participants filled out daily diaries on experience and regulation in the same emotional domains.Compared to TD individuals, parents reported that individuals with ASD experienced more anger and anxiety and less amusement, made less frequent use of a variety of adaptive ER strategies (e.g. problem solving, cognitive reappraisal), and made more frequent use of maladaptive strategies (e.g. repetitive behavior). Moreover, individuals with ASD were less effective at utilizing adaptive ER strategies. Self-reports showed differences in experience of amusement and in ER strategies for anger and anxiety, but not in experience of anger and anxiety.This study provides evidence that individuals with ASD less frequently use adaptive - but more frequently use maladaptive - ER strategies. Implications for ASD treatments that focus on increasing the use of adaptive strategies are discussed.
View details for DOI 10.1111/jcpp.12370
View details for PubMedID 25442191
A randomized controlled trial of Pivotal Response Treatment Group for parents of children with autism.
Journal of child psychology and psychiatry, and allied disciplines
2015; 56 (8): 884-892
With rates of autism diagnosis continuing to rise, there is an urgent need for effective and efficient service delivery models. Pivotal Response Treatment (PRT) is considered an established treatment for autism spectrum disorder (ASD); however, there have been few well-controlled studies with adequate sample size. The aim of this study was to conduct a randomized controlled trial to evaluate PRT parent training group (PRTG) for targeting language deficits in young children with ASD.Fifty-three children with autism and significant language delay between 2 and 6 years old were randomized to PRTG (N = 27) or psychoeducation group (PEG; N = 26) for 12 weeks. The PRTG taught parents behavioral techniques to facilitate language development. The PEG taught general information about ASD (clinical trial NCT01881750; http://www.clinicaltrials.gov).Analysis of child utterances during the structured laboratory observation (primary outcome) indicated that, compared with children in the PEG, children in the PRTG demonstrated greater improvement in frequency of utterances (F(2, 43) = 3.53, p = .038, d = 0.42). Results indicated that parents were able to learn PRT in a group format, as the majority of parents in the PRTG (84%) met fidelity of implementation criteria after 12 weeks. Children also demonstrated greater improvement in adaptive communication skills (Vineland-II) following PRTG and baseline Mullen visual reception scores predicted treatment response to PRTG.This is the first randomized controlled trial of group-delivered PRT and one of the largest experimental investigations of the PRT model to date. The findings suggest that specific instruction in PRT results in greater skill acquisition for both parents and children, especially in functional and adaptive communication skills. Further research in PRT is warranted to replicate the observed results and address other core ASD symptoms.
View details for DOI 10.1111/jcpp.12354
View details for PubMedID 25346345
- Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism PLOS ONE 2015; 10 (7)
Emotion regulation in children and adolescents with autism spectrum disorder.
2015; 8 (1): 9-18
Emotion dysregulation is not a formal criterion for the diagnosis of autism spectrum disorder (ASD). However, parents and clinicians have long noted the importance of emotional problems in individuals with ASD (e.g. tantrums and "meltdowns"). In this study, 21 high-functioning children and adolescents with ASD and 22 age and gender group-matched typically developing (TD) controls completed a Reactivity and Regulation Situation Task. This task assesses emotional reactivity and spontaneous use of emotion regulation strategies (problem solving, cognitive reappraisal, avoidance, distraction, venting, suppression, and relaxation) in the context of age-appropriate ambiguous and potentially threatening negative scenarios. After the concept of cognitive reappraisal was explained, the scenarios were presented again to participants, and they were prompted to use this strategy. Results indicated that individuals with ASD exhibited the same level of reactivity to negative stimuli as TD participants. Furthermore, youth with ASD had a different emotion regulation profile than TD individuals, characterized by a less frequent use of cognitive reappraisal and more frequent use of suppression. When prompted to use cognitive reappraisal, participants with ASD were less able to implement reappraisal, but benefitted from this strategy when they were able to generate a reappraisal. Findings from this study suggest that cognitive reappraisal strategies may be useful to children and adolescents with ASD. Therefore, the development of treatment programs that focus on enhancing the use of adaptive forms of emotion regulation might decrease emotional problems and optimize long-term outcomes in youth with ASD. Autism Res 2014, ●●: ●●-●●. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.
View details for DOI 10.1002/aur.1387
View details for PubMedID 24863869
- Emotion Regulation in Children and Adolescents With Autism Spectrum Disorder AUTISM RESEARCH 2015; 8 (1): 9-18
Arginine Vasopressin Is a Blood-Based Biomarker of Social Functioning in Children with Autism.
2015; 10 (7)
Brain arginine vasopressin (AVP) critically regulates normative social behavior in mammals, and experimental disruption of the AVP signaling pathway produces social impairments in rodent models. We therefore hypothesized that AVP signaling deficits may contribute to social impairments in children with autism spectrum disorder (ASD). Since blood measures (which are far easier to obtain than brain measures) of AVP are most meaningful if they are related to brain AVP activity, Study 1 tested the relationship between AVP concentrations in concomitantly collected blood and CSF samples from children and adults (N = 28) undergoing clinical procedures. Study 2 tested whether blood AVP concentrations: 1) differed between children with ASD (N = 57), their ASD discordant siblings (N = 47), and neurotypical controls (N = 55); and 2) predicted social functioning (using the NEPSY-II Theory of Mind and Affect Recognition tasks and the Social Responsiveness Scale) in this large, well-characterized child cohort. Blood AVP concentrations significantly and positively predicted CSF AVP concentrations (F1,26 = 7.17, r = 0.46, p = 0.0127) in Study 1. In Study 2, blood AVP concentrations did not differ between groups or by sex, but significantly and positively predicted Theory of Mind performance, specifically in children with ASD, but not in non-ASD children (F1,144 = 5.83, p = 0.017). Blood AVP concentrations can be used: 1) as a surrogate for brain AVP activity in humans; and 2) as a robust biomarker of theory of mind ability in children with ASD. These findings also suggest that AVP biology may be a promising therapeutic target by which to improve social cognition in individuals with ASD.
View details for DOI 10.1371/journal.pone.0132224
View details for PubMedID 26200852
- Brief Report: An Open-Label Study of the Neurosteroid Pregnenolone in Adults with Autism Spectrum Disorder JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS 2014; 44 (11): 2971-2977
Brief report: an open-label study of the neurosteroid pregnenolone in adults with autism spectrum disorder.
Journal of autism and developmental disorders
2014; 44 (11): 2971-2977
The objective of this study was to assess the tolerability and efficacy of pregnenolone in reducing irritability in adults with autism spectrum disorder (ASD). This was a pilot, open-label, 12-week trial that included twelve subjects with a mean age of 22.5 ± 5.8 years. Two participants dropped out of the study due to reasons unrelated to adverse effects. Pregnenolone yielded a statistically significant improvement in the primary measure, Aberrant Behavior Checklist (ABC)-Irritability [from 17.4 ± 7.4 at baseline to 11.2 ± 7.0 at 12 weeks (p = 0.028)]. Secondary measures were not statistically significant with the exception of ABC-lethargy (p = 0.046) and total Short Sensory Profile score (p = 0.009). No significant vital sign changes occurred during this study. Pregnenolone was not associated with any severe side effects. Single episodes of tiredness, diarrhea and depressive affect that could be related to pregnenolone were reported. Overall, pregnenolone was modestly effective and well-tolerated in individuals with ASD.
View details for DOI 10.1007/s10803-014-2144-4
View details for PubMedID 24849255
Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2014; 111 (33): 12258-12263
The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD.
View details for DOI 10.1073/pnas.1402236111
View details for Web of Science ID 000340438800080
View details for PubMedID 25092315
Emotion dysregulation and the core features of autism spectrum disorder.
Journal of autism and developmental disorders
2014; 44 (7): 1766-1772
The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child Behavior Checklist. Compared to typically developing controls, children and adolescents with ASD showed more emotion dysregulation and had significantly greater symptom severity on all scales. Within ASD participants, emotion dysregulation was related to all core features of the disorder, but the strongest association was with repetitive behaviors. These findings may facilitate the development of more effective therapeutic strategies targeting emotion dysregulation in order to optimize long-term outcomes for individuals with ASD.
View details for DOI 10.1007/s10803-013-2022-5
View details for PubMedID 24362795
Prenatal and perinatal risk factors in a twin study of autism spectrum disorders.
Journal of psychiatric research
2014; 54: 100-108
Multiple studies associate prenatal and perinatal complications with increased risks for autism spectrum disorders (ASDs). The objectives of this study were to utilize a twin study design to 1) Investigate whether shared gestational and perinatal factors increase concordance for ASDs in twins, 2) Determine whether individual neonatal factors are associated with the presence of ASDs in twins, and 3) Explore whether associated factors may influence males and females differently.Data from medical records and parent response questionnaires from 194 twin pairs, in which at least one twin had an ASD, were analyzed.Shared factors including parental age, prenatal use of medications, uterine bleeding, and prematurity did not increase concordance risks for ASDs in twins. Among the individual factors, respiratory distress demonstrated the strongest association with increased risk for ASDs in the group as a whole (OR 2.11, 95% CI 1.27-3.51). Furthermore, respiratory distress (OR 2.29, 95% CI 1.12-4.67) and other markers of hypoxia (OR 1.99, 95% CI 1.04-3.80) were associated with increased risks for ASDs in males, while jaundice was associated with an increased risk for ASDs in females (OR 2.94, 95% CI 1.28-6.74).Perinatal factors associated with respiratory distress and other markers of hypoxia appear to increase risk for autism in a subgroup of twins. Future studies examining potential gender differences and additional prenatal, perinatal and postnatal environmental factors are required for elucidating the etiology of ASDs and suggesting new methods for treatment and prevention.
View details for DOI 10.1016/j.jpsychires.2014.03.019
View details for PubMedID 24726638
Brain Organization Underlying Superior Mathematical Abilities in Children with Autism
2014; 75 (3): 223-230
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits. While such deficits have been the focus of most research, recent evidence suggests that individuals with ASD may exhibit cognitive strengths in domains such as mathematics.Cognitive assessments and functional brain imaging were used to investigate mathematical abilities in 18 children with ASD and 18 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate classification and regression analyses were used to investigate whether brain activity patterns during numerical problem solving were significantly different between the groups and predictive of individual mathematical abilities.Children with ASD showed better numerical problem solving abilities and relied on sophisticated decomposition strategies for single-digit addition problems more frequently than TD peers. Although children with ASD engaged similar brain areas as TD children, they showed different multivariate activation patterns related to arithmetic problem complexity in ventral temporal-occipital cortex, posterior parietal cortex, and medial temporal lobe. Furthermore, multivariate activation patterns in ventral temporal-occipital cortical areas typically associated with face processing predicted individual numerical problem solving abilities in children with ASD but not in TD children.Our study suggests that superior mathematical information processing in children with ASD is characterized by a unique pattern of brain organization and that cortical regions typically involved in perceptual expertise may be utilized in novel ways in ASD. Our findings of enhanced cognitive and neural resources for mathematics have critical implications for educational, professional, and social outcomes for individuals with this lifelong disorder.
View details for DOI 10.1016/j.biopsych.2013.06.018
View details for Web of Science ID 000329130500011
View details for PubMedID 23954299
Brain hyperconnectivity in children with autism and its links to social deficits.
2013; 5 (3): 738-747
Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting nearly 1 in 88 children, is thought to result from aberrant brain connectivity. Remarkably, there have been no systematic attempts to characterize whole-brain connectivity in children with ASD. Here, we use neuroimaging to show that there are more instances of greater functional connectivity in the brains of children with ASD in comparison to those of typically developing children. Hyperconnectivity in ASD was observed at the whole-brain and subsystems levels, across long- and short-range connections, and was associated with higher levels of fluctuations in regional brain signals. Brain hyperconnectivity predicted symptom severity in ASD, such that children with greater functional connectivity exhibited more severe social deficits. We replicated these findings in two additional independent cohorts, demonstrating again that at earlier ages, the brain of children with ASD is largely functionally hyperconnected in ways that contribute to social dysfunction. Our findings provide unique insights into brain mechanisms underlying childhood autism.
View details for DOI 10.1016/j.celrep.2013.10.001
View details for PubMedID 24210821
Head circumferences in twins with and without autism spectrum disorders.
Journal of autism and developmental disorders
2013; 43 (9): 2026-2037
To determine the genetic relationship between head circumference (HC) and Autism Spectrum Disorders (ASDs). Twin pairs with at least one twin with an ASD were assessed. HCs in affected and unaffected individuals were compared, as were HC correlations in monozygotic and dizygotic pairs. 404 subjects, ages 4-18, were included. 20 % of males and 27 % of females with an ASD had macrocephaly. Unaffected co-twins showed similar rates (16 % of males and 22 % of females). Statistical analysis revealed no significant difference in HCs between affected and unaffected twins. Twins with ASDs and unaffected co-twins have similar HCs and increased rates of macrocephaly. Correlations demonstrated partial inheritance of HCs. Thus, macrocephaly may represent an endophenotype in ASDs.
View details for DOI 10.1007/s10803-012-1751-1
View details for PubMedID 23321801
Default Mode Network in Childhood Autism: Posteromedial Cortex Heterogeneity and Relationship with Social Deficits
2013; 74 (3): 212-219
BACKGROUND: The default mode network (DMN), a brain system anchored in the posteromedial cortex, has been identified as underconnected in adults with autism spectrum disorder (ASD). However, to date there have been no attempts to characterize this network and its involvement in mediating social deficits in children with ASD. Furthermore, the functionally heterogeneous profile of the posteromedial cortex raises questions regarding how altered connectivity manifests in specific functional modules within this brain region in children with ASD. METHODS: Resting-state functional magnetic resonance imaging and an anatomically informed approach were used to investigate the functional connectivity of the DMN in 20 children with ASD and 19 age-, gender-, and IQ-matched typically developing (TD) children. Multivariate regression analyses were used to test whether altered patterns of connectivity are predictive of social impairment severity. RESULTS: Compared with TD children, children with ASD demonstrated hyperconnectivity of the posterior cingulate and retrosplenial cortices with predominately medial and anterolateral temporal cortex. In contrast, the precuneus in ASD children demonstrated hypoconnectivity with visual cortex, basal ganglia, and locally within the posteromedial cortex. Aberrant posterior cingulate cortex hyperconnectivity was linked with severity of social impairments in ASD, whereas precuneus hypoconnectivity was unrelated to social deficits. Consistent with previous work in healthy adults, a functionally heterogeneous profile of connectivity within the posteromedial cortex in both TD and ASD children was observed. CONCLUSIONS: This work links hyperconnectivity of DMN-related circuits to the core social deficits in young children with ASD and highlights fundamental aspects of posteromedial cortex heterogeneity.
View details for DOI 10.1016/j.biopsych.2012.12.013
View details for Web of Science ID 000321443100012
View details for PubMedID 23375976
Salience Network-Based Classification and Prediction of Symptom Severity in Children With Autism
2013; 70 (8): 869-879
IMPORTANCE Autism spectrum disorder (ASD) affects 1 in 88 children and is characterized by a complex phenotype, including social, communicative, and sensorimotor deficits. Autism spectrum disorder has been linked with atypical connectivity across multiple brain systems, yet the nature of these differences in young children with the disorder is not well understood. OBJECTIVES To examine connectivity of large-scale brain networks and determine whether specific networks can distinguish children with ASD from typically developing (TD) children and predict symptom severity in children with ASD. DESIGN, SETTING, AND PARTICIPANTS Case-control study performed at Stanford University School of Medicine of 20 children 7 to 12 years old with ASD and 20 age-, sex-, and IQ-matched TD children. MAIN OUTCOMES AND MEASURES Between-group differences in intrinsic functional connectivity of large-scale brain networks, performance of a classifier built to discriminate children with ASD from TD children based on specific brain networks, and correlations between brain networks and core symptoms of ASD. RESULTS We observed stronger functional connectivity within several large-scale brain networks in children with ASD compared with TD children. This hyperconnectivity in ASD encompassed salience, default mode, frontotemporal, motor, and visual networks. This hyperconnectivity result was replicated in an independent cohort obtained from publicly available databases. Using maps of each individual's salience network, children with ASD could be discriminated from TD children with a classification accuracy of 78%, with 75% sensitivity and 80% specificity. The salience network showed the highest classification accuracy among all networks examined, and the blood oxygen-level dependent signal in this network predicted restricted and repetitive behavior scores. The classifier discriminated ASD from TD in the independent sample with 83% accuracy, 67% sensitivity, and 100% specificity. CONCLUSIONS AND RELEVANCE Salience network hyperconnectivity may be a distinguishing feature in children with ASD. Quantification of brain network connectivity is a step toward developing biomarkers for objectively identifying children with ASD.
View details for DOI 10.1001/jamapsychiatry.2013.104
View details for Web of Science ID 000322833600013
View details for PubMedID 23803651
Underconnectivity between voice-selective cortex and reward circuitry in children with autism
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2013; 110 (29): 12060-12065
Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.
View details for DOI 10.1073/pnas.1302982110
View details for Web of Science ID 000322086100085
View details for PubMedID 23776244
Socio-emotional processing and functioning of youth at high risk for bipolar disorder.
Journal of affective disorders
2013; 148 (1): 112-117
The goal of this study was to investigate differences in socio-emotional processing and functioning in children and adolescents at high risk for bipolar disorder (BD) and healthy control participants.Children and adolescents with a parent with bipolar disorder, who had mood dysregulation but not fully syndromal BD (high risk, HR, n=24), were compared to participants with no personal or family history of psychopathology (healthy control, HC, n=27) across several neuropsychological domains. Social reciprocity was measured by the Social Responsiveness Scale, theory of mind was measured by use of the NEPSY, and affect recognition was measured by the NEPSY and the Diagnostic Test of Nonverbal Accuracy 2 (DANVA).The HR group demonstrated significant impairment in social reciprocity, including impairments in social awareness, social cognition, social communication, social motivation, and autistic mannerisms. There were no significant group differences in performance on theory of mind or affect recognition tasks.Lack of impairment in tasks associated with theory of mind or affect recognition indicate that social functioning difficulties are not likely due to impairments in these areas, or that the measures employed were not sufficiently sensitive to detect group differences.Youth at high risk for BD demonstrated impairments in numerous social domains, which may be due to innate differences in brain development governing socio-emotional functioning or may be due to disruptions in normal development caused by mood regulation difficulties.
View details for DOI 10.1016/j.jad.2012.08.016
View details for PubMedID 23123133
Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism
ARCHIVES OF GENERAL PSYCHIATRY
2011; 68 (11): 1095-1102
Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins.To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. Design, Setting, andTwin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services.Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD).For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55%; 95% CI, 9%-81% for autism and 58%; 95% CI, 30%-80% for ASD) in addition to moderate genetic heritability (37%; 95% CI, 8%-84% for autism and 38%; 95% CI, 14%-67% for ASD).Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.
View details for DOI 10.1001/archgenpsychiatry.2011.76
View details for Web of Science ID 000296649800004
View details for PubMedID 21727249
- Twins with KBG Syndrome and Autism JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS 2009; 39 (12): 1744-1746