[Show abstract][Hide abstract] ABSTRACT: Cross-sectional magnetic resonance imaging (MRI) studies have long hypothesized that the brain in children with autism undergoes an abnormal growth trajectory that includes a period of early overgrowth; however, this has never been confirmed by a longitudinal study. We performed the first longitudinal study of brain growth in toddlers at the time symptoms of autism are becoming clinically apparent using structural MRI scans at multiple time points beginning at 1.5 years up to 5 years of age. We collected 193 scans on 41 toddlers who received a confirmed diagnosis of autistic disorder at approximately 48 months of age and 44 typically developing controls. By 2.5 years of age, both cerebral gray and white matter were significantly enlarged in toddlers with autistic disorder, with the most severe enlargement occurring in frontal, temporal, and cingulate cortices. In the longitudinal analyses, which we accounted for age and gender effect, we found that all regions (cerebral gray, cerebral white, frontal gray, temporal gray, cingulate gray, and parietal gray) except occipital gray developed at an abnormal growth rate in toddlers with autistic disorder that was mainly characterized by a quadratic age effect. Females with autistic disorder displayed a more pronounced abnormal growth profile in more brain regions than males with the disorder. Given that overgrowth clearly begins before 2 years of age, future longitudinal studies would benefit from inclusion of even younger populations as well as further characterization of genetic and other biomarkers to determine the underlying neuropathological processes causing the onset of autistic symptoms.
Journal of Neuroscience 03/2010; 30(12):4419-27. · 6.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study characterized early language abilities in toddlers with autism spectrum disorders (n = 257) using multiple measures of language development, compared to toddlers with non-spectrum developmental delay (DD, n = 69). Findings indicated moderate to high degrees of agreement among three assessment measures (one parent report and two direct assessment measures). Performance on two of the three measures revealed a significant difference in the profile of receptive-expressive language abilities for toddlers with autism compared to the DD group, such that toddlers with autism had relatively more severe receptive than expressive language delays. Regression analyses examining concurrent predictors of language abilities revealed both similarities in significant predictors (nonverbal cognition) and differences (frequency of vocalization, imitation) across the diagnostic groups.
Journal of Autism and Developmental Disorders 03/2010; 40(10):1259-73. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) are associated with severe impairments in social functioning. Because faces provide nonverbal cues that support social interactions, many studies of ASD have examined neural structures that process faces, including the amygdala, ventromedial prefrontal cortex and superior and middle temporal gyri. However, increases or decreases in activation are often contingent on the cognitive task. Specifically, the cognitive domain of attention influences group differences in brain activation. We investigated brain function abnormalities in participants with ASD using a task that monitored attention bias to emotional faces.
Twenty-four participants (12 with ASD, 12 controls) completed a functional magnetic resonance imaging study while performing an attention cuing task with emotional (happy, sad, angry) and neutral faces.
In response to emotional faces, those in the ASD group showed greater right amygdala activation than those in the control group. A preliminary psychophysiological connectivity analysis showed that ASD participants had stronger positive right amygdala and ventromedial prefrontal cortex coupling and weaker positive right amygdala and temporal lobe coupling than controls. There were no group differences in the behavioural measure of attention bias to the emotional faces.
The small sample size may have affected our ability to detect additional group differences.
When attention bias to emotional faces was equivalent between ASD and control groups, ASD was associated with greater amygdala activation. Preliminary analyses showed that ASD participants had stronger connectivity between the amygdala ventromedial prefrontal cortex (a network implicated in emotional modulation) and weaker connectivity between the amygdala and temporal lobe (a pathway involved in the identification of facial expressions, although areas of group differences were generally in a more anterior region of the temporal lobe than what is typically reported for emotional face processing). These alterations in connectivity are consistent with emotion and face processing disturbances in ASD.
[Show abstract][Hide abstract] ABSTRACT: This study examined how restricted and repetitive behaviors and interests (RRBs) developed over time in a sample of children with autism spectrum disorders (ASD). One hundred ninety-two children referred for a diagnosis of autism at age 2, and 22 children with nonspectrum development disorders were evaluated with a battery of cognitive and diagnostic measures at age 2 and subsequently at ages 3, 5, and 9. Factor analysis of the RRB items on the Autism Diagnostic Interview-Revised revealed two RRB factors at each wave of data collection, one comprising "repetitive sensorimotor" (RSM) behaviors and the other "insistence on sameness" (IS) behaviors. For children with ASD, RSM scores remained relatively high over time, indicating consistent severity, whereas IS scores started low and increased over time, indicating worsening. Having a higher nonverbal intelligence (NVIQ) at age 2 was associated with milder concurrent RSM behaviors and with improvement in these behaviors over time. There was no relationship between NVIQ at age 2 and IS behaviors. However, milder social/communicative impairment, at age 2 was associated with more severe concurrent IS behaviors. Trajectory analysis revealed considerable heterogeneity in patterns of change over time for both kinds of behaviors. These findings are discussed in terms of their implications for our understanding of RRBs in ASD and other disorders, making prognoses about how RRBs will develop in children with ASD as they get older, and using RRBs to identify ASD phenotypes in genetic studies.
Development and Psychopathology 02/2010; 22(1):55-69. · 4.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent prevalence rates for autism spectrum disorders (ASDs) are now estimated at about 1 in 110 children in the U.S. Increases in public awareness and research funding in response to the growing numbers of children and adults with this disorder have led to numerous important scientific advances over the last several years. Nevertheless, because ASD remains a diagnosis that is defined completely on the basis of behavior, diagnostic assessment is both complex and expensive. Appropriate interventions and services are also multi-faceted and costly, and because of the pervasive nature of the disorder, are often required in some form across the lifespan. In the absence of standard societal mechanisms to pay for appropriate assessment and treatment, families must personally shoulder many of the costs associated with securing appropriate services for their children. This "Social Policy" Report summarizes selected recent studies on diagnosis, prevalence, and intervention, and discusses strategies for designing social policies to help improve the outcomes and independence of children and adults with ASDs. (Contains 2 tables and 1 figure.) [Commentaries from Geraldine Dawson, David Mandell, and Fred R. Volkmar are included, and are individually referenced.]
Society for Research in Child Development. 12/2009;
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a cognitive task, but also exists in the absence of a task (i.e., "rest"). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
Brain research 12/2009; 1313:202-14. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) have been gaining attention, partly as an example of unusual developmental trajectories related to early neurobiological differences. The present investigation addressed the process of learning new words to explore mechanisms of language delay and impairment. The sample included 21 typically developing toddlers matched on expressive vocabulary with 21 young children with ASD. Two tasks were administered to teach children a new word and were supplemented by cognitive and diagnostic measures. In most analyses, there were no group differences in performance. Children with ASD did not consistently make mapping errors, even in word learning situations that required the use of social information. These findings indicate that some children with ASD, in developmentally appropriate tasks, are able to use information from social interactions to guide word-object mappings. This result has important implications for understanding of how children with ASD learn language.
[Show abstract][Hide abstract] ABSTRACT: The sociocommunicative abnormalities of young children with Williams syndrome (WS) with limited language were compared with those of children with clinical diagnoses of autism, Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS), or nonspectrum developmental disability.
Participants were 30 children with WS and individually matched groups of participants with autism (n = 28), PDD-NOS (n = 17), and mixed etiology nonspectrum developmental disabilities (n = 16). The autism, PDD-NOS, and mixed etiology groups were matched individually to the children with WS for age, sex, and developmental level. All participants were administered the Autism Diagnostic Observation Schedule Module 1 and the Mullen Scales of Early Learning.
As a group, children with WS with limited language showed fewer sociocommunicative abnormalities than children with autism, about the same level as children with PDD-NOS, and more abnormalities in reciprocity social interaction than participants in the mixed etiology group. Examination of the subgroup of participants with WS matched and compared with children with PDD-NOS indicated that half of the children showed fewer abnormalities than their individual matches with PDD-NOS, whereas half of the children with WS showed more abnormalities than their matches with PDD-NOS.
Sociocommunicative difficulties are present for many children with WS and overlap with the autism spectrum. The results of this investigation suggest that these abnormalities are not accounted for by developmental delay alone, and care should be taken to avoid diagnostic overshadowing in young children with WS.
Journal of developmental and behavioral pediatrics: JDBP 09/2009; 30(4):289-99. · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism is a heterogeneous neurodevelopmental disorder of unknown etiology. The amygdala has long been a site of intense interest in the search for neuropathology in autism, given its role in emotional and social behavior. An interesting hypothesis has emerged that the amygdala undergoes an abnormal developmental trajectory with a period of early overgrowth in autism; however this finding has not been well established at young ages nor analyzed with boys and girls independently.
We measured amygdala volumes on magnetic resonance imaging scans from 89 toddlers at 1-5 years of age (mean = 3 years). Each child returned at approximately 5 years of age for final clinical evaluation.
Toddlers who later received a confirmed autism diagnosis (32 boys, 9 girls) had a larger right (p < .01) and left (p < .05) amygdala compared with typically developing toddlers (28 boys, 11 girls) with and without covarying for total cerebral volume. Amygdala size in toddlers with autism spectrum disorder correlated with the severity of their social and communication impairments as measured on the Autism Diagnostic Interview and Vineland scale. Strikingly, girls differed more robustly from typical in amygdala volume, whereas boys accounted for the significant relationship of amygdala size with severity of clinical impairment.
This study provides evidence that the amygdala is enlarged in young children with autism; the overgrowth must begin before 3 years of age and is associated with the severity of clinical impairments. However, neuroanatomic phenotypic profiles differ between males and females, which critically affects future studies on the genetics and etiology of autism.
[Show abstract][Hide abstract] ABSTRACT: Adaptive social skills were assessed longitudinally at approximately ages 2, 3, 5, 9, and 13 years in a sample of 192 children with a clinical diagnosis of autism (n = 93), PDD-NOS (n = 51), or nonspectrum developmental disabilities (n = 46) at age 2. Growth curve analyses with SAS proc mixed were used to analyze social trajectories over time. Both individual characteristics and environmental resources emerged as key predictors of adaptive social behavior outcome. The gap between children with autism and the other two diagnostic groups widened with time as the social skills of the latter groups improved at a higher rate. However, within diagnostic groups, improvement ranged from minimal to very dramatic. Children with autism most at risk for problems with social adaptive abilities later in life can be identified with considerable accuracy at a very young age so they can be targeted for appropriate early intervention services.
[Show abstract][Hide abstract] ABSTRACT: The Autism Diagnostic Observation Schedule (ADOS; Lord et al., J Autism Dev Disord, 30(3):205-223, 2000) is widely accepted as a "gold standard" diagnostic instrument, but it is of restricted utility with very young children. The purpose of the current project was to modify the ADOS for use in children under 30 months of age. A modified ADOS, the ADOS Toddler Module (or Module T), was used in 360 evaluations. Participants included 182 children with best estimate diagnoses of ASD, non-spectrum developmental delay or typical development. A final set of protocol and algorithm items was selected based on their ability to discriminate the diagnostic groups. The traditional algorithm "cutoffs" approach yielded high sensitivity and specificity, and a new range of concern approach was proposed.
Journal of Autism and Developmental Disorders 06/2009; 39(9):1305-20. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With increased public awareness of the early signs and recent American Academy of Pediatrics recommendations that all 18- and 24-month-olds be screened for autism spectrum disorders, there is an increasing need for diagnostic assessment of very young children. However, unique challenges exist in applying current diagnostic guidelines for autism spectrum disorders to children under the age of 2 years. In this article, we address challenges related to early detection, diagnosis, and treatment of autism spectrum disorders in this age group. We provide a comprehensive review of findings from recent studies on the early development of children with autism spectrum disorders, summarizing current knowledge on early signs of autism spectrum disorders, the screening properties of early detection tools, and current best practice for diagnostic assessment of autism spectrum disorders before 2 years of age. We also outline principles of effective intervention for children under the age of 2 with suspected/confirmed autism spectrum disorders. It is hoped that ongoing studies will provide an even stronger foundation for evidence-based diagnostic and intervention approaches for this critically important age group.
[Show abstract][Hide abstract] ABSTRACT: Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
[Show abstract][Hide abstract] ABSTRACT: The aims of this article are twofold: (a) to offer a set of recommended measures that can be used for evaluating the efficacy of interventions that target spoken language acquisition as part of treatment research studies or for use in applied settings and (b) to propose and define a common terminology for describing levels of spoken language ability in the expressive modality and to set benchmarks for determining a child's language level in order to establish a framework for comparing outcomes across intervention studies.
The National Institute on Deafness and Other Communication Disorders assembled a group of researchers with interests and experience in the study of language development and disorders in young children with autism spectrum disorders. The group worked for 18 months through a series of conference calls and correspondence, culminating in a meeting held in December 2007 to achieve consensus on these aims.
The authors recommend moving away from using the term functional speech, replacing it with a developmental framework. Rather, they recommend multiple sources of information to define language phases, including natural language samples, parent report, and standardized measures. They also provide guidelines and objective criteria for defining children's spoken language expression in three major phases that correspond to developmental levels between 12 and 48 months of age.
Journal of Speech Language and Hearing Research 05/2009; 52(3):643-52. · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This article summarizes current research related to autism spectrum disorders. Current epidemiological trends, theories about aetiology, and relevant issues in assessment and diagnosis of autism spectrum disorders are discussed.
British journal of hospital medicine (London, England: 2005) 04/2009; 70(3):132-5. · 0.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is to standardize Autism Diagnostic Observation Schedule (ADOS) scores within a large sample to approximate an autism severity metric. Using a dataset of 1,415 individuals aged 2-16 years with autism spectrum disorders (ASD) or nonspectrum diagnoses, a subset of 1,807 assessments from 1,118 individuals with ASD were divided into narrow age and language cells. Within each cell, severity scores were based on percentiles of raw totals corresponding to each ADOS diagnostic classification. Calibrated severity scores had more uniform distributions across developmental groups and were less influenced by participant demographics than raw totals. This metric should be useful in comparing assessments across modules and time, and identifying trajectories of autism severity for clinical, genetic, and neurobiological research.
Journal of Autism and Developmental Disorders 01/2009; 39(5):693-705. · 3.06 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Autism is currently viewed as a spectrum condition that includes strikingly different severity levels; IQ is consistently described as one of the primary aspects of the heterogeneity in autism. To investigate the possibility of more than one distinct subtype of autism based on IQ both latent class analysis and taxometrics methods were used to classify Mullen IQs in a sample of 456 children with autism spectrum disorder. We found evidence for multiple IQbased subgroups using both methods. Groups differed in level of intellectual functioning and patterns of verbal versus nonverbal ability. Results support the notion of distinct subtypes of autism that differ in severity of intellectual ability, patterns of cognitive strengths and weaknesses, and severity of autism symptoms.
American journal of mental retardation: AJMR 12/2008; 113:439-452. · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To replicate the factor structure and predictive validity of revised Autism Diagnostic Observation Schedule algorithms in an independent dataset (N = 1,282).
Algorithm revisions were replicated using data from children ages 18 months to 16 years collected at 11 North American sites participating in the Collaborative Programs for Excellence in Autism and the Studies to Advance Autism Research and Treatment.
Sensitivities and specificities approximated or exceeded those of the old algorithms except for young children with phrase speech and a clinical diagnosis of pervasive developmental disorders not otherwise specified.
Revised algorithms increase comparability between modules and improve the predictive validity of the Autism Diagnostic Observation Schedule for autism cases compared to the original algorithms.
Journal of the American Academy of Child and Adolescent Psychiatry 07/2008; 47(6):642-51. · 6.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: A recent hypothesis has emerged that toddlers with autism undergo abnormal neuroanatomical development that includes a period of early brain overgrowth. Cross-sectional MRI and head circumference studies suggest that the overgrowth occurs before the diagnosis is typically given in the fourth year of life. MRI studies that further partition the cerebrum into lobes find that the more anterior and higher association areas exhibit the highest degree of enlargement.
Objectives: We carried out a longitudinal MRI study of the cerebral cortex in toddlers 18 months to five years of age in order to 1) identify aberrant growth patterns in specific regions of the cerebral cortex that may contribute to early enlargement and 2) correlate behavioral and clinical features with affected cortical regions in toddlers with autism.
Methods: Clinical evaluations and MRI scans (total=220) were collected at ~12 month intervals from ~18-60 months from typically-developing toddlers (n=48) and those with provisional autism spectrum disorder (n=43). Final diagnosis was given at ~4 years of age upon completion of the study with the Autism Diagnostic Observation Schedule (ADOS) and Autism Diagnostic Interview-Revised (ADI-R). For each T1-W MRI, a semi-manual segmentation program was used to delineate cerebral gray and white matter and then the program Freesurfer further parcellated the cortex into subregions.
Results: Preliminary regression analyses revealed significant enlargement in cerebral, frontal, and temporal gray matter volumes (p<.05) in toddlers with autism relative to typically-developing controls.
Conclusions: In this first longitudinal MRI study of toddlers with autism, growth trajectories of total cerebral, frontal and temporal gray were significantly different from typical toddlers. Aberrant growth patterns observed in longitudinal MRI’s at early ages provide a developmental anatomical phenotype for autism spectrum disorder.
International Meeting for Autism Research 2008; 05/2008