Search tips
Search criteria

Results 1-11 (11)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  Early Intersubjective Skills and the Understanding of Intentionality in Young Children with Down Syndrome 
Research in developmental disabilities  2013;34(12):10.1016/j.ridd.2013.09.027.
This study examined the relationship between early intersubjective skills (joint attention and affect sharing) and the development of the understanding of intentionality in 16 young children with Down syndrome (DS) and 16 developmentally matched children with other developmental disabilities (DD). The study of intentionality focuses on how children come to understand the goal-directed actions of others and is an important precursor to the development of more complex social cognitive skills, such as theory of mind. Joint attention and affect sharing were examined using the Early Social Communication Scales (Seibert et al., 1982; Mundy et al., 1990). Meltzoff’s (1995) behavioral reenactment paradigm was used to examine the understanding of intentionality. For children with DS, higher rates of affect sharing were associated with poorer intention reading abilities. This pattern was not observed in children with other DD. These results suggest that the intersubjective strengths associated with DS may not support the development of intentionality-interpretation skills. Future research is needed to explore if children with DS have the joint attention behaviors needed to be intentional.
PMCID: PMC3882942  PMID: 24112996
Down Syndrome; Intentionality; Intersubjectivity; Joint Attention
2.  Differences in global and local level information processing in autism: an fMRI investigation 
Psychiatry research  2013;213(2):115-121.
People with autism spectrum disorders (ASD) have atypical visual perception of global and local information. Previous neuroimaging studies have examined the functional anatomy of locally-directed attention during visual processing in ASD, but few have examined differences in both globally-and locally-directed attention. We performed functional magnetic resonance imaging (fMRI) in 17 adults with ASD and 16 typically developing (TD) subjects to examine the neurobiology of both global- and local- level information processing in ASD using an abstract hierarchical design task. TD subjects showed no regions of increased brain activation relative to subjects with ASD using whole brain analysis. Subjects with ASD exhibited greater activation in right superior frontal gyrus during locally directed attention. During globally directed attention, the ASD group showed greater right lateral occipital activation. Additionally, subjects with ASD showed less deactivation in medial prefrontal cortex (part of the default mode network) in the globally directed attention condition. Our findings help elucidate networks of brain activation related to atyipcal global and local feature processing in ASD.
PMCID: PMC4012718  PMID: 23768913
(from Index Medicus): Autistic disorder; Magnetic resonance imaging; Child developmental disorders; pervasive; Asperger syndrome; Attention
3.  Phonological processing in first-degree relatives of individuals with autism: An fMRI study 
Human brain mapping  2012;34(6):1447-1463.
Autism spectrum disorders (ASD) are complex neurodevelopmental disorders. Twin studies have provided heritability estimates as high as 90% for idiopathic ASD. Further evidence for the spectrum’s heritability is provided by the presence of the broad autism phenotype (BAP) in unaffected first-degree relatives. Language ability, specifically phonological processing, is proposed to be a core BAP trait. To date, however, no functional neuroimaging investigations of phonological processing in relatives of individuals with ASD have been undertaken. We conducted a functional magnetic resonance imaging (fMRI) study in parents of children with ASD utilizing a priming task probing implicit phonological processing. In our condition that placed heavier demands on phonological recoding, parents exhibited greater hemodynamic responses than controls in a network of cortical regions involved in phonological processing. Across conditions, parents exhibited enhanced priming-induced response suppression suggesting compensatory neural processing. A nonword repetition test used in previous studies of relatives was also administered. Correlations between this measure and our functional measures also suggested compensatory processing in parents. Regions exhibiting atypical responses in parents included regions previously implicated in the spectrum’s language impairments and found to exhibit structural abnormalities in a parent study. These results suggest a possible neurobiological substrate of the phonological deficits proposed to be a core BAP trait. However, these results should be considered preliminary. No previous fMRI study has investigated phonological processing in ASD, so replication is required. Furthermore, interpretation of our fMRI results is limited by the fact that the parent group failed to exhibit behavioral evidence of phonological impairments.
PMCID: PMC4136540  PMID: 22419478
functional magnetic resonance imaging (fMRI); autism spectrum disorders (ASD); broad autism phenotype (BAP); phonology; priming; nonword repetition
4.  Increased glutamate concentration in the auditory cortex of persons with autism and first-degree relatives: A 1H-MRS study 
Lay Abstract
We investigated brain chemistry of the primary region of the brain involved in auditory processing in adults with autism spectrum disorder (ASD). Due to the highly heritable nature of ASD and the lack of prior brain chemistry data on unaffected first-degree relatives, we also enrolled parents of children with ASD (pASD), comparing both groups to a healthy adult control group. The technique used to quantify chemical signals was magnetic resonance spectroscopy (MRS), which we used to assess the concentration of auditory glutamate, the primary excitatory brain neurotransmitter, as well as other metabolites that assess neuronal integrity and metabolism. We found significantly higher levels of auditory glutamate in persons with ASD. In addition, increases in two other metabolites, n-acetyl-aspartate (NAA), and creatine (Cr), were observed in the ASD group. No differences were observed in the pASD group in any MRS measurement. We interpret the glutamate finding as suggestive of an increase in brain excitability, and the NAA and Cr findings as indicative of a change in brain energy metabolism in ASD.
Scientific Abstract
Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy (1H-MRS). Although autism spectrum disorders (ASD) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism.
Single-voxel, point resolved spectroscopy (PRESS) data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was Glx. Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI) and creatine (Cr).
The autism group had significantly higher Glx, NAA and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures and MRS variables were seen after Bonferroni correction for multiple comparisons.
The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample specific limitations such the participation of singleton families.
PMCID: PMC3580156  PMID: 23166003
glutamate; n-acetyl-aspartate; creatine; spectroscopy; auditory cortex
5.  Mode of Genetic Inheritance Modifies the Association of Head Circumference and Autism-Related Symptoms: A Cross-Sectional Study 
PLoS ONE  2013;8(9):e74940.
Frequently individuals with autism spectrum disorder (ASD) have been noted with a larger head circumference (HC) than their typical developing peers. Biologic hypotheses suggest that an overly rapid brain growth leads to the core symptoms of ASD by impairing connectivity. Literature is divided however where deleterious, protective and null associations of HC with ASD symptoms in individuals with ASD have been found.
Individuals (n = 1,416) from the Autism Genetic Resource Exchange with ASD were examined for associations of HC with ASD like symptoms. Mixed models controlling for sex, age, race/ethnicity, simplex/multiplex status and accounting for correlations between siblings were used. Interactions by simplex/multiplex were explored. Adjustments for height in a sub-population with available data were explored as well.
A Significant interaction term (p = 0.03) suggested that the effect of HC was dependent on whether the individual was simplex or multiplex. In simplex individuals at mean age (8.9 years) 1 cm increase in head circumference was associated with a 24% increase in the odds of a high social diagnostic score from the Autism Diagnostic Interview – Revised (odds ratio  = 1.24, p = 0.01). There was no association in multiplex individuals. Additionally, individuals classified with a non-verbal IQ <70 were 90% simplex and had a significantly increased head circumference (0.7 cm p = 0.03) relative to a mid-range non-verbal IQ group. Interestingly, children classified with a >110 non-verbal IQ also had an increased HC (0.4 cm p = 0.04), relative to a mid-range non-verbal IQ group, and were 90% multiplex. HC effects do not appear to be confounded by height, however, larger samples with height information are needed.
The potential link between brain growth and autism like symptoms is complex and could depend on specific etiologies. Further investigations accounting for a likely mode of inheritance will help identify an ASD subtype related to HC.
PMCID: PMC3776732  PMID: 24058641
6.  Onset patterns in autism: Correspondence between home video and parent report 
The onset of autism is usually conceptualized as occurring in one of two patterns, an early onset and a regressive pattern. This study examined the number and shape of trajectories of symptom onset evident in coded home movies of children with autism and examined their correspondence with parent report of onset.
Four social-communicative behaviors were coded from the home video of children with autism (n = 52) or typical development (n = 23). All home video from 6 through 24 months of age was coded (3199 segments). Latent class modeling was used to characterize trajectories and determine the optimal number needed to describe the coded home video. These trajectories were then compared to parent report of onset patterns, as defined by the Autism Diagnostic Interview-Revised.
A three trajectory model best fit the data from the participants with autism. One trajectory displayed low levels of social-communication across time. A second trajectory displayed high levels of social-communication early in life, followed by a significant decline over time. A third trajectory displayed initial levels of behavior that were similar to the typically developing group, but little progress in social-communication with age. There was poor correspondence between home video-based trajectories and parent report of onset.
More than two onset categories may be needed to describe the ways in which symptoms emerge in children with autism. There is low agreement between parent report and home video, suggesting that methods for improving parent report of early development must be developed.
PMCID: PMC3668453  PMID: 21784299
Autism; regression; onset; parent report
7.  Altered oscillation patterns and connectivity during picture naming in autism 
Similar behavioral deficits are shared between individuals with autism spectrum disorders (ASD) and their first-degree relatives, such as impaired face memory, object recognition, and some language aspects. Functional neuroimaging studies have reported abnormalities in ASD in at least one brain area implicated in those functions, the fusiform gyrus (FG). High frequency oscillations have also been described as abnormal in ASD in a separate line of research. The present study examined whether low- and high-frequency oscillatory power, localized in part to FG and other language-related regions, differs in ASD subjects and first-degree relatives. Twelve individuals with ASD, 16 parents of children with ASD, and 35 healthy controls participated in a picture-naming task using magnetoencephalography (MEG) to assess oscillatory power and connectivity. Relative to controls, we observed reduced evoked high-gamma activity in the right superior temporal gyrus (STG) and reduced high-beta/low-gamma evoked power in the left inferior frontal gyrus (IFG) in the ASD group. Finally, reductions in phase-locked beta-band were also seen in the ASD group relative to controls, especially in the occipital lobes (OCC). First degree relatives, in contrast, exhibited higher high-gamma band power in the left STG compared with controls, as well as increased high-beta/low-gamma evoked power in the left FG. In the left hemisphere, beta- and gamma-band functional connectivity between the IFG and FG and between STG and OCC were higher in the autism group than in controls. This suggests that, contrary to what has been previously described, reduced connectivity is not observed across all scales of observation in autism. The lack of behavioral correlation for the findings warrants some caution in interpreting the relevance of such changes for language function in ASD. Our findings in parents implicates the gamma- and beta-band ranges as potential compensatory phenomena in autism relatives.
PMCID: PMC3821038  PMID: 24265611
magnetoencephalography; gamma-band; beta-band; oscillations; functional connectivity; Granger causality; fusiform gyrus; endophenotype
8.  Abnormalities in gamma-band responses to language stimuli in first-degree relatives of children with autism spectrum disorder: an MEG study 
BMC Psychiatry  2012;12:213.
Synchronous neural oscillatory activity in the gamma range (30–80 Hz) has been shown to be abnormal in individuals with autism spectrum disorders (ASD) and their first-degree relatives in response to simple auditory stimuli. Gamma-band abnormalities in ASD probands have been seen in response to language stimuli, but this has not been investigated in first-degree relatives. This is of particular interest given that language impairments are a core symptom of ASD and may be part of the broad autism phenotype (BAP) seen in relatives.
Magnetoencephalography recordings during a continuous word recognition task were obtained for 23 parents of a child with ASD (pASD) and 28 adult control participants. Total and evoked gamma-band activity, as well as inter-trial phase-locking factor (PLF), were measured in response to the task. Beta-band activity was also measured, due to its suggested role in language processing. Participants completed a series of language measures to assess the relationship between brain activity and language function, and lateralization of task-related activity was assessed.
The pASD group showed increased evoked gamma and beta activity, while controls had decreased evoked activity. Additionally, while both groups showed a reduction in total gamma power (commonly seen in language tasks), this reduction was more prominent in the control group. The pASD group demonstrated significantly worse performance on a measure of phonology compared to controls. Significant but distinct relationships were found between gamma/beta activity and language measures within the two groups. In addition, while the overall task generally elicited left lateralized responses, pASD showed greater left lateralization than controls in some regions of interest.
Abnormalities in oscillatory responses to language were seen in pASD that are consistent with previous findings in ASD probands. Gamma-band responses to language stimuli have not previously been assessed in first-degree relatives of ASD probands and these findings are supportive of gamma-band activity as a heritable, neurophysiological biomarker of ASD. The possible relationship seen between language function and neural activity in the current study should be investigated further to assess if oscillatory response abnormalities may contribute to behavioural manifestations of the BAP.
PMCID: PMC3557147  PMID: 23194079
9.  Facing Your Fears in Adolescence: Cognitive-Behavioral Therapy for High-Functioning Autism Spectrum Disorders and Anxiety 
Autism Research and Treatment  2012;2012:423905.
Adolescents with high-functioning autism spectrum disorders (ASDs) are at high risk for developing psychiatric symptoms, with anxiety disorders among the most commonly cooccurring. Cognitive behavior therapies (CBTs) are considered the best practice for treating anxiety in the general population. Modified CBT approaches for youth with high-functioning ASD and anxiety have resulted in significant reductions in anxiety following intervention. The purpose of the present study was to develop an intervention for treating anxiety in adolescents with ASD based on a CBT program designed for school-aged children. The Facing Your Fears-Adolescent Version (FYF-A) program was developed; feasibility and acceptability data were obtained, along with initial efficacy of the intervention. Twenty-four adolescents, aged 13–18, completed the FYF-A intervention. Results indicated significant reductions in anxiety severity and interference posttreatment, with low rates of anxiety maintained at 3-month follow-up. In addition, nearly 46% of teen participants met criteria for a positive treatment response on primary diagnosis following the intervention. Initial findings from the current study are encouraging and suggest that modified group CBT for adolescents with high-functioning ASD may be effective in reducing anxiety symptoms. Limitations include small sample size and lack of control group. Future directions are discussed.
PMCID: PMC3471403  PMID: 23091719
10.  Transient and steady-state auditory gamma-band responses in first-degree relatives of people with autism spectrum disorder 
Molecular Autism  2011;2:11.
Stimulus-related γ-band oscillations, which may be related to perceptual binding, are reduced in people with autism spectrum disorders (ASD). The purpose of this study was to examine auditory transient and steady-state γ-band findings in first-degree relatives of people with ASD to assess the potential familiality of these findings in ASD.
Magnetoencephalography (MEG) recordings in 21 parents who had a child with an autism spectrum disorder (pASD) and 20 healthy adult control subjects (HC) were obtained. Gamma-band phase locking factor (PLF), and evoked and induced power to 32, 40 and 48 Hz amplitude-modulated sounds were measured for transient and steady-state responses. Participants were also tested on a number of behavioral and cognitive assessments related to the broad autism phenotype (BAP).
Reliable group differences were seen primarily for steady-state responses. In the left hemisphere, pASD subjects exhibited lower phase-locked steady-state power in all three conditions. Total γ-band power, including the non-phase-locked component, was also reduced in the pASD group. In addition, pASD subjects had significantly lower PLF than the HC group. Correlations were seen between MEG measures and BAP measures.
The reduction in steady-state γ-band responses in the pASD group is consistent with previous results for children with ASD. Steady-state responses may be more sensitive than transient responses to phase-locking errors in ASD. Together with the lower PLF and phase-locked power in first-degree relatives, correlations between γ-band measures and behavioral measures relevant to the BAP highlight the potential of γ-band deficits as a potential new autism endophenotype.
PMCID: PMC3143088  PMID: 21729257
11.  A Replication of the Autism Diagnostic Observation Schedule (ADOS) Revised Algorithms 
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.
PMCID: PMC3057666  PMID: 18434924
autism; pervasive developmental disorders not otherwise specified; Autism Diagnostic Observation Schedule; diagnosis

Results 1-11 (11)