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Geraldine Dawson

Publications and source records attributed to Geraldine Dawson.

At least 37 records · Page 2Linked to original sources
PubMed2005

Propofol sedation for longitudinal pediatric neuroimaging research.

There is disagreement about allowing propofol sedation for research magnetic resonance imaging/spectroscopy (MRI/MRS) in children. Our study is the first to provide relevant safety and efficacy data. With institutional approval, 108 research MRI/MRS procedures under propofol sedation were performed longitudinally on children at ages 3-4 years (N=59) and 6-7 years (N=49). Sedation parameters, physiological values, and outcome data were collected. Success rate for acquisition of satisfactory quality MRI/MRS during propofol sedation was compared with that in typically developing, age-matched sleeping children. Only 5 minor events (2 with need to insert an oral airway, 2 with premature termination of study, 1 with bradycardia not requiring treatment) and no major events occurred. These safety/efficacy data are equal to or better than previously reported with propofol for clinically indicated procedures. A high percentage of parents of children participating in MRI/MRS studies at 3-4 years of age returned with their child at 6-7 years of age, and longitudinal follow-up was not adversely impacted by their child's experience with sedation. The success rate of data acquisition was significantly higher during propofol sedation (98%) than during late-night sleep studies in typically developing children (30%-50%). We conclude that propofol sedation for research MRI/MRS is safe and effective when children of appropriate ASA class are selected, supplemental oxygen is delivered, and sedation and monitoring are done by an experienced anesthesiologist.

Aging↗
PubMed2005

Links between social and linguistic processing of speech in preschool children with autism: behavioral and electrophysiological measures.

Data on typically developing children suggest a link between social interaction and language learning, a finding of interest both to theories of language and theories of autism. In this study, we examined social and linguistic processing of speech in preschool children with autism spectrum disorder (ASD) and typically developing chronologically matched (TDCA) and mental age matched (TDMA) children. The social measure was an auditory preference test that pitted 'motherese' speech samples against non-speech analogs of the same signals. The linguistic measure was phonetic discrimination assessed with mismatch negativity (MMN), an event-related potential (ERP). As a group, children with ASD differed from controls by: (a) demonstrating a preference for the non-speech analog signals, and (b) failing to show a significant MMN in response to a syllable change. When ASD children were divided into subgroups based on auditory preference, and the ERP data reanalyzed, ASD children who preferred non-speech still failed to show an MMN, whereas ASD children who preferred motherese did not differ from the controls. The data support the hypothesis of an association between social and linguistic processing in children with ASD.

Autistic Disorder↗
PubMed2005

Early regression in social communication in autism spectrum disorders: a CPEA Study.

In a multisite study of 351 children with autism spectrum disorders, 21 children with developmental delays, and 31 children with typical development, this study used caregiver interviews (i.e., the Autism Diagnostic Interview-Revised) at the time of entry into other research projects and follow-up telephone interviews designed for this project to describe the children's early acquisition and loss of social-communication milestones. Children who had used words spontaneously and meaningfully and then stopped talking were described by their caregivers as showing more gestures, greater participation in social games, and better receptive language before the loss and fewer of these skills after the loss than other children with autism spectrum disorders. A significant minority of children with autism without word loss showed a very similar pattern of loss of social-communication skills, a pattern not observed in the children with developmental delays or typical development.

Age Factors↗
PubMed2005

Understanding the nature of face processing impairment in autism: insights from behavioral and electrophysiological studies.

This article reviews behavioral and electrophysiological studies of face processing and discusses hypotheses for understanding the nature of face processing impairments in autism. Based on results of behavioral studies, this study demonstrates that individuals with autism have impaired face discrimination and recognition and use atypical strategies for processing faces characterized by reduced attention to the eyes and piecemeal rather than configural strategies. Based on results of electrophysiological studies, this article concludes that face processing impairments are present early in autism, by 3 years of age. Such studies have detected abnormalities in both early (N170 reflecting structural encoding) and late (NC reflecting recognition memory) stages of face processing. Event-related potential studies of young children and adults with autism have found slower speed of processing of faces, a failure to show the expected speed advantage of processing faces versus nonface stimuli, and atypical scalp topography suggesting abnormal cortical specialization for face processing. Other electrophysiological studies have suggested that autism is associated with early and late stage processing impairments of facial expressions of emotion (fear) and decreased perceptual binding as reflected in reduced gamma during face processing. This article describes two types of hypotheses-cognitive/perceptual and motivational/affective--that offer frameworks for understanding the nature of face processing impairments in autism. This article discusses implications for intervention.

Autistic Disorder↗
PubMed2004

Genetic investigation of quantitative traits related to autism: use of multivariate polygenic models with ascertainment adjustment.

Autism is a severe developmental disorder of unknown etiology but with evidence for genetic influences. Here, we provide evidence for a genetic basis of several quantitative traits that are related to autism. These traits, from the Broader Phenotype Autism Symptom Scale (BPASS), were measured in nuclear families, each ascertained through two probands affected by autism spectrum disorder. The BPASS traits capture the continuum of severity of impairments and may be more informative for genetic studies than are the discrete diagnoses of autism that have been used by others. Using a sample of 201 nuclear families consisting of a total of 694 individuals, we implemented multivariate polygenic models with ascertainment adjustment to estimate heritabilities and genetic and environmental correlations between these traits. Our ascertainment adjustment uses conditioning on the phenotypes of probands, requires no modeling of the ascertainment process, and is applicable to multiplex ascertainment and multivariate traits. This appears to be the first such implementation for multivariate quantitative traits. The marked difference between heritability estimates of the trait for language onset with and without an ascertainment adjustment (0.08 and 0.22, respectively) shows that conclusions are sensitive to whether or not an ascertainment adjustment is used. Among the five BPASS traits that were analyzed, the traits for social motivation and range of interest/flexibility show the highest heritability (0.19 and 0.16, respectively) and also have the highest genetic correlation (0.92). This finding suggests a shared genetic basis of these two traits and that they may be most promising for future gene mapping and for extending pedigrees by phenotyping additional relatives.

Adolescent↗
PubMed2004

Alleles of a reelin CGG repeat do not convey liability to autism in a sample from the CPEA network.

A recent study by Persico et al. [2001: Mol Psychiatry 6:150-159] suggests alleles of a CGG polymorphism, just 5' of the reelin gene (RELN) initiator codon, confer liability for autism, especially alleles bearing 11 or more CGG repeats (long alleles). The association is consistent across both a case-control and family-based sample. We attempted to replicate their finding using a larger, independent family-based sample from the NIH Collaborative Programs of Excellence in Autism (CPEA) Network. In our data, allele transmissions to individuals with autism versus unaffected individuals are unbiased, both when alleles are classified by repeat length and when they are classified into long/short categories. Because of the apparent linkage of autism to chromosome 7q, particularly related to the development of language, we also evaluate the relationship between Reelin alleles and the age at which autism subjects use their first word or first phrase. Neither is significantly associated with Reelin alleles. Our results are not consistent with a major role for Reelin alleles in liability to autism.

Alleles↗
PubMed2004

Performance on Cambridge Neuropsychological Test Automated Battery subtests sensitive to frontal lobe function in people with autistic disorder: evidence from the Collaborative Programs of Excellence in Autism network.

Recent structural and functional imaging work, as well as neuropathology and neuropsychology studies, provide strong empirical support for the involvement of frontal cortex in autism. The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computer-administered set of neuropsychological tests developed to examine specific components of cognition. Previous studies document the role of frontal cortex in performance of two CANTAB subtests: the Stockings of Cambridge, a planning task, and the Intradimensional/Extradimensional Shift task, a measure of cognitive set shifting. To examine the integrity of frontal functions, these subtests were administered to 79 participants with autism and 70 typical controls recruited from seven universities who are part of the Collaborative Programs of Excellence in Autism network. The two groups were matched on age, sex, and full-scale IQ. Significant group differences were found in performance on both subtests, with the autism group showing deficits in planning efficiency and extradimensional shifting relative to controls. Deficits were found in both lower- and higher-IQ individuals with autism across the age range of 6 to 47 years. Impairment on the CANTAB executive function subtests did not predict autism severity or specific autism symptoms (as measured by the ADI-R and ADOS), but it was correlated with adaptive behavior. If these CANTAB subtests do indeed measure prefrontal function, as suggested by previous research with animals and lesion patients, this adds to the accumulating evidence of frontal involvement in autism and indicates that this brain region should remain an active area of investigation.

Adolescent↗
PubMed2004

Early social attention impairments in autism: social orienting, joint attention, and attention to distress.

This study investigated social attention impairments in autism (social orienting, joint attention, and attention to another's distress) and their relations to language ability. Three- to four-year-old children with autism spectrum disorder (ASD; n = 72), 3- to 4-year-old developmentally delayed children (n = 34), and 12- to 46-month-old typically developing children (n = 39), matched on mental age, were compared on measures of social orienting, joint attention, and attention to another's distress. Children with autism performed significantly worse than the comparison groups in all of these domains. Combined impairments in joint attention and social orienting were found to best distinguish young children with ASD from those without ASD. Structural equation modeling indicated that joint attention was the best predictor of concurrent language ability. Social orienting and attention to distress were indirectly related to language through their relations with joint attention. These results help to clarify the nature of social attention impairments in autism, offer clues to developmental mechanisms, and suggest targets for early intervention.

Attention↗
PubMed2004

Single-suture craniosynostosis: a review of neurobehavioral research and theory.

OBJECTIVE: To review research and theory regarding the neurobehavioral correlates and outcomes of single-suture, or isolated, craniosynostosis in children. METHODS: A critical review of 17 studies of the hypothesized association between isolated craniosynostosis and neurodevelopment. RESULTS: Isolated craniosynostosis is associated with a three- to fivefold increase in risk for cognitive deficits or learning/language disabilities. The causal basis for this association is unclear. No particular calvarial suture (sagittal, metopic, left or right unilateral coronal) has been associated with higher risk of problems. There is little evidence from quasi-experimental studies that cranioplastic surgery prevents or reduces risk of neurobehavioral impairment. CONCLUSIONS: Future studies would benefit from larger samples and larger control groups; measures of specific neuropsychological functions (in addition to global cognition); analyses of neuropsychological status in relation to the severity and cortical impact of synostosis; and an examination of interactions between synostosis and social/family risk factors on neurodevelopment. Routine neurodevelopmental screening of young children with isolated craniosynostosis is recommended.

Brain↗
PubMed2004

Young children with autism show atypical brain responses to fearful versus neutral facial expressions of emotion.

Evidence suggests that autism is associated with impaired emotion perception, but it is unknown how early such impairments are evident. Furthermore, most studies that have assessed emotion perception in children with autism have required verbal responses, making results difficult to interpret. This study utilized high-density event-related potentials (ERPs) to investigate whether 3-4-year-old children with autism spectrum disorder (ASD) show differential brain activity to fear versus neutral facial expressions. It has been shown that normal infants as young as 7 months of age show differential brain responses to faces expressing different emotions. ERPs were recorded while children passively viewed photos of an unfamiliar woman posing a neutral and a prototypic fear expression. The sample consisted of 29 3-4-year-old children with ASD and 22 chronological age-matched children with typical development. Typically developing children exhibited a larger early negative component (N300) to the fear than to the neutral face. In contrast, children with ASD did not show the difference in amplitude of this early ERP component to the fear versus neutral face. For a later component, typically developing children exhibited a larger negative slow wave (NSW) to the fear than to the neutral face, whereas children with autism did not show a differential NSW to the two stimuli. In children with ASD, faster speed of early processing (i. e. N300 latency) of the fear face was associated with better performance on tasks assessing social attention (social orienting, joint attention and attention to distress). These data suggest that children with ASD, as young as 3 years of age, show a disordered pattern of neural responses to emotional stimuli.

Autistic Disorder↗
PubMed2004

Event-related brain potentials reveal anomalies in temporal processing of faces in autism spectrum disorder.

BACKGROUND: Individuals with autism exhibit impairments in face recognition, and neuroimaging studies have shown that individuals with autism exhibit abnormal patterns of brain activity during face processing. The current study examined the temporal characteristics of face processing in autism and their relation to behavior. METHOD: High-density event-related brain potentials (ERPs) were recorded to images of faces, inverted faces, and objects from 9 individuals with autism spectrum disorder (15-42 years old) and 14 typical individuals (16-37 years old). RESULTS: With respect to a face-sensitive ERP component (N170), individuals with autism exhibited longer N170 latencies to faces than typical individuals but comparable latencies to objects. Typical individuals exhibited longer N170 latencies to inverted as compared to upright faces, whereas individuals with autism did not show differences in N170 latency to upright versus inverted faces. Neural speed of face processing, as reflected in N170 latency, correlated with performance on a face recognition task for individuals with autism. CONCLUSIONS: These data provide evidence for slowed neural speed of face processing in autism and highlight the role of speed of processing in face processing impairments in autism.

Adolescent↗
PubMed2003

Age-related differences in neural correlates of face recognition during the toddler and preschool years.

Research on the development of face recognition in infancy has shown that infants respond to faces as if they are special and recognize familiar faces early in development. Infants also show recognition and differential attachment to familiar people very early in development. We tested the hypothesis that infants' responses to familiar and unfamiliar faces differ at different ages. Specifically, we present data showing age-related changes in infants' brain responses to mother's face versus a stranger's face in children between 18 and 54 months of age. We propose that these changes are based on age-related differences in the perceived salience of the face of the primary caregiver versus strangers.

Arousal↗
PubMed2003

Early intervention and brain plasticity in autism.

Autism is associated with impairments in brain systems that come on line very early in life. One such system supports the development of face processing. Dawson and colleagues found that 3 year old children with autism failed to show differential event-related potentials (ERPs) to photographs of their mother's versus a stranger's face. Since differential ERP activity to familiar and unfamiliar faces is typically present by 6 months, this represents early brain dysfunction. McPartland and colleagues found that the face-specific ERP component ('N170') is atypical in older individuals with autism. N170 is typically larger to faces than non-faces, and prominent over the right hemisphere. In individuals with autism, N170 was larger for furniture than faces and bilaterally distributed. Biology and experience contribute to the development of face-processing systems. Newborns are capable of recognizing faces. Early face recognition abilities are thought to be served by a subcortical system, which is replaced by an experience-dependent cortical system. Development of a neural system specialized for faces may depend on experience with faces during an early sensitive period. Because children with autism fail to attend to faces, they might not acquire the expertise needed for a specialized face processing system to develop normally. Early interventions that enhance social attention should result in changes in brain activity, as reflected in ERPs to face stimuli, with those children showing the greatest social improvement exhibiting more normal brain activity.

Adolescent↗
PubMed2002

No evidence for linkage of liability to autism to HOXA1 in a sample from the CPEA network.

A recent study by Ingram et al. [2000b: Teratology 62:393-405] suggests a (His)73(Arg) polymorphism (A:G) in HOXA1 contributes substantially to a liability for autism. Using 68 individuals diagnosed with Autism Spectrum Disorders, they found a significant dearth of G homozygotes and biased transmission of G alleles from parents to affected offspring, especially from mothers. Because the connection between HOXA1 and liability to autism is compelling, we attempted to replicate their finding using a larger, independent sample from the Collaborative Programs of Excellence in Autism (CPEA) network. In our data, genotype frequencies conform to Hardy-Weinberg equilibrium; allele transmissions meet Mendelian expectations; and there is no obvious sex-biased allele transmission. Based on our sample size, calculations suggest that we would have at least 95% power to detect linkage and association even if the A:G polymorphism were to account for only 1% of the heritability of autism. Therefore, although we cannot exclude the possibility that the samples in the two studies are intrinsically different, our data from our sample argue against a major role for HOXA1 (His)73(Arg) in liability to autism.

Asperger Syndrome↗
PubMed2002

Presence of large deletions in kindreds with autism.

Autism is caused, in part, by inheritance of multiple interacting susceptibility alleles. To identify these inherited factors, linkage analysis of multiplex families is being performed on a sample of 105 families with two or more affected sibs. Segregation patterns of short tandem repeat polymorphic markers from four chromosomes revealed null alleles at four marker sites in 12 families that were the result of deletions ranging in size from 5 to >260 kb. In one family, a deletion at marker D7S630 was complex, with two segments deleted (37 kb and 18 kb) and two retained (2,836 bp and 38 bp). Three families had deletions at D7S517, with each family having a different deletion (96 kb, 183 kb, and >69 kb). Another three families had deletions at D8S264, again with each family having a different deletion, ranging in size from <5.9 kb to >260 kb. At a fourth marker, D8S272, a 192-kb deletion was found in five families. Unrelated subjects and additional families without autism were screened for deletions at these four sites. Families screened included 40 families from Centre d'Etude du Polymorphisme Humaine and 28 families affected with learning disabilities. Unrelated samples were 299 elderly control subjects, 121 younger control subjects, and 248 subjects with Alzheimer disease. The deletion allele at D8S272 was found in all populations screened. For the other three sites, no additional deletions were identified in any of the groups without autism. Thus, these deletions appear to be specific to autism kindreds and are potential autism-susceptibility alleles. An alternative hypothesis is that autism-susceptibility alleles elsewhere cause the deletions detected here, possibly by inducing errors during meiosis.

Adult↗
PubMed2002

Identification of a novel gene on chromosome 7q11.2 interrupted by a translocation breakpoint in a pair of autistic twins.

We report here the identification and characterization of a novel gene (AUTS2) that spans the 7q11.2 breakpoint in a monozygotic twin pair concordant for autism and a t(7;20) (q11.2; p11.2) translocation. AUTS2 is 1.2 Mb and has 19 exons. The predicted protein is 1295 amino acids and does not correspond to any known protein. DNA sequence analysis of autism subjects and controls revealed 22 biallelic polymorphic sites. For all sites, both alleles were observed in both cases and controls. Thus no autism-specific mutation was observed. Association analysis with two exonic polymorphic sites and linkage analysis of four dinucleotide repeat markers, two within and two flanking AUTS2, was negative. Thus, although it is unlikely that AUTS2 is an autism susceptibility gene for idiopathic autism, it may be the gene responsible for the disorder in the twins studied here.

Amino Acid Sequence↗
PubMed2002

Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation.

Previous work based on observations of home videotapes indicates that differences can be detected between infants with autism spectrum disorder and infants with typical development at 1 year of age. The present study addresses the question of whether autism can be distinguished from mental retardation by 1 year of age. Home videotapes of first birthday parties from 20 infants later diagnosed with autism spectrum disorder, 14 infants later diagnosed with mental retardation (without autism), and 20 typically developing infants were coded by blind raters with respect to the frequencies of specific social and communicative behaviors and repetitive motor actions. Results indicated that 1-year-olds with autism spectrum disorder can be distinguished from 1-year-olds with typical development and those with mental retardation. The infants with autism spectrum disorder looked at others and oriented to their names less frequently than infants with mental retardation. The infants with autism spectrum disorder and those with mental retardation used gestures and looked to objects held by others less frequently and engaged in repetitive motor actions more frequently than typically developing infants. These results indicate that autism can be distinguished from mental retardation and typical development by 1 year of age.

Autistic Disorder↗