Biomedical subjects

Helen Tager-Flusberg

Publications and source records attributed to Helen Tager-Flusberg.

At least 19 recordsLinked to original sources

PubMed2007

Sex differences in toddlers with autism spectrum disorders.

Although autism spectrum disorders (ASD) prevalence is higher in males than females, few studies address sex differences in developmental functioning or clinical manifestations. Participants in this study of sex differences in developmental profiles and clinical symptoms were 22 girls and 68 boys with ASD (mean age = 28 months). All children achieved strongest performance in visual reception and fine motor followed by gross motor and language functioning. Sex differences emerged in developmental profiles. Controlling for language, girls achieved higher visual reception scores than boys; boys attained higher language and motor scores and higher social-competence ratings than girls, particularly when controlling for visual reception. Longitudinal, representative studies are needed to elucidate the developmental and etiological significance of the observed sex differences.

Affect↗

PubMed2007

Abnormal activation of the social brain during face perception in autism.

ASD involves a fundamental impairment in processing social-communicative information from faces. Several recent studies have challenged earlier findings that individuals with autism spectrum disorder (ASD) have no activation of the fusiform gyrus (fusiform face area, FFA) when viewing faces. In this study, we examined activation to faces in the broader network of face-processing modules that comprise what is known as the social brain. Using 3T functional resonance imaging, we measured BOLD signal changes in 10 ASD subjects and 7 healthy controls passively viewing nonemotional faces. We replicated our original findings of significant activation of face identity-processing areas (FFA and inferior occipital gyrus, IOG) in ASD. However, in addition, we identified hypoactivation in a more widely distributed network of brain areas involved in face processing [including the right amygdala, inferior frontal cortex (IFC), superior temporal sulcus (STS), and face-related somatosensory and premotor cortex]. In ASD, we found functional correlations between a subgroup of areas in the social brain that belong to the mirror neuron system (IFC, STS) and other face-processing areas. The severity of the social symptoms measured by the Autism Diagnostic Observation Schedule was correlated with the right IFC cortical thickness and with functional activation in that area. When viewing faces, adults with ASD show atypical patterns of activation in regions forming the broader face-processing network and social brain, outside the core FFA and IOG regions. These patterns suggest that areas belonging to the mirror neuron system are involved in the face-processing disturbances in ASD.

Adult↗

PubMed2006

Function and connectivity in human primary auditory cortex: a combined fMRI and DTI study at 3 Tesla.

Human primary auditory cortex (PAC) is functionally organized in a tonotopic manner. Past studies have used neuroimaging to characterize tonotopic organization in PAC and found similar organization as that described in mammals. In contrast to what is known about PAC in primates and nonprimates, in humans, the structural connectivity within PAC has not been defined. In this study, stroboscopic event-related functional magnetic resonance imaging (fMRI) was utilized to reveal mirror symmetric tonotopic organization consisting of a high-low-high frequency gradient in PAC. Furthermore, diffusion tensor tractography and probabilistic mapping was used to study projection patterns within tonotopic areas. Based on earlier physiological and histological work in nonhuman PAC, we hypothesized the existence of cross-field isofrequency (homotopic) and within-field non-isofrequency (heterotopic)-specific axonal projections in human PAC. The presence of both projections types was found in all subjects. Specifically, the number of diffusion tensor imaging (DTI) reconstructed fibers projecting between high- and low-frequency regions was greater than those fibers projecting between 2 high-frequency areas, the latter of which are located in distinct auditory fields. The fMRI and DTI results indicate that functional and structural properties within early stages of the auditory processing stream are preserved across multiple mammalian species at distinct evolutionary levels.

Acoustic Stimulation↗

PubMed2006

Communicative competence in parents of children with autism and parents of children with specific language impairment.

While the primary language deficit in autism has been thought to be pragmatic, and in specific language impairment (SLI) structural, recent research suggests phenomenological and possibly genetic overlap between the two syndromes. To compare communicative competence in parents of children with autism, SLI, and down syndrome (DS), we used a modified pragmatic rating scale (PRS-M). Videotapes of conversational interviews with 47 autism, 47 SLI, and 21 DS parents were scored blind to group membership. Autism and SLI parents had significantly lower communication abilities than DS parents. Fifteen percent of the autism and SLI parents showed severe deficits. Our results suggest that impaired communication is part of the broader autism phenotype and a broader SLI phenotype, especially among male family members.

Adult↗

PubMed2006

Head circumference and height in autism: a study by the Collaborative Program of Excellence in Autism.

Data from 10 sites of the NICHD/NIDCD Collaborative Programs of Excellence in Autism were combined to study the distribution of head circumference and relationship to demographic and clinical variables. Three hundred thirty-eight probands with autism-spectrum disorder (ASD) including 208 probands with autism were studied along with 147 parents, 149 siblings, and typically developing controls. ASDs were diagnosed, and head circumference and clinical variables measured in a standardized manner across all sites. All subjects with autism met ADI-R, ADOS-G, DSM-IV, and ICD-10 criteria. The results show the distribution of standardized head circumference in autism is normal in shape, and the mean, variance, and rate of macrocephaly but not microcephaly are increased. Head circumference tends to be large relative to height in autism. No site, gender, age, SES, verbal, or non-verbal IQ effects were present in the autism sample. In addition to autism itself, standardized height and average parental head circumference were the most important factors predicting head circumference in individuals with autism. Mean standardized head circumference and rates of macrocephaly were similar in probands with autism and their parents. Increased head circumference was associated with a higher (more severe) ADI-R social algorithm score. Macrocephaly is associated with delayed onset of language. Although mean head circumference and rates of macrocephaly are increased in autism, a high degree of variability is present, underscoring the complex clinical heterogeneity of the disorder. The wide distribution of head circumference in autism has major implications for genetic, neuroimaging, and other neurobiological research.

Adolescent↗

PubMed2006

Atypical behaviors in children with autism and children with a history of language impairment.

The frequency, course, and inter-relationships of atypical eating, sleeping, self-injurious behavior, aggression and temper tantrums in children with autism and children with a history of language impairment (HLI), was investigated using a parent interview that was created to examine these problem behaviors. The relationships between these behaviors and language, IQ, severity of autistic symptoms and depression were also assessed. Atypical eating behavior, abnormal sleep patterns, temper tantrums, and self-injurious behavior were significantly more common in the children with autism than those with HLI. Within the autism group, children who exhibited more atypical behaviors tended to have a lower nonverbal IQ, lower levels of expressive language, more severe social deficits and more repetitive behaviors. No relationship between the number of atypical behaviors and measures of cognitive or language ability was noted in the HLI group. However, having more atypical behaviors was related to increased restricted, repetitive behaviors in children with HLI. The atypical behaviors could be divided into two groups: abnormal eating and sleeping, which were independent and tended to begin early in life; and self-injury, tantrums and aggression, which began later and were inter-related. Sleep abnormalities were more common in children (groups combined) diagnosed with major depression.

Adolescent↗

PubMed2006

Brain activation during semantic processing in autism spectrum disorders via functional magnetic resonance imaging.

Language and communication deficits are core features of autism spectrum disorders (ASD), even in high-functioning adults with ASD. This study investigated brain activation patterns using functional magnetic resonance imaging in right-handed adult males with ASD and a control group, matched on age, handedness, and verbal IQ. Semantic processing in the controls produced robust activation in Broca's area (left inferior frontal gyrus) and in superior medial frontal gyrus and right cerebellum. The ASD group had substantially reduced Broca's activation, but increased left temporal (Wernicke's) activation. Furthermore, the ASD group showed diminished activation differences between concrete and abstract words, consistent with behavioral studies. The current study suggests Broca's area is a region of abnormal neurodevelopment in ASD, which may be linked with semantic and related language deficits frequently observed in ASD.

Adult↗

PubMed2006

Is there a 'regressive phenotype' of Autism Spectrum Disorder associated with the measles-mumps-rubella vaccine? A CPEA Study.

A multi-site study of 351 children with Autism Spectrum Disorders (ASD) and 31 typically developing children used caregiver interviews to describe the children's early acquisition and loss of social-communication milestones. For the majority of children with ASD who had experienced a regression, pre-loss development was clearly atypical. Children who had lost skills also showed slightly poorer outcomes in verbal IQ and social reciprocity, a later mean age of onset of autistic symptoms, and more gastrointestinal symptoms than children with ASD and no regression. There was no evidence that onset of autistic symptoms or of regression was related to measles-mumps-rubella vaccination. The implications of these findings for the existence of a 'regressive phenotype' of ASD are discussed.

Autistic Disorder↗

PubMed2006

Familial autoimmune thyroid disease as a risk factor for regression in children with Autism Spectrum Disorder: a CPEA Study.

A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).

Autistic Disorder↗

PubMed2006

Comorbid psychiatric disorders in children with autism: interview development and rates of disorders.

The Kiddie Schedule for Affective Disorders and Schizophrenia was modified for use in children and adolescents with autism by developing additional screening questions and coding options that reflect the presentation of psychiatric disorders in autism spectrum disorders. The modified instrument, the Autism Comorbidity Interview-Present and Lifetime Version (ACI-PL), was piloted and frequently diagnosed disorders, depression, ADHD, and OCD, were tested for reliability and validity. The ACI-PL provides reliable DSM diagnoses that are valid based on clinical psychiatric diagnosis and treatment history. The sample demonstrated a high prevalence of specific phobia, obsessive compulsive disorder, and ADHD. The rates of psychiatric disorder in autism are high and are associated with functional impairment.

Adolescent↗

PubMed2006

Perceiving facial and vocal expressions of emotion in individuals with Williams syndrome.

People with Williams syndrome are extremely sociable, empathic, and expressive in communication. Some researchers suggest they may be especially sensitive to perceiving emotional expressions. We administered the Faces and Paralanguage subtests of the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA2), a standardized measure of emotion recognition for basic emotions to three groups: adolescents and adults with Williams syndrome, age and IQ-matched participants with learning/intellectual disability, and age-matched nonimpaired controls. The Williams syndrome and learning/intellectual disability groups performed significantly worse than the typically developing controls on both subtests, especially on negative emotions. Error analysis indicated the same general pattern of performance across versions and subtests of the DANVA2 for all groups. These findings suggest that emotion recognition is not spared in Williams syndrome.

Adolescent↗

PubMed2005

Anatomical differences in the mirror neuron system and social cognition network in autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

Adult↗

PubMed2005

Self-ordered pointing in children with autism: failure to use verbal mediation in the service of working memory?

This study tested the hypothesis that children with autism are impaired in using verbal encoding and rehearsal strategies in the service of working memory. Participants were 24 high-ability, school-age children with autism and a comparison group matched on verbal and non-verbal IQ, receptive and expressive vocabulary, and visual memory. Working memory was assessed using verbal and non-verbal variants of a non-spatial, self-ordered pointing test [Petrides, M., & Milner, B. (1982). Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia, 20, 249-262] in which children had to point to a new stimulus in a set upon each presentation without repeating a previous choice. In the verbal condition, the stimuli were pictures of concrete, nameable objects, whereas in the non-verbal condition, the stimuli were not easily named or verbally encoded. Participants were also administered a verbal span task to assess non-executive verbal rehearsal skills. Although the two groups were equivalent in verbal rehearsal skills, the autism group performed significantly less well in the verbal, but not the non-verbal, self-ordered pointing test. These findings suggested that children with autism are deficient in the use of verbal mediation strategies to maintain and monitor goal-related information in working memory. The findings are discussed in terms of possible autistic impairments in episodic memory as well as working memory.

Adolescent↗

PubMed2005

Brief report: the relationship between discourse deficits and autism symptomatology.

This study investigated the relationship between discourse deficits to a broader range of other symptoms in 57 children with autism. We hypothesized that autism symptomatology, as measured by the Autism Diagnostic Observation Schedule (ADOS), would be related to the children's difficulty in maintaining an ongoing topic of discourse. Children provided a natural language sample while interacting with one parent. These language samples were coded for the child's use of off-topic or noncontingent utterances. Results showed significant relationships between overall diagnostic symptomatology, and more specifically, deficits in communication as measured by the ADOS-G, and noncontingent discourse. The findings provide diagnostic validity to the ADOS-G and highlight in greater detail the significant communication impairment in autism.

Adolescent↗

PubMed2005

Social communication in children with autism: the relationship between theory of mind and discourse development.

This longitudinal study investigated the developmental trajectory of discourse skills and theory of mind in 57 children with autism. Children were tested at two time points spaced 1 year apart. Each year they provided a natural language sample while interacting with one parent, and were given standardized vocabulary measures and a developmentally sequenced battery of theory of mind tasks. The language samples were coded for conversational skills, specifically the child's use of topic-related contingent utterances. Children with autism made significant gains over 1 year in the ability to maintain a topic of discourse. Hierarchical regression analyses demonstrated that theory of mind skills contributed unique variance to individual differences in contingent discourse ability and vice versa, when measured concurrently; however, they did not predict longitudinal changes. The findings offer some empirical support for the hypothesis that theory of mind is linked to communicative competence in children with autism.

Adolescent↗

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

Executive dysfunction and its relation to language ability in verbal school-age children with autism.

This study examined executive dysfunction and its relation to language ability in verbal school-age children with autism. Participants were 37 children with autism and 31 nonautistic comparison participants who were matched on age and on verbal and nonverbal IQ but not on language ability, which was lower in the autism group. Children with autism exhibited deficits compared to the comparison group across all 3 domains of executive function that were assessed including working memory (Block Span Backward; Isaacs & Vargha-Khadem, 1989), working memory and inhibitory control (NEPSY Knock-Tap; Korkman, Kirk, & Kemp, 1998), and planning (NEPSY Tower; Korkman et al., 1998). Children with autism were less developed than the comparison group in their language skills, but correlational analyses revealed no specific association between language ability and executive performance in the autism group. In contrast, executive performance was positively correlated with language ability in the comparison group. This pattern of findings suggest that executive dysfunction in autism is not directly related to language impairment per se but rather involves an executive failure to use of language for self-regulation.

Autistic Disorder↗

PubMed2004

Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.

Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2+) currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca(2+) overload in multiple cell types. In the heart, prolonged Ca(2+) current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism.

Abnormalities, Multiple↗