Studies assessing domains pertaining to structural language in autism vary in reporting practices and approaches to assessment: A systematic review.

LAY ABSTRACT: Under the Diagnostic and Statistical Manual of Mental Disorders (5th ed.), language impairment can co-occur with autism. It is not yet clear how research defines, reports, and characterizes structural language abilities of autistic individuals eligible for school-based special education services (aged 3-21 years) in the United States. In the United States, students typically must be formally diagnosed to be eligible for services and supports. However, the quality of diagnosis is only as good as the research evidence on which diagnosis depends. To evaluate evidence quality, we examined how studies of school-aged autistic individuals report assessments of language ability. This systematic review included 57 studies using English language age-referenced assessments used to measure structural language. Findings showed many differences across studies in how language abilities were measured and reported. Also, none of the studies fully reported the variables relevant to characterizing language impairment. Outcomes were similar across versions of the Diagnostic and Statistical Manual of Mental Disorders. Findings indicate that researchers and clinicians should pay attention to reporting diagnostic and grouping criteria. Carefully interpreting research evidence is critical for ensuring that diagnostic criteria and supports are representative of and accessible to autistic individuals and relevant parties.

Longitudinal Grammaticality Judgments of Tense Marking in Complex Questions in Children With and Without Specific Language Impairment, Ages 5-18 Years.

PURPOSE: Identification of children with specific language impairment (SLI) can be difficult even though their language can lag that of age peers throughout childhood. A clinical grammar marker featuring tense marking in simple clauses is valid and reliable for young children but is limited by ceiling effects around the age of 8 years. This study evaluated a new, more grammatically challenging complex sentence task in children affected or unaffected with SLI in longitudinal data, ages 5-18 years. METHOD: Four hundred eighty-three children (213 unaffected, 270 affected) between 5 and 18 years of age participated, following a rolling recruitment longitudinal design encompassing a total of 4,148 observations. The new experimental grammaticality judgment task followed linguistic concepts of syntactic sites for finiteness and movement within complex clauses. Growth modeling methods evaluated group differences over time for four different outcomes; three were hypothesized to evaluate optional omissions of overt finiteness forms in authorized sentence sites, and one evaluated an overt error of tense marking. RESULTS: As in earlier studies of younger children, growth models for the SLI group were consistently lower than the unaffected group, although the growth trajectories across groups did not differ. The results replicated across four item types defined by omissions with minor differences for an item with an overt error of tense marking. Covariates of child nonverbal IQ, mother's education, and child sex did not significantly moderate these effects. CONCLUSION: The outcomes support the task as having potential screening value for identification of children with SLI and are consistent with linguistic interpretations of task demands.

Innovative Family-Based Genetically Informed Series of Analyses of Whole-Exome Data Supports Likely Inheritance for Grammar in Children with Specific Language Impairment.

Individuals with specific language impairment (SLI) struggle with language acquisition despite average non-verbal intelligence and otherwise typical development. One SLI account focuses on grammar acquisition delay. The current study aimed to detect novel rare genetic variants associated with performance on a grammar assessment, the Test of Early Grammatical Impairment (TEGI), in English-speaking children. The TEGI was selected due to its sensitivity and specificity, consistently high heritability estimates, and its absence from all but one molecular genetic study. We performed whole exome sequencing (WES) in eight families with SLI (n = 74 total) and follow-up Sanger sequencing in additional unrelated probands (n = 146). We prioritized rare exonic variants shared by individuals with low TEGI performance (n = 34) from at least two families under two filtering workflows: (1) novel and (2) previously reported candidate genes. Candidate variants were observed on six new genes (PDHA2, PCDHB3, FURIN, NOL6, IQGAP3, and BAHCC1), and two genes previously reported for overall language ability (GLI3 and FLNB). We specifically suggest PCDHB3, a protocadherin gene, and NOL6 are critical for ribosome synthesis, as they are important targets of SLI investigation. The proposed SLI candidate genes associated with TEGI performance emphasize the utility of precise phenotyping and family-based genetic study.

Studies pertaining to language impairment in school-age autistic individuals underreport participant socio-demographics: A systematic review.

LAY ABSTRACT: Although exclusion of racially and ethnically minoritized autistic individuals from research is a long-standing issue, we have yet to determine how exclusion impacts areas of autism research important for identifying language impairment. Diagnosis depends on the quality of the evidence (i.e. research) and is often the pathway to gaining access to services. As a first step, we examined how research studies related to language impairment in school-age autistic individuals report participant socio-demographics. We analyzed reports using age-referenced assessments in English (n = 60), which are commonly used by both practitioners and researchers to diagnose or identify language impairment. Findings showed only 28% of studies reported any information on race and ethnicity; in these studies, most (at least 77%) of the participants were white. In addition, only 56% of studies reported gender or sex and specified what they were reporting (gender, sex, or gender identity). Just 17% reported socio-economic status using multiple indicators. Altogether, findings indicate broad issues with underreporting and exclusion of racially and ethnically minoritized individuals, which might overlay with other aspects of identity including socio-economic status. It is impossible to determine the extent and precise nature of exclusion without intersectional reporting. To ensure that language in autism research is representative of the autistic population, future research must implement reporting guidelines and broaden inclusion of who participates in research studies.

In Utero Antiretroviral Exposure and Risk of Neurodevelopmental Problems in HIV-Exposed Uninfected 5-Year-Old Children.

Studies have observed neurodevelopmental (ND) challenges among young children perinatally HIV-exposed yet uninfected (CHEU) with in utero antiretroviral (ARV) exposure, without clear linkage to specific ARVs. Atazanavir (ATV) boosted with ritonavir has been a preferred protease inhibitor recommended for pregnant women, yet associations of ATV with ND problems in CHEU have been reported. Studies among early school-age children are lacking. The pediatric HIV/AIDS cohort study (PHACS) surveillance monitoring for antiretroviral therapy (ART) toxicities (SMARTT) study evaluated 5-year-old monolingual English-speaking CHEU using the behavior assessment system for children, Wechsler preschool and primary scales of intelligence, and test of language development-primary. A score ≥1.5 standard deviations worse than population norms defined a signal within each domain. Analyses of risk for signals were stratified by timing of any ARV initiation. Associations between ARV exposure and risk of ND signals were assessed using proportional odds models, adjusting for confounders. Among 230 children exposed to ARVs at conception, 15% had single and 8% had multiple ND problems; ATV exposure was not associated with higher risk of signals [adjusted cumulative odds ratio (cOR) = 0.66, confidence interval (CI): 0.28-1.56]. However, among 461 children whose mothers initiated ARVs during pregnancy, 21% had single and 12% had multiple ND problems; ATV exposure was associated with higher risk of signals (cOR = 1.70, CI: 0.82-3.54). The specific regimen tenofovir/emtricitabine/ATV was associated with higher risk (cOR = 2.31, CI: 1.08-4.97) relative to regimens using a zidovudine/lamivudine backbone combined with non-ATV ARVs. It remains important to monitor neurodevelopment of CHEU during early childhood and investigate the impact and the role of timing of in utero exposure to specific ARVs.

Language Impairment in Autistic Adolescents and Young Adults.

PURPOSE: Little is known about the specific nature of language abilities of autistic adolescents and young adults with language impairment (LI), limiting our knowledge of developmental trajectories and ability to develop efficacious speech/language supports. An important first step is establishing proof of concept of identification of LI in this population, with considerations for feasibility of assessment. This research note describes such a study in a sample of autistic adolescents and young adults with LI. METHOD: Thirteen autistic adolescents and young adults completed an assessment protocol of age-referenced language and nonverbal cognitive assessments. Assessment took place once per year for 3 years; the first two assessments were conducted in person, and the final was conducted online due to the pandemic. All assessments included measures of overall language and morphosyntax; the third added measures of expressive and receptive vocabulary, verbal working memory, and nonverbal intelligence (NVIQ). Analysis included descriptives and comparison of individual performance with epidemiological criteria for LI. RESULTS: All participants qualified for LI, with overall receptive and expressive language scores persistently in the LI range. Other outcomes were variable. Some participants had nonword repetition and vocabulary abilities within age expectations, and some consistently showed adultlike morphosyntactic performance. NVIQ was variable, with no consistent associations with language outcomes. DISCUSSION: Our findings support the use of the current protocol, as implemented in person or online, to identify LI in autistic adolescents and young adults. This exploratory work is limited by a small sample and missing data. The findings contribute to our understanding of linguistic strengths and variability in the language skills of autistic young adults with LI.

Adversity Exposure, Syntax, and Specific Language Impairment: An Exploratory Study.

PURPOSE: Children exposed to adversity (e.g., chronic poverty, traumatic events, and maltreatment) are at increased risk for performing below age expectations on norm-referenced language assessments, but it is unknown whether the risk is higher for specific language impairment (SLI). This exploratory study investigated whether adversity exposure is associated with reduced grammar knowledge and SLI. METHOD: The syntax subtest of the Diagnostic Evaluation of Language Variation-Norm-Referenced (DELV-NR) assessment was administered to 30 school-age children with known histories of adversity exposure. Their primary caregiver also completed a comprehensive adversity exposure measure, which captured adverse event type, frequency, chronicity, and severity. Analyses included t tests, correlations, Mann-Whitney U tests, and chi-square. RESULTS: Overall, the sample performed below age expectations on the DELV-NR Syntax subtest, and a higher percentage of participants (20%) met diagnostic criteria for SLI than expected. The SLI and typical language (TL) groups did not significantly differ in adversity dosage, frequency, chronicity, or severity; however, participants in the SLI group were 1.46 times more likely to have experienced physical trauma than the participants in the TL group. CONCLUSIONS: Children with known histories of adversity exposure presented with grammatical deficits and SLI more often than expected based on the DELV-NR normative sample; however, features of the adverse event did not associate with SLI status except for exposure to physical trauma (e.g., physical abuse and victimization). Future research is needed to investigate the prevalence and potential causal pathways of SLI in this population. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20483706.

Teacher Educational Decision Making for Children With Specific Language Impairment.

PURPOSE: Children with specific language impairment (SLI) are underidentified, despite a robust literature on their language abilities and a clinical grammar marker. Adlof and Hogan (2019) call for school systems to assess oral language and provide supports through response to intervention (RTI), with the aim of identifying and supporting children with SLI and other language impairments. However, it is unknown how teachers make educational decisions for children with SLI. METHOD: A web-based survey was distributed to public school teachers nationwide (N = 304). In this observational study, teachers read six vignettes featuring profiles of children systematically varying in the linguistic characteristics relevant to SLI (e.g., difficulty with verb tense) and responded to items on the educational decisions that they would make in the absence of workplace constraints. RESULTS: Teachers were likely to identify that the children in the vignettes needed language for classroom success and to indicate that they would provide in-class intervention. However, teachers were unlikely to recommend speech-language pathology services. These outcomes were mostly consistent across all child characteristics and teacher characteristics. CONCLUSIONS: Findings show that teachers were sensitive to the language-based needs of children with SLI and elected to provide in-class intervention. Future work is needed to understand how workplace characteristics, including opportunities for interprofessional collaboration, and the heterogeneity of children with SLI, inform teacher educational decision making.

Work Setting Effects on Speech-Language Pathology Practice: Implications for Identification of Children With Specific Language Impairment.

PURPOSE: Most research on language acquisition and impairments is neutral to work setting; however, work settings (e.g., schools, health care) are expected to differ in alignment with overlaid workplace models (e.g., education, medical). These differences may affect clinical service provision for individuals with specific language impairment (SLI). This article evaluates potential effects of work setting on top-down advocacy initiatives and clinical service provision for children with symptoms of SLI. METHOD: Speech-language pathologists serving pediatric populations in health care-based (n = 140) and school-based (n = 423) work settings completed a three-part survey: (a) participant demographics, (b) report of case/workload and practice patterns, and (c) clinical vignettes and eligibility belief. Data analysis included descriptives and chi-square tests. RESULTS: The work setting groups reported differences in eligibility terminology, eligibility criteria, and practice patterns from the point of referral through discharge. The reported differences aligned with overlaid workplace models. As compared to the school-based group, health care-based participants reported fewer eligibility restrictions in the workplace, agreed more often with a belief in less restrictive eligibility criteria, and reported more sensitive clinical decisions when operating under neutral workplace circumstances. Despite these findings, health care-based participants reported a smaller proportion of individuals with language impairment only on their caseload. DISCUSSION: Work setting variations influence the underidentification of individuals with SLI for speech-language pathology services. Differences in responses by workplace indicate the need for unique and targeted advocacy efforts. Shifting diagnostic terminology and criteria will be insufficient in closing the gap unless advocacy efforts also address speech-language pathologists' workplace realities.

Tools for standardized data collection: Speech, Language, and Hearing measurement protocols in the PhenX Toolkit.

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross-study analyses for biomedical research. An expert review panel (ERP) reviewed and updated the PhenX Toolkit Speech and Hearing domain to improve the precision and consistency of speech, language, and hearing disorder phenotypes. A three-member ERP convened in August 2018 to review the measurement protocols in the PhenX Speech and Hearing domain. Aided by three additional experts in voice assessment, vertigo, and stuttering, the ERP updated the 28 protocols to reflect the latest science and technology. ERP recommendations include six new protocols, five updated protocols (from the same source), and one retired protocol. New additions include two voice-related, three hearing-related, and two speech-related protocols. Additions reflect new phone/tablet applications for hearing and language, and clinical evaluations of voice. "Language" was added to the domain name, which is now "Speech, Language, and Hearing," to represent language-related protocols. These protocols can facilitate the assessment of speech, language, and hearing in clinical and population research. Common data elements (i.e., use of the same variables across studies) used by geneticists, otolaryngologists, audiologists, speech-language pathologists, and in other disciplines can lead to cross-study data integration and increased statistical power when studies are combined.

Semantic and syntactic specialization during auditory sentence processing in 7-8-year-old children.

Previous studies indicate that adults show specialized syntactic and semantic processes in both the temporal and frontal lobes during language comprehension. Neuro-cognitive models of language development argue that this specialization appears earlier in the temporal than the frontal lobe. However, there is little evidence supporting this proposed progression. Our recently published study (Wang, Rice, & Booth, 2020), using multivoxel pattern analyses, detected that children as young as 5 to 6 years old exhibit specialization and integration in the temporal lobe, but not the frontal lobe. In the current study, we used the same approach to examine semantic and syntactic specialization in children ages 7 to 8 years old. We found support for semantic specialization in the left middle temporal gyrus (MTG) for correct sentences and in the triangular part of the left inferior frontal gyrus (IFG) for incorrect sentences. We also found that the left superior temporal gyrus (STG) played an integration role and was sensitive to both semantic and syntactic processing during both correct and incorrect sentence processing. However, there was no support for syntactic specialization in 7- to 8-year-old children. As compared to our previous study on 5- to 6-year-old children, which only showed semantic specialization in the temporal lobe, the current study suggests a developmental progression to semantic specialization in the frontal lobe. This project represents an important step forward in testing neuro-cognitive models of language processing in children.

A rare missense variant in the ATP2C2 gene is associated with language impairment and related measures.

At least 5% of children present unexpected difficulties in expressing and understanding spoken language. This condition is highly heritable and often co-occurs with other neurodevelopmental disorders such as dyslexia and ADHD. Through an exome sequencing analysis, we identified a rare missense variant (chr16:84405221, GRCh38.p12) in the ATP2C2 gene. ATP2C2 was implicated in language disorders by linkage and association studies, and exactly the same variant was reported previously in a different exome sequencing study for language impairment (LI). We followed up this finding by genotyping the mutation in cohorts selected for LI and comorbid disorders. We found that the variant had a higher frequency in LI cases (1.8%, N = 360) compared with cohorts selected for dyslexia (0.8%, N = 520) and ADHD (0.7%, N = 150), which presented frequencies comparable to reference databases (0.9%, N = 24 046 gnomAD controls). Additionally, we observed that carriers of the rare variant identified from a general population cohort (N = 42, ALSPAC cohort) presented, as a group, lower scores on a range of reading and language-related measures compared to controls (N = 1825; minimum P = 0.002 for non-word reading). ATP2C2 encodes for an ATPase (SPCA2) that transports calcium and manganese ions into the Golgi lumen. Our functional characterization suggested that the rare variant influences the ATPase activity of SPCA2. Thus, our results further support the role of ATP2C2 locus in language-related phenotypes and pinpoint the possible effects of a specific rare variant at molecular level.

Family-Based Whole-Exome Analysis of Specific Language Impairment (SLI) Identifies Rare Variants in BUD13, a Component of the Retention and Splicing (RES) Complex.

Specific language impairment (SLI) is a common neurodevelopmental disorder (NDD) that displays high heritability estimates. Genetic studies have identified several loci, but the molecular basis of SLI remains unclear. With the aim to better understand the genetic architecture of SLI, we performed whole-exome sequencing (WES) in a single family (ID: 489; n = 11). We identified co-segregating rare variants in three new genes: BUD13, APLP2, and NDRG2. To determine the significance of these genes in SLI, we Sanger sequenced all coding regions of each gene in unrelated individuals with SLI (n = 175). We observed 13 additional rare variants in 18 unrelated individuals. Variants in BUD13 reached genome-wide significance (p-value < 0.01) upon comparison with similar variants in the 1000 Genomes Project, providing gene level evidence that BUD13 is involved in SLI. Additionally, five BUD13 variants showed cohesive variant level evidence of likely pathogenicity. Bud13 is a component of the retention and splicing (RES) complex. Additional supportive evidence from studies of an animal model (loss-of-function mutations in BUD13 caused a profound neural phenotype) and individuals with an NDD phenotype (carrying a CNV spanning BUD13), indicates BUD13 could be a target for investigation of the neural basis of language.

Pedigree-Based Gene Mapping Supports Previous Loci and Reveals Novel Suggestive Loci in Specific Language Impairment.

Purpose Specific language impairment (SLI) is characterized by a delay in language acquisition despite a lack of other developmental delays or hearing loss. Genetics of SLI is poorly understood. The purpose of this study is to identify SLI genetic loci through family-based linkage mapping. Method We performed genome-wide parametric linkage analysis in six families segregating with SLI. An age-appropriate standardized omnibus language measure was used to categorically define the SLI phenotype. Results A suggestive linkage region replicated a previous region of interest with the highest logarithm of odds (LOD) score of 2.40 at 14q11.2-q13.3 in Family 489. A paternal parent-of-origin effect associated with SLI and language phenotypes on a nonsynonymous single nucleotide polymorphism (SNP) in NOP9 (14q12) was reported previously. Linkage analysis identified a new SLI locus at 15q24.3-25.3 with the highest parametric LOD score of 3.06 in Family 315 under a recessive mode of inheritance. Suggestive evidence of linkage was also revealed at 4q31.23-q35.2 in Family 300, with the highest LOD score of 2.41. Genetic linkage was not identified in the other three families included in parametric linkage analysis. Conclusions These results are the first to report genome-wide suggestive linkage with a total language standard score on an age-appropriate omnibus language measure across a wide age range. Our findings confirm previous reports of a language-associated locus on chromosome 14q, report new SLI loci, and validate the pedigree-based parametric linkage analysis approach to mapping genes for SLI. Supplemental Material https://doi.org/10.23641/asha.13203218.

Causal Pathways for Specific Language Impairment: Lessons From Studies of Twins.

Purpose This review article summarizes a program of longitudinal investigation of twins' language acquisition with a focus on causal pathways for specific language impairment (SLI) and nonspecific language impairment in children at 4 and 6 years with known history at 2 years. Method The context of the overview is established by legacy scientific papers in genetics, language, and SLI. Five recent studies of twins are summarized, from 2 to 16 years of age, with a longitudinal perspective of heritability over multiple speech, language, and cognitive phenotypes. Results Replicated moderate-to-high heritability is reported across ages, phenotypes, full population estimates, and estimates for clinical groups. Key outcomes are documentation of a twinning effect of risk for late language acquisition in twins that persists through 6 years of age, greater for monozygotic than dizygotic twins (although zygosity effects disappear at 6 years); heritability is greater for grammar and morphosyntax than other linguistic dimensions, from age 2 years through age 16 years, replicated within twin samples at subsequent age levels and across twin samples at age 16 years. Conclusion There is consistent support for legacy models of genetic influences on language acquisition, updated with a more precise growth signaling disruption model supported by twin data, as well as singleton data of children with SLI and nonspecific language impairment. Presentation Video https://doi.org/10.23641/asha.13063727.

Advances in Specific Language Impairment Research and Intervention: An Overview of Five Research Symposium Papers.

Purpose This article provides an overview of five papers appearing together on the topic of "Advances in Specific Language Impairment Research and Intervention," which was the 2019 program in an ongoing series of research symposia presented at the Annual Convention of the American Speech-Language-Hearing Association. Method The article provides a historical context for the set of papers, then a short summation of each paper's content, followed by the identification of overarching themes and working conclusions. Results Each paper provides summations of empirical results, and some papers provide new empirical evidence. Conclusion The papers collectively highlight six points: (a) Children with specific language impairment (SLI) are likely to be unidentified among their age peers. (b) There is great need for better identification of children with SLI across developmental levels. (c) Progress is evident toward a better understanding of causal pathways, as examined across different research designs involving comparison of children with typical language acquisition to children with SLI and other possibly co-occurring atypical conditions. (d) Measuring multiple dimensions of language brings enhanced informativeness, with differing outcomes for differing dimensions. (e) Replicated research findings require precision of methods in order to reduce unexplained error variance especially when defining groups. (f) Accurate identification of children with SLI is the first step toward a sound treatment plan for SLI and reading disorders as well. Presentation Video https://doi.org/10.23641/asha.13063721.

Assessment of Language Abilities in Minority Adolescents and Young Adults With Autism Spectrum Disorder and Extensive Special Education Needs: A Pilot Study.

Purpose Little is known about the language abilities of adolescents and young adults with autism spectrum disorder (ASD) despite the importance of language in their other life outcomes. Even less is known about the language abilities of racial/ethnic minorities with ASD and extensive special education needs. These gaps limit our understanding of adolescents and young adults with ASD. Method A pilot study evaluated the efficacy of individualized age-referenced language assessment for minority adolescents and young adults with ASD in self-contained special education settings. Participants (n = 10) completed the Clinical Evaluation of Language Fundamentals-Third Edition, Test for Early Grammatical Impairment (TEGI), Columbia Mental Maturity Scale, and Wechsler Intelligence Scale for Children-Third Edition Digit Span. Results Clinical Evaluation of Language Fundamentals-Third Edition scores showed little variation, with most participants showing a floor effect. TEGI, Columbia Mental Maturity Scale, and Digit Span scores showed greater variation. Some participants had ceiling TEGI scores, and some had variable assessment profiles. Conclusion Assessment was sensitive to variability across some measures. The pilot study outcomes support the feasibility and potential informativeness of additional investigation of conventional language assessments and change over time.

Heritability of Specific Language Impairment and Nonspecific Language Impairment at Ages 4 and 6 Years Across Phenotypes of Speech, Language, and Nonverbal Cognition.

Purpose Early language and speech acquisition can be delayed in twin children, a twinning effect that diminishes between 4 and 6 years of age in a population-based sample. The purposes of this study were to examine how twinning effects influence the identification of children with language impairments at 4 and 6 years of age, comparing children with specific language impairment (SLI) and nonspecific language impairment (NLI); the likelihood that affectedness will be shared within monozygotic versus dizygotic twin pairs; and estimated levels of heritability for SLI and NLI. Twinning effects are predicted to result in elevated rates of language impairments in twins. Method The population-based twin sample included 1,354 children from 677 twin pairs, 214 monozygotic and 463 dizygotic, enrolled in a longitudinal study. Nine phenotypes from the same comprehensive direct behavioral assessment protocol were investigated at 4 and 6 years of age. Twinning effects were estimated for each phenotype at each age using structural equation models estimated via diagonally weighted least squares. Heritabilities were calculated for SLI and NLI. Results As predicted, the twinning effect increased the percentage of affected children in both groups across multiple language phenotypes, an effect that diminished with age yet was still not aligned to singleton age peers. Substantial heritability estimates replicated across language phenotypes and increased with age, even with the most lenient definition of affectedness, at -1 SD. Patterns of outcomes differed between SLI and NLI groups. Conclusions Nonverbal IQ is not on the same causal pathway as language impairments. Twinning effects on language acquisition affect classification of 4- and 6-year-old children as SLI and NLI, and heritability is most consistent in the SLI group. Clinical practice requires monitoring language acquisition of twins to avoid misdiagnosis when young or a missed diagnosis of language impairments at school entry.

Syntactic and Semantic Specialization and Integration in 5- to 6-Year-Old Children during Auditory Sentence Processing.

Previous studies have found specialized syntactic and semantic processes in the adult brain during language comprehension. Young children have sophisticated semantic and syntactic aspects of language, yet many previous fMRI studies failed to detect this specialization, possibly due to experimental design and analytical methods. In this current study, 5- to 6-year-old children completed a syntactic task and a semantic task to dissociate these two processes. Multivoxel pattern analysis was used to examine the correlation of patterns within a task (between runs) or across tasks. We found that the left middle temporal gyrus showed more similar patterns within the semantic task compared with across tasks, whereas there was no difference in the correlation within the syntactic task compared with across tasks, suggesting its specialization in semantic processing. Moreover, the left superior temporal gyrus showed more similar patterns within both the semantic task and the syntactic task as compared with across tasks, suggesting its role in integration of semantic and syntactic information. In contrast to the temporal lobe, we did not find specialization or integration effects in either the opercular or triangular part of the inferior frontal gyrus. Overall, our study showed that 5- to 6-year-old children have already developed specialization and integration in the temporal lobe, but not in the frontal lobe, consistent with developmental neurocognitive models of language comprehension in typically developing young children.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy.

OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.