Transition to Adulthood for Extremely Preterm Survivors.

OBJECTIVE: To compare transition into adulthood of survivors born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g) in the postsurfactant era with term-born controls. METHODS: Prospective longitudinal cohort study of all EP/ELBW survivors born in the State of Victoria, Australia between January 1, 1991 and December 31, 1992 and matched term-born controls. Outcomes include educational attainment, employment, financial status, romantic partnering, living arrangements, parenthood, physical health and mental health, risk-taking behaviors, life satisfaction, and interpersonal relationships at 25 years. RESULTS: Data were available from 165 EP/ELBW and 127 control participants. Overall, there was little evidence for differences between the EP/ELBW and control groups on most comparisons after adjustment for social risk and multiple births. However, compared with controls, the EP/ELBW group was more likely to have their main source of income from government (adjusted odds ratio [aOR] 2.49, 95% confidence interval [CI] 1.21-5.13; P = .01) and to have never moved out of the parental home (aOR 2.13, 95% CI 1.27-3.58; P = .01), and fewer had ever engaged in smoking (aOR 0.52, 95% CI 0.28-0.98; P = .04), binge drinking (aOR 0.41, 95% CI 0.18-0.93; P = .03), or street drugs (aOR 0.56, 95% CI 0.32-0.98; P = .04). CONCLUSIONS: Aside from clinically important differences in main income source, leaving the parental home, and reduced risk-taking behavior, survivors born EP/ELBW in the era since surfactant was introduced are transitioning into adulthood similarly to term-born controls in some areas assessed but not all.

Health-related quality of life in adults born extremely preterm or with extremely low birth weight in the postsurfactant era: a longitudinal cohort study.

OBJECTIVES: To compare health-related quality of life (HRQoL) at 25 and 18 years in individuals born extremely preterm (EP, <28 weeks' gestation) or with extremely low birth weight (ELBW, birth weight <1000 g) with term-born (≥37 weeks) controls. Within the EP/ELBW cohort, to determine whether HRQoL differed between those with lower and higher IQs. METHODS: HRQoL was self-reported using the Health Utilities Index Mark 3 (HUI3) at 18 and 25 years by 297 EP/ELBW and 251 controls born in 1991-1992 in Victoria, Australia. Median differences (MDs) between groups were estimated using multiple imputation to handle missing data. RESULTS: Adults born EP/ELBW had lower HRQoL (median utility 0.89) at 25 years than controls (median utility 0.93, MD -0.040), but with substantial uncertainty in the estimate (95% CI -0.088 to 0.008) and a smaller reduction at 18 years (MD -0.016, 95% CI -0.061 to 0.029). On individual HUI3 items, there was suboptimal performance on speech (OR 9.28, 95% CI 3.09 to 27.93) and dexterity (OR 5.44, 95% CI 1.04 to 28.45) in the EP/ELBW cohort. Within the EP/ELBW cohort, individuals with lower IQ had lower HRQoL compared with those with higher IQ at 25 (MD -0.031, 95% CI -0.126 to 0.064) and 18 years (MD -0.034, 95% CI -0.107 to 0.040), but again with substantial uncertainty in the estimates. CONCLUSIONS: Compared with term-born controls, young adults born EP/ELBW reported poorer HRQoL, as did those with lower IQ compared with those with higher IQ in the EP/ELBW cohort. Given the uncertainties, our findings need corroboration.

The neural basis of nonword repetition in children with developmental speech or language disorder: An fMRI study.

Developmental language disorder (DLD) and developmental speech disorder (DSD) are highly prevalent childhood conditions. An impaired ability to repeat nonsense words ("nonword repetition"), is claimed to be a robust behavioural marker for these conditions. Yet how brain function is altered during this task remains poorly understood. Previous research suggests that DLD or DSD may be associated with reduced brain activation in the inferior frontal and posterior temporal regions when compared to controls. However, this research is limited by within and between group variability in age, speech/language phenotype, and comorbidities. Here, we used functional MRI to examine brain activation during nonword repetition. As anticipated, behavioural findings confirmed that the DLD and DSD groups had poorer nonword repetition performance compared to typical controls. In contrast, fMRI revealed no statistically significant differences in brain activation, despite the groups appearing to engage slightly different regions when compared at identical thresholds. Therefore, whilst nonword repetition is a sensitive clinical marker for DLD and DSD, the findings from this study suggest that this task is not a sensitive brain MRI marker for children with these disorders, unlike for individuals with single gene mutations like FOXP2 mutations.

What predicts nonword repetition performance?

Despite the widespread use of nonword repetition in child neuropsychological research and clinical practice, the specific cognitive, linguistic and motor processes that contribute to variability in performance are unclear. The aim of this work was to determine the role of phonological memory, word reading, oromotor sequencing, and oromotor control on nonword repetition performance in the context of children's speech and language abilities. Ninety one children between the ages of 9 and 11 years, with a broad range of speech and language abilities participated in the study. Hierarchical regression was used to a) evaluate the contribution of phonological memory, word reading, oromotor sequencing and oromotor control to nonword repetition and b) determine whether speech and/or language ability moderated the relationship between these specific skills and nonword repetition performance. Results showed all four predictor variables were related to nonword repetition performance, accounting for 59% of variance. The variable with the strongest association with nonword repetition was phonological memory, followed by oromotor sequencing ability, word reading, and oromotor control. Contrary to expectations, neither speech nor language ability were significantly associated with the degree to which these specific skills were drawn upon to perform the nonword repetition task. These findings underline the multidimensional nature of the nonword repetition task and provide further evidence of the major contributions made by phonological memory, word reading, speech sequencing and control to performance on this task. Further, findings suggest that speech and language ability, as measured here, do not significantly influence the skills employed for nonword repetition performance.

Grey matter volume in developmental speech and language disorder.

Developmental language disorder (DLD) and developmental speech disorder (DSD) are common, yet their etiologies are not well understood. Atypical volume of the inferior and posterior language regions and striatum have been reported in DLD; however, variability in both methodology and study findings limits interpretations. Imaging research within DSD, on the other hand, is scarce. The present study compared grey matter volume in children with DLD, DSD, and typically developing speech and language. Compared to typically developing controls, children with DLD had larger volume in the right cerebellum, possibly associated with the procedural learning deficits that have been proposed in DLD. Children with DSD showed larger volume in the left inferior occipital lobe compared to controls, which may indicate a compensatory role of the visual processing regions due to sub-optimal auditory-perceptual processes. Overall, these findings suggest that different neural systems may be involved in the specific deficits related to DLD and DSD.

Speech and language in children with Klinefelter syndrome.

BACKGROUND: Speech and language deficits are frequent in males with Klinefelter syndrome (KS), yet the research base is slim and specific strengths and deficits in communication have not been well characterised. Nor have studies examined communication abilities across a wide age-range from infancy to adolescence. OBJECTIVE: To characterise communication in children and adolescents with KS. METHOD: Twenty-six males, aged 1;1-17;4 years, took part in the study. Oromotor, speech, language, literacy and pragmatic abilities were assessed. RESULTS: Communication impairment was seen in 92% of cases (24/26), with salient findings being impairments in social-pragmatic language (15/18; 83%), language-memory (12/15; 80%) and literacy (13/17; 76%). Mild to severe receptive and expressive language deficits were common (16/23; 70%), although performance was varied across linguistic domains of semantics, syntax, and morphology. Oromotor impairment (21/21; 100%) and speech impairments were evident from preschool through to adolescence. Whilst speech was highly intelligible (22/26; 85%), articulation errors (12/26; 46%), phonological delay (12/26; 46%), phonological disorder (5/26; 19%) and dysarthria (2/23 8.7%) were observed. Other atypical, yet mild, speech features were noted such as hyponasality (16/23; 70%). CONCLUSIONS: Language, literacy and social-pragmatic deficits are common in KS. Data suggested a trend for more notable deficits with age and increasing academic and social demands. We added novel data on the nature of speech production deficits, including persistent phonological errors in a number of cases. Earlier detection and intervention of phonological errors may reduce the risk for later language and literacy challenges and optimise academic, and ultimately social and behavioural difficulties later in life.

Speech and Language Impairments After Childhood Arterial Ischemic Stroke: Does Hemisphere Matter?

BACKGROUND: The association between left hemisphere stroke and acute speech and language impairment is well documented in adults. However, little is known about this association in childhood arterial ischemic stroke. Here we examined potential predictors of acute speech (dysarthria and apraxia) and language impairments after childhood arterial ischemic stroke, including site of lesion. METHODS: Children with radiologically confirmed acute arterial ischemic stroke, admitted to a tertiary pediatric hospital from 2004 to 2012, were identified from an institutional registry. We examined the prevalence of dysarthria, apraxia, and language impairment within two weeks of the stroke. Associations with age at stroke event, lesion side (left, right, or bilateral), and arterial territory affected (anterior, posterior, or both) were assessed using logistic regression. RESULTS: Sixty-two children with mean age eight years (range three to 17 years) were identified. Strokes were located in the left (32%), right (44%), or both hemispheres (24%). Dysarthria (74%) and language impairment (50%) were frequent. Verbal dyspraxia was less common (11%). There was little evidence that variables of interest, including site of lesion, were significantly associated with increased odds of dysarthria or language impairment (all P > 0.49). CONCLUSIONS: Regardless of age, children are at high risk of communication disorders after stroke. Unlike adults, left hemisphere stroke was not associated with either speech or language impairment in our cohort, suggesting there may be bihemispheric contribution to language function. Future studies are needed to examine whether the predictors examined here determine long-term outcomes.

Characterization of speech and language phenotype in children with NRXN1 deletions.

Neurexin 1 gene (NRXN1) deletions are associated with several neurodevelopmental disorders. Communication difficulties have been reported, yet no study has examined specific speech and language features of individuals with NRXN1 deletions. Here, we characterized speech and language phenotypes in 21 children (14 families), aged 1.8-17 years, with NRXN1 deletions. Deletions ranged from 74 to 702 kb and consisted mostly of either exons 1-3 or 1-5. Speech sound disorders were frequent (69%), although few were severe. The majority (57%) of children had difficulty with receptive and/or expressive language, although no homogeneous profiles of deficit were seen across semantic, morphological, or grammatical systems. Social language difficulties were seen in over half the sample (53%). All but two individuals with language difficulties also had intellectual disability/developmental delay. Overall, while speech and language difficulties were common, there was substantial heterogeneity in the severity and type of difficulties observed and no striking communication phenotype was seen. Rather, the speech and language deficits are likely part of broader concomitant neurodevelopmental profiles (e.g., intellectual disability, social skill deficits). Nevertheless, given the high rate of affectedness, it is important speech/language development is assessed so interventions can be applied during childhood in a targeted and timely manner.

Altered gray matter volumes in language-associated regions in children with developmental language disorder and speech sound disorder.

Developmental language disorder (DLD) and speech sound disorder (SSD) are common, and although scientific evidence for structural and functional alterations in DLD/SSD is accumulating, current neuroimaging studies provide an incongruent picture. Here, we hypothesized that children affected by DLD and SSD present with gray matter (or gray matter asymmetry) aberrations in brain areas associated with language processing compared to typically developing (TD) children. To assess this hypothesis, we enhanced MRI-based information with microscopically defined cytoarchitectonic probabilities of Broca's area (BA 45, BA 44) as well as an auditory area (TE 3.0). We detected a larger rightward gray matter asymmetry in BA 45 in children with DLD (n = 13) and with SSD (n = 18) compared to TD children (n = 18), albeit only on a trend level. Interestingly though, we observed significantly larger gray matter volumes in right BA 45 in DLD compared to SSD children (and also compared to TD children).

Atypical Callosal Morphology in Children with Speech Sound Disorder.

Speech sound disorder (SSD) is common, yet its neurobiology is poorly understood. Recent studies indicate atypical structural and functional anomalies either in one hemisphere or both hemispheres, which might be accompanied by alterations in inter-hemispheric connectivity. Indeed, abnormalities of the corpus callosum - the main fiber tract connecting the two hemispheres - have been linked to speech and language deficits in associated disorders, such as stuttering, dyslexia, aphasia, etc. However, there is a dearth of studies examining the corpus callosum in SSD. Here, we investigated whether a sample of 18 children with SSD differed in callosal morphology from 18 typically developing children carefully matched for age. Significantly reduced dimensions of the corpus callosum, particularly in the callosal anterior third, were observed in children with SSD. These findings indicating pronounced callosal aberrations in SSD make an important contribution to an understudied field of research and may suggest that SSD is accompanied by atypical lateralization of speech and language function.

Pediatric traumatic brain injury: language outcomes and their relationship to the arcuate fasciculus.

Pediatric traumatic brain injury (TBI) may result in long-lasting language impairments alongside dysarthria, a motor-speech disorder. Whether this co-morbidity is due to the functional links between speech and language networks, or to widespread damage affecting both motor and language tracts, remains unknown. Here we investigated language function and diffusion metrics (using diffusion-weighted tractography) within the arcuate fasciculus, the uncinate fasciculus, and the corpus callosum in 32 young people after TBI (approximately half with dysarthria) and age-matched healthy controls (n=17). Only participants with dysarthria showed impairments in language, affecting sentence formulation and semantic association. In the whole TBI group, sentence formulation was best predicted by combined corpus callosum and left arcuate volumes, suggesting this "dual blow" seriously reduces the potential for functional reorganisation. Word comprehension was predicted by fractional anisotropy in the right arcuate. The co-morbidity between dysarthria and language deficits therefore seems to be the consequence of multiple tract damage.

Functional magnetic resonance imaging of chronic dysarthric speech after childhood brain injury: reliance on a left-hemisphere compensatory network.

Severe and persistent speech disorder, dysarthria, may be present for life after brain injury in childhood, yet the neural correlates of this chronic disorder remain elusive. Although abundant literature is available on language reorganization after lesions in childhood, little is known about the capacity of motor speech networks to reorganize after injury. Here, we examine the structural and functional neural correlates associated with chronic dysarthria after childhood-onset traumatic brain injury. Forty-nine participants aged 12 years 3 months to 24 years 11 months were recruited to the study: (i) a group with chronic dysarthria (n = 17); matched for age and sex with two control groups of (ii) healthy control subjects (n = 17); and (iii) individuals without dysarthria after traumatic brain injury (n = 15). A high-resolution 3D T(1)-weighted whole-brain data set was acquired for voxel-based morphometry analyses of group differences in grey matter. Functional magnetic resonance imaging was used to localize activation associated with speaking single words (baseline: listening to words). Group differences on voxel-based morphometry revealed widespread grey matter reductions in the dysarthric group compared with healthy control subjects, including in numerous speech motor regions bilaterally, such as the cerebellum, the basal ganglia and primary motor cortex representation of the articulators. Relative to the non-dysarthric traumatic brain injury group, individuals with dysarthria showed reduced grey matter bilaterally in the ventral sensorimotor cortex, but this reduction was concomitant with increased functional activation only in the left-hemisphere cluster during speech. Finally, increased recruitment of Broca's area (Brodmann area 45, pars triangularis) but not its right homologue, correlated with better speech outcome, suggesting that this 'higher-level' area may be more critically involved with production when associated motor speech regions are damaged. We suggest that the bilateral morphological abnormalities within cortical speech networks in childhood prevented reorganization of speech function from the left- to right-hemisphere. Rather, functional reorganization involved over-recruitment of left-hemisphere motor regions, a reorganization method that was only partly relatively effective, given the presence of persisting yet mild speech deficits. The bilateral structural abnormalities found to limit functional reorganization here, may also be critical to poor speech prognosis for populations with congenital, degenerative or acquired neurological disorders throughout the lifespan.

Corticobulbar tract changes as predictors of dysarthria in childhood brain injury.

OBJECTIVES: To identify corticobulbar tract changes that may predict chronic dysarthria in young people who have sustained a traumatic brain injury (TBI) in childhood using diffusion MRI tractography. METHODS: We collected diffusion-weighted MRI data from 49 participants. We compared 17 young people (mean age 17 years, 10 months; on average 8 years postinjury) with chronic dysarthria who sustained a TBI in childhood (range 3-16 years) with 2 control groups matched for age and sex: 1 group of young people who sustained a traumatic injury but had no subsequent dysarthria (n = 15), and 1 group of typically developing individuals (n = 17). We performed tractography from spherical seed regions within the precentral gyrus white matter to track: 1) the hand-related corticospinal tract; 2) the dorsal corticobulbar tract, thought to correspond to the lips/larynx motor representation; and 3) the ventral corticobulbar tract, corresponding to the tongue representation. RESULTS: Despite widespread white matter damage, radial (perpendicular) diffusivity within the left dorsal corticobulbar tract was the best predictor of the presence of dysarthria after TBI. Diffusion metrics in this tract also predicted speech and oromotor performance across the whole group of TBI participants, with additional significant contributions from ventral speech tract volume in the right hemisphere. CONCLUSION: An intact left dorsal corticobulbar tract seems crucial to the normal execution of speech long term after acquired injury. Examining the speech-related motor pathways using diffusion-weighted MRI tractography offers a promising prognostic tool for people with acquired, developmental, or degenerative neurologic conditions likely to affect speech.