No abstract

Although language difficulties are common in children born prematurely, robust neuroanatomical correlates of these impairments remain to be established. This study investigated whether the greater prevalence of language problems in preterm (versus term-born) children might reflect injury to major intra- or interhemispheric white matter pathways connecting frontal and temporal language regions. To investigate this, we performed a comprehensive assessment of language and academic abilities in a group of adolescents born prematurely, some of whom had evidence of brain injury at birth (n = 50, mean age: 16 years, mean gestational age: 27 weeks) and compared them to a term-born control group (n = 30). Detailed structural magnetic resonance imaging and diffusion-tractography analyses of intrahemispheric and interhemispheric white matter bundles were performed. Analysis of intrahemispheric pathways included the arcuate fasciculus (dorsal language pathway) and uncinate fasciculus/extreme capsule (ventral language pathway). Analysis of interhemispheric pathways (in particular, connections between the temporal lobes) included the two major commissural bundles: the corpus callosum and anterior commissure. We found language impairment in 38% of adolescents born preterm. Language impairment was not related to abnormalities of the arcuate fasciculus (or its subsegments), but was associated with bilateral volume reductions in the ventral language pathway. However, the most significant volume reduction was detected in the posterior corpus callosum (splenium), which contains interhemispheric connections between the occipital, parietal and temporal lobes. Diffusion tractography showed that of the three groups of interhemispheric fibres within the splenium, only those connecting the temporal lobes were reduced. Crucially, we found that language impairment was only detectable if the anterior commissure (a second temporal lobe commissural pathway) was also small. Regression analyses showed that a combination of anatomical measures of temporal interhemispheric connectivity (through the splenium of the corpus callosum and anterior commissure) explained 57% of the variance in language abilities. This supports recent theories emphasizing the importance of interhemispheric connections for language, particularly in the developing brain.

Preterm birth has a long-term effect on cognition, behavior, and future academic success primarily as a consequence of global brain WM reduction. This emphasizes the need for early therapeutic efforts to prevent WM injury and promote or optimize its development in preterm neonates.

Cilia are ubiquitous cell surface organelles with diverse roles from embryogenesis to adult life. The neurodevelopmental functions of the cilium are currently under investigation in animal systems, but relevance to human brain development remains uncertain. We present the first systematic investigation of structural neuroanatomy in a ciliopathy-Bardet-Biedl syndrome (BBS). Qualitative and quantitative aspects of brain structure were evaluated via magnetic resonance imaging in 10 patients with BBS (ages 14-28 years). In comparison to age and gender-matched healthy controls, BBS patients had significantly reduced total gray matter (GM) volume but no total white matter (WM) or cerebrospinal fluid volume changes. Voxel-based morphometric analysis indicated regional GM volume loss bilaterally in the anterior temporal lobes and in the medial orbitofrontal cortex, and WM volume loss in the right inferior longitudinal fasciculus. Region-of-interest measurements revealed reduced volume of the hippocampus. Two patients were found to have ventriculomegaly. Global GM reduction and regional volume reductions in the temporal lobe may underlie the learning disabilities and behavioral problems experienced by some patients with BBS. These findings are consistent with previous observations in mouse models of BBS, and further implicate the cilium in neurodevelopmental processes relevant to human cognitive function.

ObjectiveTo assess speech abilities in adolescents born preterm and investigate whether there is an association between specific speech deficits and brain abnormalities.Study designFifty adolescents born prematurely (<33 weeks’ gestation) with a spectrum of brain injuries were recruited (mean age, 16 years). Speech examination included tests of speech-sound processing and production and speech and oromotor control. Conventional magnetic resonance imaging and diffusion-weighted imaging was acquired in all adolescents born preterm and 30 term-born control subjects. Radiological ratings of brain injury were recorded and the integrity of the primary motor projections was measured (corticospinal tract and speech-motor corticobulbar tract [CST/CBT]).ResultsThere were no clinical diagnoses of developmental dysarthria, dyspraxia, or a speech-sound disorder, but difficulties in speech and oromotor control were common. A regression analysis revealed that presence of a neurologic impairment, and diffusion-weighted imaging abnormalities in the left CST/CBT were significant independent predictors of poor speech and oromotor outcome. These left-lateralized abnormalities were most evident at the level of the posterior limb of the internal capsule.ConclusionDifficulties in speech and oromotor control are common in adolescents born preterm, and adolescents with injury to the CST/CBT pathways in the left-hemisphere may be most at risk.

Objective: Impairment of speech repetition following injury to the dorsal language stream is a feature of conduction aphasia, a well-described "disconnection syndrome" in adults. The impact of similar lesions sustained in infancy has not been established. Methods: We compared language outcomes in term-born individuals with confirmed neonatal stroke (n 5 30, age 5 7-18 years, left-sided lesions in 21 cases) to matched controls (n 5 40). Injury to the dorsal and/or ventral language streams was assessed using T 1 -and T 2 -weighted magnetic resonance imaging (MRI) and diffusion tractography. Language lateralization was determined using functional MRI. Results: At the group level, left dorsal language stream injury was associated with selective speech repetition impairment for nonwords (p 5 0.021) and sentences (p < 0.0001). The majority of children with significant repetition impairment had retained left hemisphere language representation, but right hemisphere dominance was correlated with minimal or absent repetition deficits. Post hoc analysis of the repetition-impaired group revealed additional language-associated deficits, but these were more subtle and variable. Interpretation: We conclude that (1) despite the considerable plasticity of the infant brain, early dorsal language stream injury can result in specific and long-lasting problems with speech repetition that are similar to the syndrome of conduction aphasia seen in adults; and (2) language reorganization to the contralateral hemisphere has a protective effect.

Reorganization of eloquent cortex enables rescue of language functions in patients who sustain brain injury. Individuals with left-sided, early-onset focal epilepsy often show atypical (i.e. bilateral or right-sided) language dominance. Surprisingly, many patients fail to show such interhemispheric shift of language despite having major epileptogenic lesions in close proximity to eloquent cortex. Although a number of epilepsy-related factors may promote interhemispheric plasticity, it has remained unexplored if neuroanatomical asymmetries linked to human language dominance modify the likelihood of atypical lateralization. Here we examined the asymmetry of the planum temporale, one of the most striking asymmetries in the human brain, in relation to language lateralization in children with left-sided focal epilepsy. Language functional magnetic resonance imaging was performed in 51 children with focal epilepsy and left-sided lesions and 36 healthy control subjects. We examined the association of language laterality with a range of potential clinical predictors and the asymmetry of the length of the planum temporale. Using voxel-based methods, we sought to determine the effect of lesion location (in the affected left hemisphere) and grey matter density (in the unaffected right hemisphere) on language laterality. Atypical language lateralization was observed in 19 patients (38%) and in four controls (11%). Language laterality was increasingly right-sided in patients who showed atypical handedness, a left perisylvian ictal electroencephalographic focus, and a lesion in left anterior superior temporal or inferior frontal regions. Most striking was the relationship between rightward asymmetry of the planum temporale and atypical language (R = 0.70, P < 0.0001); patients with a longer planum temporale in the right (unaffected) hemisphere were more likely to have atypical language dominance. Voxel-based regression analysis confirmed that increased grey matter density in the right temporo-parietal junction was correlated with right hemisphere lateralization of language. The length of the planum temporale in the right hemisphere was the main predictor of language lateralization in the epilepsy group, accounting for 48% of variance, with handedness accounting for only a further 5%. There was no correlation between language lateralization and planum temporale asymmetry in the control group. We conclude that asymmetry of the planum temporale may be unrelated to language lateralization in healthy individuals, but the size of the right, contra-lesional planum temporale region may reflect a ‘reserve capacity’ for interhemispheric language reorganization in the presence of a seizure focus and lesions within left perisylvian regions.

ObjectiveIn contrast to adult cohorts, neocortical changes in epileptic children with hippocampal damage are not well characterized. Here, we mapped multimodal neocortical markers of epilepsy‐related structural compromise in a pediatric cohort of temporal lobe epilepsy and explored how they relate to clinical factors.MethodsWe measured cortical thickness, gray–white matter intensity contrast and intracortical FLAIR intensity in 22 patients with hippocampal sclerosis (HS) and 30 controls. Surface‐based linear models assessed between‐group differences in morphological and MR signal intensity markers. Structural integrity of the hippocampus was measured by quantifying atrophy and FLAIR patterns. Linear models were used to evaluate the relationships between hippocampal and neocortical MRI markers and clinical factors.ResultsIn the hippocampus, patients demonstrated ipsilateral atrophy and bilateral FLAIR hyperintensity. In the neocortex, patients showed FLAIR signal hyperintensities and gray–white matter boundary blurring in the ipsilesional mesial and lateral temporal neocortex. In contrast, cortical thinning was minimal and restricted to a small area of the ipsilesional temporal pole. Furthermore, patients with a history of febrile convulsions demonstrated more pronounced FLAIR hyperintensity in the ipsilesional temporal neocortex.InterpretationPediatric HS patients do not yet demonstrate the widespread cortical thinning present in adult cohorts, which may reflect consequences of a protracted disease process. However, pronounced temporal neocortical FLAIR hyperintensity and blurring of the gray–white matter boundary are already detectable, suggesting that alterations in MR signal intensities may reflect a different underlying pathophysiology that is detectable earlier in the disease and more pervasive in patients with a history of febrile convulsions.