Converging data suggest recovery from injury in the preterm brain. We used functional Magnetic Resonance Imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernicke's area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600 -1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children -III (WISC -III), the Peabody Individual Achievement Test -Revised (PIAT-R) and the Peabody Picture Vocabulary Test -Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found PT subjects scored significantly lower on all components of the WISC -III (p < 0.009), the PIAT-R reading comprehension test (p = 0.013), and the PPVT-R (p = 0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernicke's area and the right inferior frontal gyrus (R IFG, Broca's area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p ≤ 0.02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

Objectives-To more precisely examine regional and subregional microstructural brain changes associated with preterm birth.Study design-We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age-and sex-matched term control subjects.Results-Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects. Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also were significantly reduced in preterm male subjects. Brain volumes of preterm female subjects were not significantly different from those of term female control subjects. Voxel-based morphometry results were not correlated with perinatal variables or cognitive outcome. Higher maternal education was associated with higher cognitive performance in preterm male subjects. Conclusions-Pretermmale children continue to demonstrate abnormal neurodevelopment at 12 years of age. However, brain morphology in preterm female children may no longer differ from that of term female children. The neurodevelopmental abnormalities we detected in preterm male subjects appear to be relatively diffuse, involving multiple neural systems. The relationship between aberrant neurodevelopment and perinatal variables may be mediated by genetic factors, environmental factors, or both reflected in maternal education level.Children born prematurely are at risk for cognitive impairments with deficits in executive functioning, language, visual-motor integration, attention, and scholastic performance. 1 Although neuroimaging studies have begun to provide an initial picture of the neural correlates of preterm birth, 2-7 additional studies are needed to more precisely elucidate the functional neuroanatomy underlying cognitive dysfunction in affected children. In this study, we aimed to more precisely examine regional and subregional microstructural changes associated with this injury to the developing brain by using our 12-year-old prematurely born cohort. We hypothesized that preterm birth would result in long-lasting changes in brain development. Extending our earlier studies, this analysis used voxel-based Several VBM studies of preterm birth have been conducted. 9-12 However, we used VBM analyses as part of a unique, multimodal study of neurodevelopment in preterm children that included semi-automated volumetric and manual region of interest measurements on the basis of specific gyral boundaries to confirm our VBM findings. METHODS SubjectsAll subjects were enrolled in the follow-up component of the Multicenter Randomized Indomethacin IVH Prevention Trial. 13 The preterm subjects were sequentially recruited for the MRI study when they reached 12 years of age. The preterm cohort consisted of children with no ultrasound scanning evidence of intraven...

Objectives-To use functional magnetic resonance imaging (fMRI) to test the hypothesis that subjects who were born prematurely develop alternative systems for processing language.Study design-Subjects who were born prematurely (n = 14; 600-1250 g birthweight) without neonatal brain injury and 10 matched term control subjects were examined with a fMRI passive listening task of language, the Clinical Evaluation of Language Fundamentals (CELF) and portions of the Comprehensive Test of Phonological Processing (CTOPP). The fMRI task was evaluated for both phonologic and semantic processing.Results-Although there were differences in CELF scores between the subjects born prematurely and control subjects, there were no significant differences in the CTOPP measures in the 2 groups. fMRI studies demonstrated that the groups differentially engaged neural systems known to process language. Children born at term were significantly more likely to activate systems for the semantic processing of language, whereas subjects born prematurely preferentially engaged regions that subserve phonology.Conclusions-At 12 years of age, children born prematurely and children born at term activate neural systems for the auditory processing of language differently. Subjects born prematurely engage different networks for phonologic processing; this strategy is associated with phonologic language scores that are similar to those of control subjects. These biologically based developmental strategies may provide the substrate for the improving language skills noted in children who are born prematurely.Magnetic resonance imaging (MRI) permits the investigation of structural aspects of the developing brain. 1,2 Volumetric, diffusion tensor imaging, and magnetic resonance spectroscopy studies suggest that preterm birth is associated with significant alterations in corticogenesis, and several investigators have suggested that those cortical regions that subserve language are particularly vulnerable to the injury associated with preterm birth. 3,4 In contrast, neural processing has been less well studied in subjects born prematurely, but may offer important insights into the functional aspects of brain development after preterm birth. 5Reprint requests: Laura R. Ment, MD, Department of Pediatrics, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520; E-mail: laura.ment@yale.edu. Functional MRI (fMRI) is used extensively to study language processing in adults and children with known developmental disorders. 6,7 Preliminary studies of auditory tasks in children who were born prematurely suggest the presence of aberrant systems for language at school age, 5,8 yet recent neuropsychological studies document improvement in testing scores and school performance with time in children who were born prematurely. 9-12 NIH Public AccessWe previously reported in a study of almost 300 children born weighing 600 to 1250 g that the median Peabody Picture Vocabulary Test-Revised (PPVT-R) score, a standard measure for receptive vocabulary, incre...