Children born preterm (PT) are at risk for white matter injuries based on complications of prematurity. They learn to read but on average perform below peers born full term (FT). Studies have yet to establish whether properties of white matter pathways at the onset of learning to read are associated with individual variation later in reading development in PT children. Here, we asked whether fractional anisotropy (FA) at age 6 years is associated with reading outcome at age 8 years in PT children in the same pathways as previously demonstrated in a sample of FT children. PT ( n = 34, mean gestational age = 29.5 weeks) and FT children ( n = 37) completed diffusion MRI and standardized measures of non-verbal IQ, language, and phonological awareness at age 6 years. Reading skills were assessed at age 8 years. Mean tract-FA was extracted from pathways that predicted reading outcome in children born FT: left arcuate fasciculus (Arc), bilateral superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP). We explored associations in additional pathways in the PT children: bilateral inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, and uncinate fasciculus. Linear regression models examined whether the prediction of reading outcome at age 8 years based on mean tract-FA at age 6 years was moderated by birth group. Children born PT and FT did not differ significantly in tract-FA at age 6 years or in reading at age 8 years. Sex, socioeconomic status, and non-verbal IQ at age 6 years were associated with reading outcome and were included as covariates in all models. Birth group status significantly moderated associations between reading outcome and mean tract-FA only in the left Arc, right SLF, and left ICP, before and after consideration of pre-literacy skills. Microstructural properties of these cerebral and cerebellar pathways predicted later reading outcome in FT but not in PT children. Children born PT may rely on alternative pathways to achieve fluent reading. These findings have implications for plasticity of neural organization after early white matter injury.

Microstructural properties of white matter pathways are associated with concurrent reading abilities in children. In this longitudinal study, we asked whether properties of white matter pathways at the onset of learning to read would be associated with reading abilities at older ages. Children (N=37) with a wide range of reading abilities completed standardized measures of language and phonological awareness and diffusion MRI at age 6 years. Mean tract-fractional anisotropy (FA) was extracted from reading-related pathways. At age 8, the same children were reassessed using a standardized reading measure. Using linear regressions, we examined the contribution of tract-FA at age 6 to reading outcome at age 8, beyond known demographic and pre-literacy predictors of reading. Tract-FA of the left arcuate, left and right superior longitudinal fasciculus (SLF), and left inferior cerebellar peduncle (ICP) made unique contributions to reading outcome after consideration of sex and family history of reading delays. Tract-FA of the left and right SLF and left ICP made unique contributions to reading outcome after the addition of preliteracy skills. Thus, cerebellar and bilateral cortical pathways represented a network associated with subsequent reading abilities. Early white matter properties may be associated with other neuropsychological functions that predict reading or may influence reading development, independent of reading-related abilities. Tract-FA at early stages of learning to read may serve as a biomarker of later reading abilities.

Background: Children born preterm are at risk for developing reading difficulties and for decrements in other cognitive skills compared to children born at term. Aims: To assess how domains of function, often negatively impacted by preterm birth, predict reading development in children born preterm and at term. Study design: Longitudinal descriptive cohort study. Subjects: Preterm (n=48; gestational age 22-32 weeks, 30 males) and term (n=41, 18 males) participants were assessed at age 6 years on a battery of verbal and non-verbal cognitive skills and reassessed at age 8 the Gray Oral Reading Tests-5. Linear regressions assessed the contributions of phonological awareness, language, executive function, and non-verbal IQ at age 6 to reading outcome at age 8. Results: Children born preterm had lower scores than children born at term on all measures (Cohen's d from 0.46-1.08, all p<.05). Phonological awareness and language abilities predicted reading in both groups (accounting for 19.9% and 25.0% of variance, respectively, p<.001). Birth group did not moderate the association. By contrast, the association between executive function and non-verbal intelligence and reading outcome was moderated by birth group (interaction accounted for 3.9-6.7% of variance, respectively, p<.05). Positive predictions to reading from executive function and non-verbal IQ were found only in children born preterm. Conclusions: Non-verbal cognitive measures improved the prediction of reading outcome only in the preterm group, suggesting that reading decrements represent a component of global deficits.

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OBJECTIVECompletion corpus callosotomy can offer further remission from disabling seizures when a prior partial corpus callosotomy has failed and residual callosal tissue is identified on imaging. Traditional microsurgical approaches to section residual fibers carry risks associated with multiple craniotomies and the proximity to the medially oriented motor cortices. Laser interstitial thermal therapy (LITT) represents a minimally invasive approach for the ablation of residual fibers following a prior partial corpus callosotomy. Here, the authors report clinical outcomes of 6 patients undergoing LITT for completion corpus callosotomy and characterize the radiological effects of ablation.METHODSA retrospective clinical review was performed on a series of 6 patients who underwent LITT completion corpus callosotomy for medically intractable epilepsy at Stanford University Medical Center and Lucile Packard Children’s Hospital at Stanford between January 2015 and January 2018. Detailed structural and diffusion-weighted MR images were obtained prior to and at multiple time points after LITT. In 4 patients who underwent diffusion tensor imaging (DTI), streamline tractography was used to reconstruct and evaluate tract projections crossing the anterior (genu and rostrum) and posterior (splenium) parts of the corpus callosum. Multiple diffusion parameters were evaluated at baseline and at each follow-up.RESULTSThree pediatric (age 8–18 years) and 3 adult patients (age 30–40 years) who underwent completion corpus callosotomy by LITT were identified. Mean length of follow-up postoperatively was 21.2 (range 12–34) months. Two patients had residual splenium, rostrum, and genu of the corpus callosum, while 4 patients had residual splenium only. Postoperative complications included asymptomatic extension of ablation into the left thalamus and transient disconnection syndrome. Ablation of the targeted area was confirmed on immediate postoperative diffusion-weighted MRI in all patients. Engel class I–II outcomes were achieved in 3 adult patients, whereas all 3 pediatric patients had Engel class III–IV outcomes. Tractography in 2 adult and 2 pediatric patients revealed time-dependent reduction of fractional anisotropy after LITT.CONCLUSIONSLITT is a safe, minimally invasive approach for completion corpus callosotomy. Engel outcomes for completion corpus callosotomy by LITT were similar to reported outcomes of open completion callosotomy, with seizure reduction primarily observed in adult patients. Serial DTI can be used to assess the presence of tract projections over time but does not classify treatment responders or nonresponders.

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The left hemisphere is dominant for language in most people, but lateralization strength varies between different tasks and individuals. A large body of literature has shown that handedness is associated with lateralization: left handers have weaker language lateralization on average, and a greater incidence of atypical (right hemisphere) lateralization; but typically, these studies have relied on a single measure of language lateralization. Here we consider the relationships between lateralization for two different language tasks. We investigated the influence of handedness on lateralization using functional transcranial Doppler sonography (fTCD), using an existing dataset (N = 151 adults, 21 left handed). We compared a speech production task (word generation) and a semantic association task. We demonstrated stronger left-lateralization for word generation than semantic association; and a moderate correlation between laterality indices for the two tasks (r = 0.59). Laterality indices were stronger for right than left handers, and left handers were more likely than right handers to have atypical (right hemisphere) lateralization or inconsistent lateralization between the two tasks. These results add to our knowledge of individual differences in lateralization and support the view that language lateralization is multifactorial rather than unitary.

Highlights Preterm infant white matter tracts uniquely predict later toddler language. Neonatal medical history moderates posterior corpus callosum–language relations. Different associations by tract may relate to brain maturation and medical history.