Visual alertness and brain diffusion tensor imaging at term age predict neurocognitive development at preschool age in extremely preterm-born children.

INTRODUCTION: Cognitive development is characterized by the structural and functional maturation of the brain. Diffusion-weighted magnetic resonance imaging (dMRI) provides methods of investigating the brain structure and connectivity and their correlations with the neurocognitive outcome. Our aim was to examine the relationship between early visual abilities, brain white matter structures, and the later neurocognitive outcome. METHODS: This study included 20 infants who were born before 28 gestational weeks and followed until the age of 6.5 years. At term age, visual alertness was evaluated and dMRI was used to investigate the brain white matter structure using fractional anisotropy (FA) in tract-based spatial statistics analysis. The JHU DTI white matter atlas was used to locate the findings. The neuropsychological assessment was used to assess neurocognitive performance at 6.5 years. RESULTS: Optimal visual alertness at term age was significantly associated with better visuospatial processing (p < .05), sensorimotor functioning (p < .05), and social perception (p < .05) at 6.5 years of age. Optimal visual alertness related to higher FA values, and further, the FA values positively correlated with the neurocognitive outcome. The tract-based spatial differences in FA values were detected between children with optimal and nonoptimal visual alertness according to performance at 6.5 years. CONCLUSION: We provide neurobiological evidence for the global and tract-based spatial differences in the white matter maturation between extremely preterm children with optimal and nonoptimal visual alertness at term age and a link between white matter maturation, visual alertness and the neurocognitive outcome at 6.5 years proposing that early visual function is a building block for the later neurocognitive development.

Extremely preterm children and relationships of minor neurodevelopmental impairments at 6 years.

Aim: This study investigated minor impairments in neurological, sensorimotor, and neuropsychological functioning in extremely preterm-born (EPT) children compared to term-born children. The aim was to explore the most affected domains and to visualize their co-occurrences in relationship maps. Methods: A prospective cohort of 56 EPT children (35 boys) and 37 term-born controls (19 boys) were assessed at a median age of 6 years 7 months with Touwen Neurological Examination, Movement Assessment Battery for Children, 2nd edition (MABC-2), Sensory Integration and Praxis Test (SIPT), and a Developmental Neuropsychological Assessment, 2nd edition (NEPSY-II). Altogether 20 test domains were used to illustrate the frequency of impaired test performances with a bar chart profile and to construct relationship maps of co-occurring impairments. Results: The EPT children were more likely to perform inferiorly compared to the term-born controls across all assessments, with a wider variance and more co-occurring impairments. When aggregating all impaired test domains, 45% of the EPT children had more impaired domains than any term-born child (more than five domains, p < 0.001). Relationship maps showed that minor neurological dysfunction (MND), NEPSY-II design copying, and SIPT finger identification constituted the most prominent relationship of co-occurring impairments in both groups. However, it was ten times more likely in the EPT group. Another relationship of co-occurring MND, impairment in NEPSY-II design copying, and NEPSY-II imitation of hand positions was present in the EPT group only. Interpretation: Multiple minor impairments accumulate among EPT children at six years, suggesting that EPT children and their families may need support and timely multi-professional interventions throughout infancy and childhood.

Newborn Neurobehavior Is Related to Later Neurodevelopment and Social Cognition Skills in Extremely Preterm-Born Children: A Prospective Longitudinal Cohort Study.

Objective: The aim of this study was to evaluate the ability of the neonatal neurobehavioral characteristics to act as an indicator for later neurodevelopment and neurocognitive performance. Methods: Sixty-six infants born extremely preterm (<28 gestational weeks) were followed until 6.5 years. Neurobehavior at term age was assessed by the behavior subscale of the Hammersmith Neonatal Neurological Examination (HNNE) using dichotomic rating, optimal, and non-optimal. The Griffiths Mental Developmental Scales (GMDS) at 2 years, and the Wechsler Intelligence Scales at 6.5 years, and a Neuropsychological Assessment at 6.5 years were used to assess neurodevelopment and neurocognitive performance including social cognition skills. Results: An optimal auditory orientation at term age was associated with better developmental quotients (DQ) in Personal-Social, and Hearing-Language GMDS subscale at 2 years (p < 0.05). An optimal visual alertness was associated with better Total (p < 0.01), Locomotor (p < 0.001), and Eye-Hand Coordination (p < 0.01) DQs at 2 years, and with sensorimotor function (p < 0.001) and social perception (p < 0.01) tests at 6.5 years. Conclusion: The neurobehavioral characteristics of newborns might serve as a precursor of social cognition skills and the HNNE behavior subscale offers a tool to identify infants at risk for later deficits in neurodevelopment and social cognition.

Secondary somatosensory cortex evoked responses and 6-year neurodevelopmental outcome in extremely preterm children.

OBJECTIVE: We assessed in extremely preterm born (EPB) children whether secondary somatosensory cortex (SII) responses recorded with magnetoencephalography (MEG) at term-equivalent age (TEA) correlate with neurodevelopmental outcome at age 6 years. Secondly, we assessed whether SII responses differ between 6-year-old EPB and term-born (TB) children. METHODS: 39 EPB children underwent MEG with tactile stimulation at TEA. At age 6 years, 32 EPB and 26 TB children underwent MEG including a sensorimotor task requiring attention and motor inhibition. SII responses to tactile stimulation were modeled with equivalent current dipoles. Neurological outcome, motor competence, and general cognitive ability were prospectively evaluated at age 6 years. RESULTS: Unilaterally absent SII response at TEA was associated with abnormal motor competence in 6-year-old EPB children (p = 0.03). At age 6 years, SII responses were bilaterally detectable in most EPB (88%) and TB (92%) children (group comparison, p = 0.69). Motor inhibition was associated with decreased SII peak latencies in TB children, but EPB children lacked this effect (p = 0.02). CONCLUSIONS: Unilateral absence of an SII response at TEA predicted poorer motor outcome in EPB children. SIGNIFICANCE: Neurophysiological methods may provide new means for outcome prognostication in EPB children.

A protocol for the analysis of DTI data collected from young children.

Analysis of scalar maps obtained by diffusion tensor imaging (DTI) produce valuable information about the microstructure of the brain white matter. The DTI scanning of child populations, compared with adult groups, requires specifically designed data acquisition protocols that take into consideration the trade-off between the scanning time, diffusion strength, number of diffusion directions, and the applied analysis techniques. Furthermore, inadequate normalization of DTI images and non-robust tensor reconstruction have profound effects on data analyses and may produce biased statistical results. Here, we present an acquisition sequence that was specifically designed for pediatric populations, and describe the analysis steps of the DTI data collected from extremely preterm-born young school-aged children and their age- and gender-matched controls. The protocol utilizes multiple software packages to address the effects of artifacts and to produce robust tensor estimation. The computation of a population-specific template and the nonlinear registration of tensorial images with this template were implemented to improve alignment of brain images from the children.

Altered working memory-related brain responses and white matter microstructure in extremely preterm-born children at school age.

Preterm birth poses a risk for neurocognitive and behavioral development. Preterm children, who have not been diagnosed with neurological or cognitive deficits, enter normal schools and are expected to succeed as their term-born peers. Here we tested the hypotheses that despite an uneventful development after preterm birth, these children might exhibit subtle abnormalities in brain function and white-matter microstructure at school-age. We recruited 7.5-year-old children born extremely prematurely (<28 weeks' gestation), and age- and gender-matched term-born controls (≥37 weeks' gestation). We applied fMRI during working-memory (WM) tasks, and investigated white-matter microstructure with diffusion tensor imaging. Compared with controls, preterm-born children performed WM tasks less accurately, had reduced activation in several right prefrontal areas, and weaker deactivation of right temporal lobe areas. The weaker prefrontal activation correlated with poorer WM performance. Preterm-born children had higher fractional anisotropy (FA) and lower diffusivity than controls in several white-matter areas, and in the posterior cerebellum, the higher FA associated with poorer visuospatial test scores. In controls, higher FA and lower diffusivity correlated with faster WM performance. Together these findings demonstrate weaker WM-related brain activations and altered white matter microstructure in children born extremely preterm, who had normal global cognitive ability.

Sensory-motor performance in seven-year-old children born extremely preterm.

BACKGROUND: Children born preterm are prone to motor problems. Research on their motor performance has, however, rarely been integrated with sensory processing. AIM: To examine sensory-motor performance in children born extremely preterm (EPT). METHOD: In a longitudinal prospective cohort study, 49 EPT (born <28 gestational weeks; 32 boys and 17 girls) and 33 term-born (16 boys and 17 girls) children were assessed with six individual subtests from the Sensory Integration and Praxis Tests at the age of 7.0 to 7.3 years. RESULTS: The rate of test z-scores indicating dysfunction [from -2 standard deviations (SD) to < -1 SD for mild and < -2 SD for moderate-to-severe] was significantly higher in EPT children than in term-born children in all the subtests. When comparing mean performance adjusted for gender and mother's education, EPT children performed worse than term-born children in Design Copying (z-score difference - 0.83; 95% confidence interval -1.32 to -0.34), Motor Accuracy (-0.82; -1.26 to -0.38), Postural Praxis (-0.95; -1.45 to -0.45), Manual Form Perception (-0.59; -1.12 to -0.06), and Finger Identification (-0.88; -1.45 to -0.31). Additional adjustment for Full-Scale Intelligence Quotient rendered difference in Manual Form Perception non-significant. CONCLUSION: Seven-year-old EPT children perform worse than their term-born peers in tests for visual-motor, somatosensory, and motor planning performance.

Lack of Cortical Correlates of Response Inhibition in 6-Year-Olds Born Extremely Preterm - Evidence from a Go/NoGo Task in Magnetoencephalographic Recordings.

Children born extremely preterm (EPT) may have difficulties in response inhibition, but the neural basis of such problems is unknown. We recorded magnetoencephalography (MEG) during a somatosensory Go/NoGo task in 6-year-old children born EPT (n = 22) and in children born full term (FT; n = 21). The children received tactile stimuli randomly to their left little (target) and index (non-target) finger and were instructed to squeeze a soft toy with the opposite hand every time they felt a stimulus on the little finger. Behaviorally, the EPT children performed worse than the FT children, both in responding to the target finger stimulation and in refraining from responding to the non-target finger stimulation. In MEG, after the non-target finger stimulation (i.e., during the response inhibition), the sensorimotor alpha oscillation levels in the contralateral-to-squeeze hemisphere were elevated in the FT children when compared with a condition with corresponding stimulation but no task (instead the children were listening to a story and not attending to the fingers). This NoGo task effect was absent in the EPT children. Further, in the sensorimotor cortex contralateral to the tactile stimulation, the post-stimulus suppression was less pronounced in the EPT than FT children. We suggest that the missing NoGo task effect and lower suppression of sensorimotor oscillations are markers of deficient functioning of the sensorimotor networks in the EPT children.