Search

ObjectiveTo examine associations between maternal mental health and involvement in developmental care in the NICU.Study DesignMothers of infants born at Results35% of screened mothers scored above the cutoff for clinical concern on ≥1 measure. No significant group differences were identified for rates, frequency, or amount of overall developmental care, kangaroo care, or holding.ConclusionMaternal mental health ratings did not relate to developmental care. Maternal developmental care engagement may not indicate mental health status. Universal screening for psychological distress is required to accurately detect symptoms in mothers of hospitalized preterm infants.

BackgroundLimited research links hospital-based experiences of Kangaroo Care (KC), or skin-to-skin holding to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient KC and cognitive abilities measured at 6- and 12-months of age in a sample of very preterm (VPT) infants.MethodsRetrospective study reviewing medical records of 132 (54% male) VPT infants (n=77) and 12 (n= 37) months.ResultsFamilies engaged in KC about 2 days/week, 20 minutes/day, and 70 minutes/session, on average, although there was substantial variability. Variation in KC was positively associated with cognitive outcomes at both 6 (frequency: r=0.32; rate: r=0.29) and 12 (frequency: r=0.53; rate: r=0.59; duration: r=0.38) months. KC significantly predicted 7 to 27% unique variance in 6- and 12-month cognitive outcomes, after controlling for GA, socioeconomic status, health acuity, visitation frequency, and prior cognitive scores. Small increases in KC frequency (e.g., 1 day/week), rate (e.g., 20 minutes/day) or duration (e.g., 20 minutes/instance) were associated with 0.5 to 1.0 SD increases in cognitive outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations.ConclusionVPT infants with more KC during hospitalization demonstrated higher scores on 6- and 12- month assessments of cognitive development. Results provide strong evidence that KC may confer neuroprotection on VPT infants through the first year of life.Article SummaryVariation in family-delivered Kangaroo Care in the NICU predicted infants’ higher cognitive performance at 6 and 12 months, beyond visitation, clinical, and demographic factors.What is Known on This SubjectKangaroo Care is a developmental care practice associated with positive short-term outcomes for preterm infants. Kangaroo Care is thought to mitigate adverse neurodevelopmental outcomes associated with preterm birth, but direct evidence of effects beyond hospital discharge is limited.What This Study addsIn this retrospective cohort study, frequency, amount, and duration of family-delivered Kangaroo Care in the NICU predicted cognitive abilities at 6 and 12 months. Kangaroo care may be a long-term neuroprotective clinical strategy for infants born preterm.

OBJECTIVESThe aim of this study was to investigate whether preterm infants whose families have lower socioeconomic status (SES) or communicate with clinical staff in a language other than English experience differences in the total amount, frequency, and duration of Kangaroo Care (KC) compared to preterm infants of higher SES or primarily English-speaking families.METHODSParticipants were infants born N=116. We defined family SES by the infants’ health insurance (private/higher vs. public/lower) and family language by the language mothers used to communicate with clinical staff (English vs. Other language). Family SES or family language groups were compared on: (1) the total amount of KC infants experienced during hospitalization; (2) frequency of KC per visitation days; and, (3) duration of KC events per day.RESULTSInfants in the lower SES and Other language groups experienced KC in reduced amounts, lower frequencies, and shorter durations than infants in either the higher SES or English language groups. SES and language group differences remained significant after controlling for family visitation and GA at birth. After controlling for SES, language group differences in KC duration remained significant.CONCLUSIONSOur findings revealed disparities in the total amount, frequency, and duration of KC in the neonatal intensive care unit as a function of both family SES and language families used to communicate with clinical staff. These disparities reduced infants’ access to this developmental care practice shown to stabilize clinical status and promote neurodevelopment. We recommend that hospital nurseries implement policies that minimize such disparities.Table of Contents SummaryTotal amount, frequency, and duration of Kangaroo Care for preterm infants in the NICU varied as a function of family’s socioeconomic status and language.What’s Known on This SubjectIn the United States, disparities in health care delivery and medical outcomes have been identified on the basis of patient or family socioeconomic status and the language patients or families use to communicate with clinical staff.What This Study AddsExtending to the NICU, the amount, frequency, and duration of Kangaroo Care experienced by preterm infants differed both by family’s socioeconomic status and the language families use to communicate with clinical staff. Policy changes are needed to reduce these disparities.Contributors’ Statement PageDr. Brignoni-Pérez conceptualized and designed the study, acquired data from the electronic medical record, analyzed the data, drafted the initial manuscript, and reviewed and revised the manuscript. Drs. Scala, Marchman, Feldman, and Travis conceptualized and designed the study, supervised data abstraction and analysis, and critically reviewed and revised the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

BackgroundPostnatal steroids are used to prevent bronchopulmonary dysplasia in extremely preterm infants but may have adverse effects on brain development. This study assessed variation in connectivity metrics of major white matter pathways in the cerebrum and cerebellum at near-term gestational age among infants who did or did not receive a standardized regimen of hydrocortisone during the first 10 days of life.MethodsRetrospective cohort study. Participants: Infants born < 28 weeks, divided into 2 groups: Protocol group had 50%-150% of the protocol, 0.5mg/kg hydrocortisone twice daily for 7 days, then 0.5 mg/kg per day for 3 days (n=33) versus Non-Protocol, (> 50% protocol dose, n=22). We assessed group differences in near-term diffusion MRI mean fractional anisotropy (FA) and mean diffusivity (MD) across the corticospinal tract, inferior longitudinal fasciculus, corpus callosum and superior cerebellar peduncle.ResultsGroups were well matched on gestational age, post-menstrual age at scan, medical complications, bronchopulmonary dysplasia, and necrotizing enterocolitis. No significant large-effect group differences were identified in mean FA or MD in any cerebral or cerebellar tract between the two groups.Conclusion(s)Low dose, early, postnatal hydrocortisone was not associated with significant differences in white matter tract microstructure at near term gestational age.Category of StudyClinicalImpactThis study compared brain microstructural connectivity as a primary outcome among extremely preterm infants who did or did not receive early postnatal hydrocortisone.Low dose hydrocortisone in the first 10 days of life was not associated with large differences in white matter microstructure in major cerebral and cerebellar pathwaysHydrocortisone did not have a significant effect on early brain white matter circuits.

Glucocorticoids (GC) are used in neonatal intensive care units to prevent or reduce the severity of chronic lung disease in preterm infants and have been implicated in impaired neurodevelopment. Our objective was to identify what is known about the effects of postnatal GC treatment in human preterm infants on structural brain development and to identify gaps in the literature. Following Arksey and O’Malley’s scoping review methodological framework, we searched scientific literature databases for original research on human preterm infants, postnatal GCs, and brain structure. 11 studies assessed the effects of GCs on structural brain outcomes. 56 studies reported brain injury, but not structure. Dexamethasone was consistently associated with decreased total and regional brain volumes, including cerebellar volumes. Hydrocortisone was often, but not always associated with absence of brain volume differences. No studies examined the impact of inhaled GC on brain structure. Additional research on the effects of neonatal GCs after preterm birth on a variety of structural brain measures is required for understanding contributions to neurodevelopment and informing practice guidelines.

Background Infants born very preterm ( Methods This randomized controlled trial assesses the long-term effects of increased maternal speech exposure on structural connectivity at 12 months of age (age adjusted for prematurity (AA)) and language outcomes between 12 and 18 months of age AA. Study participants (N = 42) will include infants born very preterm (24–31 weeks 6/7 days GA). Newborns are randomly assigned to the treatment (n = 21) or standard medical care (n = 21) group. Treatment consists of increased maternal speech exposure, accomplished by playing audio recordings of each baby’s own mother reading a children’s book via an iPod placed in their crib/incubator. Infants in the control group have the identical iPod setup but are not played recordings. The primary outcome will be measures of expressive and receptive language skills, obtained from a parent questionnaire collected at 12–18 months AA. The secondary outcome will be measures of white matter development, including the mean diffusivity and fractional anisotropy derived from diffusion magnetic resonance imaging scans performed at around 36 weeks postmenstrual age during the infants’ routine brain imaging session before hospital discharge and 12 months AA. Discussion The proposed study is expected to establish the potential impact of increased maternal speech exposure on long-term language outcomes and white matter development in infants born very preterm. If successful, the findings of this study may help to guide NICU clinical practice for promoting language and brain development. This clinical trial has the potential to advance theoretical understanding of how early language exposure directly changes brain structure for later language learning. Trial registration NIH Clinical Trials (ClinicalTrials.gov) NCT04193579. Retrospectively registered on 10 December 2019.

Brain development and aging are complex processes that unfold in multiple brain regions simultaneously. Recently, models of brain age prediction have aroused great interest, as these models can potentially help to understand neurological diseases and elucidate basic neurobiological mechanisms. We test whether quantitative magnetic resonance imaging can contribute to such age prediction models. Using R1, the longitudinal rate of relaxation, we explore lifespan dynamics in cortical gray matter. We compare R1 with cortical thickness, a well-established biomarker of brain development and aging. Using 160 healthy individuals (6–81 years old), we found that R1 and cortical thickness predicted age similarly, but the regions contributing to the prediction differed. Next, we characterized R1 development and aging dynamics. Compared with anterior regions, in posterior regions we found an earlier R1 peak but a steeper postpeak decline. We replicate these findings: firstly, we tested a subset (N = 10) of the original dataset for whom we had additional scans at a lower resolution; and second, we verified the results on an independent dataset (N = 34). Finally, we compared the age prediction models on a subset of 10 patients with multiple sclerosis. The patients are predicted older than their chronological age using R1 but not with cortical thickness.

Reading in children has been associated with microstructural properties of the cerebellar peduncles, the white matter pathways connecting the cerebellum to the cerebrum (Travis, Leitner, et al., 2015). In this study, we used two independent neuroimaging modalities to assess which features of the cerebellar peduncles would be associated with reading. Twenty-three 8-year-old children were evaluated on word reading efficiency and imaged using diffusion MRI (dMRI) and quantitative T1 relaxometry (qT1). We segmented the superior (SCP), middle, and inferior cerebellar peduncles and extracted two metrics: fractional anisotropy (FA) from dMRI and R1 from qT1. Tract-FA was significantly correlated with tract-R1 in left and right SCPs (left: r(P)(21) = .63, right: r(P)(21) = .76, p ≤ .001) suggesting that FA of these peduncles, at least in part, indexed myelin content. Tract-FA and tract R1 were not correlated in the other cerebellar peduncles. Reading efficiency negatively correlated with tract-FA of the left (r(P)(21) = −.43, p = .040) and right SCP (r(P)(21) = −.37, p = .079). Reading efficiency did not correlate with tract-R1 in the SCPs. The negative association of reading efficiency with tract-FA and the lack of association of reading efficiency with tract-R1 implicate properties other than myelin content as relevant to the information flow between the cerebellum and the cerebrum for individual differences in reading skills in children.

Objective: Quantify NICU speech exposure over multiple days in relation to NICU care practices. Methods: Continuous measures of speech exposure were obtained for preterm infants (n = 21;12 M) born 75% of care time reflecting Developmental Care. Speech counts were higher during care than no care, for mature vs. immature infants, and for infants in open cribs vs. incubators. Family participation in care ranged widely, with highest speech counts occurring during periods of intentional voice exposure. Conclusions: Care activities represent a small portion of NICU experiences. Speech exposure during Developmental Care, especially with intentional voice exposure, may be an important source of stimulation. Implications for care practices are discussed.

BackgroundChildren born very preterm (< 32 weeks gestational age), are at risk for poor growth and adverse neurodevelopmental outcomes. Poor outcomes in preterm children have been attributed to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant for neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU.ObjectiveExamine relations between the NICU speech environment and rate of weight gain during hospitalization, an important determinant of physical health and neurodevelopmental outcomes for preterm infants.MethodsParticipants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32-36 weeks postmenstrual age using a speech-counting device known as a Starling. Speech rates were averaged for each infant over the 4-week period. Average rates of weight gain (g/kg/day) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/day). Linear regressions examined associations between weight gain and both caloric intake and speech counts. Control analyses explored whether effects remained after controlling for family visitation, time in incubator, and health acuity.ResultsInfants who received more calories gained more weight, accounting for more than 30% of the variance. Importantly, speech counts accounted for nearly 29% additional variance (p < .001). These effects were not reduced when controlling for family visitation, time in incubator, or health acuity.ConclusionsEnhancing speech exposure in the NICU may be beneficial for physical growth. NICU infant care plans should consider opportunities to increase speech exposure.

Accumulating evidence suggests that the role of cerebellum includes regulation of behaviors; Cerebellar impairment may lead to behavioral problems. Behavioral problems differ by sex: internalizing problems are more common in girls, externalizing problems in boys. Behavioral problems are also elevated in children born preterm (PT) compared to children born full-term (FT). The current study examined internalizing and externalizing problems in 8-year-old children in relation to sex, birth-group, FA of the cerebellar peduncles, and interactions among these predictor variables. Participants (N=78) were 44 boys (28 PT) and 34 girls (15 PT). We assessed behavioral problems via standardized parent-reports and FA of the cerebellar peduncles using deterministic tractography. Internalizing problems were higher in children born PT compared to children born FT (p=.032); the interaction of sex and birth-group was significant (p=.044). When considering the contribution of the mean-tract FA of cerebellar peduncles to behavioral problems, there was a significant interaction of sex and mean-tract FA of the ICP with internalizing problems; the slope was negative in girls (p=.020) but not boys. In boys, internalizing problems were only associated with mean-tract FA ICP in those born preterm (p=.010). We found no other significant associations contributing to internalizing or externalizing problems. Thus, we found sexual dimorphism and birth-group differences in the association of white matter metrics of the ICP and internalizing problems in school-aged children. The findings inform theories of the origins of internalizing behavioral problems in middle childhood and may suggest approaches to treatment at school age.

A SummaryWe assessed the contribution of total behavioral problems at 6 years to text reading skills at 8 years in children born term and preterm. Birth group moderated associations among total behavioral problems and reading skills; total behavioral problems predicted reading skills in the term but not preterm group.

Diffusion magnetic resonance imaging (dMRI) studies find differences in associations between reading and white matter fractional anisotropy (FA) in children born full term (FT) versus preterm (PT). Use of complementary neuroimaging modalities may reveal neurobiological factors driving these associations. We used two MRI methods to interpret associations of reading abilities and white matter properties in FT and PT children. Participants (N=79: 36 FT and 43 PT) were administered the Gray’s Oral Reading Test at age 8 years. We segmented two dorsal and two ventral white matter tracts associated with reading abilities and quantified (1) FA from dMRI and (2) R1 from quantitative relaxometry, as a proxy for myelin content. We examined correlations between reading scores and neuroimaging metrics, assessing trajectories along the tracts. Mean reading scores fell in the typical range in both groups. Reading positively correlated with FA in segments of the left arcuate and the left and right superior longitudinal fasciculi in FT children, but not in PT children. Reading positively correlated with R1 in segments of the left superior longitudinal, right uncinate, and left inferior longitudinal fasciculi in PT children, but not in FT children. The significantly different patterns of associations between reading abilities and white matter properties across FT and PT groups suggest variations in the neurobiology of typical 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

AIMChildren born preterm (PT) experience perinatal white matter injury and later reading deficits at school age. We used two complementary neuroimaging modalities to determine if reading skills would be associated with contemporaneous white matter properties in school-aged PT children.METHODIn 8-year-old PT children (N=29), we measured diffusivity (fractional anisotropy, FA), from diffusion MRI, and myelin content (relaxation rate, R1) from quantitative relaxometry. We assessed reading (Gray’s Oral Reading Test, Fifth Edition) in each child. Whole-brain deterministic tractography coupled with automatic segmentation and quantification were applied to extract FA and R1 along four tracts and assess their statistical association with reading scores.RESULTSReading-FA correlations were not significant along the four analyzed tracts. Reading-R1 correlations were significantly positive in portions of the left superior longitudinal fasciculus, right uncinate fasciculus, and left inferior longitudinal fasciculus. FA positively correlated with R1 in limited areas of reading-R1 associations, but did not contribute to the variance in reading scores.INTERPRETATIONCombining complementary neuroimaging approaches identified relations between reading and white matter properties not found using a single MRI measure. Associations of reading skills and white matter properties may vary across white matter tracts and metrics in PT children.What this paper adds▪Preterm children’s reading was associated with white matter myelin content.▪Preterm children’s reading was not associated with white matter diffusivity.

ObjectivesTo assess the impact of the COVID-19 pandemic on rates of hospital visitation and rates and durations of developmental care practices for infants born preterm delivered by both families and clinical staff.MethodsWe analyzed electronic medical record data from infants born at less than 32 weeks gestational age (GA) cared for in the Lucile Packard Children’s Hospital neonatal intensive care unit (NICU) in a COVID-19-affected period (March 8, 2020 to May 31, 2020) and the analogous period in 2019. Our final sample consisted of 52 infants (n=27, 2019 cohort; n=25, 2020 cohort). Rates of family visitation and of family- and clinical staff-delivered developmental care were compared across cohorts, adjusting for GA at start of study period.ResultsResults indicated that families of infants in the 2020 cohort visited less frequently (47% of available days) than those in the 2019 cohort (97%; p=0.001). Infants received developmental care activities less frequently in the 2020 cohort (3.51 vs. 4.72 activities per day; p=0.04), with a lower number of minutes per day (99.91 vs. 145.14; p=0.04) and a shorter duration per instance (23.41 vs. 29.65; p=0.03). Similar reductions occurred in both family- and staff-delivered developmental care activities.ConclusionsThe COVID-19 pandemic has negatively impacted family visitation and preterm infant developmental care practices in the NICU, both experiences associated with positive health benefits. Hospitals should create programs to improve family visitation and engagement, while also increasing staff-delivered developmental care. Careful attention should be paid to long-term follow up of preterm infants and families.

Cerebellum-cerebrum connections are essential for many motor and cognitive functions and cerebellar disorders are prevalent in childhood. The middle (MCP), inferior (ICP), and superior cerebellar peduncles (SCP) are the major white matter pathways that permit communication between the cerebellum and the cerebrum. Knowledge about the microstructural properties of these cerebellar peduncles across childhood is limited. Here, we report on a diffusion magnetic resonance imaging tractography study to describe age-dependent characteristics of the cerebellar peduncles in a cross-sectional sample of infants, children, and adolescents from newborn to 17 years of age (N = 113). Scans were collected as part of clinical care; participants were restricted to those whose scans showed no abnormal findings and whose history and exam had no risk factors for cerebellar abnormalities. A novel automated tractography protocol was applied. Results showed that mean tract-FA increased, while mean tract-MD decreased from infancy to adolescence in all peduncles. Rapid changes were observed in both diffusion measures in the first 24 months of life, followed by gradual change at older ages. The shape of the tract profiles was similar across ages for all peduncles. These data are the first to characterize the variability of diffusion properties both across and within cerebellar white matter pathways that occur from birth through later adolescence. The data represent a rich normative data set against which white matter alterations seen in children with posterior fossa conditions can be compared. Ultimately, the data will facilitate the identification of sensitive biomarkers of cerebellar abnormalities.

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., Aim To determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications. Method 30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development–III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes. Results FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post-menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract. Conclusion Language at age 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

Slipped capital femoral epiphysis (SCFE) is a commonly encountered hip disorder. The goal of this study was to describe the incidence of missed contra-lateral SCFE as well as to identify risk factors. The authors hypothesized that contralateral slips are more often missed in patients with severe involvement of the treated side. After institutional review board approval was obtained, a retrospective chart review was performed of all pediatric patients who were treated for sequential and bilateral SCFE at a single institution during an 18-year period. Medical records were reviewed for demographic features and attending surgeon. Radiographs were reviewed for skeletal maturity, Klein's line, and severity of the treated slip. All radiographs were reviewed by 3 pediatric orthopedists. Contralateral SCFE was deemed present when consensus was achieved. Comparisons were made with Fisher's exact test, and P P =.0065). A contralateral slip was more likely to be present in patients who had a positive finding for Klein's line ( P Orthopedics . 2020;43(2):e114–e118.]

AIM To assess associations between white matter properties and pre-reading skills (phonological awareness and receptive and expressive language) in children born preterm and at term at the onset of reading acquisition. METHOD Six-year-old children born preterm (n=36; gestational age 22-32wks) and at term (n=43) underwent diffusion magnetic resonance imaging and behavioural assessments. Tracts were selected a priori based on findings from a study of 6-year-old children born at term: the left-hemisphere arcuate fasciculus and superior longitudinal fasciculus, and right-hemisphere uncinate fasciculus. Using linear regression, we assessed associations between fractional anisotropy of tracts and phonological awareness and receptive and expressive language scores. We investigated whether associations were moderated by prematurity. RESULTS Fractional anisotropy of the left-hemisphere arcuate fasciculus contributed unique variance to phonological awareness across birth groups. The association between fractional anisotropy of the right-hemisphere uncinate fasciculus and receptive and expressive language was significantly moderated by prematurity. INTERPRETATION A left-hemisphere tract was associated with phonological awareness in both birth groups. A right-hemisphere tract was associated with language only in the term group, suggesting that expressive and receptive language is mediated by different white matter pathways in 6-year-old children born preterm. These findings provide novel insights into similarities and differences of the neurobiology of pre-reading skills between children born preterm and at term at reading onset. WHAT THIS PAPER ADDS White matter properties and pre-reading abilities were associated in children born preterm at the onset of reading. The neurobiology of phonological awareness was similar in children born preterm versus children born at term at 6 years. The neurobiology of language was different in children born preterm versus children born at term at 6 years.

Objectives To assess the impact of the COVID-19 pandemic on rates of hospital visitation and rates and durations of developmental care practices for infants born preterm. Methods We analyzed electronic medical record data from 129 infants born at less than 32 weeks gestational age (GA) cared for in the Lucile Packard Children's Hospital neonatal intensive care unit (NICU) in a COVID-19-affected period (March 8, 2020 to Nov 30, 2020, n = 67) and the analogous period in 2019 (n = 62). Rates of family visitation and of family- and clinical staff-delivered developmental care were compared across cohorts, adjusting for covariates. Results Families of infants visited the hospital at nearly half of the rate during 2020 as during 2019 (p = 0.001). Infants experienced developmental care less frequently in 2020 vs. 2019 (3.0 vs. 4.3 activities per day; p = 0.001), resulting in fewer minutes per day (77.5 vs. 130.0; p = 0.001). In 2020, developmental care activities were 5 min shorter, on average, than in 2019, p = 0.001. Similar reductions occurred in both family- and staff-delivered developmental care. Follow-up analyses indicated that effects persisted and even worsened as the pandemic continued through fall 2020, despite relaxation of hospital visitation policies. Conclusions The COVID-19 pandemic has negatively impacted family visitation and preterm infant developmental care practices in the NICU, both experiences associated with positive health benefits. Hospitals should create programs to improve family visitation and engagement, while also increasing staff-delivered developmental care. Careful attention should be paid to long-term follow up of preterm infants and families.

AimTo determine whether variability in diffusion MRI (dMRI) white matter tract metrics, obtained in a cohort of preterm infants prior to neonatal hospital discharge, would be associated with language outcomes at age 2 years, after consideration of age at scan and number of major neonatal complications. Method: 30 children, gestational age 28.9 (2.4) weeks, underwent dMRI at mean post menstrual age 36.4 (1.4) weeks and language assessment with the Bayley Scales of Infant Development–III at mean age 22.2 (1.7) months chronological age. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for 5 white matter tracts. Hierarchical linear regression assessed associations between tract FA, moderating variables, and language outcomes. Results: FA of the left inferior longitudinal fasciculus accounted for 17% (p = 0.03) of the variance in composite language and FA of the posterior corpus callosum accounted for 19% (p = 0.02) of the variance in composite language, beyond that accounted for by post menstrual age at scan and neonatal medical complications. The number of neonatal medical complications moderated the relationship between language and posterior corpus callosum FA but did not moderate the association in the other tract. Conclusion: Language at 2 is associated with white matter metrics in early infancy in preterm children. The different pattern of associations by fiber group may relate to the stage of brain maturation and/or the nature and timing of medical complications related to preterm birth. Future studies should replicate these findings with a larger sample size to assure reliability of the findings.

Aim We previously observed a complex pattern of differences in white matter (WM) microstructure between preterm-born (PT) and full-term-born (FT) children and adolescents age 9–17 years. The aim of this study was to determine if the same differences exist as early as age 6 years. Method We obtained diffusion MRI (dMRI) scans in children born PT at age 6 years (n = 20; 11 males) and FT (n = 38; 14 males), using two scanning protocols: 30 diffusion directions (b = 1000 s/mm2) and 96 diffusion directions (b = 2500 s/mm2). We used deterministic tractography and analyzed fractional anisotropy (FA) along bilateral cerebral WM pathways that demonstrated differences in the older sample. Results Compared to the FT group, the PT group showed (1) significantly decreased FA in the uncinate fasciculi and forceps major and (2) significantly increased FA in the right anterior thalamic radiation, inferior fronto-occipital fasciculi, and inferior longitudinal fasciculi. This pattern of group differences resembles findings in the previous study of older PT and FT participants. Group differences were similar across dMRI acquisition protocols. Interpretation The underlying neurobiology driving the pattern of PT-FT differences in FA is present as early as age 6 years. Generalization across dMRI acquisition protocols demonstrates the robustness of group differences in FA. Future studies will use quantitative neuroimaging techniques to understand the tissue properties that give rise to this consistent pattern of WM differences after PT birth., Highlights • White matter properties are different in preterm and full term children at age 6 years. • Complex PT-FT differences in fractional anisotropy resemble differences found at 9–17 years. • PT-FT differences in fractional anisotropy generalize across two dMRI protocols. • PT showed higher fractional anisotropy than FT in specific tracts.

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.

Objective We combined diffusion MRI (dMRI) with quantitative T1 (qT1) relaxometry in a sample of school-aged children born preterm and full term to determine whether reduced fractional anisotropy (FA) within the corpus callosum of the preterm group could be explained by a reduction in myelin content, as indexed by R1 (1/T1) from qT1 scans. Methods 8-year-old children born preterm (n = 29; GA 22–32 weeks) and full term (n = 24) underwent dMRI and qT1 scans. Four subdivisions of the corpus callosum were segmented in individual native space according to cortical projection zones (occipital, temporal, motor and anterior-frontal). Fractional anisotropy (FA) and R1 were quantified along the tract trajectory of each subdivision and compared across two birth groups. Results Compared to controls, preterm children demonstrated significantly decreased FA in 3 of 4 analyzed corpus callosum subdivisions (temporal, motor, and anterior frontal segments) and decreased R1 in only 2 of 4 corpus callosum subdivisions (temporal and motor segments). FA and RD were significantly associated with R1 within temporal but not anterior frontal subdivisions of the corpus callosum in the term group; RD correlated with R1 in the anterior subdivision in the preterm group only. Conclusions Myelin content, as indexed by R1, drives some but not all of the differences in white matter between preterm and term born children. Other factors, such as axonal diameter and directional coherence, likely contributed to FA differences in the anterior frontal segment of the corpus callosum that were not well explained by R1., Highlights • Reduced FA in 3 corpus callosum segments may relate to myelin or axonal factors. • Reduced R1 in PT children in 2 corpus callosum segments suggests reduced myelin. • Reduced R1 explains reduced FA in the posterior but not anterior corpus callosum. • Changes in myelin content explain some but not all white matter differences in PT.

This case series assesses white matter microstructure of the cerebellar peduncles in 4 adolescents born preterm with enlarged ventricles and reduced white matter volume in the cerebrum but no apparent injury to the cerebellum. Subjects (ages 12-17 years, gestational age 26-32 weeks, birth weight 825-2211 g) were compared to a normative sample of 19 full-term controls (9-17 years, mean gestational age 39 weeks, mean birth weight 3154 g). Tract profiles for each of the cerebellar peduncles were generated by calculating fractional anisotropy at 30 points along the central portion of each tract. One or more case subjects exhibited higher fractional anisotropy beyond the 90th percentile in the inferior, middle, and superior cerebellar peduncles. Findings demonstrate that differences in cerebellar white matter microstructure can be detected in the absence of macrostructural cerebellar abnormalities.

Intact development of cerebellar connectivity is essential for healthy neuromotor and neurocognitive development. To date, limited knowledge about the microstructural properties of the cerebellar peduncles, the major white matter tracts of the cerebellum, is available for children and adolescents. Such information would be useful as a comparison for studies of normal development, clinical conditions, or associations of cerebellar structures with cognitive and motor functions. The goal of the present study was to evaluate the variability in diffusion measures of the cerebellar peduncles within individuals and within a normative sample of healthy children. Participants were 19 healthy children and adolescents, aged 9-17 years, mean age 13.0 ± 2.3. We analyzed diffusion magnetic resonance imaging (dMRI) data with deterministic tractography. We generated tract profiles for each of the cerebellar peduncles by extracting four diffusion properties (fractional anisotropy (FA) and mean, radial, and axial diffusivity) at 30 equidistant points along each tract. We were able to identify the middle cerebellar peduncle and the bilateral inferior and superior cerebellar peduncles in all participants. The results showed that within each of the peduncles, the diffusion properties varied along the trajectory of the tracts. However, the tracts showed consistent patterns of variation across individuals; the coefficient of variation for FA across individual profiles was low (≤20%) for each tract. We observed no systematic variation of the diffusion properties with age. These cerebellar tract profiles of the cerebellar peduncles can serve as a reference for future studies of children across the age range and for children and adolescents with clinical conditions that affect the cerebellum.

Reading is a critical life skill in the modern world. The neural basis of reading incorporates a distributed network of cortical areas and their white matter connections. The cerebellum has also been implicated in reading and reading disabilities. However, little is known about the contribution of cerebellar white matter pathways to major component skills of reading. We used diffusion magnetic resonance imaging (dMRI) with tractography to identify the cerebellar peduncles in a group of 9–17 year old children and adolescents born full term (n=19) or preterm (n=26). In this cohort, no significant differences were found between fractional anisotropy (FA) measures of the peduncles in the preterm and full term groups. FA of the cerebellar peduncles correlated significantly with measures of decoding and reading comprehension in the combined sample of full term and preterm subjects. Correlations were negative in the superior and inferior cerebellar peduncles and positive in the middle cerebellar peduncle. Additional analyses revealed that full term and preterm groups demonstrated similar patterns of reading associations within the left SCP, MCP and left ICP. Partial correlation analyses showed that distinct sub-skills of reading were associated with FA in segments of different cerebellar peduncles. Overall, the present findings are the first to document associations of microstructure of the cerebellar peduncles and the component skills of reading.

Recently, our laboratory has shown that the neural mechanisms for encoding lexico-semantic information in adults operate functionally by 12-18 months of age within left frontotemporal cortices (Travis et al., 2011. Spatiotemporal neural dynamics of word understanding in 12- to 18-month-old-infants. Cereb Cortex. 8:1832-1839). However, there is minimal knowledge of the structural changes that occur within these and other cortical regions important for language development. To identify regional structural changes taking place during this important period in infant development, we examined age-related changes in tissue signal properties of gray matter (GM) and white matter (WM) intensity and contrast. T1-weighted surface-based measures were acquired from 12- to 19-month-old infants and analyzed using a general linear model. Significant age effects were observed for GM and WM intensity and contrast within bilateral inferior lateral and anterovental temporal regions, dorsomedial frontal, and superior parietal cortices. Region of interest (ROI) analyses revealed that GM and WM intensity and contrast significantly increased with age within the same left lateral temporal regions shown to generate lexico-semantic activity in infants and adults. These findings suggest that neurophysiological processes supporting linguistic and cognitive behaviors may develop before cellular and structural maturation is complete within associative cortices. These results have important implications for understanding the neurobiological mechanisms relating structural to functional brain development.

We combined magnetoencephalography (MEG) with magnetic resonance imaging and electrocorticography to separate in anatomy and latency 2 fundamental stages underlying speech comprehension. The first acoustic-phonetic stage is selective for words relative to control stimuli individually matched on acoustic properties. It begins ∼60 ms after stimulus onset and is localized to middle superior temporal cortex. It was replicated in another experiment, but is strongly dissociated from the response to tones in the same subjects. Within the same task, semantic priming of the same words by a related picture modulates cortical processing in a broader network, but this does not begin until ∼217 ms. The earlier onset of acoustic-phonetic processing compared with lexico-semantic modulation was significant in each individual subject. The MEG source estimates were confirmed with intracranial local field potential and high gamma power responses acquired in 2 additional subjects performing the same task. These recordings further identified sites within superior temporal cortex that responded only to the acoustic-phonetic contrast at short latencies, or the lexico-semantic at long. The independence of the early acoustic-phonetic response from semantic context suggests a limited role for lexical feedback in early speech perception.

Reading, an essential life skill in modern society, is typically learned during childhood. Adults who can read show white matter differences compared to adults who never learned to read. Studies have not established whether children who can read show similar white matter differences compared to children who cannot read. We compared 6-year old children who could decode written English words and pseudowords (n = 31; Readers) and 6-year old children who could not decode pseudowords and had a standard score

Premature birth is highly prevalent and associated with neurodevelopmental delays and disorders. Adverse outcomes, particularly in children born before 32 weeks of gestation, have been attributed in large part to white matter injuries, often found in periventricular regions using conventional imaging. To date, tractography studies of white matter pathways in children and adolescents born preterm have evaluated only a limited number of tracts simultaneously. The current study compares diffusion properties along 18 major cerebral white matter pathways in children and adolescents born preterm (n = 27) and full term (n = 19), using diffusion magnetic resonance imaging and tractography. We found that compared to the full term group, the preterm group had significantly decreased FA in segments of the bilateral uncinate fasciculus and anterior segments of the right inferior fronto-occipital fasciculus. Additionally, the preterm group had significantly increased FA in segments of the right and left anterior thalamic radiations, posterior segments of the right inferior fronto-occipital fasciculus, and the right and left inferior longitudinal fasciculus. Increased FA in the preterm group was generally associated with decreased radial diffusivity. These findings indicate that prematurity-related white matter differences in later childhood and adolescence do not affect all tracts in the periventricular zone and can involve both decreased and increased FA. Differences in the patterns of radial diffusivity and axial diffusivity suggest that the tissue properties underlying group FA differences may vary within and across white matter tracts. Distinctive diffusion properties may relate to variations in the timing of injury in the neonatal period, extent of white matter dysmaturity and/or compensatory processes in childhood.

Congenitally deaf individuals receive little or no auditory input, and when raised by deaf parents, they acquire sign as their native and primary language. We asked two questions regarding how the deaf brain in humans adapts to sensory deprivation: (1) Is meaning extracted and integrated from signs using the same classical left hemisphere fronto-temporal network used for speech in hearing individuals, and (2) in deafness, is superior temporal cortex encompassing primary and secondary auditory regions reorganized to receive and process visual sensory information at short latencies? Using magnetoencephalography (MEG) constrained by individual cortical anatomy obtained with magnetic resonance imaging (MRI), we examined an early time window associated with sensory processing and a late time window associated with lexico-semantic integration. We found that sign in deaf individuals and speech in hearing individuals activate a highly similar left fronto-temporal network (including superior temporal regions surrounding auditory cortex) during lexico-semantic processing, but only speech in hearing individuals activates auditory regions during sensory processing. Thus, neural systems dedicated to processing high-level linguistic information are utilized for processing language regardless of modality or hearing status, and we do not find evidence for re-wiring of afferent connections from visual systems to auditory cortex.

Learning words is central in human development. However, lacking clear evidence for how or where language is processed in the developing brain, it is unknown whether these processes are similar in infants and adults. Here, we use magnetoencephalography in combination with high-resolution structural magnetic resonance imaging to noninvasively estimate the spatiotemporal distribution of word-selective brain activity in 12- to 18-month-old infants. Infants watched pictures of common objects and listened to words that they understood. A subset of these infants also listened to familiar words compared with sensory control sounds. In both experiments, words evoked a characteristic event-related brain response peaking ~400 ms after word onset, which localized to left frontotemporal cortices. In adults, this activity, termed the N400m, is associated with lexico-semantic encoding. Like adults, we find that the amplitude of the infant N400m is also modulated by semantic priming, being reduced to words preceded by a semantically related picture. These findings suggest that similar left frontotemporal areas are used for encoding lexico-semantic information throughout the life span, from the earliest stages of word learning. Furthermore, this ontogenetic consistency implies that the neurophysiological processes underlying the N400m may be important both for understanding already known words and for learning new words.

Bilingualism provides a unique opportunity for understanding the relative roles of proficiency and order of acquisition in determining how the brain represents language. In a previous study, we combined magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to examine the spatiotemporal dynamics of word processing in a group of Spanish-English bilinguals who were more proficient in their native language. We found that from the earliest stages of lexical processing, words in the second language evoke greater activity in bilateral posterior visual regions, while activity to the native language is largely confined to classical left hemisphere fronto-temporal areas. In the present study, we sought to examine whether these effects relate to language proficiency or order of language acquisition by testing Spanish-English bilingual subjects who had become dominant in their second language. Additionally, we wanted to determine whether activity in bilateral visual regions was related to the presentation of written words in our previous study, so we presented subjects with both written and auditory words. We found greater activity for the less proficient native language in bilateral posterior visual regions for both the visual and auditory modalities, which started during the earliest word encoding stages and continued through lexico-semantic processing. In classical left fronto-temporal regions, the two languages evoked similar activity. Therefore, it is the lack of proficiency rather than secondary acquisition order that determines the recruitment of non-classical areas for word processing. © 2011 Leonard et al.

The M-current (IM), comprised of Kv7 channels, is a voltage-activated K+conductance that plays a key role in the control of cell excitability. In hippocampal principal cells,IMcontrols action potential (AP) accommodation and contributes to the medium-duration afterhyperpolarization, but the role ofIMin control of interneuron excitability remains unclear. Here, we investigatedIMin hippocampal stratum oriens (SO) interneurons, both from wild-type and transgenic mice in which green fluorescent protein (GFP) was expressed in somatostatin-containing interneurons. Somatodendritic expression of Kv7.2 or Kv7.3 subunits was colocalized in a subset of GFP+ SO interneurons, corresponding to oriens-lacunosum moleculare (O-LM) cells. Under voltage clamp (VC) conditions at −30 mV, the Kv7 channel antagonists linopirdine/XE-991 abolished theIMamplitude present during relaxation from −30 to −50 mV and reduced the holding current (Ihold). In addition, 0.5 mmtetraethylammonium reducedIM, suggesting thatIMwas composed of Kv7.2-containing channels. In contrast, the Kv7 channel opener retigabine increasedIMamplitude andIhold. When strongly depolarized in VC, the linopirdine-sensitive outward current activated rapidly and comprised up to 20% of the total current. In current-clamp recordings from GFP+ SO cells, linopirdine induced depolarization and increased AP frequency, whereas retigabine induced hyperpolarization and arrested firing. In multicompartment O-LM interneuron models that incorporatedIM, somatodendritic placement of Kv7 channels best reproduced experimentally measuredIM. The models suggest that Kv3- and Kv7-mediated channels both rapidly activate during single APs; however, Kv3 channels control rapid repolarization of the AP, whereas Kv7 channels primarily control the interspike interval.

Knowledge of the neural basis of early language is limited because of the difficulties in assessing functional brain activity during infancy. Consequently, it is unclear whether infants and adults depend on similar underlying neural structures to understand words. Advances in magnetoencephalography combined with magnetic resonance imaging now make it possible to study this population. This method, dynamic statistical parametric mapping (dSPM), has been extensively validated during language processing in adults. Here, dSPM was used to examine the neural correlates of word understanding in 12–18 month old infants. Specifically, it was discovered that the lexico‐semantic neural processes indexed as the adult N400 event‐related component are functional during early stages of word learning and depend on similar left frontotemporal brain areas. These findings demonstrate that dSPM can be used to localize functional brain activity associated with language processes in pediatric populations. Moreover, discovery o...