Inpatient Skin-to-Skin Care Predicts 12-month Neurodevelopmental Outcomes in Very Preterm Infants.

Objective: Limited research links hospital-based experiences of skin-to-skin (STS) care to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient STS and neurodevelopmental scores measured at 12 months in a sample of very preterm (VPT) infants. Study Design and Methods: From a retrospective study review of medical records of 181 VPT infants (<32 weeks gestational age (GA)) we derived the STS rate, i.e., the total minutes of STS each infant received/day of hospital stay. We used scores on the Capute Scales from routine follow-up care at 12 months as the measure of neurodevelopmental outcome (n=181). Results: Families averaged approximately 17 minutes/day of STS care (2 days/week, 70 minutes/session), although there was substantial variability. Variation in STS rate was positively associated with outcomes at 12 months corrected age ( r = 0.25, p < .001). STS rate significantly predicted 6.2% unique variance in 12-month neurodevelopmental outcomes, after controlling for GA, socioeconomic status (SES), health acuity, and visitation frequency. A 20-minute increase in STS per day was associated with a 10-point increase (.67 SDs) in neurodevelopmental outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations. Conclusion: VPT infants who experienced more STS during hospitalization demonstrated higher scores on 12-month assessments of neurodevelopment. Results provide evidence that STS care may confer extended neuroprotection on VPT infants through the first year of life.

Gray matter volume differences between early bilinguals and monolinguals: A study of children and adults.

Gray matter has been shown to be greater in early bilingual adults relative to monolingual adults in regions associated with language (Mechelli et al., 2004), and executive control (EC; Olulade et al., 2016). It is not known, however, if language experience-dependent differences in gray matter volume (GMV) exist in children. Further, any such differences are likely not to be the same as those observed in early bilingual adults, as children have had relatively shorter duration of dual-language exposure and/or less development of brain regions serving EC. We tested these predictions by comparing GMV in Spanish-English early bilingual and English monolingual children, and Spanish-English early bilingual and English monolingual adults (n = 122). Comparing only children revealed relatively more GMV in the bilinguals in bilateral frontal, right inferior frontal, and right superior parietal cortices (regions associated with EC). Bilinguals, however, had less GMV in left inferior parietal cortex (region associated with language). An ANOVA including these children with bilingual and monolingual adults revealed interactions of Language Background by Age Group. There were no regions of more GMV in bilinguals relative to monolinguals that were less pronounced in children than adults, despite the children's shorter dual-language experience. There were relative differences between bilingual and monolingual children that were more pronounced than those in adults in left precentral gyrus and right superior parietal lobule (close to, but not directly in areas associated with EC). Together, early bilingual children manifest relative differences in GMV, and, surprisingly, these do not diverge much from those observed in studies of bilingual adults.

Functional neuroanatomy of English word reading in early bilingual and monolingual adults.

Skilled reading is important in daily life. While the understanding of the neurofunctional organization of this uniquely human skill has advanced significantly, it does not take into consideration the common bilingual experiences around the world. To examine the role of early bilingualism on the neural substrates supporting English word processing, we compared brain activity, as well as functional connectivity, in Spanish-English early bilingual adults (N = 25) and English monolingual adults (N = 33) during single-word processing. Activation analysis revealed no significant differences between the two groups. A seed-to-voxel analysis using eight a priori selected seed-regions (placed in regions known to be involved in reading) revealed relatively stronger functional connectivity in bilinguals between two sets of regions: left superior temporal gyrus seed positively with left lingual gyrus and left middle frontal gyrus seed negatively with left anterior cingulate cortex. Together these results suggest that an early Spanish-English bilingual experience does not modulate local brain activity for English word reading. It does, however, have some influence on the functional intercommunication between brain regions during reading, specifically in two regions associated with reading, which are functionally connected to those inside and outside of the reading network. We conclude that brain regions involved in processing English words are not that different in Spanish-English early bilingual adults relative to monolingual adult users of English.

White matter properties underlying reading abilities differ in 8-year-old children born full term and preterm: A multi-modal approach.

Many diffusion magnetic resonance imaging (dMRI) studies document associations between reading skills and fractional anisotropy (FA) within brain white matter, suggesting that efficient transfer of information across the brain contributes to individual differences in reading. Use of complementary imaging methods can determine if these associations relate to myelin content of white matter tracts. Compared to children born at term (FT), children born preterm (PT) are at risk for reading deficits. We used two MRI methods to calculate associations of reading 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. We segmented three dorsal (left arcuate and bilateral superior longitudinal fasciculus) and four ventral (bilateral inferior longitudinal fasciculus and bilateral uncinate) tracts and quantified (1) FA from dMRI and (2) R1 from quantitative T1 relaxometry. We examined correlations between reading scores and these metrics along the trajectories of the tracts. Reading positively correlated with FA in segments of left arcuate and bilateral superior longitudinal fasciculi in FT children; no FA associations were found 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; no R1 associations were found in FT children. Birth group significantly moderated the associations of reading and white matter metrics. Myelin content of white matter may contribute to individual differences in PT but not FT children.

Disparities in Kangaroo Care for Premature Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: The 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 rate, frequency, and duration of kangaroo care (KC) in the neonatal intensive care unit (NICU) compared with preterm infants of higher SES or primarily English-speaking families. METHODS: Participants were infants born <32 weeks' gestational age (GA), N = 116. We defined SES by the infants' health insurance (private/higher vs public/lower) and language by the language mothers used to communicate with clinical staff (English vs Other language). SES or language groups were compared on (1) rate of KC infants experienced during hospitalization per visitation days, (2) frequency of KC per visitation days, and (3) duration of KC events per day. RESULTS: Infants 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. CONCLUSION: Our findings revealed disparities in the rate, frequency, and duration of KC experienced in the NICU as a function of both SES and language. Such 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 these disparities.

Impact of the COVID-19 pandemic on developmental care practices for infants born preterm.

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.

Listening to Mom in the NICU: effects of increased maternal speech exposure on language outcomes and white matter development in infants born very preterm.

BACKGROUND: Infants born very preterm (< 32 weeks gestational age (GA)) are at risk for developmental language delays. Poor language outcomes in children born preterm have been linked to neurobiological factors, including impaired development of the brain's structural connectivity (white matter), and environmental factors, including decreased exposure to maternal speech in the neonatal intensive care unit (NICU). Interventions that enhance preterm infants' exposure to maternal speech show promise as potential strategies for improving short-term health outcomes. Intervention studies have yet to establish whether increased exposure to maternal speech in the NICU offers benefits beyond the newborn period for brain and language outcomes. 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.

Functional neuroanatomy of arithmetic in monolingual and bilingual adults and children.

Prior studies on the brain bases of arithmetic have not focused on (or even described) their participants' language backgrounds. Yet, unlike monolinguals, early bilinguals have the capacity to solve arithmetic problems in both of their two languages. This raises the question whether this ability, or any other experience that comes with being bilingual, affects brain activity for arithmetic in bilinguals relative to monolinguals. Here, we used functional magnetic resonance imaging to compare brain activity in 44 English monolinguals and 44 Spanish-English early bilinguals, during the solving of arithmetic problems in English. We used a factorial design to test for a main effect of bilingual Language Experience. Based on the known modulating roles of arithmetic operation and age, we used two arithmetic tasks (addition and subtraction) and studied two age groups (adults and children). When collapsing across operations and age, we found broad bilateral activation for arithmetic in both the monolingual group and the bilingual group. However, an analysis of variance revealed that there was no effect of Language Experience, nor an interaction of Language Experience with Operation or Age Group. Bayesian analyses within regions of interest chosen for their role in arithmetic further supported the finding of no effect of Language Experience on brain activity underlying arithmetic. We conclude that early bilingualism does not influence the functional neuroanatomy of simple arithmetic.

Impact of the COVID-19 pandemic on developmental care practices for infants born preterm.

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 delivered by both families and clinical staff. METHODS: We 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. RESULTS: Results 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. 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.

An fMRI study of English and Spanish word reading in bilingual adults.

Reading relies on a left-lateralized brain system, including occipito-temporal (OTC), temporo-parietal, and inferior frontal (IFC) cortices. Neuroimaging studies have investigated whether activation in these cortices is modulated by a language's orthographic depth (consistency of grapheme-to-phoneme conversion). In Spanish-English bilinguals, some but not all studies have reported activation differences between the two languages during reading. Here, we studied Spanish-English early bilingual adults living in the United States (N = 25; 17 females, 8 males). We examined local activity, functional connectivity, and spatially distributed activity patterns during English and Spanish word reading. We found overlap in local activity for the two languages in the left IFC, but no differences in activation between them and few differences in functional connectivity (none of which were in pairs of regions known to be involved in reading); yet, there were spatially distributed patterns of brain activity that differentiate English and Spanish in regions of bilateral cerebellum/left OTC, the left superior occipital gyrus, the left IFC, and the left medial frontal gyrus. Overall, we found no evidence for differences in local activation or functional connectivity during English versus Spanish word processing in regions known to be involved in reading, yet we found brain-based evidence that Spanish-English bilinguals distinguish between the two languages.

Neural structures mediating expression and extinction of platform-mediated avoidance.

Individuals use both passive and active defensive responses to environmental threats. Much is known about the neural circuits of passive defensive responses (e.g., freezing), but less is known about the substrates of active defensive responses (e.g., avoidance). We developed an active avoidance task in which rats learn to avoid a tone-signaled footshock by stepping onto a nearby platform. An advantage of this task is that freezing, which can interfere with avoidance, is reduced, thereby facilitating comparison of the effects of manipulations on avoidance versus freezing. After 10 d of avoidance training, rats were infused with muscimol to pharmacologically inactivate the prelimbic cortex (PL), infralimbic cortex (IL), ventral striatum (VS), or basolateral amygdala (BLA). Inactivating PL, VS, or BLA all impaired avoidance expression, but these areas differed with respect to freezing. Inactivating BLA decreased freezing consistent with loss of the tone-shock association, whereas inactivation of VS increased freezing consistent with loss of avoidance memory. Inactivation of PL had no effect on freezing. Inactivation of IL did not impair avoidance expression but did impair avoidance extinction. Our findings suggest that active avoidance is mediated by prefrontal-striatal circuits, which may be overactive in individuals suffering from trauma-related disorders.

Acute stress impairs the retrieval of extinction memory in humans.

Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays a critical role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent work in rodents has demonstrated that exposure to stress leads to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress response, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, a day later participants in the stress group (n=27) demonstrated significantly lower extinction retrieval (i.e., greater fear recovery) than those in the control group (n=25). Our results suggest that acute stress impairs the retrieval of extinction learning and offers insight into why treatment strategies used in the clinic may be challenging to recruit in daily life where stress is pervasive.