Growth in early infancy drives optimal brain functional connectivity which predicts cognitive flexibility in later childhood.

Functional brain network organization, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, e.g. undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onward. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5 to 24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive flexibility at pre-school age. In contrast to previously studied developmental populations, this Gambian sample exhibited long-range interhemispheric FC that decreased with age. Our results highlight the measurable effects that poor growth in early infancy has on brain development and the subsequent impact on pre-school age cognitive development, underscoring the need for early life interventions throughout global settings of adversity.

It takes a village: Caregiver diversity and language contingency in the UK and rural Gambia.

INTRODUCTION: There is substantial diversity within and between contexts globally in caregiving practices and family composition, which may have implications for the early interaction's infants engage in. We draw on data from the Brain Imaging for Global Health (BRIGHT, www.globalfnirs.org/the-bright-project) project, which longitudinally examined infants in the UK and in rural Gambia, West Africa. In The Gambia, households are commonly characterized by multigenerational, frequently polygamous family structures, which, in part, is reflected in the diversity of caregivers a child spends time with. In this paper, we aim to 1) evaluate and validate the Language Environment Analysis (LENA) for use in the Mandinka speaking families in The Gambia, 2) examine the nature (i.e., prevalence of turn taking) and amount (i.e., adult and child vocalizations) of conversation that infants are exposed to from 12 to 24 months of age and 3) investigate the link between caregiver diversity and child language outcomes, examining the mediating role of contingent turn taking. METHOD: We obtained naturalistic seven-hour-long LENA recordings at 12, 18 and 24 months of age from a cohort of N = 204 infants from Mandinka speaking households in The Gambia and N = 61 infants in the UK. We examined developmental changes and site differences in LENA counts of adult word counts (AWC), contingent turn taking (CTT) and child vocalizations (CVC). In the larger and more heterogenous Gambian sample, we also investigated caregiver predictors of turn taking frequency. We hereby examined the number of caregivers present over the recording day and the consistency of caregivers across two subsequent days per age point. We controlled for children's cognitive development via the Mullen Scales of Early Learning (MSEL). RESULTS: Our LENA validation showed high internal consistency between the human coders and automated LENA outputs (Cronbach's alpha's all >.8). All LENA counts were higher in the UK compared to the Gambian cohort. In The Gambia, controlling for overall neurodevelopment via the MSEL, CTT at 12 and 18 months predicted CVC at 18 and 24 months. Caregiver consistency was associated with CTT counts at 18 and 24 months. The number of caregivers and CTT counts showed an inverted u-shape relationship at 18 and 24 months, with an intermediate number of caregivers being associated with the highest CTT frequencies. Mediation analyses showed a partial mediation by number of caregivers and CTT and 24-month CVC. DISCUSSION: The LENA provided reliable estimates for the Mandinka language in the home recording context. We showed that turn taking is associated with subsequent child vocalizations and explored contextual caregiving factors contributing to turn taking in the Gambian cohort.

Iron status in early infancy is associated with trajectories of cognitive development up to pre-school age in rural Gambia.

INTRODUCTION: Iron deficiency is among the leading risk factors for poor cognitive development. However, interventions targeting iron deficiency have had mixed results on cognitive outcomes. This may be due to previous interventions focusing on the correction of iron deficiency anaemia in late infancy and early childhood, at which point long lasting neural impacts may already be established. We hypothesise that the relationship between iron status and cognitive development will be observable in the first months of life and will not be recovered by 5 years of age. METHODS: Using data from the Brain Imaging for Global Health (BRIGHT) Study in Gambia (n = 179), we conducted mixed effects modelling to assess the relationship between iron status at 5 months of age and trajectories of cognitive development from 5 months- 5 years using (i) a standardised measure of cognitive development (Mullen Scales of Early Learning) and (ii) an eye-tracking assessment of attention processing (visual disengagement time). RESULTS: All infants were iron sufficient at 1 month of age. At 5 and 12 months of age 30% and 55% of infants were iron deficient respectively. In fully adjusted analyses, infants in the lowest tercile of soluble transferrin receptor (sTfR) (best iron status) achieved MSEL Cognitive Scores on average 1.9 points higher than infants in the highest sTfR tercile (p = 0.009, effect size = 0.48). There was no evidence that this group difference was recovered by 5 years of age. Infants in the lowest sTfR tercile had visual disengagement time 57ms faster than the highest tercile (p = 0.001, effect size = 0.59). However, this difference diminished by early childhood (p = 0.024). CONCLUSION: Infants are at risk of iron deficiency in early infancy. A relationship between iron status and cognitive development is apparent from 5 months of age and remains observable at 5 years of age. One mechanism by which iron availability in early infancy impacts brain development may be through effects on early attentional processing, which is rapidly developing and has substantial nutritional requirements during this period. To support neurocognitive development, prevention of iron deficiency in pre- and early postnatal life may be more effective than correcting iron deficiency once already established.

Executive functioning skills and their environmental predictors among pre-school aged children in South Africa and The Gambia.

Executive functions (EFs) in early childhood are predictors of later developmental outcomes and school readiness. Much of the research on EFs and their psychosocial correlates has been conducted in high-income, minority world countries, which represent a small and biased portion of children globally. The aim of this study is to examine EFs among children aged 3-5 years in two African countries, South Africa (SA) and The Gambia (GM), and to explore shared and distinct predictors of EFs in these settings. The SA sample (N = 243, 51.9% female) was recruited from low-income communities within the Cape Town Metropolitan area. In GM, participants (N = 171, 49.7% female) were recruited from the rural West Kiang region. EFs, working memory (WM), inhibitory control (IC) and cognitive flexibility (CF), were measured using tablet-based tasks. Associations between EF task performance and indicators of socioeconomic status (household assets, caregiver education) and family enrichment factors (enrichment activities, diversity of caregivers) were assessed. Participants in SA scored higher on all EF tasks, but children in both sites predominantly scored within the expected range for their age. There were no associations between EFs and household or familial variables in SA, except for a trend-level association between caregiver education and CF. Patterns were similar in GM, where there was a trend-level association between WM and enrichment activities but no other relationships. We challenge the postulation that children in low-income settings have poorer EFs, simply due to lower socioeconomic status, but highlight the need to identify predictors of EFs in diverse, global settings. RESEARCH HIGHLIGHTS: Assessed Executive Functioning (EF) skills and their psychosocial predictors among pre-school aged children (aged 3-5 years) in two African settings (The Gambia and South Africa). On average, children within each setting performed within the expected range for their age, although children in South Africa had higher scores across tasks. There was little evidence of any association between socioeconomic variables and EFs in either site. Enrichment activities were marginally associated with better working memory in The Gambia, and caregiver education with cognitive flexibility in South Africa, both associations were trend-level significance.

Neural Marker of Habituation at 5 Months of Age Associated with Deferred Imitation Performance at 12 Months: A Longitudinal Study in the UK and The Gambia.

Across cultures, imitation provides a crucial route to learning during infancy. However, neural predictors which would enable early identification of infants at risk of suboptimal developmental outcomes are still rare. In this paper, we examine associations between ERP markers of habituation and novelty detection measured at 1 and 5 months of infant age in the UK (n = 61) and rural Gambia (n = 214) and infants' responses on a deferred imitation task at 8 and 12 months. In both cohorts, habituation responses at 5 months significantly predicted deferred imitation responses at 12 months of age in both cohorts. Furthermore, ERP habituation responses explained a unique proportion of variance in deferred imitation scores which could not be accounted for by a neurobehavioural measure (Mullen Scales of Early Learning) conducted at 5 months of age. Our findings highlight the potential for ERP markers of habituation and novelty detection measured before 6 months of age to provide insight into later imitation abilities and memory development across diverse settings.

Increased rates of dispersal of free-ranging cane toads (Rhinella marina) during their global invasion.

Invasions often accelerate through time, as dispersal-enhancing traits accumulate at the expanding range edge. How does the dispersal behaviour of individual organisms shift to increase rates of population spread? We collate data from 44 radio-tracking studies (in total, of 650 animals) of cane toads (Rhinella marina) to quantify distances moved per day, and the frequency of displacement in their native range (French Guiana) and two invaded areas (Hawai'i and Australia). We show that toads in their native-range, Hawai'i and eastern Australia are relatively sedentary, while toads dispersing across tropical Australia increased their daily distances travelled from 20 to 200 m per day. That increase reflects an increasing propensity to change diurnal retreat sites every day, as well as to move further during each nocturnal displacement. Daily changes in retreat site evolved earlier than did changes in distances moved per night, indicating a breakdown in philopatry before other movement behaviours were optimised to maximise dispersal.

Breast Milk Micronutrients and Infant Neurodevelopmental Outcomes: A Systematic Review.

Micronutrients are fundamental for healthy brain development and deficiencies during early development can have a severe and lasting impact on cognitive outcomes. Evidence indicates that undernourished lactating individuals may produce breast milk containing lower concentrations of certain vitamins and minerals. Exclusively breastfed infants born to mothers deficient in micronutrients may therefore be at risk of micronutrient deficiencies, with potential implications for neurodevelopment. This systematic review aims to consider current knowledge on the effects of breast milk micronutrients on the developmental outcomes of infants. The databases Medline, Global Health, PsychInfo, Open Grey, and the Web of Science were searched for papers published before February 2021. Studies were included if they measured micronutrients in breast milk and their association with the neurodevelopmental outcomes of exclusively breastfed infants. Also, randomised control trials investigating neurocognitive outcomes following maternal supplementation during lactation were sought. From 5477 initial results, three observational studies were eligible for inclusion. These investigated associations between breast milk levels of vitamin B6, carotenoids, or selenium and infant development. Results presented suggest that pyroxidal, ß-carotene, and lycopene are associated with infant neurodevelopmental outcomes. Limited eligible literature and heterogeneity between included papers prevented quantitative synthesis. Insufficient evidence was identified, precluding any conclusions on the relationship between breast milk micronutrients and infant developmental outcomes. Further, the evidence available was limited by a high risk of bias. This highlights the need for further research in this area to understand the long-term influence of micronutrients in breast milk, the role of other breast milk micronutrients in infant neurodevelopmental outcomes, and the impact of possible lactational interventions.

Longitudinal infant fNIRS channel-space analyses are robust to variability parameters at the group-level: An image reconstruction investigation.

The first 1000 days from conception to two-years of age are a critical period in brain development, and there is an increasing drive for developing technologies to help advance our understanding of neurodevelopmental processes during this time. Functional near-infrared spectroscopy (fNIRS) has enabled longitudinal infant brain function to be studied in a multitude of settings. Conventional fNIRS analyses tend to occur in the channel-space, where data from equivalent channels across individuals are combined, which implicitly assumes that head size and source-detector positions (i.e. array position) on the scalp are constant across individuals. The validity of such assumptions in longitudinal infant fNIRS analyses, where head growth is most rapid, has not previously been investigated. We employed an image reconstruction approach to analyse fNIRS data collected from a longitudinal cohort of infants in The Gambia aged 5- to 12-months. This enabled us to investigate the effect of variability in both head size and array position on the anatomical and statistical inferences drawn from the data at both the group- and the individual-level. We also sought to investigate the impact of group size on inferences drawn from the data. We found that variability in array position was the driving factor between differing inferences drawn from the data at both the individual- and group-level, but its effect was weakened as group size increased towards the full cohort size (N = 53 at 5-months, N = 40 at 8-months and N = 45 at 12-months). We conclude that, at the group sizes in our dataset, group-level channel-space analysis of longitudinal infant fNIRS data is robust to assumptions about head size and array position given the variability in these parameters in our dataset. These findings support a more widespread use of image reconstruction techniques in longitudinal infant fNIRS studies.

Field trials of chemical suppression of embryonic cane toads (Rhinella marina) by older conspecifics.

Laboratory experiments have shown that the viability of embryos of the invasive cane toad (Rhinella marina) can be reduced by exposure to chemical cues from older conspecific larvae. These effects (very strong in laboratory trials) may offer an exciting new approach to controlling this problematic invasive species in Australia. However, the degree to which the method works in natural environments has yet to be assessed.Our experiments in the laboratory and in seminatural outdoor waterbodies show that chemical cues from tadpoles do indeed suppress the growth, development, and survival of conspecific larvae that are exposed as embryos and do so in a dose-dependent manner; higher tadpole densities cause greater suppression of embryos.In seminatural outdoor waterbodies, suppressor-exposed tadpoles were less than half as likely to survive to metamorphosis as were controls, and were much smaller when they did so and hence, less likely to survive the metamorph stage. Additionally, female cane toads were less likely to oviposit in a waterbody containing free-ranging (but not cage-enclosed) tadpoles, suggesting that the presence of tadpoles (rather than the chemical cues they produce) may discourage oviposition.Broadly, our results suggest that the suppression effect documented in laboratory studies does indeed occur in the field also, and hence that we may be able to translate that approach to develop new and more effective ways to reduce rates of recruitment of peri-urban populations of cane toads in their invasive range.

The Role of Iron in Brain Development: A Systematic Review.

One-third of children falter in cognitive development by pre-school age. Iron plays an important role in many neurodevelopmental processes, and animal studies suggest that iron sufficiency in pregnancy and infancy is particularly important for neurodevelopment. However, it is not clear whether iron deficiency directly impacts developmental outcomes, and, if so, whether impact differs by timing of exposure or developmental domain. We searched four databases for studies on iron deficiency or iron supplementation in pregnancy, or at 0-6 months, 6-24 months, or 2-4 years of age. All studies included neurodevelopmental assessments in infants or children up to 4 years old. We then qualitatively synthesized the literature. There was no clear relationship between iron status and developmental outcomes across any of the time windows or domains included. We identified a large quantity of low-quality studies, significant heterogeneity in study design and a lack of research focused on pregnancy and early infancy. In summary, despite good mechanistic evidence for the role of iron in brain development, evidence for the impact of iron deficiency or iron supplementation on early development is inconsistent. Further high-quality research is needed, particularly within pregnancy and early infancy, which has previously been neglected.

Exposure of cane toad hatchlings to older conspecifics suppresses chemosensory food tracking behaviour and increases risk of predation post-exposure.

Attempts to control invasive species using species-specific pheromones need to incorporate an understanding of interactive effects among those pathways. The larvae of invasive cane toads (Rhinella marina) utilise chemical cues to repulse, attract or suppress conspecific larvae. We can exploit these effects to reduce toad abundance, but the effects of each cue may not be additive. That is, exposure to one type of cue may lessen the impact of exposure to another cue. To assess this possibility, we exposed toad larvae to combinations of cues. Tadpoles that had been exposed to the suppression cue during larval development exhibited no response to the attraction cue, resulting in lower capture rates in attractant-baited traps. Suppression, however, did not affect a tadpole's response to the alarm cue, and exposure to the alarm cue during tadpole development did not affect response to the attraction cue. Tadpoles exposed to the suppression cue were smaller than control tadpoles at 10 days post-exposure, and consequently were more vulnerable to gape-limited invertebrate predators. Our results demonstrate that the responses by toad tadpoles to chemical cues interact in important ways, and are not simply additive when combined. Control efforts need to incorporate an understanding of such interactions if we are to most effectively use chemical-communication pathways to control invasive amphibians.

ERP markers are associated with neurodevelopmental outcomes in 1-5 month old infants in rural Africa and the UK.

INTRODUCTION: Infants and children in low- and middle-income countries are frequently exposed to a range of poverty-related risk factors, increasing their likelihood of poor neurodevelopmental outcomes. There is a need for culturally objective markers, which can be used to study infants from birth, thereby enabling early identification and ultimately intervention during a critical time of neurodevelopment. METHOD: In this paper, we investigate developmental changes in auditory event related potentials (ERP) associated with habituation and novelty detection in infants between 1 and 5 months living in the United Kingdom and The Gambia, West Africa. Previous research reports that whereas newborns' ERP responses are increased when presented with stimuli of higher intensity, this sensory driven response decreases over the first few months of life, giving rise to a cognitively driven, novelty-based response. Anthropometric measures were obtained concurrently with the ERP measures at 1 and 5 months of age. Neurodevelopmental outcome was measured using the Mullen Scales of Early Learning (MSEL) at 5 months of age. RESULTS: The described developmental change was observed in the UK cohort, who exhibited an intensity-based response at 1 month and a novelty-based response at 5 months of age. This change was accompanied by greater habituation to stimulus intensity at 5 compared to 1 month. In the Gambian cohort we did not see a change from an intensity-to a novelty-based response, and no change in habituation to stimulus intensity across the two age points. The degree of change from an intensity towards a novelty-based response was further found to be associated with MSEL scores at 5 months of infant age, whereas infants' growth between 1 and 5 months was not. DISCUSSION: Our study highlights the utility of ERP-based markers to study young infants in rural Africa. By implementing a well-established paradigm in a previously understudied population we have demonstrated its use as a culturally objective tool to better understand early learning in diverse settings world-wide. Results offer insight into the neurodevelopmental processes underpinning early neurocognitive development, which may in the future contribute to early identification of infants at heightened risk of adverse neurodevelopmental outcome.

Implementing neuroimaging and eye tracking methods to assess neurocognitive development of young infants in low- and middle-income countries.

Infants and children in low- and middle-income countries (LMICs) are frequently exposed to a range of environmental risk factors which may negatively affect their neurocognitive development. The mechanisms by which factors such as undernutrition and poverty impact development and cognitive outcomes in early childhood are poorly understood. This lack of knowledge is due in part to a paucity of objective assessment tools which can be implemented across different cultural settings and in very young infants. Over the last decade, technological advances, particularly in neuroimaging, have opened new avenues for research into the developing human brain, allowing us to investigate novel biological associations. This paper presents functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG) and eye tracking (ET) as objective, cross-cultural methods for studying infant neurocognitive development in LMICs, and specifically their implementation in rural Gambia, West Africa. These measures are currently included, as part of a broader battery of assessments, in the Brain Imaging for Global Health (BRIGHT) project, which is developing brain function for age curves in Gambian and UK infants from birth to 24 months of age. The BRIGHT project combines fNIRS, EEG and ET with behavioural, growth, health and sociodemographic measures. The implementation of these measures in rural Gambia are discussed, including methodological and technical challenges that needed to be addressed to ensure successful data acquisition. The aim is to provide guidance to other groups seeking to implement similar methods in their research in other LMICs to better understand associations between environmental risk and early neurocognitive development.

Habituation and novelty detection fNIRS brain responses in 5- and 8-month-old infants: The Gambia and UK.

The first 1,000 days of life are a critical window of vulnerability to exposure to socioeconomic and health challenges (i.e. poverty/undernutrition). The Brain Imaging for Global Health (BRIGHT) project has been established to deliver longitudinal measures of brain development from 0 to 24 months in UK and Gambian infants and to assess the impact of early adversity. Here results from the Habituation-Novelty Detection (HaND) functional near-infrared spectroscopy (fNIRS) task at 5 and 8 months are presented (N = 62 UK; N = 115 Gambia). In the UK cohort distinct patterns of habituation and recovery of response to novelty are seen, becoming more robust from 5 to 8 months of age. In The Gambia, an attenuated habituation response is evident: a larger number of trials are required before the response sufficiently suppresses relative to the response during the first presented trials. Furthermore, recovery of response to novelty is not evident at 5 or 8 months of age. As this longitudinal study continues in The Gambia, the parallel collection of socioeconomic, caregiving, health and nutrition data will allow us to stratify how individual trajectories of habituation and recovery of response to novelty associate with different risk factors and adaptive mechanisms in greater depth. Given the increasing interest in the use of neuroimaging methods within global neurocognitive developmental studies, this study provides a novel cross-culturally appropriate paradigm for the study of brain responses associated with attention and learning mechanisms across early development.

Physiological plasticity in a successful invader: rapid acclimation to cold occurs only in cool-climate populations of cane toads (Rhinella marina).

Physiological plasticity may facilitate invasion of novel habitats; but is such plasticity present in all populations of the invader or is it elicited only by specific climatic challenges? In cold-climate areas of Australia, invasive cane toads (Rhinella marina) can rapidly acclimate to cool conditions. To investigate whether this physiological plasticity is found in all invasive cane toads or is only seen in cool climates, we measured the acclimation ability of toads from across Australia and the island of Hawai'i. We collected toads from the field and placed them at either 12 or 24°C for 12 h before measuring their righting response as a proxy for critical thermal minimum (CTmin). Toads from the coolest Australian region (New South Wales) demonstrated plasticity (as previously reported), with exposure to 12°C (vs. 24°C) decreasing CTmin by 2°C. In toads from other Australian populations, CTmins were unaffected by our thermal treatments. Hawai'ian toads from a cool, wet site also rapidly acclimated to cool conditions, whereas those from warmer and drier Hawai'ian sites did not. Thermal plasticity has diverged among populations of invasive cane toads, with rapid acclimation manifested only in two cool-climate populations from widely separated sites. Predictions about the potential range of invasive species thus must consider the possibility of geographic (intraspecific) heterogeneity in thermal plasticity; data from other parts of the species' range may fail to predict levels of plasticity elicited by thermal challenges.