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.

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.

Longitudinal fNIRS and EEG metrics of habituation and novelty detection are correlated in 1-18-month-old infants.

INTRODUCTION: Habituation and novelty detection are two fundamental and widely studied neurocognitive processes. Whilst neural responses to repetitive and novel sensory input have been well-documented across a range of neuroimaging modalities, it is not yet fully understood how well these different modalities are able to describe consistent neural response patterns. This is particularly true for infants and young children, as different assessment modalities might show differential sensitivity to underlying neural processes across age. Thus far, many neurodevelopmental studies are limited in either sample size, longitudinal scope or breadth of measures employed, impeding investigations of how well common developmental trends can be captured via different methods. METHOD: This study assessed habituation and novelty detection in N = 204 infants using EEG and fNIRS measured in two separate paradigms, but within the same study visit, at 1, 5 and 18 months of age in an infant cohort in rural Gambia. EEG was acquired during an auditory oddball paradigm during which infants were presented with Frequent, Infrequent and Trial Unique sounds. In the fNIRS paradigm, infants were familiarised to a sentence of infant-directed speech, novelty detection was assessed via a change in speaker. Indices for habituation and novelty detection were extracted for both EEG and NIRS RESULTS: We found evidence for weak to medium positive correlations between responses on the fNIRS and the EEG paradigms for indices of both habituation and novelty detection at most age points. Habituation indices correlated across modalities at 1 month and 5 months but not 18 months of age, and novelty responses were significantly correlated at 5 months and 18 months, but not at 1 month. Infants who showed robust habituation responses also showed robust novelty responses across both assessment modalities. DISCUSSION: This study is the first to examine concurrent correlations across two neuroimaging modalities across several longitudinal age points. Examining habituation and novelty detection, we show that despite the use of two different testing modalities, stimuli and timescale, it is possible to extract common neural metrics across a wide age range in infants. We suggest that these positive correlations might be strongest at times of greatest developmental change.

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.

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.