Cognitive control in infancy: Attentional predictors using a tablet-based measure.

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-month. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-month. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N = 60, 30 female) completed the tablet-task at 18- and 24-month of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-month using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-month, but faster disengagement at 18-month, predicted higher cognitive control scores at 24-month. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development.

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.

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.

Habitual night waking associates with dynamics of waking cortical theta power in infancy.

The implications of the substantial individual differences in infant sleep for early brain development remain unclear. Here, we examined whether night sleep quality relates to daytime brain activity, operationalized through measures of EEG theta power and its dynamic modulation, which have been previously linked to later cognitive development. For this longitudinal study, 76 typically developing infants were studied (age: 4-14 months, 166 individual study visits) over the course of 6 months with one, two, three, or four lab visits. Habitual sleep was measured with a 7-day sleep diary and actigraphy, and the Brief Infant Sleep Questionnaire. Twenty-channel EEG was recorded while infants watched multiple rounds of videos of women singing nursery rhymes; oscillatory power in the theta band was extracted. Key metrics were average theta across stimuli and the slope of change in theta within the first novel movie. Both objective and subjective sleep assessment methods showed a relationship between more night waking and higher overall theta power and reduced dynamic modulation of theta over the course of the novel video stimuli. These results may indicate altered learning and consolidation in infants with more disrupted night sleep, which may have implications for cognitive development.

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.

Construction and validation of a database of head models for functional imaging of the neonatal brain.

The neonatal brain undergoes dramatic structural and functional changes over the last trimester of gestation. The accuracy of source localisation of brain activity recorded from the scalp therefore relies on accurate age-specific head models. Although an age-appropriate population-level atlas could be used, detail is lost in the construction of such atlases, in particular with regard to the smoothing of the cortical surface, and so such a model is not representative of anatomy at an individual level. In this work, we describe the construction of a database of individual structural priors of the neonatal head using 215 individual-level datasets at ages 29-44 weeks postmenstrual age from the Developing Human Connectome Project. We have validated a method to segment the extra-cerebral tissue against manual segmentation. We have also conducted a leave-one-out analysis to quantify the expected spatial error incurred with regard to localising functional activation when using a best-matching individual from the database in place of a subject-specific model; the median error was calculated to be 8.3 mm (median absolute deviation 3.8 mm). The database can be applied for any functional neuroimaging modality which requires structural data whereby the physical parameters associated with that modality vary with tissue type and is freely available at www.ucl.ac.uk/dot-hub.

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.

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.

Using functional near-infrared spectroscopy to assess social information processing in poor urban Bangladeshi infants and toddlers.

Children living in low-resource settings are at risk for failing to reach their developmental potential. While the behavioral outcomes of growing up in such settings are well-known, the neural mechanisms underpinning poor outcomes have not been well elucidated, particularly in the context of low- and middle-income countries. In this study, we measure brain metabolic responses to social and nonsocial stimuli in a cohort of 6- and 36-month-old Bangladeshi children. Study participants in both cohorts lived in an urban slum and were exposed to a broad range of adversity early in life including extreme poverty, malnutrition, recurrent infections, and low maternal education. We observed brain regions that responded selectively to social stimuli in both ages indicating that these specialized brain responses are online from an early age. We additionally show that the magnitude of the socially selective response is related to maternal education, maternal stress, and the caregiving environment. Ultimately our results suggest that a variety of psychosocial hazards have a measurable relationship with the developing social brain.

Adaptation of the Mullen Scales of Early Learning for use among infants aged 5- to 24-months in rural Gambia.

Infants in low-resource settings are at heightened risk for compromised cognitive development due to a multitude of environmental insults in their surroundings. However, the onset of adverse outcomes and trajectory of cognitive development in these settings is not well understood. The aims of the present study were to adapt the Mullen Scales of Early Learning (MSEL) for use with infants in a rural area of The Gambia, to examine cognitive development in the first 24-months of life and to assess the association between cognitive performance and physical growth. In Phase 1 of this study, the adapted MSEL was tested on 52 infants aged 9- to 24-months (some of whom were tested longitudinally at two time points). Further optimization and training were undertaken and Phase 2 of the study was conducted, where the original measures were administered to 119 newly recruited infants aged 5- to 24-months. Infant length, weight and head circumference were measured concurrently in both phases. Participants from both phases were split into age categories of 5-9 m (N = 32), 10-14 m (N = 92), 15-19 m (N = 53) and 20-24 m (N = 43) and performance was compared across age groups. From the ages of 10-14 m, Gambian infants obtained lower MSEL scores than US norms. Performance decreased with age and was lowest in the 20-24 m old group. Differential onsets of reduced performance were observed in the individual MSEL domains, with declines in visual perception and motor performance detected as early as at 10-14 months, while reduced language scores became evident after 15-19 months of age. Performance on the MSEL was significantly associated with measures of growth.

Modelling confounding effects from extracerebral contamination and systemic factors on functional near-infrared spectroscopy.

Haemodynamics-based neuroimaging is widely used to study brain function. Regional blood flow changes characteristic of neurovascular coupling provide an important marker of neuronal activation. However, changes in systemic physiological parameters such as blood pressure and concentration of CO2 can also affect regional blood flow and may confound haemodynamics-based neuroimaging. Measurements with functional near-infrared spectroscopy (fNIRS) may additionally be confounded by blood flow and oxygenation changes in extracerebral tissue layers. Here we investigate these confounds using an extended version of an existing computational model of cerebral physiology, 'BrainSignals'. Our results show that confounding from systemic physiological factors is able to produce misleading haemodynamic responses in both positive and negative directions. By applying the model to data from previous fNIRS studies, we demonstrate that such potentially deceptive responses can indeed occur in at least some experimental scenarios. It is therefore important to record the major potential confounders in the course of fNIRS experiments. Our model may then allow the observed behaviour to be attributed among the potential causes and hence reduce identification errors.

Cortical activation to action perception is associated with action production abilities in young infants.

The extent to which perception and action share common neural processes is much debated in cognitive neuroscience. Taking a developmental approach to this issue allows us to assess whether perceptual processing develops in close association with the emergence of related action skills within the same individual. The current study used functional near-infrared spectroscopy (fNIRS) to investigate the perception of human action in 4- to 6-month-old human infants. In addition, the infants' manual dexterity was assessed using the fine motor component of The Mullen Scales of Early Learning and an in-house developed Manual Dexterity task. Results show that the degree of cortical activation, within the posterior superior temporal sulcus--temporoparietal junction (pSTS-TPJ) region, to the perception of manual actions in individual infants correlates with their own level of fine motor skills. This association was not fully explained by either measures of global attention (i.e., looking time) or general developmental stage. This striking concordance between the emergence of motor skills and related perceptual processing within individuals is consistent with experience-related cortical specialization in the developing brain.

Near Infrared Light Scattering Changes Following Acute Brain Injury.

Acute brain injury (ABI) is associated with changes in near infrared light absorption reflecting haemodynamic and metabolic status via changes in cerebral oxygenation (haemoglobin oxygenation and cytochrome-c-oxidase oxidation). Light scattering has not been comprehensively investigated following ABI and may be an important confounding factor in the assessment of chromophore concentration changes, and/or a novel non-invasive optical marker of brain tissue morphology, cytostructure, hence metabolic status. The aim of this study is to characterize light scattering following adult ABI. Time resolved spectroscopy was performed as a component of multimodal neuromonitoring in critically ill brain injured patients. The scattering coefficient (µ's), absorption coefficient and cerebral haemoglobin oxygen saturation (SO2) were derived by fitting the time resolved data. Cerebral infarction was subsequently defined on routine clinical imaging. In total, 21 patients with ABI were studied. Ten patients suffered a unilateral frontal infarction, and mean µ' s was lower over infarcted compared to non-infarcted cortex (injured 6.9/cm, non-injured 8.2/cm p=0.002). SO2 did not differ significantly between the two sides (injured 69.3%, non-injured 69.0% p=0.7). Cerebral infarction is associated with changes in µ' s which might be a novel marker of cerebral injury and will interfere with quantification of haemoglobin/cytochrome c oxidase concentration. Although further work combining optical and physiological analysis is required to elucidate the significance of these results, µ' s may be uniquely placed as a non-invasive biomarker of cerebral energy failure as well as gross tissue changes.

Monitoring cerebral autoregulation after brain injury: multimodal assessment of cerebral slow-wave oscillations using near-infrared spectroscopy.

BACKGROUND: Continuous monitoring of cerebral autoregulation might provide novel treatment targets and identify therapeutic windows after acute brain injury. Slow oscillations of cerebral hemodynamics (0.05-0.003 Hz) are visible in multimodal neuromonitoring and may be analyzed to provide novel, surrogate measures of autoregulation. Near-infrared spectroscopy (NIRS) is an optical neuromonitoring technique, which shows promise for widespread clinical applicability because it is noninvasive and easily delivered across a wide range of clinical scenarios. The aim of this study is to identify the relationship between NIRS signal oscillations and multimodal neuromonitoring, examining the utility of near infrared derived indices of cerebrovascular reactivity. METHODS: Twenty-seven sedated, ventilated, brain-injured patients were included in this observational study. Intracranial pressure, transcranial Doppler-derived flow velocity in the middle cerebral artery, and ipsilateral cerebral NIRS variables were continuously monitored. Signals were compared using wavelet measures of phase and coherence to examine the spectral features involved in reactivity index calculations. Established indices of autoregulatory reserve such as the pressure reactivity index (PRx) and mean velocity index (Mx) and the NIRS indices such as total hemoglobin reactivity index (THx) and tissue oxygen reactivity index (TOx) were compared using correlation and Bland-Altman analysis. RESULTS: NIRS indices correlated significantly between PRx and THx (rs = 0.63, P < 0.001), PRx and TOx (r = 0.40, P = 0.04), and Mx and TOx (r = 0.61, P = 0.004) but not between Mx and THx (rs = 0.26, P = 0.28) and demonstrated wide limits between these variables: PRx and THx (bias, -0.06; 95% limits, -0.44 to 0.32) and Mx and TOx (bias, +0.15; 95% limits, -0.34 to 0.64). Analysis of slow-wave activity throughout the intracranial pressure, transcranial Doppler, and NIRS recordings revealed statistically significant interrelationships, which varied dynamically and were nonsignificant at frequencies <0.008 Hz. CONCLUSIONS: Although slow-wave activity in intracranial pressure, transcranial Doppler, and NIRS is significantly similar, it varies dynamically in both time and frequency, and this manifests as incomplete agreement between reactivity indices. Analysis informed by a priori knowledge of physiology underpinning NIRS variables combined with sophisticated analysis techniques has the potential to deliver noninvasive surrogate measures of autoregulation, guiding therapy.

Twenty years of functional near-infrared spectroscopy: introduction for the special issue.

Papers from four different groups were published in 1993 demonstrating the ability of functional near infrared spectroscopy (fNIRS) to non-invasively measure hemoglobin concentration responses to brain function in humans. This special issue commemorates the first 20years of fNIRS research. The 9 reviews and 49 contributed papers provide a comprehensive survey of the exciting advances driving the field forward and of the myriad of applications that will benefit from fNIRS.

Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin.

The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin.

Analysis of slow wave oscillations in cerebral haemodynamics and metabolism following subarachnoid haemorrhage.

Aneurysmal subarachnoid haemorrhage (SAH) causes the greatest loss of productive life years of any form of stroke. Emerging concepts of pathophysiology highlight early abnormalities of microvascular function, including impaired autoregulation of cerebral blood flow and flow-metabolism coupling, as key causes of cerebral ischaemia and poor outcome. Near infrared spectroscopy (NIRS) is a non-invasive optical technique which may help identify cerebral microvascular dysfunction. The aim of this research is to investigate the status of flow-metabolism coupling by examining phase relationships between NIRS-derived concentrations of oxy-haemoglobin ([HbO2]), deoxy-haemoglobin ([HHb]) and cytochrome c oxidase oxidation ([oxCCO]). Eight sedated ventilated patients with SAH were investigated. A combined NIRS broadband and frequency domain spectroscopy system was used to measure [HbO2], [HHb] and [oxCCO] alongside other multimodal neuromonitoring. Wavelet analysis of phase relationships revealed antiphase [HbO2]-[oxCCO] and in-phase [HbO2]-[HHb] oscillations between 0.1Hz-0.01Hz consistent with compromised flow-metabolism coupling. NIRS derived variables might offer unique insights into microvascular and metabolic dysfunction following SAH, and in the future identify therapeutic windows or targets.

The influence of carbon dioxide on cerebral metabolism and oxygen consumption: combining multimodal monitoring with dynamic systems modelling.

Hypercapnia increases cerebral blood flow. The effects on cerebral metabolism remain incompletely understood although studies show an oxidation of cytochrome c oxidase, Complex IV of the mitochondrial respiratory chain. Systems modelling was combined with previously published non-invasive measurements of cerebral tissue oxygenation, cerebral blood flow, and cytochrome c oxidase redox state to evaluate any metabolic effects of hypercapnia. Cerebral tissue oxygen saturation and cytochrome oxidase redox state were measured with broadband near infrared spectroscopy and cerebral blood flow velocity with transcranial Doppler ultrasound. Data collected during 5-min hypercapnia in awake human volunteers were analysed using a Fick model to determine changes in brain oxygen consumption and a mathematical model of cerebral hemodynamics and metabolism (BrainSignals) to inform on mechanisms. Either a decrease in metabolic substrate supply or an increase in metabolic demand modelled the cytochrome oxidation in hypercapnia. However, only the decrease in substrate supply explained both the enzyme redox state changes and the Fick-calculated drop in brain oxygen consumption. These modelled outputs are consistent with previous reports of CO2 inhibition of mitochondrial succinate dehydrogenase and isocitrate dehydrogenase. Hypercapnia may have physiologically significant effects suppressing oxidative metabolism in humans and perturbing mitochondrial signalling pathways in health and disease.

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.

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.