Modelling Noninvasively Measured Cerebral Signals during a Hypoxemia Challenge: Steps towards Individualised Modelling

Noninvasive approaches to measuring cerebral circulation and metabolism are crucial to furthering our understanding of brain function. These approaches also have considerable potential for clinical use “at the bedside”. However, a highly nontrivial task and precondition if such methods are to be used routinely is the robust physiological interpretation of the data. In this paper, we explore the ability of a previously developed model of brain circulation and metabolism to explain and predict quantitatively the responses of physiological signals. The five signals all noninvasively-measured during hypoxemia in healthy volunteers include four signals measured using near-infrared spectroscopy along with middle cerebral artery blood flow measured using transcranial Doppler flowmetry. We show that optimising the model using partial data from an individual can increase its predictive power thus aiding the interpretation of NIRS signals in individuals. At the same time such optimisation can also help refine model parametrisation and provide confidence intervals on model parameters. Discrepancies between model and data which persist despite model optimisation are used to flag up important questions concerning the underlying physiology, and the reliability and physiological meaning of the signals

Using multi-modal neuroimaging to characterise social brain specialisation in infants

The specialised regional functionality of the mature human cortex partly emerges through experience-dependent specialisation during early development. Our existing understanding of functional specialisation in the infant brain is based on evidence from unitary imaging modalities and has thus focused on isolated estimates of spatial or temporal selectivity of neural or haemodynamic activation, giving an incomplete picture. We speculate that functional specialisation will be underpinned by better coordinated haemodynamic and metabolic changes in a broadly orchestrated physiological response. To enable researchers to track this process through development, we develop new tools that allow the simultaneous measurement of coordinated neural activity (EEG), metabolic rate, and oxygenated blood supply (broadband near-infrared spectroscopy) in the awake infant. In 4- to 7-month-old infants, we use these new tools to show that social processing is accompanied by spatially and temporally specific increases in coupled activation in the temporal-parietal junction, a core hub region of the adult social brain. During non-social processing, coupled activation decreased in the same region, indicating specificity to social processing. Coupling was strongest with high-frequency brain activity (beta and gamma), consistent with the greater energetic requirements and more localised action of high-frequency brain activity. The development of simultaneous multimodal neural measures will enable future researchers to open new vistas in understanding functional specialisation of the brain

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

Hyperoxia results in increased aerobic metabolism following acute brain injury

Acute brain injury is associated with depressed aerobic metabolism. Below a critical mitochondrial pO2 cytochrome c oxidase, the terminal electron acceptor in the mitochondrial respiratory chain, fails to sustain oxidative phosphorylation. After acute brain injury, this ischaemic threshold might be shifted into apparently normal levels of tissue oxygenation. We investigated the oxygen dependency of aerobic metabolism in 16 acutely brain-injured patients using a 120-min normobaric hyperoxia challenge in the acute phase (24–72 h) post-injury and multimodal neuromonitoring, including transcranial Doppler ultrasound-measured cerebral blood flow velocity, cerebral microdialysis-derived lactate-pyruvate ratio (LPR), brain tissue pO2 (pbrO2), and tissue oxygenation index and cytochrome c oxidase oxidation state (oxCCO) measured using broadband spectroscopy. Increased inspired oxygen resulted in increased pbrO2 [ΔpbrO2 30.9 mmHg p < 0.001], reduced LPR [ΔLPR −3.07 p = 0.015], and increased cytochrome c oxidase (CCO) oxidation (Δ[oxCCO] + 0.32 µM p < 0.001) which persisted on return-to-baseline (Δ[oxCCO] + 0.22 µM, p < 0.01), accompanied by a 7.5% increase in estimated cerebral metabolic rate for oxygen (p = 0.038). Our results are consistent with an improvement in cellular redox state, suggesting oxygen-limited metabolism above recognised ischaemic pbrO2 thresholds. Diffusion limitation or mitochondrial inhibition might explain these findings. Further investigation is warranted to establish optimal oxygenation to sustain aerobic metabolism after acute brain injury

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

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-months. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-months. 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-months of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-months 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-months, but faster disengagement at 18-months, predicted higher cognitive control scores at 24-months. 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

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

A Model of Brain Circulation and Metabolism: NIRS Signal Changes during Physiological Challenges

We construct a model of brain circulation and energy metabolism. The model is designed to explain experimental data and predict the response of the circulation and metabolism to a variety of stimuli, in particular, changes in arterial blood pressure, CO2 levels, O2 levels, and functional activation. Significant model outputs are predictions about blood flow, metabolic rate, and quantities measurable noninvasively using near-infrared spectroscopy (NIRS), including cerebral blood volume and oxygenation and the redox state of the CuA centre in cytochrome c oxidase. These quantities are now frequently measured in clinical settings; however the relationship between the measurements and the underlying physiological events is in general complex. We anticipate that the model will play an important role in helping to understand the NIRS signals, in particular, the cytochrome signal, which has been hard to interpret. A range of model simulations are presented, and model outputs are compared to published data obtained from both in vivo and in vitro settings. The comparisons are encouraging, showing that the model is able to reproduce observed behaviour in response to various stimuli

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