Early development of sleep and brain functional connectivity in term-born and preterm infants

The proper development of sleep and sleep-wake rhythms during early neonatal life is crucial to lifelong neurological well-being. Recent data suggests that infants who have poor quality sleep demonstrate a risk for impaired neurocognitive outcomes. Sleep ontogenesis is a complex process, whereby alternations between rudimentary brain states-active vs. wake and active sleep vs. quiet sleep-mature during the last trimester of pregnancy. If the infant is born preterm, much of this process occurs in the neonatal intensive care unit, where environmental conditions might interfere with sleep. Functional brain connectivity (FC), which reflects the brain's ability to process and integrate information, may become impaired, with ensuing risks of compromised neurodevelopment. However, the specific mechanisms linking sleep ontogenesis to the emergence of FC are poorly understood and have received little investigation, mainly due to the challenges of studying causal links between developmental phenomena and assessing FC in newborn infants. Recent advancements in infant neuromonitoring and neuroimaging strategies will allow for the design of interventions to improve infant sleep quality and quantity. This review discusses how sleep and FC develop in early life, the dynamic relationship between sleep, preterm birth, and FC, and the challenges associated with understanding these processes. Impact Sleep in early life is essential for proper functional brain development, which is essential for the brain to integrate and process information. This process may be impaired in infants born preterm. The connection between preterm birth, early development of brain functional connectivity, and sleep is poorly understood. This review discusses how sleep and brain functional connectivity develop in early life, how these processes might become impaired, and the challenges associated with understanding these processes. Potential solutions to these challenges are presented to provide direction for future research.Peer reviewe

Wearable HD-DOT for investigating functional connectivity in the adult brain: A single subject, multi-session study

We applied a wearable 24-module high-density diffuse optical tomography (HD-DOT) system in a resting state (RS) paradigm repeatedly in one subject. Seed-based correlation maps show large field-of-view RS functional connectivity

Review of recent advances in frequency-domain near-infrared spectroscopy technologies [Invited]

Over the past several decades, near-infrared spectroscopy (NIRS) has become a popular research and clinical tool for non-invasively measuring the oxygenation of biological tissues, with particular emphasis on applications to the human brain. In most cases, NIRS studies are performed using continuous-wave NIRS (CW-NIRS), which can only provide information on relative changes in chromophore concentrations, such as oxygenated and deoxygenated hemoglobin, as well as estimates of tissue oxygen saturation. Another type of NIRS known as frequency-domain NIRS (FD-NIRS) has significant advantages: it can directly measure optical pathlength and thus quantify the scattering and absorption coefficients of sampled tissues and provide direct measurements of absolute chromophore concentrations. This review describes the current status of FD-NIRS technologies, their performance, their advantages, and their limitations as compared to other NIRS methods. Significant landmarks of technological progress include the development of both benchtop and portable/wearable FD-NIRS technologies, sensitive front-end photonic components, and high-frequency phase measurements. Clinical applications of FD-NIRS technologies are discussed to provide context on current applications and needed areas of improvement. The review concludes by providing a roadmap toward the next generation of fully wearable, low-cost FD-NIRS systems

Wearable, Integrated EEG-fNIRS Technologies: A Review.

There has been considerable interest in applying electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) simultaneously for multimodal assessment of brain function. EEG-fNIRS can provide a comprehensive picture of brain electrical and hemodynamic function and has been applied across various fields of brain science. The development of wearable, mechanically and electrically integrated EEG-fNIRS technology is a critical next step in the evolution of this field. A suitable system design could significantly increase the data/image quality, the wearability, patient/subject comfort, and capability for long-term monitoring. Here, we present a concise, yet comprehensive, review of the progress that has been made toward achieving a wearable, integrated EEG-fNIRS system. Significant marks of progress include the development of both discrete component-based and microchip-based EEG-fNIRS technologies; modular systems; miniaturized, lightweight form factors; wireless capabilities; and shared analogue-to-digital converter (ADC) architecture between fNIRS and EEG data acquisitions. In describing the attributes, advantages, and disadvantages of current technologies, this review aims to provide a roadmap toward the next generation of wearable, integrated EEG-fNIRS systems

Cot-side imaging of functional connectivity in the developing brain during sleep using wearable high-density diffuse optical tomography

Studies of cortical function in newborn infants in clinical settings are extremely challenging to undertake with traditional neuroimaging approaches. Partly in response to this challenge, functional near-infrared spectroscopy (fNIRS) has become an increasingly common clinical research tool but has significant limitations including a low spatial resolution and poor depth specificity. Moreover, the bulky optical fibres required in traditional fNIRS approaches present significant mechanical challenges, particularly for the study of vulnerable newborn infants. A new generation of wearable, modular, high-density diffuse optical tomography (HD-DOT) technologies has recently emerged that overcomes many of the limitations of traditional, fibre-based and low-density fNIRS measurements. Driven by the development of this new technology, we have undertaken the first cot-side study of newborn infants using wearable HD-DOT in a clinical setting. We use this technology to study functional brain connectivity (FC) in newborn infants during sleep and assess the effect of neonatal sleep states, active sleep (AS) and quiet sleep (QS), on resting state FC. Our results demonstrate that it is now possible to obtain high-quality functional images of the neonatal brain in the clinical setting with few constraints. Our results also suggest that sleep states differentially affect FC in the neonatal brain, consistent with prior reports

Review of recent advances in frequency-domain near-infrared spectroscopy technologies

Over the past several decades, near-infrared spectroscopy (NIRS) has become a popular research and clinical tool for non-invasively measuring the oxygenation of biological tissues, with particular emphasis on applications to the human brain. In most cases, NIRS studies are performed using continuous-wave NIRS (CW-NIRS), which can only provide information on relative changes in chromophore concentrations, such as oxygenated and deoxygenated hemoglobin, as well as estimates of tissue oxygen saturation. Another type of NIRS known as frequency-domain NIRS (FD-NIRS) has significant advantages: it can directly measure optical pathlength and thus quantify the scattering and absorption coefficients of sampled tissues and provide direct measurements of absolute chromophore concentrations. This review describes the current status of FD-NIRS technologies, their performance, their advantages, and their limitations as compared to other NIRS methods. Significant landmarks of technological progress include the development of both benchtop and portable/wearable FD-NIRS technologies, sensitive front-end photonic components, and high-frequency phase measurements. Clinical applications of FD-NIRS technologies are discussed to provide context on current applications and needed areas of improvement. The review concludes by providing a roadmap toward the next generation of fully wearable, low-cost FD-NIRS systems

Functional Imaging the Neonatal Brain with Wearable Diffuse Optical Tomography

Studying brain development poses significant methodological challenges when working with vulnerable newborn infant populations. Non-invasive and wearable optical brain imaging technologies may allow for the cot-side study of newborn infants in clinical settings. This has particularly important implications for preterm infants in intensive care, for whom traditional neuroimaging techniques are not readily feasible. Wearable high-density diffuse optical tomography (HD-DOT) has emerged as a promising technology in this pursuit. In this thesis, I describe the development and application of wearable HD-DOT for newborn infants in clinical settings. Specifically, this technology is applied to study the features of functional brain connectivity (FC) associated with neonatal sleep states, active sleep and quiet sleep, in both term-born and preterm infants. HD-DOT is also electromechanically combined with electroencephalography (EEG) to concurrently study haemodynamic cortical and electrical cortical brain activity in the preterm infant. As a result of the constraints posed by lock-down conditions and a pause on clinical studies during the COVID-19 pandemic, the HD- DOT device is also used to study resting state functional connectivity (RSFC) in the adult brain in the home setting. Findings from this work demonstrate the potential of wearable HD-DOT, and combined EEG-HD-DOT, for the cot-side study of cerebral function during sleep in newborn infants, as well as at-home neuroimaging of resting-state networks in adults. This work was supervised by: Dr. Topun Austin, Department of Paediatrics, University of Cambridge, and Dr. Robert J. Cooper, Department of Medical Physics and Biomedical Engineering, UCL

Editorial: Representation in neuroscience and humanities

Peer reviewed: Tru

Reliability and similarity of resting state functional connectivity networks imaged using wearable, high-density diffuse optical tomography in the home setting

Background: When characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. Methods: Resting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. Results: We observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a &lt;10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. Discussion: Using RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.</p

Role of pediatricians, pediatric associations, and academic departments in ensuring optimal early childhood development globally: Position paper of the international pediatric association

Early childhood (birth-8 years), particularly the first 3 years, is the most critical time in development because of the highly sensitive developing brain. Providing appropriate developmental care (i.e., nurturing care, as defined by the World Health Organization [WHO]) during early childhood is key to ensuring a child\u27s holistic development. Pediatricians are expected to play a critical role in supporting early childhood development (ECD) through providing developmental services such as developmental monitoring, anticipatory guidance, screening, and referral to medical and/or community-based services when delay is identified. Pediatricians are also expected to serve as advocates within their clinics and communities for improved delivery of ECD services, such as advocating for increasing funding for ECD initiatives, increasing insurance coverage of ECD services, and working to increase other pediatricians\u27 awareness of the principles of ECD and how to deliver developmental services. However, this does not always occur. Typically, pediatricians\u27 training and practice emphasizes treating disease rather than enhancing ECD. Pediatricians are further hindered by a lack of uniformity across nations in guidelines for developmental monitoring and screening. In this article, we present the vision of the International Pediatric Association (IPA) of the roles that pediatricians, academic departments, medical training programs, and pediatric associations should fulfill to help support ECD, including raising ECD to higher levels of priority in routine pediatric care. First, we present the challenges that face these goals in supporting ECD. We then propose, with supportive literature, strategies and resources to overcome these challenges in collaboration with local and international stakeholders, including the IPA, the WHO, UNICEF, and the World Bank