Autonomic cardiovascular control is unaffected in children referred for assessment of excessive daytime sleepiness.

There is conflicting evidence for impaired autonomic control of heart rate (HR) in adults with narcolepsy and idiopathic hypersomnolence (IH). Despite these chronic hypersomnia conditions primarily being diagnosed around the age of puberty, there are limited studies in children. The present study investigated cardiovascular control using heart rate variability (HRV) and the extent of nocturnal HR dipping during sleep in children and adolescents with narcolepsy and IH. Children having an overnight polysomnographic study followed by a multiple sleep latency test (MSLT) for investigation of excessive daytime sleepiness (EDS) between May 2010 to December 2023 were included: 28 children diagnosed with narcolepsy, 11 with IH, and 26 subjectively sleepy children who did not meet the diagnostic criteria for either narcolepsy or IH. Each clinically referred child was matched for age and sex with a control. Time domain and frequency domain HRV were calculated from ECG recorded at 512 Hz. There were no differences in either time domain or spectral analysis of HRV between clinical groups or between clinical groups and their control group. The expected sleep state differences in HRV were observed in all groups. There was also no difference in HR nocturnal dipping between groups. Despite evidence for abnormal autonomic function in adults with narcolepsy and IH, our study did not identify any abnormalities in HR, HR control, or nocturnal dipping of HR in children referred for assessment of EDS. This suggests that autonomic dysfunction may be a feature of these conditions that develops in later life.

The development of aperiodic and periodic resting-state power between early childhood and adulthood: New insights from optically pumped magnetometers.

Neurophysiological signals, comprised of both periodic (e.g., oscillatory) and aperiodic (e.g., non-oscillatory) activity, undergo complex developmental changes between childhood and adulthood. With much of the existing literature primarily focused on the periodic features of brain function, our understanding of aperiodic signals is still in its infancy. Here, we are the first to examine age-related changes in periodic (peak frequency and power) and aperiodic (slope and offset) activity using optically pumped magnetometers (OPMs), a new, wearable magnetoencephalography (MEG) technology that is particularly well-suited for studying development. We examined age-related changes in these spectral features in a sample (N=65) of toddlers (1-3 years), children (4-5 years), young adults (20-26 years), and adults (27-38 years). Consistent with the extant literature, we found significant age-related decreases in the aperiodic slope and offset, and changes in peak frequency and power that were frequency-specific; we are the first to show that the effect sizes of these changes also varied across brain regions. This work not only adds to the growing body of work highlighting the advantages of using OPMs, especially for studying development, but also contributes novel information regarding the variation of neurophysiological changes with age across the brain.

Inherited defects of piRNA biogenesis cause transposon de-repression, impaired spermatogenesis, and human male infertility.

piRNAs are crucial for transposon silencing, germ cell maturation, and fertility in male mice. Here, we report on the genetic landscape of piRNA dysfunction in humans and present 39 infertile men carrying biallelic variants in 14 different piRNA pathway genes, including PIWIL1, GTSF1, GPAT2, MAEL, TDRD1, and DDX4. In some affected men, the testicular phenotypes differ from those of the respective knockout mice and range from complete germ cell loss to the production of a few morphologically abnormal sperm. A reduced number of pachytene piRNAs was detected in the testicular tissue of variant carriers, demonstrating impaired piRNA biogenesis. Furthermore, LINE1 expression in spermatogonia links impaired piRNA biogenesis to transposon de-silencing and serves to classify variants as functionally relevant. These results establish the disrupted piRNA pathway as a major cause of human spermatogenic failure and provide insights into transposon silencing in human male germ cells.

Paediatric Magnetoencephalography and its Role in Neurodevelopmental Disorders.

Magnetoencephalography (MEG) is a non-invasive neuroimaging technique that assesses neurophysiology, through detection of the magnetic fields generated by neural currents. In this way, it is sensitive to brain activity, both in individual regions and brain-wide networks. Conventional MEG systems employ an array of sensors that must be cryogenically cooled to low temperature, in a rigid one-size-fits-all helmet. Systems are typically designed to fit adults and are therefore challenging to use for paediatric measurements. Despite this, MEG has been employed successfully in research to investigate neurodevelopmental disorders, and clinically for presurgical planning for paediatric epilepsy. Here, we review the applications of MEG in children, specifically focussing on autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Our review demonstrates the significance of MEG in furthering our understanding of these neurodevelopmental disorders, whilst also highlighting the limitations of current instrumentation. We also consider the future of paediatric MEG, with a focus on newly developed instrumentation based on optically pumped magnetometers (OPM-MEG). We provide a brief overview of the development of OPM-MEG systems, and how this new technology might enable investigation of brain function in very young children and infants.

Early nutritional influences on brain regions related to processing speed in children born preterm: A secondary analysis of a randomized trial.

BACKGROUND: Processing speed is a foundational skill supporting intelligence and executive function, areas often delayed in preterm-born children. The impact of early-life nutrition on gray matter facilitating processing speed for this vulnerable population is unknown. METHODS: Magnetic resonance imaging and the Wechsler Preschool and Primary Scale of Intelligence-IV Processing Speed Index were acquired in forty 5-year-old children born preterm with very low birth weight. Macronutrient (grams per kilogram per day) and mother's milk (percentage of feeds) intakes were prospectively collected in the first postnatal month and associations between early-life nutrition and the primary outcome of brain regions supporting processing speed were investigated. RESULTS: Children had a mean (SD) gestational age of 27.8 (1.8) weeks and 45% were male. Macronutrient intakes were unrelated, but mother's milk was positively related, to greater volumes in brain regions, including total cortical gray matter, cingulate gyri, and occipital gyri. CONCLUSION: First postnatal month macronutrient intakes showed no association, but mother's milk was positively associated, with volumetric measures of total and regional cortical gray matter related to processing speed in preterm-born children. This exploratory analysis suggests early-life mother's milk supports processing speed by impacting structural underpinnings. Further research is needed on this potential strategy to improve preterm outcomes.

Optical redox imaging to screen synthetic hydrogels for stem cell-derived cardiomyocyte differentiation and maturation.

Significance: Heart disease is the leading cause of death in the United States, yet research is limited by the inability to culture primary cardiac cells. Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (iPSCs) are a promising solution for drug screening and disease modeling. Aim: Induced pluripotent stem cell-derived CM (iPSC-CM) differentiation and maturation studies typically use heterogeneous substrates for growth and destructive verification methods. Reproducible, tunable substrates and touch-free monitoring are needed to identify ideal conditions to produce homogenous, functional CMs. Approach: We generated synthetic polyethylene glycol-based hydrogels for iPSC-CM differentiation and maturation. Peptide concentrations, combinations, and gel stiffness were tuned independently. Label-free optical redox imaging (ORI) was performed on a widefield microscope in a 96-well screen of gel formulations. We performed live-cell imaging throughout differentiation and early to late maturation to identify key metabolic shifts. Results: Label-free ORI confirmed the expected metabolic shifts toward oxidative phosphorylation throughout the differentiation and maturation processes of iPSC-CMs on synthetic hydrogels. Furthermore, ORI distinguished high and low differentiation efficiency cell batches in the cardiac progenitor stage. Conclusions: We established a workflow for medium throughput screening of synthetic hydrogel conditions with the ability to perform repeated live-cell measurements and confirm expected metabolic shifts. These methods have implications for reproducible iPSC-CM generation in biomanufacturing.

Strain Differences in Bloodstream and Skin Infection: Methicillin-Resistant Staphylococcus aureus Isolated in 2018-2021 in a Single Health System.

Staphylococcus aureus is a common cause of skin and soft-tissue infections (SSTIs) and has become the most common cause of bloodstream infections (BSIs) in recent years, but whether the strains causing these two clinical syndromes overlap has not been studied adequately. USA300/500 (clonal complex [CC] 8-sequence type [ST] 8) and USA100 (CC5-ST5) have dominated among methicillin-resistant S aureus (MRSA) strains in the United States since the early 2000s. We compared the genomes of unselected MRSA isolates from 131 SSTIs with those from 145 BSIs at a single US center in overlapping periods in 2018-2021. CC8 MRSA was more common among SSTIs, and CC5 was more common among BSIs, consistent with prior literature. Based on clustering genomes with a threshold of 15 single-nucleotide polymorphisms, we identified clusters limited to patients with SSTI and separate clusters exclusively comprising patients with BSIs. However, we also identified eight clusters that included at least one SSTI and one BSI isolate. This suggests that virulent MRSA strains are transmitted from person to person locally in the healthcare setting or the community and that single lineages are often capable of causing both SSTIs and BSIs.

Periodic limb movements during sleep in children with neuromuscular disease or cerebral palsy - An important potential contributor to sleep-related morbidity.

OBJECTIVES: Poor sleep is frequently reported in children with neuromuscular diseases (NMD) and cerebral palsy (CP) however breathing disorders during sleep are often the clinical focus. Periodic limb movements (PLMs) have an increased prevalence in adults with NMD and may contribute to sleep disturbance in this population. We assessed the prevalence of PLMs in children with NMD or CP. METHODS: Retrospective review of polysomnography (PSG) with leg electromyography in children age 1-18 years with NMD (including Duchenne muscular dystrophy, myotonic dystrophy, spinal muscular atrophy) or CP performed at a paediatric sleep centre 2004-2022. RESULTS: Leg electromyography was available in at least 1 PSG in 239 children (125 NMD, 114 CP), and in 2 PSGs in 105 children (73 NMD, 32 CP). At initial PSG, 72 (30 %) were female with a median age 9y and respiratory disturbance index 3.5/h (interquartile range 1.3-9.9/h). Elevated PLM index (PLMI; >5/h) occurred in 9.6 % of each of the CP and NMD groups, quantified by initial PSG. Overall, PLMI increased from baseline (median 0, maximum 33/h) to follow-up (median 0, maximum 55.8/h; p < 0.05). In those with an elevated PLMI, arousal percentage attributable to PLMs was up to 25 % (median 7.5 %). CONCLUSIONS: Elevated PLMI occurred at a higher prevalence in children with NMD and CP than reported in other clinic-referred paediatric populations. It is important that PLMs are not overlooked as identification and treatment may help improve sleep outcomes. Further research is required to understand the pathophysiology and consequences of PLMs specifically in this population.

The surge in heart rate and blood pressure at respiratory event termination is dampened in children with down syndrome.

BACKGROUND: Children with Down syndrome (DS) have a high prevalence of sleep disordered breathing (SDB) and altered cardiovascular autonomic control. We aimed to analyze the effect of DS on the surge in heart rate (HR) and pulse transit time (PTT, an inverse surrogate measure of blood pressure change) at respiratory event termination. METHODS: 44 children (3-19 y) with DS and 44 typically developing (TD) children matched for SDB severity, age and sex underwent overnight polysomnography. Multilevel modelling determined the effect of DS on HR and PTT changes between a 10s pre-event to the latter half of each respiratory event (late-event) and 15s post-event during NREM and REM, accounting for SDB severity and event length. RESULTS: The children with DS had a significantly smaller % change in HR late-event to post-event (NREM: DS 26.4 % ± 17.5 % (mean ± SD), TD 30.7 % ± 21.0 %; REM DS 16.9 % ± 15.3 %, TD 21.0 % ± 14.0 %; p < 0.05 for both) compared with TD children for obstructive events, and central events (13.2 % ± 17.0 %, TD 18.8 % ± 17.0 %; p < 0.01) during REM. %change in PTT was significantly smaller in the DS group during NREM and REM from pre-event and late-event to post-event compared with TD children for obstructive and central events. CONCLUSION: These results suggest children with DS have dampened HR and BP responses to respiratory events compared with TD children. Whether this is symptomatic of autonomic dysfunction or a protective factor for the cardiovascular system in children with DS remains to be elucidated.

Decreased spermatogonial numbers in boys with severe haematological diseases.

This study examines spermatogonial numbers in testicular samples from 43 prepubertal patients undergoing haematopoietic stem cell transplantation (HSCT). High-dose chemotherapy and/or radiation during HSCT can impact spermatogenesis requiring fertility preservation. Results show that 49% of patients have decreased and 19% severely depleted spermatogonial pool prior to HSCT. Patients with Fanconi anaemia exhibit significantly reduced spermatogonial numbers. Patients with immunodeficiency or aplastic anaemia generally present within the normal range, while results in patients with myelodysplastic syndrome or myeloproliferative neoplasm vary. The study emphasizes the importance of assessing spermatogonial numbers in patients with severe haematological diseases for informed fertility preservation decisions.

Early-life nutrition is associated with processing speed at age 5 in children born preterm with very low birth weight.

OBJECTIVE: Processing speed is suboptimal among preterm-born children which is of concern as it is a foundational skill supporting higher-level cognitive functions. The study objective was to evaluate associations between early-life nutrition and processing speed in childhood. METHODS: Macronutrient and human milk (mother's own, donor) intakes from 137 children born preterm with very low birth weight enrolled in a nutrition feeding trial were included. Processing speed was evaluated at age 5 using the Wechsler Preschool and Primary Scale of Intelligence-fourth edition Processing Speed Index. Associations between early-life nutrition and processing speed were explored through linear regression. RESULTS: Children had a mean (standard deviation [SD]) birth gestational age of 28.1 (2.5) weeks, weight of 1036 (260) g and 52% were male. The mean (SD) assessment age was 5.7 (0.2) years. Sex-dependent relationships were identified between first postnatal month protein, lipid and energy intakes and processing speed at 5 years. For females, lower protein (per 0.1 g/kg/d: -0.88, 95% confidence interval [CI]: -1.53, -0.23; p = 0.01) and energy (per 10 kcal/kg/d: -2.38, 95% CI: -4.70, -0.05; p = 0.03) intakes were related to higher processing speed scores. Mother's milk provision was positively associated (per 10% increase: 0.80, 95% CI: 0.22, 1.37; p = 0.01) and donor milk was negatively associated (per 10% increase: -1.15, 95% CI: -2.22, -0.08; p = 0.04) with processing speed scores; no sex differences were observed. CONCLUSIONS: First postnatal month nutrition was related to processing speed at age 5 in children born preterm with very low birth weight. Early-life nutrition that supports processing speed may be leveraged to improve later cognitive outcomes for this vulnerable population.

Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts.

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist - Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = -0.97; FC feature vectors, rPOND-HBN = -0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = -0.99; FC feature vectors, rPOND-HBN = -0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

Gender diversity is correlated with dimensional neurodivergent traits but not categorical neurodevelopmental diagnoses in children.

BACKGROUND: Gender clinic and single-item questionnaire-based data report increased co-occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under-studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. METHODS: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4-12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi-dimensionally using a well-validated parent-report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex-assigned-at-birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. RESULTS: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC-derived scores. Instead, higher early-childhood dimensional autistic social-communication traits correlated with higher current overall gender incongruence (as defined by GIQC-14 score). This correlation was potentially moderated by sex-assigned-at-birth: greater early-childhood autistic social-communication traits were associated with higher current overall gender incongruence in assigned-males-at-birth, but not assigned-females-at-birth. For fine-grained gender diversity domains, greater autistic restricted-repetitive behavior traits were associated with greater diversity in gender identity across sexes-assigned-at-birth; greater autistic social-communication traits were associated with lower stereotypical male expression across sexes-assigned-at-birth. CONCLUSIONS: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early-childhood autistic social-communication traits and overall current gender diversity was most evident in assigned-males-at-birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender-diverse populations.

Using optically pumped magnetometers to replicate task-related responses in next generation magnetoencephalography.

Optically pumped magnetometers (OPMs) offer a new wearable means to measure magnetoencephalography (MEG) signals, with many advantages compared to conventional systems. However, OPMs are an emerging technology, thus characterizing and replicating MEG recordings is essential. Using OPM-MEG and SQUID-MEG, this study investigated evoked responses, oscillatory power, and functional connectivity during emotion processing in 20 adults, to establish replicability across the two technologies. Five participants with dental fixtures were included to assess the validity of OPM-MEG recordings in those with irremovable metal. Replicable task-related evoked responses were observed in both modalities. Similar patterns of oscillatory power to faces were observed in both systems. Increased connectivity was found in SQUID-versus OPM-MEG in an occipital and parietal anchored network. Notably, high quality OPM-MEG data were retained in participants with metallic fixtures, from whom no useable data were collected using conventional MEG.

Factors associated with foreign body infection in methicillin-resistant Staphylococcus aureus bacteremia.

Background: We aimed to compare patient characteristics, MRSA sequence types, and biofilm production of MRSA strains that did and did not cause a foreign body infection in patients with MRSA bloodstream infections (BSI). Methods: All adult patients with MRSA BSI hospitalized in two hospitals were identified by clinical microbiology laboratory surveillance. Only patients who had at least one implanted foreign body during the episode of BSI were included. Results: In July 2018 - March 2022, of 423 patients identified with MRSA BSI, 118 (28%) had ≥1 foreign body. Among them, 51 (43%) had one or more foreign body infections. In multivariable analysis, factors associated with foreign body infection were history of MRSA infection in the last year (OR=4.7 [1.4-15.5], p=0.012) community-associated BSI (OR=68.1 [4.2-1114.3], p=0.003); surgical site infection as source of infection (OR=11.8 [2-70.4], p=0.007); presence of more than one foreign body (OR=3.4 [1.1-10.7], p=0.033); interval between foreign body implantation and infection <18 months (OR=3.3 [1.1-10], p=0.031); and positive blood culture ≥48h (OR=16.7 [4.3-65.7], p<0.001). The most prevalent sequence type was ST8 (39%), followed by ST5 (29%), and ST105 (20%) with no significant difference between patients with or without foreign body infection. Only 39% of MRSA isolates formed a moderate/strong biofilm. No significant difference was observed between patients with foreign body infection and those without foreign body infection. In multivariable analysis, subjects infected with a MRSA isolate producing moderate/strong in vitro biofilm were more likely to have a history of MRSA infection in the last year (OR=3.41 [1.23-9.43]), interval between foreign body implantation and MRSA BSI <18 months (OR=3.1 [1.05-9.2]) and ST8 (OR=10.64 [2-57.3]). Conclusion: Most factors associated with foreign body infection in MRSA BSI were also characteristic of persistent infections. Biofilm-forming isolates were not associated with a higher risk of foreign-body infection but appeared to be associated with MRSA genetic lineage, especially ST8.

Effect of sleep disordered breathing severity in children with Down syndrome on parental wellbeing and social support.

INTRODUCTION: Sleep disorders, particularly sleep disordered breathing (SDB), are common in children with Down syndrome (DS). We investigated the relationship between SDB severity and parental psychological wellbeing and their perception of social support. METHODS: 44 children with DS (3-19 years) underwent overnight polysomnography and were categorised into three groups: primary snoring, Mild and Moderate/Severe obstructive sleep apnoea (OSA). Parents completed questionnaires about their child's behaviour (Child Behavior Checklist), sleep symptoms (Pediatric Sleep Survey Instrument) and SDB-related quality of life (OSA-18), together with the DUKE-UNC Functional Social Support (DUKE) and Psychological General Well-Being Index (PGWBI) questionnaires for themselves. 34 children completed a follow-up study after 2 years. RESULTS: There were no significant differences between SDB severity groups for parental perceived social support or psychological wellbeing. Total scores on the DUKE were below average and PGWBI scores were indicative of moderate psychological distress in all three groups. Reduced perceived levels of social support were significantly correlated with externalising child behaviour and sleep disturbance. Diminished parental psychological wellbeing was also significantly correlated with increased sleep disturbances and reduced quality of life in children. At follow-up there were no significant changes in any questionnaire outcome, however parents of children with improved SDB severity had improved PGWBI vitality scores. CONCLUSION: The degree of parent-reported sleep disturbance in children with DS was linked to suboptimal perceived parental social support and poor psychological wellbeing. Our results emphasise the need for enhanced awareness of the detrimental effects of sleep problems in children with DS on parental wellbeing.

Improvement in quality of life with continuous positive airway pressure outweighs the treatment burden in children with obstructive sleep apnea.

INTRODUCTION: Continuous positive airway pressure (CPAP) for treatment of obstructive sleep apnea (OSA) may pose a significant burden on families. We assessed the impact of CPAP for children on quality of life (QOL) and caregiver treatment burden. METHODS: Prospective cohort study of children commencing outpatient CPAP in a specialist sleep centre 2020-2022. Questionnaires regarding sleep-related symptoms (PROMIS Pediatric Sleep Disturbance and Sleep-Related Impairment), QOL (OSA-18, QI-Disability), caregiver burden (Caregiver Strain Questionnaire) and overall health impact (Glasgow Children's Benefit Inventory) were completed by caregivers at CPAP commencement and 6 weeks later. RESULTS: Twenty-six patients completed follow-up (7 female; median age 11.4 year, baseline obstructive apnea hypopnea index 10.3/h; 77% overweight or obese, 73% comorbidity other than obesity). OSA-related QOL (OSA-18) significantly improved at follow-up (p < 0.01), as did child general QOL (p < 0.001), sleep disturbance (p < 0.01) and sleep-related impairment (p < 0.001). Caregivers mostly rated CPAP as beneficial to their child's health but 19% rated CPAP as harmful or having no effect. Caregiver strain reduced at follow-up (p < 0.001) and benefit outweighed inconvenience (p < 0.0001) in 81%. CPAP adherence was correlated with overall health impact (r = 0.67, p < 0.01) but not with caregiver rating of inconvenience. CONCLUSIONS: CPAP resulted in improvements in QOL and sleep-related symptoms, and reduced caregiver strain. Perceived benefits outweighed the burden of treatment for most but not all families. CPAP adherence was moderately correlated with family-reported measures of benefit but not related to perceived inconvenience. This study provides reassuring evidence regarding the benefits and impacts of CPAP for children, many of whom already have complex health care needs.

Is there a role for repeating the multiple sleep latency test across childhood when initially non-diagnostic?

BACKGROUND: The gold standard investigation for central disorders of hypersomnolence is the Multiple Sleep Latency Test (MSLT). As the clinical features of these disorders of hypersomnolence evolve with time in children, clinicians may consider repeating a previously non-diagnostic MSLT. Currently there are no guidelines available regards the utility and timing of repeating paediatric MSLTs. METHODS: Retrospective review of children aged 3-18years with ≥2MSLTs between 2005 and 2022. Narcolepsy was defined as mean sleep latency (MSL) <8min with ≥2 sleep onset REM (SOREM); idiopathic hypersomnia (IH) was defined as MSL <8min with <2 SOREM. MSLTs not meeting these criteria were labelled non-diagnostic. RESULTS: 19 children (9 female) with initial non-diagnostic MSLT underwent repeat MSLT, with 6 proceeding to a 3rd MSLT following 2 non-diagnostic MSLTs. The 2nd MSLT resulted in diagnosis in 6/19 (32 %) (3 narcolepsy, 3 IH); and 2/6 (33 %) 3rd MSLT were diagnostic (2 IH). Median age at initial MSLT was 7.5y (range 3.4-17.8y), with repeat performed after median of 2.9y (range 0.9-8.2y), and 3rd after a further 1.9 years (range 1.2-4.2y). Mean change in MSL on repeat testing was -2min (range -15.5min to +4.9min, p = 0.18). Of the 8 diagnostic repeat MSLTs, in addition to the MSL falling below 8 min, 2 children also developed ≥2 SOREM that had not been previously present. CONCLUSIONS: A third of repeat MSLTs became diagnostic, suggesting repeat MSLT should be considered in childhood if clinical suspicion persists. Further work needs to address the ideal interval between MSLTs and diagnostic cut-points specific to the paediatric population.

The neurodevelopmental trajectory of beta band oscillations: an OPM-MEG study.

Neural oscillations mediate the coordination of activity within and between brain networks, supporting cognition and behaviour. How these processes develop throughout childhood is not only an important neuroscientific question but could also shed light on the mechanisms underlying neurological and psychiatric disorders. However, measuring the neurodevelopmental trajectory of oscillations has been hampered by confounds from instrumentation. In this paper, we investigate the suitability of a disruptive new imaging platform - Optically Pumped Magnetometer-based magnetoencephalography (OPM-MEG) - to study oscillations during brain development. We show how a unique 192-channel OPM-MEG device, which is adaptable to head size and robust to participant movement, can be used to collect high-fidelity electrophysiological data in individuals aged between 2 and 34 years. Data were collected during a somatosensory task, and we measured both stimulus-induced modulation of beta oscillations in sensory cortex, and whole-brain connectivity, showing that both modulate significantly with age. Moreover, we show that pan-spectral bursts of electrophysiological activity drive task-induced beta modulation, and that their probability of occurrence and spectral content change with age. Our results offer new insights into the developmental trajectory of beta oscillations and provide clear evidence that OPM-MEG is an ideal platform for studying electrophysiology in neurodevelopment.