0335 Frontal Expression of NREM Sleep Oscillations are Associated with Executive Function in Children and Adolescents

Abstract Introduction The prefrontal cortex, an area known for executive functioning (including inhibition and self-monitoring) develops during childhood and adolescents, with a pattern of posterior to anterior brain development. Slow-wave activity (SWA) in NREM sleep, tracks brain development with high SWA power migrating from occipital to frontal region as brain maturation occurs. This pilot study aimed to examine whether slow wave topography is correlated with executive function in youth. Methods Seventeen healthy children and adolescents (ages 11-17; 10 females) underwent overnight polysomnography (PSG) with high-density electroencephalography (hdEEG). Behavior Rating Inventory of Executive Function (BRIEF) was administered to assess executive function. SWA (SWA1: 0.5-1 Hz; SWA2: 1-4.5 Hz) and spindle (slow sigma: 11-13 Hz; fast sigma: 13-16 Hz) activity was analyzed with spectral analysis using Welch’s method. BRIEF subscales of inhibition and monitor were correlated with SWA and sigma power across all derivations, with Holm-Bonferroni correction (126 channels). Significant derivations were then controlled for sex and self-reported Tanner stage using multiple regression Results BRIEF-Inhibition scale (i.e., ability to repress impulsivity) and SWA1 in anterior frontal derivations were negatively correlated (R2=0.58, p=0.047 corrected). BRIEF-Monitor scale (i.e., self-perception of one’s own behavior and interpersonal awareness) was negatively correlated with fast sigma in anterior frontal derivations (R2=0.65, p=0.013 corrected). These associations were significant after controlling for sex and Tanner stage. Conclusion These results support the hypothesis that NREM sleep oscillations are associated with executive function and reflect changes in neuroplasticity related to “back-to-front” brain maturation. Future longitudinal studies should combine multi-modal neuroimaging of brain structure and local sleep with comprehensive assessments of executive function to evaluate the possible link between local sleep and development of higher-order cognition in frontal brain regions in youth. Support NCATS grant #UL1TR001414 & PERC Systems Biology Fund

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146 Better Aerobic Fitness Is Associated with Distinct Sleep Characteristics in Adolescents

SLEEP ◽

10.1093/sleep/zsab072.145 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A60-A60

Author(s):

Ariel Neikrug ◽

Shlomit Radom-Aizik ◽

Ivy Chen ◽

Annamarie Stehli ◽

Kitty Lui ◽

...

Keyword(s):

Eye Movement ◽

Slow Wave ◽

Aerobic Fitness ◽

Nrem Sleep ◽

Brain Maturation ◽

Rapid Eye Movement ◽

Sleep Spindle ◽

Sleep Patterns ◽

Peak Vo2 ◽

Local Sleep

Abstract Introduction Aerobic fitness facilitates brain synaptic plasticity, which influences global and local sleep expression. While it is known that sleep patterns/behavior and non-rapid eye movement (NREM) sleep slow wave activity (SWA) tracks brain maturation, little is known about how aerobic fitness and sleep interact during development in youth. The aim of this pilot was to characterize relationships among aerobic fitness, measures of global/local sleep expression, and habitual sleep patterns in children and adolescents. We hypothesized that greater aerobic fitness would be associated with better sleep quality, indicated by increased SWA. Methods 20 adolescents (mean age=14.6±2.3 years old, range 11-17, 11 females) were evaluated for AF (peak VO2 assessed by ramp-type progressive cycle ergometry in the laboratory), habitual sleep duration and efficiency (continuous 7-14 day actigraphy with sleep diary), and topographic patterns of spectral power in slow wave, theta, and sleep spindle frequency ranges in non-rapid eye movement (NREM) sleep using overnight polysomnography with high-density electroencephalography (hdEEG, 128 channels). Results Significant relationships were observed between peak VO2 and habitual bedtime (r=-0.604, p=0.013) and wake-up time (r=-0.644, p=0.007), with greater fitness associated with an earlier sleep schedule (going to bed and waking up earlier). Peak VO2 was a significant predictor of slow oscillations (0.5-1Hz, p=0.018) and theta activity (4.5-7.5Hz, p=0.002) over anterior frontal and central derivations (p<0.001 and p=0.001, respectively) after adjusting for sex and pubertal development stage. Similar associations were detected for fast sleep spindle activity (13-16Hz, p=0.006), which was greater over temporo-parietal derivations. Conclusion Greater AF was associated with earlier habitual sleep times and with enhanced expression of developmentally-relevant sleep oscillations during NREM sleep. These data suggest that AF may 1) minimize the behavioral sleep delay commonly seen during adolescence, and 2) impact topographically-specific features of sleep physiology known to mechanistically support neuroplasticity and cognitive processes which are dependent on prefrontal cortex and hippocampal function in adolescents and adults. Support (if any) NCATS grant #UL1TR001414 & PERC Systems Biology Fund

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Executive function and brain development in adolescents with severe congenital heart disease (Teen Heart Study): protocol of a prospective cohort study

BMJ Open ◽

10.1136/bmjopen-2019-032363 ◽

2019 ◽

Vol 9 (10) ◽

pp. e032363

Author(s):

Melanie Ehrler ◽

Nadja Naef ◽

Ruth O'Gorman Tuura ◽

Beatrice Latal

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Executive Function ◽

Brain Development ◽

Children And Adolescents ◽

Prospective Cohort ◽

Congenital Heart ◽

Healthy Children ◽

Functional Brain ◽

Developmental Problems

IntroductionCongenital heart disease (CHD) is the most frequent congenital malformation. With recent advances in medical care, the majority of patients with CHD survive into adulthood. As a result, interest has shifted towards the neurodevelopmental outcome of these patients, and particularly towards the early detection and treatment of developmental problems. A variety of mild to moderate cognitive impairments as well as emotional and behavioural problems has been observed in this population. However, a more detailed assessment of the various domains of executive function and their association with structural and functional brain development is lacking. Therefore, the current study will examine all domains of executive function and brain development in detail in a large sample of children and adolescents with CHD and healthy control children.Methods and analysisA total of 192 children and adolescents with CHD aged 10–15 years, who participated in prospective cohort studies at the University Children’s Hospital Zurich, will be eligible for this study. As a control group, approximately 100 healthy children will be enrolled. Primary outcome measures will include executive function abilities, while secondary outcomes will consist of other neurodevelopmental measures, including intelligence, processing speed, attention, fine motor abilities and brain development. An MRI will be performed to assess structural and functional brain development. Linear regression analyses will be applied to investigate group differences and associations between executive function performance and neurodevelopmental measures.Ethics and disseminationThis study is supported by the Swiss National Science Foundation (SNF 32003B_172914) and approved by the ethical committee of the Canton Zurich (KEK 2019–00035). Written informed consent will be obtained from all the parents and from children aged 14 years or older. Findings from this study will be published in peer-reviewed journals and presented at national and international conferences for widespread dissemination of the results.

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145 Aerobic Fitness Is Associated with Advanced Circadian Rhythms in Adolescents

SLEEP ◽

10.1093/sleep/zsab072.144 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A59-A60

Author(s):

Ariel Neikrug ◽

Shlomit Radom-Aizik ◽

Ivy Chen ◽

Annamarie Stehli ◽

Kitty Lui ◽

...

Keyword(s):

Eye Movement ◽

Slow Wave ◽

Aerobic Fitness ◽

Nrem Sleep ◽

Brain Maturation ◽

Rapid Eye Movement ◽

Sleep Spindle ◽

Sleep Patterns ◽

Peak Vo2 ◽

Local Sleep

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0325 Better Aerobic Fitness is Associated with Distinct Sleep Characteristics in Children and Adolescents - A Pilot Study

SLEEP ◽

10.1093/sleep/zsaa056.322 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A123-A124

Author(s):

A B Neikrug ◽

S Radom-Aizik ◽

I Y Chen ◽

A Stehli ◽

K K Lui ◽

...

Keyword(s):

Pilot Study ◽

Sleep Quality ◽

Children And Adolescents ◽

Aerobic Fitness ◽

Time Consistency ◽

Sleep Time ◽

Brain Maturation ◽

Circadian Activity ◽

Sleep Patterns ◽

Local Sleep

Abstract Introduction Aerobic fitness facilitates brain synaptic plasticity, which influences global and local sleep expression. While it is known that sleep patterns/behavior and non-rapid eye movement (NREM) sleep slow wave activity (SWA) tracks brain maturation, little is known about how aerobic fitness and sleep interact during growth and development in children and adolescents. The aim of this pilot study was to characterize relationships among aerobic fitness, measures of global/local sleep expression, and habitual sleep patterns in children and adolescents. We hypothesized that greater aerobic fitness would be associated with better sleep quality, indicated by increased SWA. Methods Twenty healthy youth (11-17 years-old, 11 female) were evaluated during summer vacation (no school schedule constraints). Aerobic fitness (VO2peak) was measured using ramp-type progressive cycle ergometry, habitual sleep (i.e., sleep-time consistency and circadian activity patterns) was assessed with 7-day actigraphy, and ad lib sleep was evaluated during overnight polysomnography (PSG) with high-density electroencephalography (hdEEG; 128 channels). Spectral analysis was implemented to quantify SWA (0.5-4.5Hz). Data were analyzed using linear regression analyses and exploratory independent samples t-tests. Results Negative correlations were observed between VO2peak and sleep measures including sleep-time consistency (partial r=-0.53, p=0.045) and timing/acrophase of the circadian activity rhythm (partial r=-0.64, p=0.01) while controlling for sex and age. Additionally, after accounting for Tanner stage and sex, data demonstrated significant effects in SWA at frontal derivations (p=0.024) between low and high fitness levels at topographically specific and meaningful EEG derivations, e.g. over frontal cortex. Conclusion These results suggest that children and adolescents with greater fitness have less variability in sleep-times (improved sleep consistency), tend to have a more advanced circadian activity phase (i.e., go to sleep earlier), and express greater frontal SWA, supporting the hypothesis that fitness is associated with improved local and global sleep quality. Future research with larger samples is necessary to further evaluate these relationships, and to determine if interventions that improve fitness also improve sleep and related brain plasticity. Support NCATS grant #UL1TR001414 & PERC Systems Biology Fund

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Local Targeted Memory Reactivation in Human Sleep

10.1101/539114 ◽

2019 ◽

Cited By ~ 1

Author(s):

Ella Bar ◽

Anat Arzi ◽

Ofer Perl ◽

Ethan Livne ◽

Noam Sobel ◽

...

Keyword(s):

Slow Wave ◽

Visual Fields ◽

Nrem Sleep ◽

Wave Activity ◽

Functional Neuroanatomy ◽

Memory Reactivation ◽

Odor Cues ◽

Human Sleep ◽

Global Action ◽

Local Sleep

AbstractMemory consolidation can be promoted via Targeted Memory Reactivation (TMR) that re-presents training cues or context during sleep. Whether TMR acts locally or globally on cortical sleep oscillations remains unknown. Here we exploit the unique functional neuroanatomy of olfaction with its ipsilateral stimulus processing to perform local TMR in one brain hemisphere. Participants learned associations between words and locations in left or right visual fields with contextual odor throughout. During post-learning naps, odors were presented to one nostril throughout NREM sleep. We found improved memory for specific words processed in the cued hemisphere (ipsilateral to stimulated nostril). Unilateral odor cues locally modulated slow wave activity (SWA) such that regional SWA increase in the cued hemisphere negatively correlated with select memories for cued words. Moreover, local TMR improved slow wave-spindle coupling specifically in the cued hemisphere. Thus, TMR in human sleep transcends global action by selectively promoting specific memories associated with local sleep oscillations.

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Complex Biological Pattern of Fertility Hormones in Children and Adolescents: A Study of Healthy Children from the CALIPER Cohort and Establishment of Pediatric Reference Intervals

Clinical Chemistry ◽

10.1373/clinchem.2013.204123 ◽

2013 ◽

Vol 59 (8) ◽

pp. 1215-1227 ◽

Cited By ~ 50

Author(s):

Danijela Konforte ◽

Jennifer L Shea ◽

Lianna Kyriakopoulou ◽

David Colantonio ◽

Ashley H Cohen ◽

...

Keyword(s):

Children And Adolescents ◽

Clinical Laboratory ◽

Pediatric Population ◽

Pubertal Development ◽

Tanner Stage ◽

Reference Intervals ◽

Sex Hormone Binding Globulin ◽

Specific Reference ◽

Healthy Children ◽

Pubertal Stage

BACKGROUND Pediatric endocrinopathies are commonly diagnosed and monitored by measuring hormones of the hypothalamic-pituitary-gonadal axis. Because growth and development can markedly influence normal circulating concentrations of fertility hormones, accurate reference intervals established on the basis of a healthy, nonhospitalized pediatric population and that reflect age-, gender-, and pubertal stage–specific changes are essential for test result interpretation. METHODS Healthy children and adolescents (n = 1234) were recruited from a multiethnic population as part of the CALIPER study. After written informed parental consent was obtained, participants filled out a questionnaire including demographic and pubertal development information (assessed by self-reported Tanner stage) and provided a blood sample. We measured 7 fertility hormones including estradiol, testosterone (second generation), progesterone, sex hormone–binding globulin, prolactin, follicle-stimulating hormone, and luteinizing hormone by use of the Abbott Architect i2000 analyzer. We then used these data to calculate age-, gender-, and Tanner stage–specific reference intervals according to Clinical Laboratory Standards Institute C28-A3 guidelines. RESULTS We observed a complex pattern of change in each analyte concentration from the neonatal period to adolescence. Consequently, many age and sex partitions were required to cover the changes in most fertility hormones over this period. An exception to this was prolactin, for which no sex partition and only 3 age partitions were necessary. CONCLUSIONS This comprehensive database of pediatric reference intervals for fertility hormones will be of global benefit and should lead to improved diagnosis of pediatric endocrinopathies. The new database will need to be validated in local populations and for other immunoassay platforms as recommended by the Clinical Laboratory Standards Institute.

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Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2010.2316 ◽

2011 ◽

Vol 278 (1717) ◽

pp. 2419-2428 ◽

Cited By ~ 72

Author(s):

John A. Lesku ◽

Alexei L. Vyssotski ◽

Dolores Martinez-Gonzalez ◽

Christiane Wilzeck ◽

Niels C. Rattenborg

Keyword(s):

Slow Wave ◽

Rem Sleep ◽

Visual Processing ◽

Slow Wave Sleep ◽

Brain Activity ◽

Brain Regions ◽

Avian Brain ◽

Brain Functioning ◽

Sleep Homeostasis ◽

Local Sleep

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5–4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium—a primary visual processing region—neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.

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Calendar age and puberty-related development of regional gray matter volume and white matter tracts during adolescence

Brain Structure and Function ◽

10.1007/s00429-020-02208-1 ◽

2021 ◽

Author(s):

Ayaka Ando ◽

Peter Parzer ◽

Michael Kaess ◽

Susanne Schell ◽

Romy Henze ◽

...

Keyword(s):

White Matter ◽

Brain Development ◽

Gray Matter ◽

Gray Matter Volume ◽

Brain Maturation ◽

Healthy Children ◽

White Matter Tract ◽

Pubertal Status ◽

Matter Volume ◽

The Impact

Abstract Background Adolescence is a critical time for brain development. Findings from previous studies have been inconsistent, failing to distinguish the influence of pubertal status and aging on brain maturation. The current study sought to address these inconsistencies, addressing the trajectories of pubertal development and aging by longitudinally tracking structural brain development during adolescence. Methods Two cohorts of healthy children were recruited (cohort 1: 9–10 years old; cohort 2: 12–13 years old at baseline). MRI data were acquired for gray matter volume and white matter tract measures. To determine whether age, pubertal status, both or their interaction best modelled longitudinal data, we compared four multi-level linear regression models to the null model (general brain growth indexed by total segmented volume) using Bayesian model selection. Results Data were collected at baseline (n = 116), 12 months (n = 97) and 24 months (n = 84) after baseline. Findings demonstrated that the development of most regional gray matter volume, and white matter tract measures, were best modelled by age. Interestingly, precentral and paracentral regions of the cortex, as well as the accumbens demonstrated significant preference for the pubertal status model. None of the white matter tract measures were better modelled by pubertal status. Limitations: The major limitation of this study is the two-cohort recruitment. Although this allowed a faster coverage of the age span, a complete per person trajectory over 6 years of development (9–15 years) could not be investigated. Conclusions Comparing the impact of age and pubertal status on regional gray matter volume and white matter tract measures, we found age to best predict longitudinal changes. Further longitudinal studies investigating the differential influence of puberty status and age on brain development in more diverse samples are needed to replicate the present results and address mechanisms underlying norm-variants in brain development.

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Vitamin D Deficiency in Children and Adolescents: Role of Puberty and Obesity on Vitamin D Status

Nutrition and Metabolic Insights ◽

10.1177/11786388211018726 ◽

2021 ◽

Vol 14 ◽

pp. 117863882110187

Author(s):

Hedyeh Saneifard ◽

Marjan Shakiba ◽

Ali Sheikhy ◽

Leila Baniadam ◽

Fatemeh Abdollah Gorji ◽

...

Keyword(s):

Vitamin D ◽

Children And Adolescents ◽

Vitamin D Deficiency ◽

Tanner Stage ◽

Additional Risk Factor ◽

Healthy Children ◽

Vitamin D Status ◽

Obese Children ◽

Increased Risk ◽

Vitamin D Levels

Background: Vitamin D deficiency is common among children and adolescents and can be affected by several factors such as puberty and obesity. Objective: The aim of this study was to evaluate vitamin D status in children and adolescents and to analyse the influence of puberty and obesity on its level. Method: A cross-sectional study was carried-out, in which clinical and biochemical data were gathered from 384 healthy children and adolescents between May 2019 to May 2020. Results: 220 females and 164 males were enrolled (aged 7-16 years; mean ± SD: 11 ± 2.5). Vitamin D deficiency was found in 49% of the total cases and was significantly more prevalent in females than males (33.1% in female; 15.9% in male, P < .001). Mean vitamin D level was lower in obese children compared with non-obese ( P < .001). Non-obese group had significantly higher levels of vitamin D in Tanner stage IV of puberty than obese individuals (20.1 ± 17.0 vs 5.4 ± 2.0) ( P = .03). Vitamin D levels were significantly lower in females than males only in Tanner stage II (12.3 ± 9.0 vs 19.6 ± 16.6) ( P = .005). The lowest level of Vitamin D was in Tanner stage Ⅳ-Ⅴ in boys and in Tanner stage Ⅱ-Ⅲ in girls ( P < .001). Conclusion: Puberty is an additional risk factor for vitamin D deficiency especially in girls and obese children. This increased risk, together with the fact that most important time for building a proper skeleton is during childhood and adolescent, makes it essential to monitor vitamin D in these age groups.

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T1 white/gray contrast as a predictor of chronological age, and an index of cognitive performance

10.1101/171892 ◽

2017 ◽

Author(s):

John D Lewis ◽

Alan C Evans ◽

Jussi Tohka

Keyword(s):

Brain Development ◽

Cognitive Performance ◽

Gray Matter ◽

Brain Regions ◽

Brain Maturation ◽

Chronological Age ◽

Brain Images ◽

Cortical Gray Matter ◽

The Brain ◽

Age Prediction

The maturational schedule of human brain development appears to be narrowly confined. The chronological age of an individual can be predicted from brain images with considerable accuracy, and deviation from the typical pattern of brain maturation has been related to cognitive performance. Methods using multi-modal data, or complex measures derived from voxels throughout the brain have shown the greatest accuracy, but are difficult to interpret in terms of the biology. Measures based on the cortical surface(s) have yielded less accurate predictions, suggesting that perhaps developmental changes related to cortical gray matter are not strongly related to chronological age, and that perhaps development is more strongly related to changes in subcortical regions or in deep white matter. We show that a simple metric based on the white/gray contrast at the inner border of the cortical gray-matter is a comparably good predictor of chronological age, and our usage of an elastic net penalized linear regression model reveals the brain regions which contribute most to age-prediction. We demonstrate this in two large datasets: the NIH Pediatric Data, with 832 scans of typically developing children, adolescents, and young adults; and the Pediatric Imaging, Neurocognition, and Genetics data, with 760 scans of individuals in a similar age-range. Moreover, we show that the residuals of age-prediction based on this white/gray contrast metric are more strongly related to IQ than are those from cortical thickness, suggesting that this metric is more sensitive to aspects of brain development that reflect cognitive performance.

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