Biology subjects

Huber, R.

Publications and source records attributed to Huber, R..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Discovery of anti-infective compounds against Mycobacterium marinum after biotransformation of simple natural stilbene scaffolds by a fungal secretome

This study evaluated the efficacy of a high-throughput Dictyostelium discoideum - Mycobacterium marinum Dd-Mm infection system by first benchmarking it against a set of antibiotics and second in screening a library of natural product (NP) derivatives for anti-infective activity against intracellular Mycobacterium marinum (Mm). The study observed no activity of pyrazinamide against Mm, consistent with known resistance patterns, and confirmed other antibiotics, such as rifampicin and bedaquiline, with activity below defined antibacterial susceptibility breakpoints. From screening a small library of NP derivatives, trans-{delta}-viniferins emerged as promising anti-infective scaffolds, particularly two compounds which exhibited an anti-infective activity on Mm during infection but not on Mm in broth, 17 with an IC50 of 18.1 {micro}M, and 19 with an IC50 of 9 {micro}M). Subsequent exploration via halogenation and structure-activity relationship (SAR) studies led to the identification of derivatives with improved selectivity and potency. The observed anti-infective phenotype may involve mechanisms such as blocking mycobacterial virulence factors or boosting host defense. Furthermore, the study highlights the potential of natural product-inspired derivatization approaches for drug discovery and underscores the utility of the Dd-Mm infection system in identifying novel anti-infective compounds. IMPORTANCEThis study underscores the significance of leveraging natural product-inspired approaches and innovative infection models in search for novel anti-infective compounds. By benchmarking and employing high-throughput Dictyostelium discoideum-Mycobacterium marinum infection system on a small, focused library of natural product derivatives, the study identified trans-{delta}-viniferins as promising anti-infective scaffolds against Mycobacterium marinum, opening potential therapeutic avenues for combating tuberculosis. The findings highlight the value of exploring nature-inspired chemistry for drug discovery and addressing global health challenges.

microbiology↗

bioRxiv2024

Wake EEG oscillation dynamics reflect both sleep need and brain maturation across childhood and adolescence

1An objective measure of brain maturation is highly insightful for monitoring both typical and atypical development. Slow wave activity, recorded in the sleep electroencephalogram (EEG), reliably indexes age-related changes in sleep pressure as well as deficits related to developmental disorders such as attention-deficit hyperactivity disorder (ADHD). We aimed to determine whether wake EEG measured before and after sleep could index the same developmental changes in sleep pressure, using data collected from 163 participants 3-25 years old. We analyzed ageand sleep-dependent changes in two measures of oscillatory activity, amplitudes and density, as well as two measures of aperiodic activity, offsets and exponents. We then compared these wake measures to sleep slow wave amplitudes and slopes. Finally, we compared wake EEG in children with ADHD (N=58) to neurotypical controls. Of the four wake measures, only oscillation amplitudes consistently exhibited the same changes as sleep slow waves. Wake amplitudes decreased with age, decreased after sleep, and this overnight decrease decreased with age. Furthermore, wake amplitudes were significantly related to both sleep slow wave amplitudes and slopes. Wake oscillation densities decreased overnight in children but increased overnight in adolescents and adults. Aperiodic offsets decreased linearly with age, decreased after sleep, and were significantly related to sleep slow wave amplitudes. Aperiodic exponents also decreased with age, but increased after sleep. No wake measure showed significant effects of ADHD. Overall, our results indicate that wake oscillation amplitudes, and to some extent aperiodic offsets, behave like sleep slow waves across sleep and development. At the same time, overnight changes in oscillation densities independently reflect some yet-unknown shift in neural activity around puberty.

neuroscience↗

bioRxiv2023

EEG markers of drowsiness do not predict lapses in attention during sleep deprivation

During drowsiness, maintaining consistent attention becomes difficult, leading to behavioral lapses. Oscillation bursts in the electroencephalogram (EEG) might predict such lapses, since alpha bursts increase with inattention and theta bursts increase with time spent awake. However, while lapses increase with time awake, paradoxically alpha bursts decrease, and the behavioral relevance of theta bursts is unknown. Therefore, we investigated whether theta or alpha bursts predicted lapses either when well rested (baseline, BL) or sleep deprived (SD). EEG was measured in 18 young adults performing the lateralized attention task, and the timing of bursts was related to trial outcomes (fast, slow, and lapse trials). Against expectations, neither theta nor alpha bursts were more likely during lapses, either at BL or SD. Both were more likely before fast trials, but only at BL. Fast and slow trials were followed by decreases in both theta and alpha bursts, but the effect was reduced during SD, partially due to local increases in bursts. Considering prior literature, these results indicate that bursts have a non-linear relationship with vigilance. The lack of a direct relationship to lapses may be because bursts originate from task-unrelated areas, and the differences during SD suggest these areas change with time awake.

neuroscience↗

bioRxiv2023

Olfactory learning modulates a neural circuit mediating innate odor-guided behavior in Drosophila

Behavior is often categorized as being innate or learned, with the specific circuits being assigned to one of these categories. In Drosophila, neural circuits mediating an innate behavioral response are considered as being "hard-wired", as activation of these neuronal pathways leads to stereotyped behaviors. However, only a limited number of studies assessed whether innate behaviors and their underlying neural circuits are plastic or show experience-dependent modulation. Here, we show that experience modulates second-order olfactory neurons involved in innate behavioral responses. We focus on the neural circuit defined by multiglomerular projection neurons (mPNs) that target the lateral horn, a structure relevant in the genesis of innate behavior. We show that mPNs, coding for odor attraction, are bidirectionally modulated after olfactory associative learning: when an olfactory stimulus is paired with an aversive electric shock, the activity of these neurons is decreased, while when the odor is paired with a sucrose-reward they are potentiated. We further show that this modulation requires glutamate and serotonin signaling, and that downstream third-order neurons are consequently affected. The bidirectional nature of the plasticity in these neurons is reflected in behavior: silencing mPN activity leads to odor avoidance, while artificial activation induces approach. While output from the mPNs is not required in aversive olfactory conditioning, silencing these neurons during retrieval of appetitive memories leads to a significant memory impairment. Artificially activating these neurons during odor presentation is sufficient to generate a 3 h appetitive memory. Our study in flies shows that a neural circuit coding for innate odor attraction can contribute to learned behavior, is modulated by olfactory learning and can provide reward-like reinforcement.

neuroscience↗

bioRxiv2023

Fractal cycles of sleep: a new aperiodic activity-based definition of sleep cycles

Nocturnal human sleep consists of 4 - 6 ninety-minute cycles defined as episodes of non-rapid eye movement (non-REM) sleep followed by an episode of REM sleep. While sleep cycles are considered fundamental components of sleep, their functional significance largely remains unclear. One of the reasons for a lack of research progress in this field is the absence of a data-driven definition of sleep cycles. Here, we proposed to base such a definition on fractal (aperiodic) neural activity, a well-established marker of arousal and sleep stages. We explored temporal dynamics of fractal activity during nocturnal sleep using electroencephalography. Based on the observed pattern of fractal fluctuations, we introduced a new concept of fractal activity-based cycles of sleep or "fractal cycles" for short, defined as a time interval during which fractal activity descends from its local maximum to its local minimum and then leads back to the next local maximum. Next, we assessed correlations between fractal and classical (i.e., non-REM - REM) sleep cycle durations. We also studied cycles with skipped REM sleep, i.e., the cycles where the REM phase is expected to appear except that it does not, being replaced by lightening of sleep. Regarding the sample, we examined fractal cycles in healthy adults (age range: 18 - 75 years, n = 205) as well as in children and adolescents (range: 8 - 17 years, n = 21), the group characterized by deeper sleep and a higher frequency of cycles with skipped REM sleep. Further, we studied fractal cycles in major depressive disorder (n = 111), the condition characterized by altered REM sleep (in addition to its clinical symptoms). We found that fractal and classical cycle durations (89 {+/-} 34 min vs 90 {+/-} 25 min) correlated positively (r = 0.5, p < 0.001). Cycle-to-cycle overnight dynamics showed an inverted U-shape of both fractal and classical cycle durations and a gradual decrease in absolute amplitudes of the fractal descents and ascents from early to late cycles. In adults, the fractal cycle duration and participants age correlated negatively (r = -0.2, p = 0.006). Children and adolescents had shorter fractal cycles compared to young adults (76 {+/-} 34 vs 94 {+/-} 32 min, p < 0.001). The fractal cycle algorithm detected cycles with skipped REM sleep in 91 - 98% of cases. Medicated patients with depression showed longer fractal cycles compared to their own unmedicated state (107 {+/-} 51 min vs 92 {+/-} 38 min, p < 0.001) and age-matched controls (104 {+/-} 49 vs 88 {+/-} 31 min, p < 0.001). In conclusion, fractal cycles are an objective, quantifiable, continuous and biologically plausible way to display sleep neural activity and its cycles. They are useful in healthy adult and pediatric populations as well as in patients with major depressive disorder. Fractal cycles should be extensively studied to advance theoretical research on sleep structure. Highlights- Fractal activity-based cycles of sleep or "fractal cycles" for short is a new concept based on cyclic changes in fractal (aperiodic) neural activity during sleep. - Durations of fractal and classical cycles correlate, and both show an inverted U-shape when seen from early to late cycles. - The fractal cycle algorithm is effective in detecting cycles with skipped REM sleep. - Older healthy adults shower shorter fractal - but not classical - cycle durations. - Fractal cycle duration is shorter in children and adolescents compared to young adults. - In major depressive disorder, antidepressant medication is associated with longer fractal cycles.

neuroscience↗

bioRxiv2023

Acoustically evoked K-complexes are sufficient to boost verbal memory consolidation during sleep

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1 Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.

neuroscience↗

bioRxiv2023

Fast layer-fMRI VASO with short stimuli and event-related designs at 7T

Layers and columns are the dominant processing units in the human (neo)cortex at the meso-scopic scale. While the blood oxygenation dependent (BOLD) signal has a high detection sensitivity, it is biased towards unwanted signals from large draining veins at the cortical sur-face. The additional fMRI contrast of vascular space occupancy (VASO) has the potential to augment the neuroscientific interpretability of layer-fMRI results by means of capturing com-plementary information of locally specific changes in cerebral blood volume (CBV). Specifically, VASO is not subject to unwanted sensitivity amplifications of large draining veins. Because of constrained sampling efficiency, it has been mainly applied in combination with efficient block task designs and long trial durations. However, to study cognitive processes in neuroscientific contexts, or probe vascular reactivity, short stimulation periods are often necessary. Here, we developed a VASO acquisition procedure with a short acquisition period (895 ms volume acqui-sition) and sub-millimetre resolution. During visual event-related stimulation, we show reliable responses in visual cortices within a reasonable number of trials ([~]20). Furthermore, the short TR and high spatial specificity of our VASO implementation enabled us to show differences in laminar reactivity and onset times. Finally, we explore the generalizability to a different stimu-lus modality (somatosensation). With this, we showed that CBV-sensitive VASO provides the means to capture layer-specific haemodynamic responses with high spatio-temporal resolution and is able to be used with event-related paradigms.

neuroscience↗

bioRxiv2023

Theta and alpha EEG oscillations reflect sleep need -- except during the wake maintenance zone

Increasing time spent awake results in accumulated sleep need, a process known as sleep homeostasis. Sleep homeostasis combines with a 24 h circadian rhythm to determine when and for how long we sleep. Both sleep homeostasis and the circadian rhythm substantially affect spectral power of the wake electroencephalogram (EEG), but not in ways predicted by current models. Specifically, these models hypothesize that time spent awake increases neuronal synaptic strength, which increases synchronization and should therefore increase oscillatory activity. However, the dominant wake EEG oscillations, measured as theta (4-8 Hz) and alpha power (8-12 Hz), do not follow the predicted buildup in homeostatic sleep pressure with time awake. This is due to a limitation of spectral power analysis, which does not distinguish between changes in the amplitude of oscillations from changes in the quantity of oscillations present in the signal. We wished to determine whether the amplitudes of EEG oscillations would specifically reflect homeostatic sleep pressure, independently from changes in quantity. We collected data from 18 young healthy adults during a 4-h sleep / 24-h extended wake paradigm. We indeed found that theta and alpha oscillation amplitudes reflect homeostatic sleep pressure, increasing along a saturating exponential function with time awake. Instead, theta quantities increased linearly with time awake, and alpha quantities decreased. Notably, theta and alpha amplitudes temporarily decreased during the wake maintenance zone (WMZ), a 3-4 h time window just before bedtime when it is difficult to fall asleep. Using pupillometry, we also found that mean pupil diameter increased during this window, while variance decreased. These results suggest that the WMZ is dependent on an alerting signal from the ascending arousal system. The WMZ therefore counteracts the observed build-up in homeostatic sleep pressure reflected in EEG amplitudes by temporarily desynchronizing cortical activity.

neuroscience↗

bioRxiv2022

Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.

neuroscience↗

bioRxiv2022

Molecular elucidation of drug-induced abnormal assemblies of the Hepatitis B Virus capsid protein by solid-state NMR

Hepatitis B virus (HBV) capsid assembly modulators (CAMs) represent a new class of anti-HBV antivirals. CAMs disturb proper nucleocapsid assembly, by inducing formation of either aberrant assemblies (CAM-A) or of apparently normal but genome-less empty capsids (CAM-E). Classical structural approaches have revealed the CAM binding sites on the capsid protein (Cp), but conformational information on the CAM-induced off-path aberrant assemblies is lacking. We show that solid-state NMR can provide such information, including for wild-type full-length Cp183, and we find that in these assemblies, the asymmetric unit comprises a single Cp molecule rather than the four quasi-equivalent conformers typical for the icosahedral T=4 symmetry of the normal HBV capsids. Furthermore, while in contrast to truncated Cp149, full-length Cp183 assemblies appear, on the mesoscopic level, unaffected by CAM-A, NMR reveals that on the molecular level, Cp183 assemblies are equally aberrant. Finally, we use a eukaryotic cell-free system to reveal how CAMs modulate capsid-RNA interactions and capsid phosphorylation. Our results establish a structural view on assembly modulation of the HBV capsid, and they provide a rationale for recently observed differences between in-cell versus in vitro capsid assembly modulation.

biophysics↗

bioRxiv2022

'High-Density-SleepCleaner': An open-source, semi-automatic artifact removal routine tailored to high-density sleep EEG

BackgroundWith up to 256 channels, high-density electroencephalography (hd-EEG) has become essential to the sleep research field. The vast amount of data resulting from this magnitude of channels in overnight EEG recordings complicates the removal of artifacts. New MethodWe present a new, semi-automatic artifact removal routine specifically designed for sleep hd-EEG recordings. By employing a graphical user interface (GUI), the user assesses epochs in regard to four sleep quality markers (SQMs). Based on their topography and underlying EEG signal, the user eventually removes artifactual values. To identify artifacts, the user is required to have basic knowledge of the typical (patho-)physiological EEG they are interested in, as well as artifactual EEG. The final output consists of a binary matrix (channels x epochs). Channels affected by artifacts can be restored in afflicted epochs using epoch-wise interpolation, a function included in the online repository. ResultsThe routine was applied in 54 overnight sleep hd-EEG recordings. The proportion of bad epochs highly depends on the number of channels required to be artifact-free. Between 95% and 100% of bad epochs could be restored using epoch-wise interpolation. We furthermore present a detailed examination of two extreme cases (with few and many artifacts). For both nights, the topography and cyclic pattern of delta power look as expected after artifact removal. Comparison with Existing MethodsNumerous artifact removal methods exist, yet their scope of application usually targets short wake EEG recordings. The proposed routine provides a transparent, practical, and efficient approach to identify artifacts in overnight sleep hd-EEG recordings. ConclusionsThis method reliably identifies artifacts simultaneously in all channels and epochs.

neuroscience↗

bioRxiv2022

The theta paradox: 4-8 Hz EEG oscillations reflect both local sleep and cognitive control

Human brain activity generates electroencephalographic (EEG) oscillations that characterize specific behavioral and vigilance states. The frequency of these oscillations is typically sufficient to distinguish a given state, however theta oscillations (4-8 Hz) have instead been found in near-opposite conditions of drowsiness during sleep deprivation and alert cognitive control. While the latter has been extensively studied and is often referred to as "frontal midline theta", the former has been investigated far less but is considered to be a marker for local sleep during wake. In this study we investigated to what extent theta oscillations differed during cognitive tasks and sleep deprivation. We measured high-density EEG in 18 young healthy adults performing 6 tasks under 3 levels of sleep deprivation. We found both cognitive load and sleep deprivation increased theta power in medial prefrontal cortical areas, however sleep deprivation caused additional increases in theta in many other, predominantly frontal, areas. The sources of sleep deprivation theta were task-dependent, with a visual-spatial task and short-term memory task showing the most widespread effects. Notably, theta was highest in supplementary motor areas during passive music listening, and highest in the inferior temporal cortex during a spatial game. This suggests that theta caused by sleep deprivation may preferentially occur in cortical areas not involved in ongoing behavior. While our results find differences in topography from frontal midline theta, they raise the possibility that a common mechanism may underly both theta oscillations during cognition and during sleep deprivation.

neuroscience↗

bioRxiv2022

High resolution analysis of proteolytic substrate processing

Proteolysis is a key catalytic event in protein and thus cellular homeostasis. Despite the importance and wide implications of proteolytic processing and degradation, methods describing the degradation of folded proteins at high temporal and spatial resolution are not well established. However, this information is required to obtain a deep mechanistic understanding of proteolytic events and their consequences. Here, we describe an integrated method comprising time-resolved mass spectrometry, circular dichroism spectroscopy and bioinformatics to reveal the sequential degradation and unfolding of the model substrate annexin A1 by the human serine protease HTRA1. This workflow represents a general strategy for obtaining precise molecular insights into protease-substrate interactions that can be conveniently adapted to studying other posttranslational modifications such as phosphorylation in dynamic protein complexes.

biochemistry↗

bioRxiv2022

Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics

Sleep modulation techniques to elucidate the functional role of sleep brain oscillations in brain and body functions have gained large interest. Slow waves, the hallmark feature of deep non-rapid eye movement sleep, do potentially drive restorative effects on brain and cardiovascular functions. Auditory stimulation to modulate slow waves is a promising tool, however, directly comparing different auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included stimulation nights. We found a large and global increase in slow wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA and thus, our findings provide mechanistic insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow wave enhancements translates into a more rested cardiovascular system on the subsequent day.

neuroscience↗

bioRxiv2021

Mesoscopic Quantification of Cortical Architecture in the Living Human Brain

AO_SCPLOWBSTRACTC_SCPLOWMesoscopic (0.1-0.5 mm) interrogation of the living human brain is critical for advancing neuroscience and bridging the resolution gap with animal models. Despite the variety of MRI contrasts measured in recent years at the mesoscopic scale, in vivo quantitative imaging of T2* has not been performed. Here we provide a dataset containing empirical T2* measurements acquired at 0.35 x 0.35 x 0.35 mm3 voxel resolution using 7 Tesla MRI. To demonstrate unique features and high quality of this dataset, we generate flat map visualizations that reveal fine-scale cortical substructures such as layers and vessels, and we report quantitative depth-dependent T2* (as well as R2*) values in primary visual cortex and auditory cortex that are highly consistent across subjects. This dataset is freely available at https://doi.org/10.17605/OSF.IO/N5BJ7, and may prove useful for anatomical investigations of the human brain, as well as for improving our understanding of the basis of the T2* -weighted (f)MRI signal.

neuroscience↗

bioRxiv2021

An Infant Sleep Electroencephalographic Marker of Thalamocortical Connectivity Predicts Behavioral Outcome in Late Infancy

Infancy represents a critical period during which thalamocortical brain connections develop and mature. Deviations in the maturation of thalamocortical connectivity are linked to neurodevelopmental disorders. There is a lack of early biomarkers to detect and localize neuromaturational deviations, which can be overcome with mapping through high-density electroencephalography (hdEEG) assessed in sleep. Specifically, slow waves and spindles in non-rapid eye movement (NREM) sleep are generated by the thalamocortical system, and their characteristics, slow wave slope and spindle density, are closely related to neuroplasticity and learning. Recent studies further suggest that information processing during sleep underlying sleep-dependent learning is promoted by the temporal coupling of slow waves and spindles, yet slow wave-spindle coupling remains unexplored in infancy. Thus, we evaluated three potential biomarkers: 1) slow wave slope, 2) spindle density, and 3) the temporal coupling of slow waves with spindles. We use hdEEG to first examine the occurrence and spatial distribution of these three EEG features in healthy infants and second to evaluate a predictive relationship with later behavioral outcomes. We report four key findings: First, infants EEG features appear locally: slow wave slope is maximal in occipital and frontal areas, whereas spindle density is most pronounced frontocentrally. Second, slow waves and spindles are temporally coupled in infancy, with maximal coupling strength in the occipital areas of the brain. Third, slow wave slope, spindle density, and slow wave-spindle coupling are not associated with concurrent behavioral status (6 months). Fourth, spindle density in central and frontocentral regions at age 6 months predicts later behavioral outcomes at 12 and 24 months. Neither slow wave slope nor slow wave-spindle coupling predict behavioral development. Our results propose spindle density as an early EEG biomarker for identifying thalamocortical maturation, which can potentially be used for early diagnosis of neurodevelopmental disorders in infants. These findings are complemented by our companion paper that demonstrates the linkage of spindle density to infant nighttime movement, framing the possible role of spindles in sensorimotor microcircuitry development. Together, our studies suggest that early sleep habits, thalamocortical maturation, and behavioral outcome are closely interwoven. A crucial next step will be to evaluate whether early therapeutic interventions may be effective to reverse deviations in identified individuals at risk. HighlightsO_LISlow waves and spindles occur in a temporally coupled manner in infancy C_LIO_LISlow wave slope, spindle density, and slow wave-spindle coupling are not related to concurrent behavioral development C_LIO_LISpindle density at 6 months predicts behavioral status at 12 and 24 months C_LIO_LISlow wave slope and slow wave-spindle coupling are not predictive of behavioral development C_LI

neuroscience↗

bioRxiv2021

Bedtime to the brain: How infants sleep habits intertwine with sleep neurophysiology

Adequate sleep is critical for development and facilitates the maturation of the neurophysiological circuitries at the basis of cognitive and behavioral function. Observational research has associated sleep problems in early life with worse later cognitive, psychosocial, and somatic health outcomes. Yet, the extent to which day-to-day sleep habits in early life relate to neurophysiology - acutely and long-term - remains to be explored. Here, we report that sleep habits in 32 healthy 6-month-olds assessed with actimetry are linked to fundamental aspects of their neurophysiology measured with high-density electroencephalography (hdEEG). Our study reveals four key findings: First, daytime sleep habits are linked to EEG slow wave activity (SWA). Second, habits of nighttime movement and awakenings from sleep are connected with spindle density. Third, habitual sleep timing is linked to neurophysiological connectivity quantified as Delta-coherence. And lastly, Delta-coherence at age 6 months predicts nighttime sleep duration at age 12 months. These novel findings widen our understanding that infants sleep habits are closely intertwined with three particular levels of neurophysiology: sleep pressure (determined by SWA), the maturation of the thalamocortical system (spindles), and the maturation of cortical connectivity (coherence). Our companion paper complements this insight in the perspective of later developmental outcomes: early thalamocortical connectivity (spindle density) at age 6 months predicts later behavioural status at 12 and 24 months. The crucial next step is to extend this concept to clinical groups to objectively characterize infants sleep habits "at risk" that foster later neurodevelopmental problems. HighlightsO_LIInfants habitual sleep behavior (actimetry) is linked with their sleep neurophysiology (EEG) C_LIO_LIHabits of daytime sleeping (naps) are related to slow wave activity C_LIO_LIInfants movements and awakenings at nighttime are linked to their sleep spindles C_LIO_LISleep timing (infants bedtimes) is associated with cortical connectivity in the EEG C_LI

neuroscience↗

bioRxiv2021

A Comprehensive Overview of the Physical Health of the Adolescent Brain Cognitive Development Study (ABCD) Cohort at Baseline

Physical health in childhood is crucial for neurobiological as well as overall development, and can shape long-term outcomes into adulthood. The landmark, longitudinal Adolescent Brain Cognitive Development StudySM (ABCD study(R)), was designed to investigate brain development and health in almost 12,000 youth who were recruited when they were 9-10 years old and will be followed through adolescence and early adulthood. The overall goal of this paper is to provide descriptive analyses of physical health measures in the ABCD study at baseline, including but not limited to sleep, physical activity and sports involvement, and body mass index, and how these measures vary across demographic groups. This paper outlines how the physical health of the ABCD sample corresponds with that of the US population and highlights important avenues for health disparity research. This manuscript will provide important information for ABCD users and help guide analyses investigating physical health as it pertains to adolescent and young adult development.

developmental biology↗