Repeated caffeine intake suppresses cerebral grey matter responses to chronic sleep restriction in an A1 adenosine receptor-dependent manner: a double-blind randomized controlled study with PET-MRI.

Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chronic sleep restriction, CSR), and (2) whether the potential impact on GM plasticity depends on individual differences in the availability of adenosine receptors, which are involved in mediating effects of caffeine on sleep and waking function. Thirty-six healthy adults participated in this double-blind, randomized, controlled study (age = 28.9 ± 5.2 y/; F:M = 15:21; habitual level of caffeine intake < 450 mg; 29 homozygous C/C allele carriers of rs5751876 of ADORA2A, an A2A adenosine receptor gene variant). Each participant underwent a 9-day laboratory visit consisting of one adaptation day, 2 baseline days (BL), 5-day sleep restriction (5 h time-in-bed), and a recovery day (REC) after an 8-h sleep opportunity. Nineteen participants received 300 mg caffeine in coffee through the 5 days of CSR (CAFF group), while 17 matched participants received decaffeinated coffee (DECAF group). We examined GM changes on the 2nd BL Day, 5th CSR Day, and REC Day using magnetic resonance imaging and voxel-based morphometry. Moreover, we used positron emission tomography with [18F]-CPFPX to quantify the baseline availability of A1 adenosine receptors (A1R) and its relation to the GM plasticity. The results from the voxel-wise multimodal whole-brain analysis on the Jacobian-modulated T1-weighted images controlled for variances of cerebral blood flow indicated a significant interaction effect between caffeine and CSR in four brain regions: (a) right temporal-occipital region, (b) right dorsomedial prefrontal cortex (DmPFC), (c) left dorsolateral prefrontal cortex (DLPFC), and (d) right thalamus. The post-hoc analyses on the signal intensity of these GM clusters indicated that, compared to BL, GM on the CSR day was increased in the DECAF group in all clusters  but decreased in the thalamus, DmPFC, and DLPFC in the CAFF group. Furthermore, lower baseline subcortical A1R availability predicted a larger GM reduction in the CAFF group after CSR of all brain regions except for the thalamus. In conclusion, our data suggest an adaptive GM upregulation after 5-day CSR, while concomitant use of caffeine instead leads to a GM reduction. The lack of consistent association with individual A1R availability may suggest that CSR and caffeine affect thalamic GM plasticity predominantly by a different mechanism. Future studies on the role of adenosine A2A receptors in CSR-induced GM plasticity are warranted.

Dynamic neuroreceptor positron emission tomography in non-anesthetized rats using point source based motion correction: A feasibility study with [11C]ABP688.

To prevent motion artifacts in small animal positron emission tomography (PET), animals are routinely scanned under anesthesia or physical restraint. Both may potentially alter metabolism and neurochemistry. This study investigates the feasibility of fully awake acquisition and subsequent absolute quantification of dynamic brain PET data via pharmacokinetic modelling in moving rats using the glutamate 5 receptor radioligand [11C]ABP688 and point source based motion correction. Five male rats underwent three dynamic [11C]ABP688 PET scans: two test-retest awake PET scans and one scan under anesthesia for comparison. Specific radioligand binding was determined via the simplified reference tissue model (reference: cerebellum) and outcome parameters BPND and R1 were evaluated in terms of stability and reproducibility. Test-retest measurements in awake animals gave reliable results with high correlations of BPND (y = 1.08 × -0.2, r = 0.99, p < 0.01) and an acceptable variability (mean over all investigated regions 15.7 ± 2.4%). Regional [11C]ABP688 BPNDs under awake and anesthetized conditions were comparable although in awake scans, absolute radioactive peak uptakes were lower and relative blood flow in terms of R1 was higher. Awake small animal PET with absolute quantification of neuroreceptor availability is technically feasible and reproducible thereby providing a suitable alternative whenever effects of anesthesia are undesirable, e.g. in sleep research.

Period of hospitalization and mortality in transferred versus non-transferred COVID-19 patients: results from Germany.

COVID-19 was a challenge for health-care systems worldwide, causing large numbers of hospitalizations and inter-hospital transfers. We studied whether transfer, as well as its reason, was associated with the duration of hospitalization in non-ICU and ICU patients. For this purpose, all patients hospitalized due to COVID-19 between August 1st and December 31st, 2021, in a network of hospitals in Southern Germany were comprehensively characterized regarding their clinical course, therapy, complications, transfers, reasons for transfer, involved levels of care, total period of hospitalization and in-hospital mortality, using univariate and multiple regression analyses. While mortality was not significantly associated with transfer, the period of hospitalization was. In non-ICU patients (n = 545), median (quartiles) time was 7.0 (4.0-11.0) in non-transferred (n = 458) and 18.0 (11.0-29.0) days in transferred (n = 87) patients (p < 0.001). In ICU patients (n = 100 transferred, n = 115 non-transferred) it was 12.0 (8.3-18.0) and 22.0 (15.0-34.0) days (p < 0.001). Beyond ECMO therapy (4.5%), reasons for transfer were medical (33.2%) or capacity (61.9%) reasons, with medical/capacity reasons in 32/49 of non-ICU and 21/74 of ICU patients. Thus, the transfer of COVID-19 patients between hospitals was associated with longer periods of hospitalization, corresponding to greater health care utilization, for which specific patient characteristics and clinical decisions played a role.

Adverse childhood experiences and crime outcomes in early adulthood: A multi-method approach in a Brazilian birth cohort.

This study aimed to investigate alternative approaches to a cumulative risk score in the relationship between adverse childhood experiences (ACEs) and crime. Using data from the 1993 Pelotas (Brazil) Birth Cohort (n = 3236), we measured 12 ACEs up to 15 years, and past-year violent and non-violent crime at 22 years. We used four analytical approaches: single adversities, cumulative risk, latent class analysis, and network analysis. When examined individually, physical abuse, emotional abuse, and domestic violence were associated with both crime outcomes, whereas maternal mental illness and discrimination were associated with violent crime only, and parental divorce and poverty with non-violent crime only. There was a cumulative effect of ACEs on crime. The class with child maltreatment and household challenges was associated with both crime outcomes; exposure to household challenges and social risks was associated with violent crime only. In network models, crime showed conditional associations with physical abuse, maternal mental illness, and parental divorce. Although cumulative ACEs did associate with crime, some individual and combinations of ACEs showed particularly strong and robust effects, which were not captured by the cumulative score. Many ACEs are closely connected and/or cluster together, and the usefulness of the ACE score needs to be further evaluated.

Maternal experienced bereavement and offspring mental health in early adulthood: the role of modifiable parental factors.

BACKGROUND: It is estimated that 78% of children experience the death of a close friend or family member by 16 years of age, yet longitudinal research examining the mental health outcomes of wider experiences of bereavement is scarce. We conducted a longitudinal investigation of the association between maternal experienced bereavement before the age of 11 years and offspring depressive and anxiety disorders at age 18 and examined moderation of this association by modifiable parental factors. METHODS: We analysed data from the Avon Longitudinal Study of Parents and Children, a UK-based birth cohort, including 9,088 child participants with data available on bereavement. Bereavement was measured via maternal report at eight timepoints until children were 11 years. Offspring depressive and anxiety-related disorders were self-reported at 18 years old using the Clinical Interview Schedule-Revised (CIS-R). The potential moderating roles of maternal anxiety, maternal depression, parental monitoring, positive parenting and negative parenting practices were examined. RESULTS: Maternal experienced bereavement was not associated with depression or anxiety-related disorders in early adulthood among offspring. In addition, no support was found for negative parenting practices, parental monitoring or maternal anxiety and depression as moderators of the relationship between maternal experienced bereavement and offspring mental health problems at 18 years old. Findings in relation to the moderating role of positive parenting practices were inconsistent. CONCLUSIONS: Findings suggest that a large number of children are exposed to maternal experienced bereavement. We found no evidence that maternal experienced bereavement during childhood increases the risk for offspring psychiatric disorders in early adulthood. Several methodological considerations prudent to bereavement research are discussed.

Intraoperative contrast-enhanced ultrasound has an outcome-relevant impact on surgery of primary and metastatic liver lesions.

PURPOSE: Complete resection of the affected tissue remains the best curative treatment option for liver-derived tumors and colorectal liver metastases. In addition to preoperative cross-sectional imaging, contrast-enhanced intraoperative ultrasound (CE-IOUS) plays a crucial role in the detection and localization of all liver lesions. However, its exact role is unclear. This study was designed to evaluate the clinical and oncological impact of using CE-IOUS in the surgical treatment of these diseases. MATERIALS AND METHODS: Over the three-year study period, 206 patients with primary liver tumors and hepatic metastases were enrolled in this prospective, monocentric study to evaluate the impact of CE-IOUS in liver surgery. Secondary outcomes included comparing the sensitivity and specificity of CE-IOUS with existing preoperative imaging modalities and identifying preoperative parameters that could predict a strategic impact of CE-IOUS. In addition, the oncological significance of CE-IOUS was evaluated using a case-cohort design with a minimum follow-up of 18 months. RESULTS: CE-IOUS findings led to a change in surgical strategy in 34% of cases (n=70/206). The accuracy in cases with a major change could be confirmed histopathologically in 71.4% of cases (n=25/35). The impact could not be predicted using parameters assumed to be clinically relevant. An oncological benefit of a CE-IOUS adapted surgical approach was demonstrated in patients suffering from HCC and colorectal liver metastases. CONCLUSION: CE-IOUS may significantly increase R0 resection rates and should therefore be used routinely as an additional staging method, especially in complex liver surgery.

Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation.

The inverse effects of creatine supplementation and sleep deprivation on high energy phosphates, neural creatine, and cognitive performances suggest that creatine is a suitable candidate for reducing the negative effects of sleep deprivation. With this, the main obstacle is the limited exogenous uptake by the central nervous system (CNS), making creatine only effective over a long-term diet of weeks. Thus far, only repeated dosing of creatine over weeks has been studied, yielding detectable changes in CNS levels. Based on the hypothesis that a high extracellular creatine availability and increased intracellular energy consumption will temporarily increase the central creatine uptake, subjects were orally administered a high single dose of creatinemonohydrate (0.35 g/kg) while performing cognitive tests during sleep deprivation. Two consecutive 31P-MRS scans, 1H-MRS, and cognitive tests were performed each at evening baseline, 3, 5.5, and 7.5 h after single dose creatine (0.35 g/kg) or placebo during sub-total 21 h sleep deprivation (SD). Our results show that creatine induces changes in PCr/Pi, ATP, tCr/tNAA, prevents a drop in pH level, and improves cognitive performance and processing speed. These outcomes suggest that a high single dose of creatine can partially reverse metabolic alterations and fatigue-related cognitive deterioration.

Early risk factors for conduct problem trajectories from childhood to adolescence: the 2004 Pelotas (BRAZIL) Birth Cohort.

Conduct problems are associated with an increased risk of a wide range of physical, mental, and social problems. However, there is still uncertainty about how early risk factors differentiate different developmental patterns of conduct problems and whether findings replicate across diverse social contexts. We aimed to identify developmental trajectories of conduct problems, and test early risk factors, in the 2004 Pelotas Birth Cohort in Brazil. Conduct problems were measured at ages 4, 6, 11, and 15 years from caregiver reports on the Child Behaviour Checklist (CBCL) and Strengths and Difficulties Questionnaire (SDQ). Conduct problem trajectories were estimated using group-based semi-parametric modeling (n = 3938). Multinomial logistic regression was used to examine associations between early risk factors and conduct problem trajectories. We identified four trajectories: three with elevated conduct problems, including early-onset persistent (n = 150; 3.8%), adolescence-onset (n = 286; 17.3%), and childhood-limited (n = 697; 17.7%), and one with low conduct problems (n = 2805; 71.2%). The three elevated conduct problem trajectories were associated with a wide range of sociodemographic risk factors, prenatal smoking, maternal mental health, harsh parenting, childhood trauma, and child neurodevelopmental risk factors. Early-onset persistent conduct problems were particularly associated with trauma, living without a father figure, and attention difficulties. The four trajectories of conduct problems from ages 4 to 15 years in this Brazilian cohort have similar longitudinal patterns to those identified in high-income countries. The results confirm previous longitudinal research and developmental taxonomic theories on the etiology of conduct problems in a Brazilian sample.

Pathways from maternal depression to child resilience: Socioeconomic, family, and individual factors in the 2004 Pelotas (Brazil) birth cohort.

Background: The negative impacts of maternal depression on child mental health outcomes are well-documented. However, some children show adaptive functioning following exposure to maternal depression, demonstrating resilience. In a large birth cohort from Brazil, a middle-income country, we examined direct and indirect pathways, considering socioeconomic, family, and individual factors, contributing to the development of resilience. Methods: Using data from the 2004 Pelotas Birth Cohort (N = 4231), we restricted the sample to those exposed to maternal depression up to age 6 years (depression present at ≥2 out of 5 assessment waves; n = 1132; 50% boys). Resilience was defined as scoring below or equal to the mean of the unexposed group on all four problem subscales of the parent-report Strengths and Difficulties Questionnaire at age 11 years. We examined pathways from socioeconomic status (SES; measured at birth) to resilience via cognitive stimulation (CS) (at 24 and 48 months) and Intelligence quotient (IQ) (at 6 years), and from CS to resilience via IQ, using counterfactual mediation. Results: A minority of children exposed to maternal depression showed resilience (12.4%). There was evidence of indirect pathways from SES to resilience via CS (odds ratio (OR) = 1.76, 95% confidence interval (CI) 1.02-3.38) and IQ (OR = 1.19, 95% CI 1.01-1.42), such that higher SES was associated with resilience via both higher levels of CS and higher IQ, which, in turn, were each positively associated with resilience. Furthermore, there was evidence of a direct (OR = 1.86, 95% CI 1.01-3.76) and total effect (OR = 1.94, 95% CI 1.05-3.89) of CS on resilience, even after controlling for SES. However, these effects varied depending on how persistent and severe depression was defined. Conclusions: These findings suggest that CS in early childhood may represent a modifiable protective factor for children exposed to maternal depression and a promising intervention target to promote child resilience in the context of maternal depression exposure.

Fiber alignment in 3D collagen networks as a biophysical marker for cell contractility.

Cells cultured in 3D fibrous biopolymer matrices exert traction forces on their environment that induce deformations and remodeling of the fiber network. By measuring these deformations, the traction forces can be reconstructed if the mechanical properties of the matrix and the force-free matrix configuration are known. These requirements limit the applicability of traction force reconstruction in practice. In this study, we test whether force-induced matrix remodeling can instead be used as a proxy for cellular traction forces. We measure the traction forces of hepatic stellate cells and different glioblastoma cell lines and quantify matrix remodeling by measuring the fiber orientation and fiber density around these cells. In agreement with simulated fiber networks, we demonstrate that changes in local fiber orientation and density are directly related to cell forces. By resolving Rho-kinase (ROCK) inhibitor-induced changes of traction forces, fiber alignment, and fiber density in hepatic stellate cells, we show that the method is suitable for drug screening assays. We conclude that differences in local fiber orientation and density, which are easily measurable, can be used as a qualitative proxy for changes in traction forces. The method is available as an open-source Python package with a graphical user interface.

NECAB2 is an endosomal protein important for striatal function.

Synaptic signaling depends on ATP generated by mitochondria. Dysfunctional mitochondria shift the redox balance towards a more oxidative environment. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction. We found that neuronal calcium-binding protein 2 (NECAB2) plays a role in striatal function and mitochondrial homeostasis. NECAB2 is a predominantly endosomal striatal protein which partially colocalizes with mitochondria. This colocalization is enhanced by mild oxidative stress. Global knockout of Necab2 in the mouse results in increased superoxide levels, increased DNA oxidation and reduced levels of the antioxidant glutathione which correlates with an altered mitochondrial shape and function. Striatal mitochondria from Necab2 knockout mice are more abundant and smaller and characterized by a reduced spare capacity suggestive of intrinsic uncoupling respectively mitochondrial dysfunction. In line with this, we also found an altered stress-induced interaction of endosomes with mitochondria in Necab2 knockout striatal cultures. The predominance of dysfunctional mitochondria and the pro-oxidative redox milieu correlates with a loss of striatal synapses and behavioral changes characteristic of striatal dysfunction like reduced motivation and altered sensory gating. Together this suggests an involvement of NECAB2 in an endosomal pathway of mitochondrial stress response important for striatal function.

A genetic variation in the adenosine A2A receptor gene contributes to variability in oscillatory alpha power in wake and sleep EEG and A1 adenosine receptor availability in the human brain.

The EEG alpha rhythm (∼ 8-13 Hz) is one of the most salient human brain activity rhythms, modulated by the level of attention and vigilance and related to cerebral energy metabolism. Spectral power in the alpha range in wakefulness and sleep strongly varies among individuals based on genetic predisposition. Knowledge about the underlying genes is scarce, yet small studies indicated that the variant rs5751876 of the gene encoding A2A adenosine receptors (ADORA2A) may contribute to the inter-individual variation. The neuromodulator adenosine is directly linked to energy metabolism as product of adenosine tri-phosphate breakdown and acts as a sleep promoting molecule by activating A1 and A2A adenosine receptors. We performed sleep and positron emission tomography studies in 59 healthy carriers of different rs5751876 alleles, and quantified EEG oscillatory alpha power in wakefulness and sleep, as well as A1 adenosine receptor availability with 18F-CPFPX. Oscillatory alpha power was higher in homozygous C-allele carriers (n = 27, 11 females) compared to heterozygous and homozygous carriers of the T-allele (n(C/T) = 23, n(T/T) = 5, 13 females) (F(18,37) = 2.35, p = 0.014, Wilk's Λ = 0.487). Furthermore, a modulatory effect of ADORA2A genotype on A1 adenosine receptor binding potential was found across all considered brain regions (F(18,40) = 2.62, p = 0.006, Wilk's Λ = 0.459), which remained significant for circumscribed occipital region of calcarine fissures after correction for multiple comparisons. In female participants, a correlation between individual differences in oscillatory alpha power and A1 receptor availability was observed. In conclusion, we confirmed that a genetic variant of ADORA2A affects individual alpha power, while a direct modulatory effect via A1 adenosine receptors in females is suggested.

Quantum oscillations of the quasiparticle lifetime in a metal.

Following nearly a century of research, it remains a puzzle that the low-lying excitations of metals are remarkably well explained by effective single-particle theories of non-interacting bands1-4. The abundance of interactions in real materials raises the question of direct spectroscopic signatures of phenomena beyond effective single-particle, single-band behaviour. Here we report the identification of quantum oscillations (QOs) in the three-dimensional topological semimetal CoSi, which defy the standard description in two fundamental aspects. First, the oscillation frequency corresponds to the difference of semiclassical quasiparticle (QP) orbits of two bands, which are forbidden as half of the trajectory would oppose the Lorentz force. Second, the oscillations exist up to above 50 K, in strong contrast to all other oscillatory components, which vanish below a few kelvin. Our findings are in excellent agreement with generic model calculations of QOs of the QP lifetime (QPL). Because the only precondition for their existence is a nonlinear coupling of at least two electronic orbits, for example, owing to QP scattering on defects or collective excitations, such QOs of the QPL are generic for any metal featuring Landau quantization with several orbits. They are consistent with certain frequencies in topological semimetals5-9, unconventional superconductors10,11, rare-earth compounds12-14 and Rashba systems15, and permit to identify and gauge correlation phenomena, for example, in two-dimensional materials16,17 and multiband metals18.

Resonant Elastic X-Ray Scattering of Antiferromagnetic Superstructures in EuPtSi_{3}.

We report resonant elastic x-ray scattering of long-range magnetic order in EuPtSi_{3}, combining different scattering geometries with full linear polarization analysis to unambiguously identify magnetic scattering contributions. At low temperatures, EuPtSi_{3} stabilizes type A antiferromagnetism featuring various long-wavelength modulations. For magnetic fields applied in the hard magnetic basal plane, well-defined regimes of cycloidal, conical, and fanlike superstructures may be distinguished that encompass a pocket of commensurate type A order without superstructure. For magnetic field applied along the easy axis, the phase diagram comprises the cycloidal and conical superstructures only. Highlighting the power of polarized resonant elastic x-ray scattering, our results reveal a combination of magnetic phases that suggest a highly unusual competition between antiferromagnetic exchange interactions with Dzyaloshinsky-Moriya spin-orbit coupling of similar strength.

Effects of electroconvulsive therapy on cerebral A1 adenosine receptor availability: a PET study in patients suffering from treatment-resistant major depressive disorder.

Introduction: Sleep deprivation and electroconvulsive therapy (ECT) effectively ameliorate symptoms in major depressive disorder (MDD). In rodents, both are associated with an enhancement of cerebral adenosine levels, which in turn likely influence adenosinergic receptor expression. The aim of the current study was to investigate cerebral A1 adenosine receptor (A1AR) availability in patients with MDD as a potential mediating factor of antidepressant effects of ECT using [18F]CPFPX and positron emission tomography (PET). Methods: Regional A1AR availability was determined before and after a series of ECT applications (mean number ± SD 10.4 ± 1.2) in 14 subjects (4 males, mean age 49.5 ± 11.8 years). Clinical outcome, measured by neuropsychological testing, and ECT parameters were correlated with changes in A1AR availability. Results: ECT had a strong antidepressive effect (p < 0.01) while on average cerebral A1AR availability remained unaltered between pre-and post-ECT conditions (F = 0.65, p = 0.42, mean difference ± SD 3.93% ± 22.7%). There was no correlation between changes in clinical outcome parameters and regional A1AR availability, although individual patients showed striking bidirectional alterations of up to 30-40% in A1AR availability after ECT. Solely, for the mean seizure quality index of the applied ECTs a significant association with changes in A1AR availability was found (rs = -0.6, p = 0.02). Discussion: In the present study, therapeutically effective ECT treatment did not result in coherent changes of A1AR availability after a series of ECT treatments. These findings do not exclude a potential role for cerebral A1ARs in ECT, but shift attention to rather short-termed and adaptive mechanisms during ECT-related convulsive effects.

Noninvasive Assessment of Arterial Pulse-Pressure Variation During General Anesthesia: Clinical Evaluation of a New High-Fidelity Upper Arm Cuff.

OBJECTIVES: To compare noninvasive pulse-pressure variation (PPV) measurements obtained from a new high-fidelity upper arm cuff using a hydraulic coupling technique to corresponding intraarterial PPV measurements. DESIGN: The authors used prospective multicenter comparison and development studies for the new high-fidelity upper arm cuff. SETTING: The study was performed in the departments of Anesthesiology at the Ludwig-Maximilians-Universität München Hospital, the University Hospital of Bonn, and the RoMed Hospital in Rosenheim (all Germany). PARTICIPANTS: A total of 153 patients were enrolled, undergoing major abdominal surgery or neurosurgery with mechanical ventilation. For the evaluation of PPV, 1,467 paired measurements in 107 patients were available after exclusion due to predefined quality criteria. INTERVENTIONS: Simultaneous measurements of PPV were performed from a reference femoral arterial catheter (PPVref) and the high-fidelity upper arm cuff (PPVcuff). The new device uses a semirigid conical shell. It incorporates a hydraulic sensor pad with a pressure transducer, leading to a tissue pressure-pulse contour with all characteristics of an arterial- pulse contour. MEASUREMENTS AND MAIN RESULTS: The comparative analysis of the included measurements showed that PPVref and PPVcuff were closely correlated (r = 0.92). The mean of the differences between PPVref and PPVcuff was 0.1 ± 2.0%, with 95% limits of agreement between -4.1% and 3.9%. To track absolute changes in PPV >2%, the concordance rate between the 2 methods was 93%. CONCLUSIONS: The new high-fidelity upper arm cuff method provided a clinically reliable estimate of PPV.

Associations between resting state brain activity and A1 adenosine receptor availability in the healthy brain: Effects of acute sleep deprivation.

Introduction: Previous resting-state fMRI (Rs-fMRI) and positron emission tomography (PET) studies have shown that sleep deprivation (SD) affects both spontaneous brain activity and A1 adenosine receptor (A1AR) availability. Nevertheless, the hypothesis that the neuromodulatory adenosinergic system acts as regulator of the individual neuronal activity remains unexplored. Methods: Therefore, fourteen young men underwent Rs-fMRI, A1AR PET scans, and neuropsychological tests after 52 h of SD and after 14 h of recovery sleep. Results: Our findings suggested higher oscillations or regional homogeneity in multiple temporal and visual cortices, whereas decreased oscillations in cerebellum after sleep loss. At the same time, we found that connectivity strengths increased in sensorimotor areas and decreased in subcortical areas and cerebellum. Discussion: Moreover, negative correlations between A1AR availability and rs-fMRI metrics of BOLD activity in the left superior/middle temporal gyrus and left postcentral gyrus of the human brain provide new insights into the molecular basis of neuronal responses induced by high homeostatic sleep pressure.

External to internal cranial perfusion shifts during simulated weightlessness: Results from a randomized cross-over trial.

The exact pathophysiology of the spaceflight-associated neuro-ocular syndrome (SANS) has so far not been completely elucidated. In this study we assessed the effect of acute head-down tilt position on the mean flow of the intra- and extracranial vessels. Our results suggest a shift from the external to the internal system that might play an important role in the pathomechanism of SANS.

Total Sleep Deprivation Increases Brain Age Prediction Reversibly in Multisite Samples of Young Healthy Adults.

Sleep loss pervasively affects the human brain at multiple levels. Age-related changes in several sleep characteristics indicate that reduced sleep quality is a frequent characteristic of aging. Conversely, sleep disruption may accelerate the aging process, yet it is not known what will happen to the age status of the brain if we can manipulate sleep conditions. To tackle this question, we used an approach of brain age to investigate whether sleep loss would cause age-related changes in the brain. We included MRI data of 134 healthy volunteers (mean chronological age of 25.3 between the age of 19 and 39 years, 42 females/92 males) from five datasets with different sleep conditions. Across three datasets with the condition of total sleep deprivation (>24 h of prolonged wakefulness), we consistently observed that total sleep deprivation increased brain age by 1-2 years regarding the group mean difference with the baseline. Interestingly, after one night of recovery sleep, brain age was not different from baseline. We also demonstrated the associations between the change in brain age after total sleep deprivation and the sleep variables measured during the recovery night. By contrast, brain age was not significantly changed by either acute (3 h time-in-bed for one night) or chronic partial sleep restriction (5 h time-in-bed for five continuous nights). Together, the convergent findings indicate that acute total sleep loss changes brain morphology in an aging-like direction in young participants and that these changes are reversible by recovery sleep.SIGNIFICANCE STATEMENT Sleep is fundamental for humans to maintain normal physical and psychological functions. Experimental sleep deprivation is a variable-controlling approach to engaging the brain among different sleep conditions for investigating the responses of the brain to sleep loss. Here, we quantified the response of the brain to sleep deprivation by using the change of brain age predictable with brain morphologic features. In three independent datasets, we consistently found increased brain age after total sleep deprivation, which was associated with the change in sleep variables. Moreover, no significant change in brain age was found after partial sleep deprivation in another two datasets. Our study provides new evidence to explain the brainwide effect of sleep loss in an aging-like direction.