Surge of neurophysiological coupling and connectivity of gamma oscillations in the dying human brain.

The brain is assumed to be hypoactive during cardiac arrest. However, animal models of cardiac and respiratory arrest demonstrate a surge of gamma oscillations and functional connectivity. To investigate whether these preclinical findings translate to humans, we analyzed electroencephalogram and electrocardiogram signals in four comatose dying patients before and after the withdrawal of ventilatory support. Two of the four patients exhibited a rapid and marked surge of gamma power, surge of cross-frequency coupling of gamma waves with slower oscillations, and increased interhemispheric functional and directed connectivity in gamma bands. High-frequency oscillations paralleled the activation of beta/gamma cross-frequency coupling within the somatosensory cortices. Importantly, both patients displayed surges of functional and directed connectivity at multiple frequency bands within the posterior cortical "hot zone," a region postulated to be critical for conscious processing. This gamma activity was stimulated by global hypoxia and surged further as cardiac conditions deteriorated in the dying patients. These data demonstrate that the surge of gamma power and connectivity observed in animal models of cardiac arrest can be observed in select patients during the process of dying.

Gut bacterial and fungal dysbiosis in tuberculosis patients.

BACKGROUND: Recent studies have more focused on gut microbial alteration in tuberculosis (TB) patients. However, no detailed study on gut fungi modification has been reported till now. So, current research explores the characteristics of gut microbiota (bacteria)- and mycobiota (fungi)-dysbiosis in TB patients and also assesses the correlation between the gut microbiome and serum cytokines. It may help to screen the potential diagnostic biomarker for TB. RESULTS: The results show that the alpha diversity of the gut microbiome (including bacteria and fungi) decreased and altered the gut microbiome composition of TB patients. The bacterial genera Bacteroides and Prevotella were significantly increased, and Blautia and Bifidobacterium decreased in the TB patients group. The fungi genus Saccharomyces was increased while decreased levels of Aspergillus in TB patients. It indicates that gut microbial equilibrium between bacteria and fungi has been altered in TB patients. The fungal-to-bacterial species ratio was significantly decreased, and the bacterial-fungal trans-kingdom interactions have been reduced in TB patients. A set model including Bacteroides, Blautia, Eubacterium_hallii_group, Apiotrichum, Penicillium, and Saccharomyces may provide a better TB diagnostics option than using single bacterial or fungi sets. Also, gut microbial dysbiosis has a strong correlation with the alteration of IL-17 and IFN-γ. CONCLUSIONS: Our results demonstrate that TB patients exhibit the gut bacterial and fungal dysbiosis. In the clinics, some gut microbes may be considered as potential biomarkers for auxiliary TB diagnosis.

The third case of Marbach-Rustad progeroid syndrome caused by a de novo LEMD2 variant.

Marbach-Rustad progeroid syndrome is an extremely rare disease caused by a heterozygous variant in the LEMD2 gene. To date, only two patients and one LEMD2 pathogenic variant have been reported in Marbach-Rustad progeroid syndrome. Here we describe the third case of Marbach-Rustad progeroid syndrome worldwide, which is also the first case in China. The proband was affected with premature birth, failed to thrive, facial abnormalities, feeding difficulties, skull defects and delayed motor milestones, but had a normal intelligence and speech. Whole exome sequencing (WES) initially did not find a phenotype-causing variant when the proband was 1 year of age. The reanalysis of WES data 4 years later revealed the proband harbored a de novo heterozygous c.1436C>T(p.Ser479Phe) variant in the LEMD2 gene, which is known responsible for Marbach-Rustad progeroid syndrome. Sanger sequencing confirmed the presence of this variant in the proband and absence in his parents and two elder sisters. Our study provides accurate clinical diagnosis for the proband and adds a new patient with Marbach-Rustad progeroid syndrome. Our study suggests the LEMD2 c.1436C>T(p.Ser479Phe) variant as a hotspot. Our work also indicates reanalysis of WES data of negative cases might identify pathogenic variant and improve diagnostic efficiency.

Consciousness and the Dying Brain.

The near-death experience has been reported since antiquity and is often characterized by the perception of light, interactions with other entities, and life recall. Near-death experiences can occur in a variety of situations, but they have been studied systematically after in-hospital cardiac arrest, with an incidence of 10 to 20%. Long attributed to metaphysical or supernatural causes, there have been recent advances in understanding the neurophysiologic basis of this unique category of conscious experience. This article reviews the epidemiology and neurobiology of near-death experiences, with a focus on clinical and laboratory evidence for a surge of neurophysiologic gamma oscillations and cortical connectivity after cardiac and respiratory arrest.

State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness.

BACKGROUND: Identifying the state-related "neural correlates of consciousness" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine). METHODS: The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia. RESULTS: The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001). CONCLUSIONS: Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.

Changes in information integration and brain networks during propofol-, dexmedetomidine-, and ketamine-induced unresponsiveness.

BACKGROUND: Information integration and network science are important theories for quantifying consciousness. However, whether these theories propose drug- or conscious state-related changes in EEG during anaesthesia-induced unresponsiveness remains unknown. METHODS: A total of 72 participants were randomised to receive i.v. infusion of propofol, dexmedetomidine, or ketamine at a constant infusion rate until loss of responsiveness. High-density EEG was recorded during the consciousness transition from the eye-closed baseline to the unresponsiveness state and then to the recovery of the responsiveness state. Permutation cross mutual information (PCMI) and PCMI-based brain networks in broadband (0.1-45 Hz) and sub-band frequencies were used to analyse drug- and state-related EEG signature changes. RESULTS: PCMI and brain networks exhibited state-related changes in certain brain regions and frequency bands. The within-area PCMI of the frontal, parietal, and occipital regions, and the between-area PCMI of the parietal-occipital region (median [inter-quartile ranges]), baseline vs unresponsive were as follows: 0.54 (0.46-0.58) vs 0.46 (0.40-0.50), 0.58 (0.52-0.60) vs 0.48 (0.44-0.53), 0.54 (0.49-0.59) vs 0.47 (0.42-0.52) decreased during anaesthesia for three drugs (P<0.05). Alpha PCMI in the frontal region, and gamma PCMI in the posterior area significantly decreased in the unresponsive state (P<0.05). The frontal, parietal, and occipital nodal clustering coefficients and parietal nodal efficiency decreased in the unresponsive state (P<0.05). The increased normalised path length in delta, theta, and gamma bands indicated impaired global integration (P<0.05). CONCLUSIONS: The three anaesthetics caused changes in information integration patterns and network functions. Thus, it is possible to build a quantifying framework for anaesthesia-induced conscious state changes on the EEG scale using PCMI and network science.

Measures of Information Content during Anesthesia and Emergence in the Caenorhabditis elegans Nervous System.

BACKGROUND: Suppression of behavioral and physical responses defines the anesthetized state. This is accompanied, in humans, by characteristic changes in electroencephalogram patterns. However, these measures reveal little about the neuron or circuit-level physiologic action of anesthetics nor how information is trafficked between neurons. This study assessed whether entropy-based metrics can differentiate between the awake and anesthetized state in Caenorhabditis elegans and characterize emergence from anesthesia at the level of interneuronal communication. METHODS: Volumetric fluorescence imaging measured neuronal activity across a large portion of the C. elegans nervous system at cellular resolution during distinct states of isoflurane anesthesia, as well as during emergence from the anesthetized state. Using a generalized model of interneuronal communication, new entropy metrics were empirically derived that can distinguish the awake and anesthetized states. RESULTS: This study derived three new entropy-based metrics that distinguish between stable awake and anesthetized states (isoflurane, n = 10) while possessing plausible physiologic interpretations. State decoupling is elevated in the anesthetized state (0%: 48.8 ± 3.50%; 4%: 66.9 ± 6.08%; 8%: 65.1 ± 5.16%; 0% vs. 4%, P < 0.001; 0% vs. 8%, P < 0.001), while internal predictability (0%: 46.0 ± 2.94%; 4%: 27.7 ± 5.13%; 8%: 30.5 ± 4.56%; 0% vs. 4%, P < 0.001; 0% vs. 8%, P < 0.001), and system consistency (0%: 2.64 ± 1.27%; 4%: 0.97 ± 1.38%; 8%: 1.14 ± 0.47%; 0% vs. 4%, P = 0.006; 0% vs. 8%, P = 0.015) are suppressed. These new metrics also resolve to baseline during gradual emergence of C. elegans from moderate levels of anesthesia to the awake state (n = 8). The results of this study show that early emergence from isoflurane anesthesia in C. elegans is characterized by the rapid resolution of an elevation in high frequency activity (n = 8, P = 0.032). The entropy-based metrics mutual information and transfer entropy, however, did not differentiate well between the awake and anesthetized states. CONCLUSIONS: Novel empirically derived entropy metrics better distinguish the awake and anesthetized states compared to extant metrics and reveal meaningful differences in information transfer characteristics between states.

Electroencephalographic Biomarkers, Cerebral Oximetry, and Postoperative Cognitive Function in Adult Noncardiac Surgical Patients: A Prospective Cohort Study.

BACKGROUND: Perioperative neurocognitive disorders are a major public health issue, although there are no validated neurophysiologic biomarkers that predict cognitive function after surgery. This study tested the hypothesis that preoperative posterior electroencephalographic alpha power, alpha frontal-parietal connectivity, and cerebral oximetry would each correlate with postoperative neurocognitive function. METHODS: This was a single-center, prospective, observational study of adult (older than 18 yr) male and female noncardiac surgery patients. Whole-scalp, 16-channel electroencephalography and cerebral oximetry were recorded in the preoperative, intraoperative, and immediate postoperative settings. The primary outcome was the mean postoperative T-score of three National Institutes of Health Toolbox Cognition tests-Flanker Inhibitory Control and Attention, List Sorting Working Memory, and Pattern Comparison Processing Speed. These tests were obtained at preoperative baseline and on the first two postoperative mornings. The lowest average score from the first two postoperative days was used for the primary analysis. Delirium was a secondary outcome (via 3-min Confusion Assessment Method) measured in the postanesthesia care unit and twice daily for the first 3 postoperative days. Last, patient-reported outcomes related to cognition and overall well-being were collected 3 months postdischarge. RESULTS: Sixty-four participants were recruited with a median (interquartile range) age of 59 (48 to 66) yr. After adjustment for baseline cognitive function scores, no significant partial correlation (ρ) was detected between postoperative cognition scores and preoperative relative posterior alpha power (%; ρ = -0.03, P = 0.854), alpha frontal-parietal connectivity (via weight phase lag index; ρ = -0.10, P = 0.570, respectively), or preoperative cerebral oximetry (%; ρ = 0.21, P = 0.246). Only intraoperative frontal-parietal theta connectivity was associated with postoperative delirium (F[1,6,291] = 4.53, P = 0.034). No electroencephalographic or oximetry biomarkers were associated with cognitive or functional outcomes 3 months postdischarge. CONCLUSIONS: Preoperative posterior alpha power, frontal-parietal connectivity, and cerebral oximetry were not associated with cognitive function after noncardiac surgery.

Image plane wavefront sensing and Kalman filtering for automated alignment of off-axis aspherics.

Automated alignment can significantly increase optical system precision and flexibility, and reduce time and labor costs in system setup and maintenance. We present an automated alignment technique on a double off-axis parabolic mirror system, which poses challenging alignment problems due to the mirrors' high sensitivity to aberrations, rotational asymmetry, and non-orthogonality in stage adjustments. In our methodology, we use focal plane wavefront sensing to eliminate the non-common path error, increase optical throughput, and reduce cost and system complexity. We incorporate model-based optimal estimation and control to better handle the nonlinearity, model uncertainty, and noise. Using either an iterated extended Kalman filter or a square-root unscented Kalman filter as the optimal nonlinear misalignment state estimator, we are able to consistently reduce the linear misalignment from around 1 mm to <5µm and the angular misalignment from around 500 to <6a r c s e c in simulation, achieving a final wavefront error of <5∗10-5 waves in the field of view when tested at wavelength 635 nm. We discover a multi-state coupling effect, which implies that different misalignment states have compensating effects on system measurements, thus interfering with the estimator's observation of misalignment state changes. We further investigate the coupling's effects on alignment quality through observability analysis.

Erythropoietin promotes myocardial infarction repair in mice by improving the function of Sca-1+ stem cells.

Myocardial infarction (MI) is one of the leading causes of death in the world. With the improvement of clinical therapy, the mortality of acute MI has been significantly reduced. However, as for the long-term impact of MI on cardiac remodeling and cardiac function, there is no effective prevention and treatment measures. Erythropoietin (EPO), a glycoprotein cytokine essential to hematopoiesis, has anti-apoptotic and pro-angiogenetic effects. Studies have shown that EPO plays a protective role in cardiomyocytes in cardiovascular diseases, such as cardiac ischemia injury and heart failure. EPO has been demonstrated to protect ischemic myocardium and improve MI repair by promoting the activation of cardiac progenitor cells (CPCs). This study aimed to investigate whether EPO can promote MI repair by enhancing the activity of stem cell antigen 1 positive stem cells (Sca-1+ SCs). Darbepoetin alpha (a long-acting EPO analog, EPOanlg) was injected into the border zone of MI in adult mice. Infarct size, cardiac remodeling and performance, cardiomyocyte apoptosis and microvessel density were measured. Lin- Sca-1+ SCs were isolated from neonatal and adult mouse hearts by magnetic sorting technology, and were used to identify the colony forming ability and the effect of EPO, respectively. The results showed that, compared to MI alone, EPOanlg reduced the infarct percentage, cardiomyocyte apoptosis ratio and left ventricular (LV) chamber dilatation, improved cardiac performance, and increased the numbers of coronary microvessels in vivo. In vitro, EPO increased the proliferation, migration and clone formation of Lin- Sca-1+ SCs likely via the EPO receptor and downstream STAT-5/p38 MAPK signaling pathways. These results suggest that EPO participates in the repair process of MI by activating Sca-1+ SCs.

[Effects of family dignity intervention on male infertility patients and their spouses].

OBJECTIVE: To investigate the effects of family dignity intervention (FDI) on anxiety, depression, hope level and quality of life (QOL) of male infertility patients and their spouses. METHODS: Using quasi-experimental design, we selected male infertility patients and their spouses undergoing human-assisted reproductive technology (ART) in our Center of Reproductive Medicine from June to December 2022 and divided them into an intervention group (38 couples) and a control group (40 couples). The former underwent a four-stage FDI, including ovulation promotion cycle assessment, family sharing, pre-transplantation interview and post-transplantation follow-up, while the latter received routine nursing. Using Hospital Anxiety and Depression Scale, Herth Hope Index and Fertility Quality of Life Scale, we evaluated the effects of FDI before and after transplantation. RESULTS: After FDI, the anxiety and depression scores were significantly lower (P < 0.05) and the total scores on the hope level and all other dimensions remarkably higher in the intervention group than in the control (P < 0.05). The self-confidence of the couples in the intervention groups in ART treatment was markedly increased in comparison with that of the controls, and their scores on physical and mental health were significantly higher than those of the latter (P < 0.05). CONCLUSION: FDI can effectively relieve the anxiety and depression, raise the hope level and improve the quality of life of both male infertility patients and their spouses.

Glutamatergic Neurons in the Preoptic Hypothalamus Promote Wakefulness, Destabilize NREM Sleep, Suppress REM Sleep, and Regulate Cortical Dynamics.

Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2+) neurons and show that their activation initiates wakefulness, decreases non-rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness.SIGNIFICANCE STATEMENT Historically, the preoptic area of the hypothalamus has been considered a key site for sleep generation. However, emerging modeling and empirical data suggest that this region might play a dual role in sleep-wake control. We demonstrate that chemogenetic stimulation of preoptic glutamatergic neurons produces brief arousals that fragment sleep, persistently suppresses REM sleep, causes hypothermia, and shifts EEG patterns toward a "lighter" NREM sleep state. We propose that preoptic glutamatergic neurons can initiate, but not maintain, arousal from sleep and gate REM sleep generation, possibly to block REM-like intrusions during NREM-to-wake transitions. In contrast to the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic, we provide further evidence that preoptic neurons also generate wakefulness.

IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis.

IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.

Dynamic reconfiguration of frequency-specific cortical coactivation patterns during psychedelic and anesthetized states induced by ketamine.

Recent neuroimaging studies have demonstrated that spontaneous brain activity exhibits rich spatiotemporal structure that can be characterized as the exploration of a repertoire of spatially distributed patterns that recur over time. The repertoire of brain states may reflect the capacity for consciousness, since general anesthetics suppress and psychedelic drugs enhance such dynamics. However, the modulation of brain activity repertoire across varying states of consciousness has not yet been studied in a systematic and unified framework. As a unique drug that has both psychedelic and anesthetic properties depending on the dose, ketamine offers an opportunity to examine brain reconfiguration dynamics along a continuum of consciousness. Here we investigated the dynamic organization of cortical activity during wakefulness and during altered states of consciousness induced by different doses of ketamine. Through k-means clustering analysis of the envelope data of source-localized electroencephalographic (EEG) signals, we identified a set of recurring states that represent frequency-specific spatial coactivation patterns. We quantified the effect of ketamine on individual brain states in terms of fractional occupancy and transition probabilities and found that ketamine anesthesia tends to shift the configuration toward brain states with low spatial variability. Furthermore, by assessing the temporal dynamics of the occurrence and transitions of brain states, we showed that subanesthetic ketamine is associated with a richer repertoire, while anesthetic ketamine induces dynamic changes in brain state organization, with the repertoire richness evolving from a reduced level to one comparable to that of normal wakefulness before recovery of consciousness. These results provide a novel description of ketamine's modulation of the dynamic configuration of cortical activity and advance understanding of the neurophysiological mechanism of ketamine in terms of the spatial, temporal, and spectral structures of underlying whole-brain dynamics.

Urethane anaesthesia exhibits neurophysiological correlates of unconsciousness and is distinct from sleep.

Urethane is a general anaesthetic widely used in animal research. The state of urethane anaesthesia is unique because it alternates between macroscopically distinct electrographic states: a slow-wave state that resembles non-rapid eye movement (NREM) sleep and an activated state with features of both REM sleep and wakefulness. Although it is assumed that urethane produces unconsciousness, this has been questioned because of states of cortical activation during drug exposure. Furthermore, the similarities and differences between urethane anaesthesia and physiological sleep are still unclear. In this study, we recorded the electroencephalogram (EEG) and electromyogram in chronically prepared rats during natural sleep-wake states and during urethane anaesthesia. We subsequently analysed the power, coherence, directed connectivity and complexity of brain oscillations and found that EEG under urethane anaesthesia has clear signatures of unconsciousness, with similarities to other general anaesthetics. In addition, the EEG profile under urethane is different in comparison with natural sleep states. These results suggest that consciousness is disrupted during urethane. Furthermore, despite similarities that have led others to conclude that urethane is a model of sleep, the electrocortical traits of depressed and activated states during urethane anaesthesia differ from physiological sleep states.

The first Chinese case of Siddiqi syndrome caused by a homozygous FITM2 variant.

A. The family pedigree. B. Whole exome sequencing of the proband-parent trio revealed c.611_612dupTG(p.M205*) variant of FITM2 gene as suspicious variant. C. Sanger sequencing confirmed that c.611_612dupTG(p.M205*) variant of FITM2 gene was homozygous in the proband, while the unaffected parents were heterozygous.

Brain Complexities and Anesthesia: Their Meaning and Measurement.

SUMMARY: A complex system is often associated with emergence of new phenomena from the interactions between the system's components. General anesthesia reduces brain complexity and so inhibits the emergence of consciousness. An understanding of complexity is necessary for the interpretation of brain monitoring algorithms. Complexity indices capture the "difficulty" of understanding brain activity over time and/or space. Complexity-entropy plots reveal the types of complexity indices and their balance of randomness and structure. Lempel-Ziv complexity is a common index of temporal complexity for single-channel electroencephalogram containing both power spectral and nonlinear effects, revealed by phase-randomized surrogate data. Computing spatial complexities involves forming a connectivity matrix and calculating the complexity of connectivity patterns. Spatiotemporal complexity can be estimated in multiple ways including temporal or spatial concatenation, estimation of state switching, or integrated information. This article illustrates the concept and application of various complexities by providing working examples; a website with interactive demonstrations has also been created.

Constrained Functional Connectivity Dynamics in Pediatric Surgical Patients Undergoing General Anesthesia.

BACKGROUND: Functional connectivity in cortical networks is thought to be important for consciousness and can be disrupted during the anesthetized state. Recent work in adults has revealed dynamic connectivity patterns during stable general anesthesia, but whether similar connectivity state transitions occur in the developing brain remains undetermined. The hypothesis was that anesthetic-induced unconsciousness is associated with disruption of functional connectivity in the developing brain and that, as in adults, there are dynamic shifts in connectivity patterns during the stable maintenance phase of general anesthesia. METHODS: This was a preplanned analysis of a previously reported single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists status I or II) children aged 8 to 16 yr undergoing surgery with general anesthesia (n = 50) at Michigan Medicine. Whole-scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Functional connectivity was measured using a weighted phase lag index, and discrete connectivity states were classified using cluster analysis. RESULTS: Changes in functional connectivity were associated with anesthetic state transitions across multiple regions and frequency bands. An increase in prefrontal-frontal alpha (median [25th, 75th]; baseline, 0.070 [0.049, 0.101] vs. maintenance 0.474 [0.286, 0.606]; P < 0.001) and theta connectivity (0.038 [0.029, 0.048] vs. 0.399 [0.254, 0.488]; P < 0.001), and decrease in parietal-occipital alpha connectivity (0.171 [0.145, 0.243] vs. 0.089 [0.055, 0.132]; P < 0.001) were among those with the greatest effect size. Contrary to the hypothesis, connectivity patterns during the maintenance phase of general anesthesia were dominated by stable theta and alpha prefrontal-frontal and alpha frontal-parietal connectivity and exhibited high between-cluster similarity (r = 0.75 to 0.87). CONCLUSIONS: Changes in functional connectivity are associated with anesthetic state transitions but, unlike in adults, connectivity patterns are constrained during general anesthesia in late childhood and early adolescence.

Blastocyst euploidy rates in low-prognosis patients according to the POSEIDON criteria: a retrospective analysis of 3016 embryos.

RESEARCH QUESTION: Do embryo euploidy rates differ in the four groups of women with low prognosis as stratified by the POSEIDON criteria? DESIGN: This was a retrospective cohort study of low-prognosis patients who met the POSEIDON criteria and underwent preimplantation genetic testing for aneuploidies (PGT-A) from January 2013 to June 2020 at the Center for Reproductive Medicine, Shandong University, China. A total of 3016 blastocysts from 1269 PGT-A cycles were included in the study. The primary outcome was the euploidy rate of the blastocysts. For each group, regression analyses were performed to quantitatively describe the relationship between maternal age and embryo euploidy rate. RESULTS: The euploidy rate of embryos in women with poor ovarian response (POR) was 39.1% in total. There were 727, 1052, 275 and 962 blastocysts in groups 1, 2, 3 and 4, respectively, with corresponding embryo euploidy rates of 57.2%, 34.9%, 52.4% and 26.2% (P < 0.001). Within each group, the euploidy rate decreased with age, especially in women aged 35 years or older (i.e. groups 2 and 4). CONCLUSIONS: Euploidy rates were more favourable in groups 1 and 3, of a young age, re-emphasizing that oocyte quality is the primary factor determining embryo euploidy rate. The study's findings demonstrated the reasonability of categorizing women with POR by the POSEIDON criteria depending on female age and ovarian reserve biomarkers. These results also provide information for women with POR in different subgroups so they can receive proper counselling on the possible prognosis.

Cortical Acetylcholine Levels Correlate With Neurophysiologic Complexity During Subanesthetic Ketamine and Nitrous Oxide Exposure in Rats.

BACKGROUND: Neurophysiologic complexity has been shown to decrease during states characterized by a depressed level of consciousness, such as sleep or anesthesia. Conversely, neurophysiologic complexity is increased during exposure to serotonergic psychedelics or subanesthetic doses of dissociative anesthetics. However, the neurochemical substrates underlying changes in neurophysiologic complexity are poorly characterized. Cortical acetylcholine appears to relate to cortical activation and changes in states of consciousness, but the relationship between cortical acetylcholine and complexity has not been formally studied. We addressed this gap by analyzing simultaneous changes in cortical acetylcholine (prefrontal and parietal) and neurophysiologic complexity before, during, and after subanesthetic ketamine (10 mg/kg/h) or 50% nitrous oxide. METHODS: Under isoflurane anesthesia, adult Sprague Dawley rats (n = 24, 12 male and 12 female) were implanted with stainless-steel electrodes across the cortex to record monopolar electroencephalogram (0.5-175 Hz; 30 channels) and guide canulae in prefrontal and parietal cortices for local microdialysis quantification of acetylcholine levels. One subgroup of these rats was instrumented with a chronic catheter in jugular vein for ketamine infusion (n = 12, 6 male and 6 female). The electroencephalographic data were analyzed to determine subanesthetic ketamine or nitrous oxide-induced changes in Lempel-Ziv complexity and directed frontoparietal connectivity. Changes in complexity and connectivity were analyzed for correlation with concurrent changes in prefrontal and parietal acetylcholine. RESULTS: Subanesthetic ketamine produced sustained increases in normalized Lempel-Ziv complexity (0.5-175 Hz; P < .001) and high gamma frontoparietal connectivity (125-175 Hz; P < .001). This was accompanied by progressive increases in prefrontal (104%; P < .001) and parietal (159%; P < .001) acetylcholine levels that peaked after 50 minutes of infusion. Nitrous oxide induction produced a transient increase in complexity (P < .05) and high gamma connectivity (P < .001), which was accompanied by increases (P < .001) in prefrontal (56%) and parietal (43%) acetylcholine levels. In contrast, the final 50 minutes of nitrous oxide administration were characterized by a decrease in prefrontal (38%; P < .001) and parietal (45%; P < .001) acetylcholine levels, reduced complexity (P < .001), and comparatively weaker frontoparietal high gamma connectivity (P < .001). Cortical acetylcholine and complexity were correlated with both subanesthetic ketamine (prefrontal: cluster-weighted marginal correlation [CW r] [144] = 0.42, P < .001; parietal: CW r[144] = 0.42, P < .001) and nitrous oxide (prefrontal: CW r[156] = 0.46, P < .001; parietal: CW r[156] = 0.56, P < .001) cohorts. CONCLUSIONS: These data bridge changes in cortical acetylcholine with concurrent changes in neurophysiologic complexity, frontoparietal connectivity, and the level of consciousness.