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Abstract The primate including the human hippocampus implicated in episodic memory and navigation represents a spatial view, very different from the place representations in rodents. To understand this system in humans, and the computations performed, the pathway for this spatial view information to reach the hippocampus was analysed in humans. Whole-brain effective connectivity was measured with magnetoencephalography between 30 visual cortical regions and 150 other cortical regions using the HCP-MMP1 atlas in 21 participants while performing a 0-back scene memory task. In a ventromedial visual stream, V1–V4 connect to the ProStriate region where the retrosplenial scene area is located. The ProStriate region has connectivity to ventromedial visual regions VMV1–3 and VVC. These ventromedial regions connect to the medial parahippocampal region PHA1–3, which, with the VMV regions, include the parahippocampal scene area. The medial parahippocampal regions have effective connectivity to the entorhinal cortex, perirhinal cortex, and hippocampus. In contrast, when viewing faces, the effective connectivity was more through a ventrolateral visual cortical stream via the fusiform face cortex to the inferior temporal visual cortex regions TE2p and TE2a. A ventromedial visual cortical ‘Where’ stream to the hippocampus for spatial scenes was supported by diffusion topography in 171 HCP participants at 7 T.

Abstract Parkinson’s disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

Abstract Adolescents exhibit remarkable heterogeneity in the structural architecture of brain development. However, due to limited large-scale longitudinal neuroimaging studies, existing research has largely focused on population averages, and the neurobiological basis underlying individual heterogeneity remains poorly understood. Here we identify, using the IMAGEN adolescent cohort followed up over 9 years (14–23 y), three groups of adolescents characterized by distinct developmental patterns of whole-brain gray matter volume (GMV). Group 1 show continuously decreasing GMV associated with higher neurocognitive performances than the other two groups during adolescence. Group 2 exhibit a slower rate of GMV decrease and lower neurocognitive performances compared with Group 1, which was associated with epigenetic differences and greater environmental burden. Group 3 show increasing GMV and lower baseline neurocognitive performances due to a genetic variation. Using the UK Biobank, we show these differences may be attenuated in mid-to-late adulthood. Our study reveals clusters of adolescent neurodevelopment based on GMV and the potential long-term impact.

Abstract Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal ‘trajectory’ of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

Abstract The genetic contribution of protein-coding variants to immune-mediated diseases (IMDs) remains underexplored. Through whole exome sequencing of 40 IMDs in 350,770 UK Biobank participants, we identified 162 unique genes in 35 IMDs, among which 124 were novel genes. Several genes, including FLG which is associated with atopic dermatitis and asthma, showed converging evidence from both rare and common variants. 91 genes exerted significant effects on longitudinal outcomes (interquartile range of Hazard Ratio: 1.12-5.89). Mendelian randomization identified five causal genes, of which four were approved drug targets (CDSN, DDR1, LTA, and IL18BP). Proteomic analysis indicated that mutations associated with specific IMDs might also affect protein expression in other IMDs. For example, DXO (celiac disease-related gene) and PSMB9 (alopecia areata-related gene) could modulate CDSN (autoimmune hypothyroidism-, psoriasis-, asthma-, and Graves’ disease-related gene) expression. Identified genes predominantly impact immune and biochemical processes, and can be clustered into pathways of immune-related, urate metabolism, and antigen processing. Our findings identified protein-coding variants which are the key to IMDs pathogenesis and provided new insights into tailored innovative therapies.

Abstract Alcohol consumption is a heritable behavior seriously endangers human health. However, genetic studies on alcohol consumption primarily focuses on common variants, while insights from rare coding variants are lacking. Here we leverage whole exome sequencing data across 304,119 white British individuals from UK Biobank to identify protein-coding variants associated with alcohol consumption. Twenty-five variants are associated with alcohol consumption through single variant analysis and thirteen genes through gene-based analysis, ten of which have not been reported previously. Notably, the two unreported alcohol consumption-related genes GIGYF1 and ANKRD12 show enrichment in brain function-related pathways including glial cell differentiation and are strongly expressed in the cerebellum. Phenome-wide association analyses reveal that alcohol consumption-related genes are associated with brain white matter integrity and risk of digestive and neuropsychiatric diseases. In summary, this study enhances the comprehension of the genetic architecture of alcohol consumption and implies biological mechanisms underlying alcohol-related adverse outcomes.

Abstract Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson’s (STAB1, KCNA10), Alzheimer’s (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson’s. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.

Abstract Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort. Most genes we discovered exhibited the potential to predict future VTE events in longitudinal analysis. Notably, we provide evidence for the additive contribution of rare coding variants to known genome-wide polygenic risk in shaping VTE risk. The identified genes were enriched in pathways affecting coagulation and platelet activation, along with liver-specific expression. The pleiotropic effects of these genes indicated the potential involvement of coagulation factors, blood cell traits, liver function, and immunometabolic processes in VTE pathogenesis. In conclusion, our study unveils the valuable contribution of protein-coding variants in VTE etiology and sheds new light on its risk stratification.

Abstract Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining an uncertainty-variation threat anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we train a brain model that accurately predicts subjective anxious arousal intensity during anticipation and test it across 9 samples (total n = 572, both gender). Using publicly available datasets, we demonstrate that the whole-brain signature specifically predicts anxious anticipation and is not sensitive in predicting pain, general anticipation or unspecific emotional and autonomic arousal. The signature is also functionally and spatially distinguishable from representations of subjective fear or negative affect. We develop a sensitive, generalizable, and specific neuroimaging marker for the subjective experience of uncertain threat anticipation that can facilitate model development.

Background: Whether there is hypothalamic degeneration in Parkinson's disease (PD) and its association with clinical symptoms and pathophysiological changes remains controversial. Objectives: We aimed to quantify microstructural changes in hypothalamus using a novel deep learning-based tool in patients with PD and those with probable rapid-eye-movement sleep behavior disorder (pRBD). We further assessed whether these microstructural changes associated with clinical symptoms and free thyroxine (FT4) levels. Methods: This study included 186 PD, 67 pRBD, and 179 healthy controls. Multi-shell diffusion MRI were scanned and mean kurtosis (MK) in hypothalamic subunits were calculated. Participants were assessed using Unified Parkinson's Disease Rating Scale (UPDRS), RBD Questionnaire-Hong Kong (RBDQ-HK), Hamilton Depression Rating Scale (HAMD), and Activity of Daily Living (ADL) Scale. Additionally, a subgroup of PD (n = 31) underwent assessment of FT4. Results: PD showed significant decreases of MK in anterior-superior (a-sHyp), anterior-inferior (a-iHyp), superior tubular (supTub), and inferior tubular hypothalamus when compared with healthy controls. Similarly, pRBD exhibited decreases of MK in a-iHyp and supTub. In PD group, MK in above four subunits were significantly correlated with UPDRS-I, HAMD, and ADL. Moreover, MK in a-iHyp and a-sHyp were significantly correlated with FT4 level. In pRBD group, correlations were observed between MK in a-iHyp and UPDRS-I. Conclusions: Our study reveals that microstructural changes in the hypothalamus are already significant at the early neurodegenerative stage. These changes are associated with emotional alterations, daily activity levels, and thyroid hormone levels.

Abstract Whether peripheral immunity prospectively influences brain health remains controversial. This study aims to investigate the longitudinal associations between peripheral immunity markers with incident brain disorders. A total of 161,968 eligible participants from the UK Biobank were included. We investigated the linear and non-linear effects of peripheral immunity markers including differential leukocytes counts, their derived ratios and C-reactive protein (CRP) on the risk of dementia, Parkinson’s disease (PD), stroke, schizophrenia, bipolar affective disorder (BPAD), major depressive disorder (MDD) and anxiety, using Cox proportional hazard models and restricted cubic spline models. Linear regression models were used to explore potential mechanisms driven by brain structures. During a median follow-up of 9.66 years, 16,241 participants developed brain disorders. Individuals with elevated innate immunity markers including neutrophils, monocytes, platelets, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) had an increased risk of brain disorders. Among these markers, neutrophils exhibited the most significant correlation with risk of dementia (hazard ratio 1.08, 95% confidence interval 1.04–1.12), stroke (HR 1.06, 95% CI 1.03–1.09), MDD (HR 1.13, 95% CI 1.10–1.16) and anxiety (HR 1.07, 95% CI 1.04–1.10). Subgroup analysis revealed age-specific and sex-specific associations between innate immunity markers with risk of dementia and MDD. Neuroimaging analysis highlighted the associations between peripheral immunity markers and alterations in multiple cortical, subcortical regions and white matter tracts, typically implicated in dementia and psychiatric disorders. These findings support the hypothesis that neuroinflammation is important to the etiology of various brain disorders, offering new insights into their potential therapeutic approaches.

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms that consist of social deficits and repetitive behaviors. Unfortunately, no effective medication is available thus far to target the core symptoms of ASD, since the pathogenesis remains largely unknown. To investigate the pathogenesis of the core symptoms in ASD, we constructed Shank1 P1812L-knock-in (KI) mice corresponding to a recurrent ASD-related mutation, SHANK1 P1806L, to achieve construct validity and face validity. Shank1 P1812L-KI heterozygous (HET) mice presented with social deficits and repetitive behaviors without the presence of confounding comorbidities. HET mice also exhibited downregulation of metabotropic glutamate receptor (mGluR1) and associated signals, along with structural abnormalities in the dendritic spines and postsynaptic densities. Combined with findings from Shank1 R882H-KI mice, our study confirms that mGluR1-mediated signaling dysfunction is a pivotal mechanism underlying the core symptoms of ASD. Interestingly, Shank1 P1812L-KI homozygous (HOM) mice manifested behavioral signs of impaired long-term memory rather than autistic-like core traits; thus, their phenotype was markedly different from that of Shank1 P1812L-KI HET mice. Correspondingly, at the molecular level, Shank1 P1812L-KI HOM displayed upregulation of AMPA receptor (GluA2)-related signals. The different patterns of protein changes in HOM and HET mice may explain the differences in behaviors. Our study emphasizes the universality of mGluR1-signaling hypofunction in the pathogenesis of the core symptoms in ASD, providing a potential target for therapeutic drugs. The precise correspondence between genotype and phenotype, as shown in HOM and HET mice, indicates the importance of reproducing disease-related genotypes in mouse models.

Recent experimental observations have supported the hypothesis that the cerebral cortex operates in a dynamical regime near criticality, where the neuronal network exhibits a mixture of ordered and disordered patterns. However, A comprehensive study of how criticality emerges and how to reproduce it is still lacking. In this study, we investigate coupled networks with conductance-based neurons and illustrate the co-existence of different spiking patterns, including asynchronous irregular (AI) firing and synchronous regular (SR) state, along with a scale-invariant neuronal avalanche phenomenon (criticality). We show that fast-acting synaptic coupling can evoke neuronal avalanches in the mean-dominated regime but has little effect in the fluctuation-dominated regime. In a narrow region of parameter space, the network exhibits avalanche dynamics with power-law avalanche size and duration distributions. We conclude that three stages which may be responsible for reproducing the synchronized bursting: mean-dominated subthreshold dynamics, fast-initiating a spike event, and time-delayed inhibitory cancellation. Remarkably, we illustrate the mechanisms underlying critical avalanches in the presence of noise, which can be explained as a stochastic crossing state around the Hopf bifurcation under the mean-dominated regime. Moreover, we apply the ensemble Kalman filter to determine and track effective connections for the neuronal network. The method is validated on noisy synthetic BOLD signals and could exactly reproduce the corresponding critical network activity. Our results provide a special perspective to understand and model the criticality, which can be useful for large-scale modeling and computation of brain dynamics.

Abstract Macroinvertebrates play a vital role in coastal ecosystems and are an important indicator of ecosystem quality. Both anthropogenic activity and environmental changes may lead to significant changes in the marine macroinvertebrate community. However, the assembly process of benthic biodiversity and its mechanism driven by environmental factors at large scales remains unclear. Here, using the benthic field survey data of 15 years at large spatial and temporal scales from the Yellow Sea Large Marine Ecosystem, we investigated the relative importance of environmental selection, dispersal processes, random‐deterministic processes of macroinvertebrates community diversity assembly, and the responses of this relative importance driven by temperature and nutrients. Results showed that the macroinvertebrates community diversity is mainly affected by dispersal. Nitrogen and phosphorus are the most important negative factors among environmental variables, while geographical distance is the main limiting factor of β diversity. Within the range of 0.35–0.70 mg/L of nutrients, increasing nutrient concentration can significantly facilitate the contribution of the decay effect to β diversity. Within the temperature range studied (15.0–18.0°C), both warming and cooling can lead to a greater tendency for species diversity assembly processes to be dominated by deterministic processes. The analysis contributes to a better understanding of the assembly process of the diversity of coastal marine macroinvertebrates communities and how they adapt to global biogeochemical processes.

Exposure routes are important for health risk assessment of chemical risks. The application of physiologically based toxicokinetic (PBTK) models to predict concentrations in vivo can determine the effects of harmful substances and tissue accumulation on the premise of saving experimental costs. In this study, Tri(2-chloroethyl) phosphate (TCEP), an organophosphate ester (OPE), was used as an example to study the PBTK model of mice exposed to different exposure doses by multiple routes. Different routes of exposure (gavage and intradermal injection) can cause differences in the concentration of chemicals in the organs. TCEP that enters the body through the mouth is mainly concentrated in the gastrointestinal tract and liver. However, the concentrations of chemicals that enter the skin into the mice are higher in skin, rest of body, and blood. In addition, TCEP was absorbed and accumulated very rapidly in mice, within half an hour after a single exposure. We have successfully established a mouse PBTK model of the TCEP accounting for multiple exposure Routes and obtained a series of kinetic parameters. The model includes blood, liver, kidney, stomach, intestine, skin, and rest of body compartments. Oral and dermal exposure route was considered for PBTK model. The PBTK model established in this study has a good predictive ability. More than 70% of the predicted values deviated from the measured values by less than 5-fold. In addition, we extrapolated the model to humans. A human PBTK model is built. We performed a health risk assessment for world populations based on human PBTK model. The risk of TCEP in dust is greater through mouth than through skin. The risk of TCEP in food of Chinese population is greater than dust.

Abstract Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.

Abstract Background Comorbidity is the rule rather than the exception for childhood and adolescent onset mental disorders, but we cannot predict its occurrence and do not know the neural mechanisms underlying comorbidity. We investigate if the effects of comorbid internalizing and externalizing disorders on anatomical differences represent a simple aggregate of the effects on each disorder and if these comorbidity-associated cortical surface differences relate to a distinct genetic underpinning. Methods We studied the cortical surface area (SA) and thickness (CT) of 11,878 preadolescents (9–10 years) from the Adolescent Brain and Cognitive Development Study. Linear mixed models were implemented in comparative and association analyses among internalizing (dysthymia, major depressive disorder, disruptive mood dysregulation disorder, agoraphobia, panic disorder, specific phobia, separation anxiety disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder), externalizing (attention-deficit/hyperactivity disorder, oppositional defiant disorder, conduct disorder) diagnostic groups, a group with comorbidity of the two and a healthy control group. Genome-wide association analysis (GWAS) and cell type specificity analysis were performed on 4468 unrelated European participants from this cohort. Results Smaller cortical surface area but higher thickness was noted across patient groups when compared to controls. Children with comorbid internalizing and externalizing disorders had more pronounced areal reduction than those without comorbidity, indicating an additive burden. In contrast, cortical thickness had a non-linear effect with comorbidity: the comorbid group had no significant CT differences, while those patient groups without comorbidity had significantly higher thickness compare to healthy controls. Distinct biological pathways were implicated in regional SA and CT differences. Specifically, CT differences were associated with immune-related processes implicating astrocytes and oligodendrocytes, while SA-related differences related mainly to inhibitory neurons. Conclusion The emergence of comorbidity across distinct clusters of psychopathology is unlikely to be due to a simple additive neurobiological effect alone. Distinct developmental risk moderated by immune-related adaptation processes, with unique genetic and cell-specific factors, may contribute to underlying SA and CT differences. Children with the highest risk but lowest resilience, both captured in their developmental morphometry, may develop a comorbid illness pattern.

Abstract Increasing evidence suggests that Parkinson’s disease (PD) exhibits disparate spatial and temporal patterns of progression. Here we used a machine-learning technique—Subtype and Stage Inference (SuStaIn) — to uncover PD subtypes with distinct trajectories of clinical and neurodegeneration events. We enrolled 228 PD patients and 119 healthy controls with comprehensive assessments of olfactory, autonomic, cognitive, sleep, and emotional function. The integrity of substantia nigra (SN), locus coeruleus (LC), amygdala, hippocampus, entorhinal cortex, and basal forebrain were assessed using diffusion and neuromelanin-sensitive MRI. SuStaIn model with above clinical and neuroimaging variables as input was conducted to identify PD subtypes. An independent dataset consisting of 153 PD patients and 67 healthy controls was utilized to validate our findings. We identified two distinct PD subtypes: subtype 1 with rapid eye movement sleep behavior disorder (RBD), autonomic dysfunction, and degeneration of the SN and LC as early manifestations, and cognitive impairment and limbic degeneration as advanced manifestations, while subtype 2 with hyposmia, cognitive impairment, and limbic degeneration as early manifestations, followed later by RBD and degeneration of the LC in advanced disease. Similar subtypes were shown in the validation dataset. Moreover, we found that subtype 1 had weaker levodopa response, more GBA mutations, and poorer prognosis than subtype 2. These findings provide new insights into the underlying disease biology and might be useful for personalized treatment for patients based on their subtype.

The digital twin brain (DTB) computing model from brain-inspired computing research is an emerging artificial intelligence technique, which is realized by a computational modeling approach of hardware and software. It can achieve various cognitive abilities and their synergistic mechanisms in a manner similar to the human brain. Given that the task of the DTB is to simulate the functions of the human brain, comparing the similarities and differences between the two is crucial. However, the visualization study of the DTB is still under-researched. Moreover, the complexity of the datasets (multilevel spatiotemporal granularity and different types of comparison tasks) presents new challenges to the analysis and exploration of visualization. Therefore, in this study, we proposed DTBVis, a visual analytics system that supports comparison tasks for the DTB. DTBVis supports iterative explorations from different levels and at different granularities. Combined with automatic similarity recommendation, and high-dimensional exploration, DTBVis can assist experts in understanding the similarities and differences between the DTB and the human brain, thus helping them adjust their model and enhance its functionality. The highest level of DTBVis shows an overview of the datasets from the brain, which is used for comparison and exploration of the function and structure of the DTB and the human brain. The medium level is used for the comparison and exploration of a designated brain region. The low level can analyze a designated brain voxel. We worked closely with experts of brain science and held regular seminars with them. Feedback from the experts indicates that our approach helps them conduct comparative studies of the DTB and human brain and make modeling adjustments of the DTB through intuitive visual comparisons and interactive explorations.

How to retrieve latent neurobehavioural processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioural processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso‑limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dorsal anterior cingulate cortex and insula. Furthermore, we anticipate our novel analytical principle to be applied generally in decoding multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.

Functional MRI data from Chinese-English bilingual participants during a reading task reveals linguistic feature-specific accommodation and assimilation between first and second languages.

A passive microwave instrument will be carried by China’s geostationary microwave satellite. A microwave hyper-spectral band included by the instrument ranges from 52.6 to 57.3 GHz, and totally has 89 channels in this spectral domain. The design of the hyper-spectral band is described from the aspects of scientific objectives and specifications. The weighting functions for each channel are calculated utilizing radiative transfer simulations under clear sky conditions. Then, the information content as well as the degree of freedom for signal are computed and analyzed to characterize this hyper-spectral sounding for atmospheric temperature profiling. Both the vertical distribution of the weighting functions and the width of retrieval averaging kernels indicate that the hyper-spectral band can provide more denser sampling for atmospheric temperature. The information content for the hyper-spectral band is approximately 46% higher than that of the ATMS-type channel 3 to 15, indicating that hyper-spectral measurement can improve the accuracy of retrieval. The most informative channels mainly locate near 57 GHz, having good consistency with the existing channels. The height range where the retrieval using the hyper-spectral observations is sensitive to the true profile, begins from about 800 to 1 hPa. Some channels can be considered as alternatives to each other since they have very similar information content and weighting functions. These results are expected to provide a valuable reference for future applications of the microwave hyper-spectral measurements.

Understanding the underlying dynamical mechanisms of the brain and controlling it is a crucial issue in brain science. The energy landscape and transition path approach provides a possible route to address these challenges. Here, taking working memory as an example, we quantified its landscape based on a large-scale macaque model. The working memory function is governed by the change of landscape and brain-wide state switching in response to the task demands. The kinetic transition path reveals that information flow follows the direction of hierarchical structure. Importantly, we propose a landscape control approach to manipulate brain state transition by modulating external stimulation or inter-areal connectivity, demonstrating the crucial roles of associative areas, especially prefrontal and parietal cortical areas in working memory performance. Our findings provide new insights into the dynamical mechanism of cognitive function, and the landscape control approach helps to develop therapeutic strategies for brain disorders.

The interaction between metals is ubiquitous, but there is still a lack of quantitative models considering the interaction between metals, which leads to the deviations in predicting the joint toxicity of metals. The present study estimated the uptake rate constants (kin) and elimination rate constants (kout) and elucidated how the presence of one metal (Cu or Cd) affects the absorption and excretion of another metal (Cd or Cu) in zebrafish larvae. The results showed that Cd and Cu inhibited each other in the process of absorption and excretion by comparing separately kin and kout of Cd or Cu with the other metal Cu or Cd mixed concentrations increased, thereby affecting the Cd and Cu bioaccumulation in the zebrafish larvae. Then the interactions between Cd and Cu in the uptake and elimination processes were quantified to obtain a refined toxicokinetic model. Verification with independent experiment data showed that the refined toxicokinetic model could significantly improve the prediction of the Cd or Cu bioaccumulation in the zebrafish larvae. This study contributes to understand the toxicokinetic process of the Cd-Cu mixture in the zebrafish larvae, and the developed model could be used to predict the toxicity of the metal mixtures.

Close friendships are important for mental health and cognition in late childhood. However, whether the more close friends the better, and the underlying neurobiological mechanisms are unknown. Using the Adolescent Brain Cognitive Developmental study, we identified nonlinear associations between the number of close friends, mental health, cognition, and brain structure. Although few close friends were associated with poor mental health, low cognitive functions, and small areas of the social brain (e.g., the orbitofrontal cortex, the anterior cingulate cortex, the anterior insula, and the temporoparietal junction), increasing the number of close friends beyond a level (around 5) was no longer associated with better mental health and larger cortical areas, and was even related to lower cognition. In children having no more than five close friends, the cortical areas related to the number of close friends revealed correlations with the density of μ-opioid receptors and the expression of OPRM1 and OPRK1 genes, and could partly mediate the association between the number of close friends, attention-deficit/hyperactivity disorder (ADHD) symptoms, and crystalized intelligence. Longitudinal analyses showed that both too few and too many close friends at baseline were associated with more ADHD symptoms and lower crystalized intelligence 2 y later. Additionally, we found that friendship network size was nonlinearly associated with well-being and academic performance in an independent social network dataset of middle-school students. These findings challenge the traditional idea of ‘the more, the better,’ and provide insights into potential brain and molecular mechanisms.

Abstract Circadian rhythm disruption (CRD) is a shared characteristic of various brain disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and major depression disorder (MDD). Disruption of circadian rhythm might be a risk factor for brain disorder incidents. From 7-day accelerometry data of 72,242 participants in UK Biobank, we derived a circadian relative amplitude variable, which to some extent reflected the degree of circadian rhythm disruption. Records of brain disorder incidents were obtained from a wide range of health outcomes across self-report, primary care, hospital inpatient data, and death data. Using multivariate Cox proportional hazard ratio regression, we created two models adjusting for different covariates. Then, linear correlations between relative amplitude and several brain morphometric measures were examined in participants with brain MRI data. After a median follow-up of around 6.1 years, 72,242 participants were included in the current study (female 54.9%; mean age 62.1 years). Individuals with reduced relative amplitude had increasing risk of all-cause dementia (Hazard ratio 1.23 [95% CI 1.15 to 1.31]), PD (1.33 [1.25 to 1.41]), stroke (1.13 [1.06 to 1.22]), MDD (1.18 [1.13 to 1.23]), and anxiety disorder (1.14 [1.09 to 1.20]) in fully adjusted models. Additionally, significant correlations were found between several cortical regions and white matter tracts and relative amplitude that have been linked to dementia and psychiatric disorders. We confirm CRD to be a risk factor for various brain disorders. Interventions for regulating circadian rhythm may have clinical relevance to reducing the risk of various brain disorders.

Abstract Background Chronic infection with hepatitis B virus (HBV) has been proved highly associated with the development of hepatocellular carcinoma (HCC). Aims The purpose of the study is to investigate the association between HBV preS region quasispecies and HCC development, as well as to develop HCC diagnosis model using HBV preS region quasispecies. Methods A total of 104 chronic hepatitis B (CHB) patients and 117 HBV-related HCC patients were enrolled. HBV preS region was sequenced using next generation sequencing (NGS) and the nucleotide entropy was calculated for quasispecies evaluation. Sparse logistic regression (SLR) was used to predict HCC development and prediction performances were evaluated using receiver operating characteristic curves. Results Entropy of HBV preS1, preS2 regions and several nucleotide points showed significant divergence between CHB and HCC patients. Using SLR, the classification of HCC/CHB groups achieved a mean area under the receiver operating characteristic curve (AUC) of 0.883 in the training data and 0.795 in the test data. The prediction model was also validated by a completely independent dataset from Hong Kong. The 10 selected nucleotide positions showed significantly different entropy between CHB and HCC patients. The HBV quasispecies also classified three clinical parameters, including HBeAg, HBVDNA, and Alkaline phosphatase (ALP) with the AUC value greater than 0.6 in the test data. Conclusions Using NGS and SLR, the association between HBV preS region nucleotide entropy and HCC development was validated in our study and this could promote the understanding of HCC progression mechanism.

Abstract Purpose We develop a new risk score to predict patients with stroke-associated pneumonia (SAP) who have an acute intracranial hemorrhage (ICH). Method We applied logistic regression to develop a new risk score called ICH-LR2S2. It was derived from examining a dataset of 70,540 ICH patients between 2015 and 2018 from the Chinese Stroke Center Alliance (CSCA). During the training of ICH-LR2S2, patients were randomly divided into two groups – 80% for the training set and 20% for model validation. A prospective test set was developed using 12,523 patients recruited in 2019. To further verify its effectiveness, we tested ICH-LR2S2 on an external dataset of 24,860 patients from the China National Stroke Registration Management System II (CNSR II). The performance of ICH-LR2S2 was measured by the area under the receiver operating characteristic curve (AUROC). Results The incidence of SAP in the dataset was 25.52%. A 24-point ICH-LR2S2 was developed from independent predictors, including age, modified Rankin Scale, fasting blood glucose, National Institutes of Health Stroke Scale admission score, Glasgow Coma Scale score, C-reactive protein, dysphagia, Chronic Obstructive Pulmonary Disease, and current smoking. The results showed that ICH-LR2S2 achieved an AUC = 0.749 [95% CI 0.739–0.759], which outperforms the best baseline ICH-APS (AUC = 0.704) [95% CI 0.694–0.714]. Compared with the previous ICH risk scores, ICH-LR2S2 incorporates fasting blood glucose and C-reactive protein, improving its discriminative ability. Machine learning methods such as XGboost (AUC = 0.772) [95% CI 0.762–0.782] can further improve our prediction performance. It also performed well when further validated by the external independent cohort of patients (n = 24,860), ICH-LR2S2 AUC = 0.784 [95% CI 0.774–0.794]. Conclusion ICH-LR2S2 accurately distinguishes SAP patients based on easily available clinical features. It can help identify high-risk patients in the early stages of diseases.

IntroductionIn marine ecosystems, microbial communities are important drivers of material circulation and energy flow. The complex interactions between phytoplankton and bacterial communities constitute one of the most crucial ecological relationships in the marine environment. Inorganic nitrogen can affect the type of relationship between algae and bacteria. However, the quantitative relationship between the bacterial communities, inorganic nitrogen, and phytoplankton remains unclear.MethodsUnder laboratory conditions, we altered the forms (nitrate and ammonium) and amounts of nitrogen sources to study the dynamics of bacterial biomass, diversity, and community structure in the phycosphere of the marine model species Phaeodactylum tricornutum. The bacterial community structure during P. tricornutum growth was analyzed using Illumina HiSeq sequencing of 16S rDNA amplicons.ResultsThe results indicated that inorganic nitrogen concentration was the main factor promoting P. tricornutum biomass growth. The change in the algal biomass would significantly increase the phycosphere bacterial biomass. The bacterial biomass in the algal-bacteria co-culture system was 1.5 ~ 5 times that of the conditional control groups without microalgae under the same culture conditions. The variation of P. tricornutum biomass also affected the bacterial communities in the phycosphere. When P. tricornutum was in the exponential phase (96 ~ 192 h), the bacterial community structure differed between the high- and low-concentration groups. The difference in the bacterial communities over time in the high-concentration groups was more prominent than in the low-concentration groups. Under high-concentration groups (HA and HN), the relative abundance of Marivita and Marinobacter, engaged in the transformation of aquatic inorganic nitrogen, gradually decreased with time. However, the relative abundance of Oceanicaulis, closely related to algal growth, gradually increased with time.DiscussionThe above phenomena might be related to the change in P. tricornutum biomass. Our results explain when and how the phycosphere bacterial communities responded to algal biomass variations. The study provides a foundation for the quantitative relationship among nutrients, microalgae, and bacteria in this system.

Fluid intelligence is a cognitive domain that encompasses general reasoning, pattern recognition, and problem-solving abilities independent of task-specific experience. Understanding its genetic and neural underpinnings is critical yet challenging for predicting human development, lifelong health, and well-being. One approach to address this challenge is to map the network of correlations between intelligence and other constructs. In the current study, we performed a genome-wide association study using fluid intelligence quotient scores from the UK Biobank to explore the genetic architecture of the associations between obesity risk and fluid intelligence. Our results revealed novel common genetic loci (SH2B1, TUFM, ATP2A1, and FOXO3) underlying the association between fluid intelligence and body metabolism. Surprisingly, we demonstrated that SH2B1 variation influenced fluid intelligence independently of its effects on metabolism but partially mediated its association with bilateral hippocampal volume. Consistently, selective genetic ablation of Sh2b1 in the mouse hippocampus, particularly in inhibitory neurons, but not in excitatory neurons, significantly impaired working memory, short-term novel object recognition memory, and behavioral flexibility, but not spatial learning and memory, mirroring the human intellectual performance. Single-cell genetic profiling of Sh2B1-regulated molecular pathways revealed that Sh2b1 deletion resulted in aberrantly enhanced extracellular signal-regulated kinase (ERK) signaling, whereas pharmacological inhibition of ERK signaling reversed the associated behavioral impairment. Our cross-species study thus provides unprecedented insight into the role of SH2B1 in fluid intelligence and has implications for understanding the genetic and neural underpinnings of lifelong mental health and well-being.

The predicted age difference (PAD) between an individual’s predicted brain age and chronological age has been commonly viewed as a meaningful phenotype relating to aging and brain diseases. However, the systematic bias appears in the PAD achieved using machine learning methods. Recent studies have designed diverse bias correction methods to eliminate it for further downstream studies. Strikingly, here we demonstrate that bias still exists in the PAD of samples with the same age even after kind of correction. Therefore, current PAD may not be taken as a reliable phenotype and more investigations are needed to solve this fundamental defect. To this end, we propose an age-level bias correction method and demonstrate its efficacy in numerical experiments.

Accurate brain tissue extraction on magnetic resonance imaging (MRI) data is crucial for analyzing brain structure and function. While several conventional tools have been optimized to handle human brain data, there have been no generalizable methods to extract brain tissues for multimodal MRI data from rodents, nonhuman primates, and humans. Therefore, developing a flexible and generalizable method for extracting whole brain tissue across species would allow researchers to analyze and compare experiment results more efficiently. Here, we propose a domain-adaptive and semi-supervised deep neural network, named the Brain Extraction Net (BEN), to extract brain tissues across species, MRI modalities, and MR scanners. We have evaluated BEN on 18 independent datasets, including 783 rodent MRI scans, 246 nonhuman primate MRI scans, and 4601 human MRI scans, covering five species, four modalities, and six MR scanners with various magnetic field strengths. Compared to conventional toolboxes, the superiority of BEN is illustrated by its robustness, accuracy, and generalizability. Our proposed method not only provides a generalized solution for extracting brain tissue across species but also significantly improves the accuracy of atlas registration, thereby benefiting the downstream processing tasks. As a novel fully automated deep-learning method, BEN is designed as an open-source software to enable high-throughput processing of neuroimaging data across species in preclinical and clinical applications.

Summary: Background: Hearing impairment was recently identified as the most prominent risk factor for dementia. However, the mechanisms underlying the link between hearing impairment and dementia are still unclear. Methods: We investigated the association of hearing performance with cognitive function, brain structure and cerebrospinal fluid (CSF) proteins in cross-sectional, longitudinal, mediation and genetic association analyses across the UK Biobank (N = 165,550), the Chinese Alzheimer's Biomarker and Lifestyle (CABLE, N = 863) study, and the Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 1770) database. Findings: Poor hearing performance was associated with worse cognitive function in the UK Biobank and in the CABLE study. Hearing impairment was significantly related to lower volume of temporal cortex, hippocampus, inferior parietal lobe, precuneus, etc., and to lower integrity of white matter (WM) tracts. Furthermore, a higher polygenic risk score (PRS) for hearing impairment was strongly associated with lower cognitive function, lower volume of gray matter, and lower integrity of WM tracts. Moreover, hearing impairment was correlated with a high level of CSF tau protein in the CABLE study and in the ADNI database. Finally, mediation analyses showed that brain atrophy and tau pathology partly mediated the association between hearing impairment and cognitive decline. Interpretation: Hearing impairment is associated with cognitive decline, brain atrophy and tau pathology, and hearing impairment may reflect the risk for cognitive decline and dementia as it is related to bran atrophy and tau accumulation in brain. However, it is necessary to assess the mechanism in future animal studies. Funding: A full list of funding bodies that supported this study can be found in the Acknowledgements section.

Abstract Background Multimorbidities greatly increase the global health burdens, but the landscapes of their genetic risks have not been systematically investigated. Methods We used the hospital inpatient data of 385,335 patients in the UK Biobank to investigate the multimorbid relations among 439 common diseases. Post-GWAS analyses were performed to identify multimorbidity shared genetic risks at the genomic loci, network, as well as overall genetic architecture levels. We conducted network decomposition for the networks of genetically interpretable multimorbidities to detect the hub diseases and the involved molecules and functions in each module. Results In total, 11,285 multimorbidities among 439 common diseases were identified, and 46% of them were genetically interpretable at the loci, network, or overall genetic architecture levels. Multimorbidities affecting the same and different physiological systems displayed different patterns of the shared genetic components, with the former more likely to share loci-level genetic components while the latter more likely to share network-level genetic components. Moreover, both the loci- and network-level genetic components shared by multimorbidities converged on cell immunity, protein metabolism, and gene silencing. Furthermore, we found that the genetically interpretable multimorbidities tend to form network modules, mediated by hub diseases and featuring physiological categories. Finally, we showcased how hub diseases mediating the multimorbidity modules could help provide useful insights for the genetic contributors of multimorbidities. Conclusions Our results provide a systematic resource for understanding the genetic predispositions of multimorbidities and indicate that hub diseases and converged molecules and functions may be the key for treating multimorbidities. We have created an online database that facilitates researchers and physicians to browse, search, or download these multimorbidities ( https://multimorbidity.comp-sysbio.org ).

To advance understanding of brain networks involved in language, the effective connectivity between 26 cortical regions implicated in language by a community analysis and 360 cortical regions was measured in 171 humans from the Human Connectome Project, and complemented with functional connectivity and diffusion tractography, all using the HCP multimodal parcellation atlas. A (semantic) network (Group 1) involving inferior cortical regions of the superior temporal sulcus cortex (STS) with the adjacent inferior temporal visual cortex TE1a and temporal pole TG, and the connected parietal PGi region, has effective connectivity with inferior temporal visual cortex (TE) regions; with parietal PFm which also has visual connectivity; with posterior cingulate cortex memory-related regions; with the frontal pole, orbitofrontal cortex, and medial prefrontal cortex; with the dorsolateral prefrontal cortex; and with 44 and 45 for output regions. It is proposed that this system can build in its temporal lobe (STS and TG) and parietal parts (PGi and PGs) semantic representations of objects incorporating especially their visual and reward properties. Another (semantic) network (Group 3) involving superior regions of the superior temporal sulcus cortex and more superior temporal lobe regions including STGa, auditory A5, TPOJ1, the STV and the Peri-Sylvian Language area (PSL) has effective connectivity with auditory areas (A1, A4, A5, Pbelt); with relatively early visual areas involved in motion, e.g., MT and MST, and faces/words (FFC); with somatosensory regions (frontal opercular FOP, insula and parietal PF); with other TPOJ regions; and with the inferior frontal gyrus regions (IFJa and IFSp). It is proposed that this system builds semantic representations specialising in auditory and related facial motion information useful in theory of mind and somatosensory / body image information, with outputs directed not only to regions 44 and 45, but also to premotor 55b and midcingulate premotor cortex. Both semantic networks (Groups 1 and 3) have access to the hippocampal episodic memory system via parahippocampal TF. A third largely frontal network (Group 2) (44, 45, 47l; 55b; the Superior Frontal Language region SFL; and including temporal pole TGv) receives effective connectivity from the two semantic systems, and is implicated in syntax and speech output.

Summary: Background: Subjective or objective subtle cognitive decline (SCD) is considered the preclinical manifestation of Alzheimer's disease (AD), which is a potentially crucial window for preventing or delaying the progression of the disease. Methods: To explore the potential mechanism of disease progression and identify relevant biomarkers, we comprehensively assessed the peripheral blood transcriptomic alterations in SCD, covering lncRNA, mRNA, and miRNA. Findings: Dysregulated protein-coding mRNA at both gene and isoform levels implicated impairment in the type I interferon signaling pathway in SCD. Specifically, this pathway was regulated by the transcription factor STAT1 and ncRNAs NRIR and has-miR-146a-5p. The miRNA-mRNA-lncRNA co-expression network revealed hub genes for the interferon module. Individuals with lower interferon signaling activity and lower expression of a hub gene STAT1 exhibited a higher conversion rate to mild cognitive impairment (MCI). Interpretation: Our findings illustrated the down-regulation of interferon signaling activity would potentially increase the risk of disease progression and thus serve as a pre-disease biomarker. Funding: This work was partly supported by National Key R&D Program of China (2020YFA0712403), National Natural Science Foundation of China (61932008), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01), the 111 Project (No. B18015) of China, Greater Bay Area Institute of Precision Medicine (Guangzhou) (Grand No. IPM21C008), Natural Science Foundation of Shanghai (21ZR1403200), and Shanghai Center for Brain Science and Brain-Inspired Technology.

Magnetic Resonance Imaging (MRI) technology has been increasingly used in neuroscience studies. Reproducibility of statistically significant findings generated by MRI-based studies, especially association studies (phenotype vs. MRI metric) and task-induced brain activation, has been recently heavily debated. However, most currently available reproducibility measures depend on thresholds for the test statistics and cannot be use to evaluate overall study reproducibility. It is also crucial to elucidate the relationship between overall study reproducibility and sample size in an experimental design. In this study, we proposed a model-based reproducibility index to quantify reproducibility which could be used in large-scale high-throughput MRI-based studies including both association studies and task-induced brain activation. We performed the model-based reproducibility assessments for a few association studies and task-induced brain activation by using several recent large sMRI/fMRI databases. For large sample size association studies between brain structure/function features and some basic physiological phenotypes (i.e. Sex, BMI), we demonstrated that the model-based reproducibility of these studies is more than 0.99. For MID task activation, similar results could be observed. Furthermore, we proposed a model-based analytical tool to evaluate minimal sample size for the purpose of achieving a desirable model-based reproducibility. Additionally, we evaluated the model-based reproducibility of gray matter volume (GMV) changes for UK Biobank (UKB) vs. Parkinson Progression Marker Initiative (PPMI) and UK Biobank (UKB) vs. Human Connectome Project (HCP). We demonstrated that both sample size and study-specific experimental factors play important roles in the model-based reproducibility assessments for different experiments. In summary, a systematic assessment of reproducibility is fundamental and important in the current large-scale high-throughput MRI-based studies.

Child behavior has been associated with parenting behavior. Here, the authors investigate associations between child behavior, parental behavior, and structural MRI using the Adolescent Brain Cognitive Developmental (ABCD) study dataset.

Abstract Emerging evidence shows that the coronavirus disease 2019 (COVID-19) pandemic is negatively affecting mental health around the globe. Interventions to alleviate the psychological impact of the pandemic are urgently needed. Whether mindfulness practice may protect against the harmful emotional effects of a pandemic crisis remains hitherto unknown. We investigated the influence of mindfulness training on mental health during the COVID-19 outbreak in China. We hypothesized that mindfulness practitioners might manifest less pandemic-related distress, depression, anxiety, and stress than non-practitioners and that more frequent practice would be associated with an improvement in mental health during the pandemic. Therefore, we assessed pandemic-related distress and symptoms of depression, anxiety, and stress, as well as the frequency of meditation practice at the peak of new infections (Feb 4–5; N = 673) and three weeks later (Feb 29–30; N = 521) in mindfulness practitioners via online questionnaires. Self-reported symptoms were also collected from non-practitioners at peak time only (N = 1550). We found lower scores of pandemic-related distress in mindfulness practitioners compared to non-practitioners. In general, older participants showed fewer symptoms of depression and anxiety. In younger practitioners, pandemic-related distress decreased from peak to follow-up. Importantly, increased mindfulness training during the preceding two weeks was associated with lower scores of depression and anxiety at both assessments. Likewise, practice frequency predicted individual improvement in scores of depression, anxiety, and stress at follow-up. Our results indicate that mindfulness meditation might be a viable low-cost intervention to mitigate the psychological impact of the COVID-19 crisis and future pandemics.

Summary: Background: Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with longer screen time utilization (STU) at the behavioral level. However, whether there are shared neural links between ADHD symptoms and prolonged STU is not clear and has not been explored in a single large-scale dataset. Methods: Leveraging the genetics, neuroimaging and behavioral data of 11,000+ children aged 9–11 from the Adolescent Brain Cognitive Development cohort, this study investigates the associations between the polygenic risk and trait for ADHD, STU, and white matter microstructure through cross-sectionally and longitudinal analyses. Findings: Children with higher polygenic risk scores for ADHD tend to have longer STU and more severe ADHD symptoms. Fractional anisotropy (FA) values in several white matter tracts are negatively correlated with both the ADHD polygenic risk score and STU, including the inferior frontal-striatal tract, inferior frontal-occipital fasciculus, superior longitudinal fasciculus and corpus callosum. Most of these tracts are linked to visual-related functions. Longitudinal analyses indicate a directional effect of white matter microstructure on the ADHD scale, and a bi-directional effect between the ADHD scale and STU. Furthermore, reduction of FA in several white matter tracts mediates the association between the ADHD polygenic risk score and STU. Interpretation: These findings shed new light on the shared neural overlaps between ADHD symptoms and prolonged STU, and provide evidence that the polygenic risk for ADHD is related, via white matter microstructure and the ADHD trait, to STU. Funding: This study was mainly supported by NSFC and National Key R&D Program of China.

Summary: Background: Childhood traumatic events are risk factors for psychopathology, but large-scale studies of how childhood traumatic events relate to mental health and cognition in adulthood, and how the brain is involved, are needed. Methods: The associations between childhood traumatic events (such as abuse and neglect, and defined by the ‘Childhood Trauma’ questions in the UK Biobank database) and brain functional connectivity, mental health problems, and cognitive performance were investigated by a univariate correlation analysis with 19,535 participants aged 45–79 from the UK Biobank dataset. The results were replicated with 17,747 independent participants in the second release from the same dataset. Findings: Childhood traumatic events were significantly associated with mental health problems in adulthood including anxiety (r=0.19, p

Summary: The respective value of clinical data and CT examinations in predicting COVID-19 progression is unclear, because the CT scans and clinical data previously used are not synchronized in time. To address this issue, we collected 119 COVID-19 patients with 341 longitudinal CT scans and paired clinical data, and we developed an AI system for the prediction of COVID-19 deterioration. By combining features extracted from CT and clinical data with our system, we can predict whether a patient will develop severe symptoms during hospitalization. Complementary to clinical data, CT examinations show significant add-on values for the prediction of COVID-19 progression in the early stage of COVID-19, especially in the 6th to 8th day after the symptom onset, indicating that this is the ideal time window for the introduction of CT examinations. We release our AI system to provide clinicians with additional assistance to optimize CT usage in the clinical workflow.

Risk-taking differs between humans, and is associated with the personality measures of impulsivity and sensation-seeking. To analyse the brain systems involved, self-report risk-taking, resting state functional connectivity, and related behavioral measures were analyzed in 18,740 participants of both sexes from the UK Biobank. Functional connectivities of the medial orbitofrontal cortex, ventromedial prefrontal cortex (VMPFC), and the parahippocampal areas were significantly higher in the risk-taking group (p

Abstract Schizophrenia is a neurocognitive illness of synaptic and brain network-level dysconnectivity that often reaches a persistent chronic stage in many patients. Subtle language deficits are a core feature even in the early stages of schizophrenia. However, the primacy of language network dysconnectivity and language-related genetic variants in the observed phenotype in early stages of illness remains unclear. This study used two independent schizophrenia dataset consisting of 138 and 53 drug-naïve first-episode schizophrenia (FES) patients, and 112 and 56 healthy controls, respectively. A brain-wide voxel-level functional connectivity analysis was conducted to investigate functional dysconnectivity and its relationship with illness duration. We also explored the association between critical language-related genetic (such as FOXP2) mutations and the altered functional connectivity in patients. We found elevated functional connectivity involving Broca’s area, thalamus and temporal cortex that were replicated in two FES datasets. In particular, Broca’s area - anterior cingulate cortex dysconnectivity was more pronounced for patients with shorter illness duration, while thalamic dysconnectivity was predominant in those with longer illness duration. Polygenic risk scores obtained from FOXP2-related genes were strongly associated with functional dysconnectivity identified in patients with shorter illness duration. Our results highlight the criticality of language network dysconnectivity, involving the Broca’s area in early stages of schizophrenia, and the role of language-related genes in this aberration, providing both imaging and genetic evidence for the association between schizophrenia and the determinants of language.

Abstract We describe advances in the understanding of brain dynamics that are important for understanding the operation of the cerebral cortex in health and disease. In data from 1017 participants from the Human Connectome Project, we show that early visual and connected areas have low temporal variability of their functional connectivity. We show that a low temporal variability of the connectivity of cortical areas is related to high mean functional connectivity between those areas, and provide an account of how these dynamics arise. We then investigate how these concepts help to understand brain dynamics in mental disorders. We find that in both first episode and long-term schizophrenia, reduced functional connectivity of early visual and related temporal cortex areas is associated with increased temporal variability of the functional connectivity, consistent with decreased stability of attractor networks related to sensory processing. In ADHD, we find these functional connectivities are increased and their temporal variability is decreased, and relate this to increased engagement with visual sensory input as manifest in high screen time usage in ADHD. We further show that these differences in the dynamics of the cortex in schizophrenia, and ADHD can be related to differences in the functional connectivity of the specific sensory vs. association thalamic nuclei. These discoveries help to advance our understanding of cortical operation in health, and in some mental disorders.

A complete mitochondrial genome (mitogenome) can provide important information for gene rearrangement, molecular evolution and phylogenetic analysis. Currently, only a few mitogenomes of hermit crabs (superfamily Paguridae) in the infraorder Anomura have been reported. This study reports the first complete mitogenome of the hermit crab Diogenes edwardsii assembled using high-throughput sequencing. The mitogenome of Diogenes edwardsii is 19,858 bp in length and comprises 13 protein-coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. There are 28 and six genes observed on the heavy and light strands, respectively. The genome composition was highly A + T biased (72.16%), and exhibited a negative AT-skew (−0.110) and positive GC-skew (0.233). Phylogenetic analyses based on the nucleotide dataset of 16 Anomura species indicated that D. edwardsii was closest related to Clibanarius infraspinatus in the same family, Diogenidae. Positive selection analysis showed that two residues located in cox1 and cox2 were identified as positively selected sites with high BEB value (>95%), indicating that these two genes are under positive selection pressure. This is the first complete mitogenome of the genus Diogenes, and this finding helps us to represent a new genomic resource for hermit crab species and provide data for further evolutionary status of Diogenidae in Anomura.

Abstract Background Childhood trauma increases the risk for adult obesity through multiple complex pathways, and the neural substrates are yet to be determined. Methods Participants from three population-based neuroimaging cohorts, including the IMAGEN cohort, the UK Biobank (UKB), and the Human Connectome Project (HCP), were recruited. Voxel-based morphometry analysis of both childhood trauma and body mass index (BMI) was performed in the longitudinal IMAGEN cohort; validation of the findings was performed in the UKB. White-matter connectivity analysis was conducted to study the structural connectivity between the identified brain region and subdivisions of the hypothalamus in the HCP. Results In IMAGEN, a smaller frontopolar cortex (FPC) was associated with both childhood abuse (CA) (β = − .568, 95%CI − .942 to − .194; p = .003) and higher BMI (β = − .086, 95%CI − .128 to − .043; p

Hemispheric lateralization constitutes a core architectural principle of human brain organization underlying cognition, often argued to represent a stable, trait-like feature. However, emerging evidence underlines the inherently dynamic nature of brain networks, in which time-resolved alterations in functional lateralization remain uncharted. Integrating dynamic network approaches with the concept of hemispheric laterality, we map the spatiotemporal architecture of whole-brain lateralization in a large sample of high-quality resting-state fMRI data (N = 991, Human Connectome Project). We reveal distinct laterality dynamics across lower-order sensorimotor systems and higher-order associative networks. Specifically, we expose 2 aspects of the laterality dynamics: laterality fluctuations (LF), defined as the standard deviation of laterality time series, and laterality reversal (LR), referring to the number of zero crossings in laterality time series. These 2 measures are associated with moderate and extreme changes in laterality over time, respectively. While LF depict positive association with language function and cognitive flexibility, LR shows a negative association with the same cognitive abilities. These opposing interactions indicate a dynamic balance between intra and interhemispheric communication, i.e., segregation and integration of information across hemispheres. Furthermore, in their time-resolved laterality index, the default mode and language networks correlate negatively with visual/sensorimotor and attention networks, which are linked to better cognitive abilities. Finally, the laterality dynamics are associated with functional connectivity changes of higher-order brain networks and correlate with regional metabolism and structural connectivity. Our results provide insights into the adaptive nature of the lateralized brain and new perspectives for future studies of human cognition, genetics, and brain disorders. Hemispheric lateralization constitutes a core architectural principle of human brain organization, often argued to represent a stable, trait-like feature, but how does this fit with our increasing appreciation of the inherently dynamic nature of brain networks? This neuroimaging study reveals the dynamic nature of functional brain lateralization at resting-state and its relationship with language function and cognitive flexibility.