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1.
Biol Psychiatry ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38718879

ABSTRACT

BACKGROUND: The right MFG has been proposed as a convergence site for the DAN and VAN, regulating both networks and enabling flexible modulation of attention. However, it is unclear if the connections between the right MFG and these networks can predict changes in ADHD symptoms. METHODS: This study used data from the Children School Functions and Brain Development project (n = 713, 56.2% boys). Resting-state fMRI was employed to analyze the connections of the right MFG with DAN/VAN, connectome-based predictive modeling was applied for longitudinal prediction, and ADHD PRS were used for genetic analysis. RESULTS: The ADHD symptoms were associated with the connections between the right MFG and DAN subregion, including the FEF, as well as the VAN subregions, namely the IPL and IFG. Furthermore, these connections of the right MFG with FEF, IPL, and IFG could significantly predict changes in ADHD symptoms over one year and mediate the prediction of ADHD symptom changes by PRS for ADHD. Finally, the validation samples confirmed that the functional connectivity between the right MFG and FEF/IPL in ADHD patients was significantly weaker than that in the typically developing controls, and this difference disappeared after medication. CONCLUSIONS: The connection of right MFG with DAN and VAN can serve as a predictive indicator for changes in ADHD symptoms over the following year, while also mediating the prediction of ADHD symptom changes by PRS for ADHD. These findings hold promise as potential biomarkers for early identification of children at risk of developing ADHD.

2.
Gut Microbes ; 16(1): 2334970, 2024.
Article in English | MEDLINE | ID: mdl-38563680

ABSTRACT

Gastrointestinal (GI) infection is evidenced with involvement in COVID-19 pathogenesis caused by SARS-CoV-2. However, the correlation between GI microbiota and the distinct pathogenicity of SARS-CoV-2 Proto and its emerging variants remains unclear. In this study, we aimed to determine if GI microbiota impacted COVID-19 pathogenesis and if the effect varied between SARS-CoV-2 Proto and its variants. We performed an integrative analysis of histopathology, microbiomics, and transcriptomics on the GI tract fragments from rhesus monkeys infected with SARS-CoV-2 proto or its variants. Based on the degree of pathological damage and microbiota profile in the GI tract, five of SARS-CoV-2 strains were classified into two distinct clusters, namely, the clusters of Alpha, Beta and Delta (ABD), and Proto and Omicron (PO). Notably, the abundance of potentially pathogenic microorganisms increased in ABD but not in the PO-infected rhesus monkeys. Specifically, the high abundance of UCG-002, UCG-005, and Treponema in ABD virus-infected animals positively correlated with interleukin, integrins, and antiviral genes. Overall, this study revealed that infection-induced alteration of GI microbiota and metabolites could increase the systemic burdens of inflammation or pathological injury in infected animals, especially in those infected with ABD viruses. Distinct GI microbiota and metabolite profiles may be responsible for the differential pathological phenotypes of PO and ABD virus-infected animals. These findings improve our understanding the roles of the GI microbiota in SARS-CoV-2 infection and provide important information for the precise prevention, control, and treatment of COVID-19.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Animals , SARS-CoV-2 , Virulence , Macaca mulatta
3.
Transl Psychiatry ; 14(1): 117, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38403656

ABSTRACT

The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6-15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.


Subject(s)
Problem Behavior , Subthalamic Nucleus , Humans , Adolescent , Subthalamic Nucleus/diagnostic imaging , Longitudinal Studies , Red Nucleus , Substantia Nigra/diagnostic imaging , Cohort Studies
4.
Am Psychol ; 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38300575

ABSTRACT

From childhood to adulthood, the human brain develops highly specialized yet interacting neural modules that give rise to nuanced attention and other cognitive functions. Each module can specialize over development to support specific functions, yet also coexist in multiple neurobiological modes to support distinct processes. Advances in cognitive neuroscience have conceptualized human attention as a set of cognitive processes anchored in highly specialized yet interacting neural systems. The underlying mechanisms of how these systems interplay to support children's cognitive development of multiple attention processes remain unknown. Leveraging developmental functional magnetic resonance imaging with attention network test paradigm, we demonstrate differential neurocognitive development of three core attentional processes from childhood to adulthood, with alerting reaching adult-like level earlier, followed by orienting and executive attention with more protracted development throughout middle and late childhood. Relative to adults, young children exhibit immature specialization with less pronounced dissociation of neural systems specific to each attentional process. Children manifest adult-like distributed representations in the ventral attention and cingulo-opercular networks, but less stable and weaker generalizable representations across multiple processes in the dorsal attention network. Our findings provide insights into the functional specialization and generalization of neural representations scaffolding cognitive development of core attentional processes from childhood to adulthood. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

5.
Dev Cogn Neurosci ; 66: 101346, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38290421

ABSTRACT

Risk-taking often occurs in childhood as a compex outcome influenced by individual, family, and social factors. The ability to govern risky decision-making in a balanced manner is a hallmark of the integrity of cognitive and affective development from childhood to adulthood. The Triadic Neural Systems Model posits that the nuanced coordination of motivational approach, avoidance and prefrontal control systems is crucial to regulate adaptive risk-taking and related behaviors. Although widely studied in adolescence and adulthood, how these systems develop in childhood remains elusive. Here, we show heterogenous age-related differences in the triadic neural systems involved in risky decision-making in 218 school-age children relative to 80 young adults. Children were generally less reward-seeking and less risk-taking than adults, and exhibited gradual increases in risk-taking behaviors from 6 to 12 years-old, which are associated with age-related differences in brain activation patterns underlying reward and risk processing. In comparison to adults, children exhibited weaker activation in control-related prefrontal systems, but stronger activation in reward-related striatal systems. Network analyses revealed that children showed greater reward-related functional connectivity within and between the triadic systems. Our findings support an immature and unbalanced developmental view of the core neurocognitive systems involved in risky decision-making and related behaviors in middle to late childhood.

6.
NMR Biomed ; 37(5): e5098, 2024 May.
Article in English | MEDLINE | ID: mdl-38224670

ABSTRACT

The overlapping peaks of the target chemical exchange saturation transfer (CEST) solutes and other unknown CEST solutes affect the quantification results and accuracy of the chemical exchange parameters-the fractional concentration, f b , exchange rate, k b , and transverse relaxation rate, R 2 b -for the target solutes. However, to date, no method has been established for assessing the overlapping peaks. This study aimed to develop a method for quantifying the f b , k b , and R 2 b values of a specific CEST solute, as well as assessing the overlap between the CEST peaks of the specific solute(s) and other unknown solutes. A simplified R 1 ρ model was proposed, assuming linear approximation of the other solutes' contributions to R 1 ρ . A CEST data acquisition scheme was applied with various saturation offsets and saturation powers. In addition to fitting the f b , k b , and R 2 b values of the specific solute, the overlapping condition was evaluated based on the root mean square error (RMSE) between the trajectories of the acquired and synthesized data. Single-solute and multi-solute phantoms with various phosphocreatine (PCr) concentrations and pH values were used to calculate the f b and k b of PCr and the corresponding RMSE. The feasibility of RMSE for evaluating the overlapping condition, and the accurate fitting of f b and k b in weak overlapping conditions, were verified. Furthermore, the method was employed to quantify the nuclear Overhauser effect signal in rat brains and the PCr signal in rat skeletal muscles, providing results that were consistent with those reported in previous studies. In summary, the proposed approach can be applied to evaluate the overlapping condition of CEST peaks and quantify the f b , k b , and R 2 b values of specific solutes, if the weak overlapping condition is satisfied.


Subject(s)
Algorithms , Magnetic Resonance Imaging , Rats , Animals , Magnetic Resonance Imaging/methods , Phantoms, Imaging
8.
Nat Commun ; 15(1): 784, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38278807

ABSTRACT

Cortical thinning is an important hallmark of the maturation of brain morphology during childhood and adolescence. However, the connectome-based wiring mechanism that underlies cortical maturation remains unclear. Here, we show cortical thinning patterns primarily located in the lateral frontal and parietal heteromodal nodes during childhood and adolescence, which are structurally constrained by white matter network architecture and are particularly represented using a network-based diffusion model. Furthermore, connectome-based constraints are regionally heterogeneous, with the largest constraints residing in frontoparietal nodes, and are associated with gene expression signatures of microstructural neurodevelopmental events. These results are highly reproducible in another independent dataset. These findings advance our understanding of network-level mechanisms and the associated genetic basis that underlies the maturational process of cortical morphology during childhood and adolescence.


Subject(s)
Connectome , White Matter , Humans , Adolescent , Brain/diagnostic imaging , Brain/anatomy & histology , Connectome/methods , Cerebral Cortical Thinning , White Matter/diagnostic imaging , White Matter/anatomy & histology , Magnetic Resonance Imaging
9.
J Neurosci Methods ; 401: 110010, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37956928

ABSTRACT

BACKGROUND: Recent advances in highly sensitive miniaturized optically pumped magnetometers (OPMs) have enabled the development of wearable magnetoencephalography (MEG) offering great flexibility in experimental setting. The OPM array for wearable MEG is typically attached to a flexible cap and exhibits a variable spatial layout across different subjects, which imposes challenges concerning the efficient positioning and labelling of OPMs. NEW METHOD: A pair of reflective markers are affixed to each triaxial OPM sensor above its cable to determine its location and sensitive axes. A non-rigid registration of optically digitized marker locations with a pre-labelled template of marker locations is performed to map newly digitized markers to OPMs. RESULTS: The positioning and labelling of 66 OPM sensors could be completed within 35 s. Across ten experiments, all OPMs were accurately labelled, and the mean test-retest errors were 0.48 mm for sensor locations and 0.20 degree for sensitive axes. By combining six OPMs' positions with their respective recordings, magnetic dipoles inside a phantom were located with a mean error of 5.5 mm, and the best fitted dipole for MEG with auditory stimuli presented was located on a subject's primary auditory cortex. COMPARISON WITH EXISTING METHODS: The proposed method reduces the reliance on error-prone and laborious manual operations inherent in existing methods, therefore significantly improving the efficiency of OPM positioning and labelling on a flexible cap. CONCLUSION: We developed a method for the precise and rapid positioning and labelling triaxial OPMs on a flexible cap, thereby facilitating the practical implementation of wearable OPM-MEG.


Subject(s)
Magnetoencephalography , Wearable Electronic Devices , Humans , Magnetoencephalography/methods , Phantoms, Imaging , Brain
10.
Commun Biol ; 6(1): 1257, 2023 12 12.
Article in English | MEDLINE | ID: mdl-38087047

ABSTRACT

From childhood to adolescence, the spatiotemporal development pattern of the human brain white matter connectome and its underlying transcriptomic and cellular mechanisms remain largely unknown. With a longitudinal diffusion MRI cohort of 604 participants, we map the developmental trajectory of the white matter connectome from global to regional levels and identify that most brain network properties followed a linear developmental trajectory. Importantly, connectome-transcriptomic analysis reveals that the spatial development pattern of white matter connectome is potentially regulated by the transcriptomic architecture, with positively correlated genes involve in ion transport- and development-related pathways expressed in excitatory and inhibitory neurons, and negatively correlated genes enriches in synapse- and development-related pathways expressed in astrocytes, inhibitory neurons and microglia. Additionally, the macroscale developmental pattern is also associated with myelin content and thicknesses of specific laminas. These findings offer insights into the underlying genetics and neural mechanisms of macroscale white matter connectome development from childhood to adolescence.


Subject(s)
Connectome , White Matter , Adolescent , Humans , Child , White Matter/diagnostic imaging , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Gene Expression Profiling
11.
bioRxiv ; 2023 Sep 19.
Article in English | MEDLINE | ID: mdl-37745373

ABSTRACT

The functional connectome of the human brain represents the fundamental network architecture of functional interdependence in brain activity, but its normative growth trajectory across the life course remains unknown. Here, we aggregate the largest, quality-controlled multimodal neuroimaging dataset from 119 global sites, including 33,809 task-free fMRI and structural MRI scans from 32,328 individuals ranging in age from 32 postmenstrual weeks to 80 years. Lifespan growth charts of the connectome are quantified at the whole cortex, system, and regional levels using generalized additive models for location, scale, and shape. We report critical inflection points in the non-linear growth trajectories of the whole-brain functional connectome, particularly peaking in the fourth decade of life. Having established the first fine-grained, lifespan-spanning suite of system-level brain atlases, we generate person-specific parcellation maps and further show distinct maturation timelines for functional segregation within different subsystems. We identify a spatiotemporal gradient axis that governs the life-course growth of regional connectivity, transitioning from primary sensory cortices to higher-order association regions. Using the connectome-based normative model, we demonstrate substantial individual heterogeneities at the network level in patients with autism spectrum disorder and patients with major depressive disorder. Our findings shed light on the life-course evolution of the functional connectome and serve as a normative reference for quantifying individual variation in patients with neurological and psychiatric disorders.

12.
Arch Womens Ment Health ; 26(6): 803-817, 2023 12.
Article in English | MEDLINE | ID: mdl-37730923

ABSTRACT

Laboratory studies reveal that young women with premenstrual syndrome (PMS) often exhibit decreased reward processing during the late luteal phase. However, studies based on the self-reports find opposite results (e.g., higher craving for high-sweet-fat food). These differences may lie in the difference between the stimulus used and measuring the different aspects of the reward. The present study was designed to expand previous work by using a classic monetary reward paradigm, simultaneously examining the motivational (i.e., reward anticipation, "wanting") and emotional (i.e., reward outcome, "liking") components of reward processing in women with high premenstrual symptoms (High PMS). College female students in their early twenties with High PMS (n = 20) and low premenstrual symptoms (Low PMS, n = 20) completed a monetary incentive delay task during their late luteal phase when the premenstrual symptoms typically peak. Brain activities in the reward anticipation phase and outcome phase were recorded using the magnetoencephalographic (MEG) imaging technique. No group differences were found in various behavioral measurements. For the MEG results, in the anticipation phase, when High PMS participants were presented with cues that predicted the upcoming monetary gains, they showed higher event-related magnetic fields (ERFs) than when they were presented with neutral non-reward cues. This pattern was reversed in Low PMS participants, as they showed lower reward cue-elicited ERFs than non-reward cue-elicited ones (cluster mass = 2560, cluster size = 891, p = .03, corrected for multiple comparisons), mainly in the right medial orbitofrontal and lateral orbitofrontal cortex (cluster mass = 375, cluster size = 140, p = .03, corrected for multiple comparisons). More importantly, women with High PMS had an overall significantly higher level of ERFs than women with Low PMS (cluster mass = 8039, cluster size = 2937, p = .0009, corrected for multiple comparisons) in the bilateral precentral gyrus, right postcentral gyrus, and left superior temporal gyrus (right: cluster mass = 410, cluster size = 128, p = .03; left: cluster mass = 352, cluster size = 98, p = .05; corrected for multiple comparisons). In the outcome phase, women with High PMS showed significantly lower theta power than the Low PMS ones for the expected non-reward feedback in the bilateral temporal-parietal regions (cluster mass = 47620, cluster size = 18308, p = .01, corrected for multiple comparisons). These findings reveal that the severity of PMS might alter reward anticipation. Specifically, women with High PMS displayed increased brain activities to reward-predicting cues and increased action preparation after the cues appear.


Subject(s)
Magnetoencephalography , Premenstrual Syndrome , Female , Humans , Premenstrual Syndrome/psychology , Brain , Luteal Phase , Reward
13.
Dev Cogn Neurosci ; 63: 101296, 2023 10.
Article in English | MEDLINE | ID: mdl-37690374

ABSTRACT

Predicting the risk for general psychopathology (the p factor) requires the examination of multiple factors ranging from brain to cognitive skills. While an increasing number of findings have reported the roles of the cerebral cortex and executive functions, it is much less clear whether and how the cerebellum and cognitive flexibility (a core component of executive function) may be associated with the risk for general psychopathology. Based on the data from more than 400 children aged 6-12 in the Children School Functions and Brain Development (CBD) Project, this study examined whether the left cerebellar lobule VIIb and its connectivity within the cerebellum may prospectively predict the risk for general psychopathology one year later and whether cognitive flexibility may mediate such predictions in school-age children. The reduced gray matter volume in the left cerebellar lobule VIIb and the increased connectivity of this region to the left cerebellar lobule VI prospectively predicted the risk for general psychopathology and was partially mediated by worse cognitive flexibility. Deficits in cognitive flexibility may play an important role in linking cerebellar structure and function to the risk for general psychopathology.


Subject(s)
Cerebellum , Mental Disorders , Humans , Child , Cerebellum/pathology , Cerebral Cortex , Brain , Cognition , Mental Disorders/pathology , Magnetic Resonance Imaging
14.
J Neural Eng ; 20(4)2023 08 24.
Article in English | MEDLINE | ID: mdl-37615416

ABSTRACT

Objective.Magnetoencephalography (MEG) is a powerful non-invasive diagnostic modality for presurgical epilepsy evaluation. However, the clinical utility of MEG mapping for localising epileptic foci is limited by its low efficiency, high labour requirements, and considerable interoperator variability. To address these obstacles, we proposed a novel artificial intelligence-based automated magnetic source imaging (AMSI) pipeline for automated detection and localisation of epileptic sources from MEG data.Approach.To expedite the analysis of clinical MEG data from patients with epilepsy and reduce human bias, we developed an autolabelling method, a deep-learning model based on convolutional neural networks and a hierarchical clustering method based on a perceptual hash algorithm, to enable the coregistration of MEG and magnetic resonance imaging, the detection and clustering of epileptic activity, and the localisation of epileptic sources in a highly automated manner. We tested the capability of the AMSI pipeline by assessing MEG data from 48 epilepsy patients.Main results.The AMSI pipeline was able to rapidly detect interictal epileptiform discharges with 93.31% ± 3.87% precision based on a 35-patient dataset (with sevenfold patientwise cross-validation) and robustly rendered accurate localisation of epileptic activity with a lobar concordance of 87.18% against interictal and ictal stereo-electroencephalography findings in a 13-patient dataset. We also showed that the AMSI pipeline accomplishes the necessary processes and delivers objective results within a much shorter time frame (∼12 min) than traditional manual processes (∼4 h).Significance.The AMSI pipeline promises to facilitate increased utilisation of MEG data in the clinical analysis of patients with epilepsy.


Subject(s)
Artificial Intelligence , Epilepsy , Humans , Magnetoencephalography , Algorithms , Neural Networks, Computer , Epilepsy/diagnosis
15.
J Neurosci ; 43(40): 6760-6778, 2023 10 04.
Article in English | MEDLINE | ID: mdl-37607820

ABSTRACT

Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus → SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal → prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.


Subject(s)
Awareness , Learning , Female , Humans , Awareness/physiology , Learning/physiology , Prefrontal Cortex/physiology , Reaction Time/physiology , Electroencephalography
16.
Genomics Proteomics Bioinformatics ; 21(5): 1014-1029, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37451436

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of the original SARS-CoV-2 strain and its variants of concern (VOCs; including Alpha, Beta, and Delta) in vitro, as well as differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques, were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells, and its VOCs markedly increased the levels of subgenomic RNAs, such as N, Orf9b, Orf6, and Orf7ab, which are known as the innate immune antagonists and the inhibitors of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Animals , SARS-CoV-2/genetics , Macaca mulatta , COVID-19/genetics , Gene Expression Profiling
17.
CNS Neurosci Ther ; 29(11): 3528-3548, 2023 11.
Article in English | MEDLINE | ID: mdl-37287420

ABSTRACT

AIMS: Increasing evidence indicates that major neurodevelopmental disorders have potential links to abnormal cerebellar development. However, the developmental trajectories of cerebellar subregions from childhood to adolescence are lacking, and it is not clear how emotional and behavioral problems affect them. We aim to map the developmental trajectories of gray matter volume (GMV), cortical thickness (CT), and surface area (SA) in cerebellar subregions from childhood to adolescence and examine how emotional and behavioral problems change the cerebellar development trajectory in a longitudinal cohort study. METHOD: This population-based longitudinal cohort study used data on a representative sample of 695 children. Emotional and behavioral problems were assessed at baseline and at three annual follow-ups with the Strengths and Difficulties Questionnaire (SDQ). RESULTS: Using an innovative automated image segmentation technique, we quantified the GMV, CT, and SA of the whole cerebellum and 24 subdivisions (lobules I-VI, VIIB, VIIIA&B, and IX-X plus crus I-II) with 1319 MRI scans from a large longitudinal sample of 695 subjects aged 6-15 years and mapped their developmental trajectories. We also examined sex differences and found that boys showed more linear growth, while girls showed more nonlinear growth. Boys and girls showed nonlinear growth in the cerebellar subregions; however, girls reached the peak earlier than boys. Further analysis found that emotional and behavioral problems modulated cerebellar development. Specifically, emotional symptoms impede the expansion of the SA of the cerebellar cortex, and no gender differences; conduct problems lead to inadequate cerebellar GMV development only in girls, but not boys; hyperactivity/inattention delays the development of cerebellar GMV and SA, with left cerebellar GMV, right VIIIA GMV and SA in boys and left V GMV and SA in girls; peer problems disrupt CT growth and SA expansion, resulting in delayed GMV development, with bilateral IV, right X CT in boys and right Crus I GMV, left V SA in girls; and prosocial behavior problems impede the expansion of the SA and lead to excessive CT growth, with bilateral IV, V, right VI CT, left cerebellum SA in boys and right Crus I GMV in girls. CONCLUSIONS: This study maps the developmental trajectories of GMV, CT, and SA in cerebellar subregions from childhood to adolescence. In addition, we provide the first evidence for how emotional and behavioral problems affect the dynamic development of GMV, CT, and SA in the cerebellum, which provides an important basis and guidance for the prevention and intervention of cognitive and emotional behavioral problems in the future.


Subject(s)
Gray Matter , Problem Behavior , Humans , Child , Male , Female , Adolescent , Gray Matter/diagnostic imaging , Longitudinal Studies , Emotions , Cohort Studies , Magnetic Resonance Imaging/methods
18.
J Med Virol ; 95(6): e28846, 2023 06.
Article in English | MEDLINE | ID: mdl-37282766

ABSTRACT

Since the first SARS-CoV-2 outbreak in late 2019, the SARS-CoV-2 genome has harbored multiple mutations, especially spike protein mutations. The currently fast-spreading Omicron variant that manifests without symptoms or with upper respiratory diseases has been recognized as a serious global public health problem. However, its pathological mechanism is largely unknown. In this work, rhesus macaques, hamsters, and BALB/C mice were employed as animal models to explore the pathogenesis of Omicron (B.1.1.529). Notably, Omicron (B.1.1.529) infected the nasal turbinates, tracheae, bronchi, and lungs of hamsters and BALB/C mice with higher viral loads than in those of rhesus macaques. Severe histopathological damage and inflammatory responses were observed in the lungs of Omicron (B.1.1.529)-infected animals. In addition, viral replication was found in multiple extrapulmonary organs. Results indicated that hamsters and BALB/c mice are potential animal models for studies on the development of drugs/vaccines and therapies for Omicron (B.1.1.529).


Subject(s)
COVID-19 , SARS-CoV-2 , Mice , Animals , Cricetinae , Macaca mulatta , Mice, Inbred BALB C , Bronchi
19.
Nat Genet ; 55(7): 1126-1137, 2023 07.
Article in English | MEDLINE | ID: mdl-37337106

ABSTRACT

The hippocampus is critical for memory and cognition and neuropsychiatric disorders, and its subfields differ in architecture and function. Genome-wide association studies on hippocampal and subfield volumes are mainly conducted in European populations; however, other ancestral populations are under-represented. Here we conduct cross-ancestry genome-wide association meta-analyses in 65,791 individuals for hippocampal volume and 38,977 for subfield volumes, including 7,009 individuals of East Asian ancestry. We identify 339 variant-trait associations at P < 1.13 × 10-9 for 44 hippocampal traits, including 23 new associations. Common genetic variants have similar effects on hippocampal traits across ancestries, although ancestry-specific associations exist. Cross-ancestry analysis improves the fine-mapping precision and the prediction performance of polygenic scores in under-represented populations. These genetic variants are enriched for Wnt signaling and neuron differentiation and affect cognition, emotion and neuropsychiatric disorders. These findings may provide insight into the genetic architectures of hippocampal and subfield volumes.


Subject(s)
Genome-Wide Association Study , Magnetic Resonance Imaging , Humans , Hippocampus/diagnostic imaging , Cognition
20.
eNeuro ; 10(6)2023 06.
Article in English | MEDLINE | ID: mdl-37328296

ABSTRACT

Native speakers excel at parsing continuous speech into smaller elements and entraining their neural activities to the linguistic hierarchy at different levels (e.g., syllables, phrases, and sentences) to achieve speech comprehension. However, how a nonnative brain tracks hierarchical linguistic structures in second language (L2) speech comprehension and whether it relates to top-down attention and language proficiency remains elusive. Here, we applied a frequency-tagging paradigm in human adults and investigated the neural tracking responses to hierarchically organized linguistic structures (i.e., the syllabic rate of 4 Hz, the phrasal rate of 2 Hz, and the sentential rate of 1 Hz) in both first language (L1) and L2 listeners when they attended to a speech stream or ignored it. We revealed disrupted neural responses to higher-order linguistic structures (i.e., phrases and sentences) for L2 listeners in which the phrasal-level tracking was functionally related to an L2 subject's language proficiency. We also observed less efficient top-down modulation of attention in L2 speech comprehension than in L1 speech comprehension. Our results indicate that the reduced δ-band neuronal oscillations that subserve the internal construction of higher-order linguistic structures may compromise listening comprehension in a nonnative language.


Subject(s)
Comprehension , Speech Perception , Adult , Humans , Comprehension/physiology , Speech Perception/physiology , Auditory Perception , Linguistics , Language
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