Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles.

Chronic insomnia (CI) is a complex disease involving multiple factors including genetics, gut microbiota, and brain structure and function. However, there lacks a unified framework to elucidate how these factors interact in CI. By combining data of clinical assessment, sleep behavior recording, cognitive test, multimodal MRI (structural, functional, and perfusion), gene, and gut microbiota, this study demonstrated that enhanced cerebral blood flow (CBF) similarities of the somatomotor network (SMN) acted as a key mediator to link multiple factors in CI. Specifically, we first demonstrated that only CBF but not morphological or functional networks exhibited alterations in patients with CI, characterized by increases within the SMN and between the SMN and higher-order associative networks. Moreover, these findings were highly reproducible and the CBF similarity method was test-retest reliable. Further, we showed that transcriptional profiles explained 60.4 % variance of the pattern of the increased CBF similarities with the most correlated genes enriched in regulation of cellular and protein localization and material transport, and gut microbiota explained 69.7 % inter-individual variance in the increased CBF similarities with the most contributions from Negativicutes and Lactobacillales. Finally, we found that the increased CBF similarities were correlated with clinical variables, accounted for sleep behaviors and cognitive deficits, and contributed the most to the patient-control classification (accuracy = 84.4 %). Altogether, our findings have important implications for understanding the neuropathology of CI and may inform ways of developing new therapeutic strategies for the disease.

Association between hearing ability and cortical morphology in the elderly: multiparametric mapping, cognitive relevance, and neurobiological underpinnings.

BACKGROUND: Hearing impairment is a common condition in the elderly. However, a comprehensive understanding of its neural correlates is still lacking. METHODS: We recruited 284 elderly adults who underwent structural MRI, magnetic resonance spectroscopy, audiometry, and cognitive assessments. Individual hearing abilities indexed by pure tone average (PTA) were correlated with multiple structural MRI-derived cortical morphological indices. For regions showing significant correlations, mediation analyses were performed to examine their role in the relationship between hearing ability and cognitive function. Finally, the correlation maps between hearing ability and cortical morphology were linked with publicly available connectomic gradient, transcriptomic, and neurotransmitter maps. FINDINGS: Poorer hearing was related to cortical thickness (CT) reductions in widespread regions and gyrification index (GI) reductions in the right Area 52 and Insular Granular Complex. The GI in the right Area 52 mediated the relationship between hearing ability and executive function. This mediating effect was further modulated by glutamate and N-acetylaspartate levels in the right auditory region. The PTA-CT correlation map followed microstructural connectomic hierarchy, were related to genes involved in certain biological processes (e.g., glutamate metabolic process), cell types (e.g., excitatory neurons and astrocytes), and developmental stages (i.e., childhood to young adulthood), and covaried with dopamine receptor 1, dopamine transporter, and fluorodopa. The PTA-GI correlation map was related to 5-hydroxytryptamine receptor 2a. INTERPRETATION: Poorer hearing is associated with cortical thinning and folding reductions, which may be engaged in the relationship between hearing impairment and cognitive decline in the elderly and have different neurobiological substrates. FUNDING: See the Acknowledgements section.

Altered Cortical Information Interaction During Respiratory Events in Children with Obstructive Sleep Apnea-Hypopnea Syndrome.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) significantly impairs children's growth and cognition. This study aims to elucidate the pathophysiological mechanisms underlying OSAHS in children, with a particular focus on the alterations in cortical information interaction during respiratory events. We analyzed sleep electroencephalography before, during, and after events, utilizing Symbolic Transfer Entropy (STE) for brain network construction and information flow assessment. The results showed a significant increase in STE after events in specific frequency bands during N2 and rapid eye movement (REM) stages, along with increased STE during N3 stage events. Moreover, a noteworthy rise in the information flow imbalance within and between hemispheres was found after events, displaying unique patterns in central sleep apnea and hypopnea. Importantly, some of these alterations were correlated with symptom severity. These findings highlight significant changes in brain region coordination and communication during respiratory events, offering novel insights into OSAHS pathophysiology in children.

m6A/m1A/m5C-Associated Methylation Alterations and Immune Profile in MDD.

Major depressive disorder (MDD) is a prevalent psychiatric condition often accompanied by severe impairments in cognitive and functional capacities. This research was conducted to identify RNA modification-related gene signatures and associated functional pathways in MDD. Differentially expressed RNA modification-related genes in MDD were first identified. And a random forest model was developed and distinct RNA modification patterns were discerned based on signature genes. Then, comprehensive analyses of RNA modification-associated genes in MDD were performed, including functional analyses and immune cell infiltration. The study identified 29 differentially expressed RNA modification-related genes in MDD and two distinct RNA modification patterns. TRMT112, MBD3, NUDT21, and IGF2BP1 of the risk signature were detected. Functional analyses confirmed the involvement of RNA modification in pathways like phosphatidylinositol 3-kinase signaling and nucleotide oligomerization domain (NOD)-like receptor signaling in MDD. NUDT21 displayed a strong positive correlation with type 2 T helper cells, while IGF2BP1 negatively correlated with activated CD8 T cells, central memory CD4 T cells, and natural killer T cells. In summary, further research into the roles of NUDT21 and IGF2BP1 would be valuable for understanding MDD prognosis. The identified RNA modification-related gene signatures and pathways provide insights into MDD molecular etiology and potential diagnostic biomarkers.

Examining associations of folic acid supplements administered to mothers during pre-conceptional and prenatal periods with autism spectrum disorders in their offspring: insights from a multi-center study in China.

Objective: To investigate the relationship between maternal folic acid (FA) supplementation during the pre-conceptional and prenatal periods and the subsequent risk of autism spectrum disorder (ASD) in offspring. Methods: A total of 6,049 toddlers aged 16-30 months were recruited from August 2016 to March 2017 for this cross-sectional study conducted in China. The parents of the enrolled toddlers provided information on maternal supplemental FA, socio-demographic information, and related covariates. Standard diagnostic procedures were implemented to identify toddlers with ASD. Results: Among the 6,049 children included in the study, consisting of 3,364 boys with an average age of 22.7 ± 4.1 months, a total of 71 children (1.2%) were diagnosed with ASD. Mothers who did not consume FA supplements during the prenatal period were found to have a significantly increased risk of having offspring with ASD, in comparison to those who were exposed to FA supplements (odds ratio [OR] = 2.47). However, we did not find a similar association during the pre-conceptional period. Compared to mothers who consistently used FA supplements from pre-conception to the prenatal period, those who never used FA supplements were statistically significantly associated with a higher risk of ASD in their offspring (OR = 2.88). Conclusion: This study indicated that providing continuous maternal FA supplementation during the pre-conceptional and prenatal periods may decrease the risk of ASD in offspring. The prenatal period is considered to be the most crucial time for intervention.

The cognitive dysfunction of claustrum on Alzheimer's disease: A mini-review.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases characterized by cognitive deficits and dementia. AD entails predominant pathological characteristics including amyloid beta (Aß) plaque formation, neurofibrillary entanglements, and brain atrophy, which gradually result in cognitive dysfunctions. Studies showed that these pathological changes are found in a myriad of brain structures, including the claustrum (CLA), a nucleus that penetrates deeply into the brain and is extensively interconnected to various brain structures. The CLA modulates many aspects of cognitive functions, with attention, executive function, visuospatial ability, language, and memory in particular. It is also implicated in multiple neuropsychiatric disorders, of which one worthy of particular attention is AD-related cognitive impairments. To inspire novel AD treatment strategies, this review has summarized the CLA functionality in discriminative cognitive dysfunctions in AD. And then propose an array of potential mechanisms that might contribute to the cognitive impairments caused by an abnormal CLA physiology. We advocate that the CLA might be a new promising therapeutic target in combination with existing anti-AD drugs and brain stimulation approaches for future AD treatment.

Selective Impairments in Fine Neural Tuning for Print in Chinese Children with Developmental Dyslexia.

Neural tuning for print refers to differential neural responses (e.g., the N1 component of event-related potentials) to different orthographic forms and other visual stimuli. While impaired neural tuning for print has been well established in dyslexic children who read alphabetic scripts, it remains unclear whether such effects exist in dyslexic children who read Chinese, which dramatically differs in visual and linguistic characteristics from alphabetic words. To fill this gap, we examined two levels of the neural tuning for print: coarse tuning (i.e., false character vs. stroke combination), and fine tuning (i.e., sub-lexical tuning: pseudo character vs. false character; and lexical tuning: real character vs. pseudo character). Using the event-related potential technique, we examined 14 typically developing children and 16 dyslexic children who were screened from 216 nine-year-old children in the third grade. For typically developing children, we observed both coarse and sub-lexical tuning. Critically, for dyslexic children, we found stronger N1 for false character than for stroke combination, suggesting intact coarse tuning, but a reduced N1 difference between false character and pseudo character, suggesting impaired sub-lexical tuning. These results clearly show selective impairments in fine neural tuning at the sub-lexical level in Chinese dyslexic children. Our findings may be associated with unique features of Chinese characters.

Prevalence of Autism Spectrum Disorder in the United States is Stable in the COVID-19 Era.

Although the United States (US) have been monitoring the autism spectrum disorder (ASD) prevalence, whether the prevalence has continued to increase, decrease, fluctuate or reached a stable level remained unclear during the COVID-19 pandemic. We have requested the 2016-2021 National Survey of Children's Health (NSCH) data in the United States to estimate weighted ASD prevalence and assess linearity/nonlinearity in the time trend. We did not observe linear or nonlinear trends of the ASD prevalence during the 2016-2021 periods. The current ASD prevalence experienced a 0.3% drop from 2019 to 2020 but a 0.3% uptick in 2021, suggesting a stable trend during the COVID-19 pandemic. Our findings shed lights on the need for the modified strategy of monitor ASD prevalence during the COVID-19 era.

Top-down modulation and cortical-AMG/HPC interaction in familiar face processing.

Humans can accurately recognize familiar faces in only a few hundred milliseconds, but the underlying neural mechanism remains unclear. Here, we recorded intracranial electrophysiological signals from ventral temporal cortex (VTC), superior/middle temporal cortex (STC/MTC), medial parietal cortex (MPC), and amygdala/hippocampus (AMG/HPC) in 20 epilepsy patients while they viewed faces of famous people and strangers as well as common objects. In posterior VTC and MPC, familiarity-sensitive responses emerged significantly later than initial face-selective responses, suggesting that familiarity enhances face representations after they are first being extracted. Moreover, viewing famous faces increased the coupling between cortical areas and AMG/HPC in multiple frequency bands. These findings advance our understanding of the neural basis of familiar face perception by identifying the top-down modulation in local face-selective response and interactions between cortical face areas and AMG/HPC.

Aberrant single-subject morphological brain networks in first-episode, treatment-naive adolescents with major depressive disorder.

Background: Neuroimaging-based connectome studies have indicated that major depressive disorder (MDD) is associated with disrupted topological organization of large-scale brain networks. However, the disruptions and their clinical and cognitive relevance are not well established for morphological brain networks in adolescent MDD. Objective: To investigate the topological alterations of single-subject morphological brain networks in adolescent MDD. Methods: Twenty-five first-episode, treatment-naive adolescents with MDD and 19 healthy controls (HCs) underwent T1-weighted magnetic resonance imaging and a battery of neuropsychological tests. Single-subject morphological brain networks were constructed separately based on cortical thickness, fractal dimension, gyrification index, and sulcus depth, and topologically characterized by graph-based approaches. Between-group differences were inferred by permutation testing. For significant alterations, partial correlations were used to examine their associations with clinical and neuropsychological variables in the patients. Finally, a support vector machine was used to classify the patients from controls. Results: Compared with the HCs, the patients exhibited topological alterations only in cortical thickness-based networks characterized by higher nodal centralities in parietal (left primary sensory cortex) but lower nodal centralities in temporal (left parabelt complex, right perirhinal ectorhinal cortex, right area PHT and right ventral visual complex) regions. Moreover, decreased nodal centralities of some temporal regions were correlated with cognitive dysfunction and clinical characteristics of the patients. These results were largely reproducible for binary and weighted network analyses. Finally, topological properties of the cortical thickness-based networks were able to distinguish the MDD adolescents from HCs with 87.6% accuracy. Conclusion: Adolescent MDD is associated with disrupted topological organization of morphological brain networks, and the disruptions provide potential biomarkers for diagnosing and monitoring the disease.

Effects of Long-Term Exposure to 2260 m Altitude on Working Memory and Resting-State Activity in the Prefrontal Cortex: A Large-Sample Cross-Sectional Study.

It has been well established that very-high-altitude (>4000 m) environments can affect human cognitive function and brain activity. However, the effects of long-term exposure to moderate altitudes (2000−3000 m) on cognitive function and brain activity are not well understood. In the present cross-sectional study, we utilized an N-back working memory task and resting-state functional near-infrared spectroscopy to examine the effects of two years of exposure to 2260 m altitude on working memory and resting-state brain activity in 208 college students, compared with a control group at the sea level. The results showed that there was no significant change in spatial working memory performance after two years of exposure to 2260 m altitude. In contrast, the analysis of resting-state brain activity revealed changes in functional connectivity patterns in the prefrontal cortex (PFC), with the global efficiency increased and the local efficiency decreased after two years of exposure to 2260 m altitude. These results suggest that long-term exposure to moderate altitudes has no observable effect on spatial working memory performance, while significant changes in functional connectivity and brain network properties could possibly occur to compensate for the effects of mild hypoxic environments. To our knowledge, this study is the first to examine the resting state activity in the PFC associated with working memory in people exposed to moderate altitudes.

Prevalence of developmental dyslexia in primary school children: a protocol for systematic review and meta-analysis.

BACKGROUND: Developmental dyslexia (DD) is a specific impairment during the acquisition of reading skills and may have a lifelong negative impact on individuals. Reliable estimates of the prevalence of DD serve as the basis for evidence-based health resource allocation and policy making. However, the prevalence of DD in primary school children varies largely across studies. Moreover, it is unclear whether there are differences in prevalence in different genders and writing systems. Hence, the present study aims to conduct a systematic review and meta-analysis to assess the global prevalence of DD and to explore related factors. METHODS: We will undertake a comprehensive literature search in 14 databases, including EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure and Cochrane, from their inception to June 2021. Cross-sectional and longitudinal studies that describe the prevalence of DD will be eligible. The quality of the included observational studies will be assessed using the Strengthening the Reporting of Observational Studies in Epidemiology statement. The risk of bias will be determined by sensitivity analysis to identify publication bias. RESULTS: One meta-analysis will be conducted to estimate the prevalence of DD in primary school children. Heterogeneity will be assessed in terms of the properties of subjects (e.g., gender, grade and writing system) and method of diagnosis in the included primary studies. Subgroup analyses will also be performed for population and secondary outcomes. CONCLUSION: The results will synthesize the prevalence of DD and provide information for policy-makers and public health specialists.

Early visual exposure primes future cross-modal specialization of the fusiform face area in tactile face processing in the blind.

The fusiform face area (FFA) is a core cortical region for face information processing. Evidence suggests that its sensitivity to faces is largely innate and tuned by visual experience. However, how experience in different time windows shape the plasticity of the FFA remains unclear. In this study, we investigated the role of visual experience at different time points of an individual's early development in the cross-modal face specialization of the FFA. Participants (n = 74) were classified into five groups: congenital blind, early blind, late blind, low vision, and sighted control. Functional magnetic resonance imaging data were acquired when the participants haptically processed carved faces and other objects. Our results showed a robust and highly consistent face-selective activation in the FFA region in the early blind participants, invariant to size and level of abstraction of the face stimuli. The cross-modal face activation in the FFA was much less consistent in other groups. These results suggest that early visual experience primes cross-modal specialization of the FFA, and even after the absence of visual experience for more than 14 years in early blind participants, their FFA can engage in cross-modal processing of face information.

Subregion-specific, modality-dependent and timescale-sensitive hippocampal connectivity alterations in patients with first-episode, drug-naïve major depression disorder.

BACKGROUND: Despite accumulating evidence for the hippocampus as a key dysfunctional node in major depressive disorder (MDD), previous findings are controversial possibly due to heterogeneous and small clinical samples, complicated hippocampal structure, and different imaging modalities and analytical methods. METHODS: We collected structural and resting-state functional MRI data from 100 first-episode, drug-naïve MDD patients and 99 healthy controls. A subset of the participants (34 patients and 33 controls) also completed a battery of neuropsychological tests and childhood trauma questionnaires. Seed-based morphological and functional (static and dynamic) connectivity were calculated for ten hippocampal subregions, followed by analyses of dynamic functional connectivity states (k-means clustering), connectivity cross-modality relationships (cosine similarity), and connectivity associations with clinical and neuropsychological variables (Spearman correlation). RESULTS: Between-group comparisons revealed abnormal hippocampal connectivity in the patients that depended on 1) hippocampal subdivisions: the cornu ammonis (CA) was the most seriously affected subregion, in particular the right CA1 for functional connectivity alterations; 2) imaging modality: morphological connectivity revealed seldom and sporadic alterations with different lobes, while functional connectivity identified numerous and convergent alterations with prefrontal regions; and 3) time scale: dynamic functional connectivity was more sensitive than static functional connectivity, in particular in revealing alterations between the right CA1 and contralateral prefrontal cortex. Among the 34 patients, functional connectivity alterations of the CA1 were related to the history of childhood trauma in the patients. LIMITATIONS: Only a subset of the patients completed the neuropsychological tests, which may cause underestimation of cognitive relevance of hippocampal connectivity alterations. CONCLUSIONS: Disrupted hippocampal CA1 functional connectivity plays key roles in the pathophysiology of MDD and may act as a potential diagnostic biomarker for the disease.

Prevalence of Developmental Dyslexia in Primary School Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Developmental dyslexia (DD) is a specific learning disorder concerning reading acquisition that may has a lifelong negative impact on individuals. A reliable estimate of the prevalence of DD serves as the basis for diagnosis, intervention, and evidence-based health resource allocation and policy-making. Hence, the present meta-analysis aims to generate a reliable prevalence estimate of DD worldwide in primary school children and explore the potential variables related to that prevalence. METHODS: Studies from the 1950s to June 2021 were collated using a combination of search terms related to DD and prevalence. Study quality was assessed using the STROBE guidelines according to the study design, with study heterogeneity assessed using the I2 statistic, and random-effects meta-analyses were conducted. Variations in the prevalence of DD in different subgroups were assessed via subgroup meta-analysis and meta-regression. RESULTS: The pooled prevalence of DD was 7.10% (95% CI: 6.27-7.97%). The prevalence in boys was significantly higher than that in girls (boys: 9.22%, 95%CI, 8.07-10.44%; girls: 4.66%, 95% CI, 3.84-5.54%; p < 0.001), but no significant difference was found in the prevalence across different writing systems (alphabetic scripts: 7.26%, 95%CI, 5.94-8.71%; logographic scripts: 6.97%, 95%CI, 5.86-8.16%; p > 0.05) or across different orthographic depths (shallow: 7.13%, 95% CI, 5.23-9.30%; deep: 7.55%, 95% CI, 4.66-11.04%; p > 0.05). It is worth noting that most articles had small sample sizes with diverse operational definitions, making comparisons challenging. CONCLUSIONS: This study provides an estimation of worldwide DD prevalence in primary school children. The prevalence was higher in boys than in girls but was not significantly different across different writing systems.

Neural responses to facial attractiveness in the judgments of moral goodness and moral beauty.

The judgments of moral goodness and moral beauty objectively refer to the perception and evaluation of moral traits, which are generally influenced by facial attractiveness. For centuries, people have equated beauty with the possession of positive qualities, but it is not clear whether the association between beauty and positive qualities exerts a similarly implicit influence on people's responses to moral goodness and moral beauty, how it affects those responses, and what is the neural basis for such an effect. The present study is the first to examine the neural responses to facial attractiveness in the judgments of moral goodness and moral beauty. We found that beautiful faces in both moral judgments activated the left ventral occipitotemporal cortices sensitive to the geometric configuration of the faces, demonstrating that both moral goodness and moral beauty required the automatic visual analysis of geometrical configuration of attractive faces. In addition, compared to beautiful faces during moral goodness judgment, beautiful faces during moral beauty judgment induced unique activity in the ventral medial prefrontal cortex and midline cortical structures involved in the emotional-valenced information about attractive faces. The opposite comparison elicited specific activity in the left superior temporal cortex and premotor area, which play a critical role in the recognition of facial identity. Our results demonstrated that the neural responses to facial attractiveness in the process of higher order moral decision-makings exhibit both task-general and task-specific characteristics. Our findings contribute to the understanding of the essence of the relationship between morality and aesthetics.

DeepHBV: a deep learning model to predict hepatitis B virus (HBV) integration sites.

BACKGROUND: The hepatitis B virus (HBV) is one of the main causes of viral hepatitis and liver cancer. HBV integration is one of the key steps in the virus-promoted malignant transformation. RESULTS: An attention-based deep learning model, DeepHBV, was developed to predict HBV integration sites. By learning local genomic features automatically, DeepHBV was trained and tested using HBV integration site data from the dsVIS database. Initially, DeepHBV showed an AUROC of 0.6363 and an AUPR of 0.5471 for the dataset. The integration of genomic features of repeat peaks and TCGA Pan-Cancer peaks significantly improved model performance, with AUROCs of 0.8378 and 0.9430 and AUPRs of 0.7535 and 0.9310, respectively. The transcription factor binding sites (TFBS) were significantly enriched near the genomic positions that were considered. The binding sites of the AR-halfsite, Arnt, Atf1, bHLHE40, bHLHE41, BMAL1, CLOCK, c-Myc, COUP-TFII, E2A, EBF1, Erra, and Foxo3 were highlighted by DeepHBV in both the dsVIS and VISDB datasets, revealing a novel integration preference for HBV. CONCLUSIONS: DeepHBV is a useful tool for predicting HBV integration sites, revealing novel insights into HBV integration-related carcinogenesis.

Higher-order sensorimotor circuit of the brain's global network supports human consciousness.

Consciousness is a mental characteristic of the human mind, whose exact neural features remain unclear. We aimed to identify the critical nodes within the brain's global functional network that support consciousness. To that end, we collected a large fMRI resting state dataset with subjects in at least one of the following three consciousness states: preserved (including the healthy awake state, and patients with a brain injury history (BI) that is fully conscious), reduced (including the N1-sleep state, and minimally conscious state), and lost (including the N3-sleep state, anesthesia, and unresponsive wakefulness state). We also included a unique dataset of subjects in rapid eye movement sleep state (REM-sleep) to test for the presence of consciousness with minimum movements and sensory input. To identify critical nodes, i.e., hubs, within the brain's global functional network, we used a graph-theoretical measure of degree centrality conjoined with ROI-based functional connectivity. Using these methods, we identified various higher-order sensory and motor regions including the supplementary motor area, bilateral supramarginal gyrus (part of inferior parietal lobule), supragenual/dorsal anterior cingulate cortex, and left middle temporal gyrus, that could be important hubs whose degree centrality was significantly reduced when consciousness was reduced or absent. Additionally, we identified a sensorimotor circuit, in which the functional connectivity among these regions was significantly correlated with levels of consciousness across the different groups, and remained present in the REM-sleep group. Taken together, we demonstrated that regions forming a higher-order sensorimotor integration circuit are involved in supporting consciousness within the brain's global functional network. That offers novel and more mechanism-guided treatment targets for disorders of consciousness.