Cognitive and psychiatric relevance of dynamic functional connectivity states in a large (N > 10,000) children population.

Children's brains dynamically adapt to the stimuli from the internal state and the external environment, allowing for changes in cognitive and mental behavior. In this work, we performed a large-scale analysis of dynamic functional connectivity (DFC) in children aged 9~11 years, investigating how brain dynamics relate to cognitive performance and mental health at an early age. A hybrid independent component analysis framework was applied to the Adolescent Brain Cognitive Development (ABCD) data containing 10,988 children. We combined a sliding-window approach with k-means clustering to identify five brain states with distinct DFC patterns. Interestingly, the occurrence of a strongly connected state with the most within-network synchrony and the anticorrelations between networks, especially between the sensory networks and between the cerebellum and other networks, was negatively correlated with cognitive performance and positively correlated with dimensional psychopathology in children. Meanwhile, opposite relationships were observed for a DFC state showing integration of sensory networks and antagonism between default-mode and sensorimotor networks but weak segregation of the cerebellum. The mediation analysis further showed that attention problems mediated the effect of DFC states on cognitive performance. This investigation unveils the neurological underpinnings of DFC states, which suggests that tracking the transient dynamic connectivity may help to characterize cognitive and mental problems in children and guide people to provide early intervention to buffer adverse influences.

Multiple cognition associated multimodal brain networks in major depressive disorder.

Major depressive disorder frequently leads to cognitive impairments, significantly affecting patients' quality of life. However, the neurobiological mechanisms underlying cognitive deficits remain unclear. This study aimed to explore multimodal imaging biomarkers associated with cognitive function in major depressive disorder. Five cognitive scores (sustained attention, visual recognition memory, pattern recognition memory, executive function, and working memory) were used as references to guide the fusion of gray matter volume and amplitude of the low frequency fluctuation. Social function was assessed after 2 yr. Linear regression analysis was performed to identify brain features that were associated with social function of patients with major depressive disorder. Finally, we included 131 major depressive disorder and 145 healthy controls. A multimodal frontal-insula-occipital network associated with sustained attention was found to be associated with social functioning in major depressive disorders. Analysis across different cognitive domains revealed that gray matter volume exhibited greater sensitivity to differences, while amplitude of the low frequency fluctuation consistently decreased in the right temporal-occipital-hippocampus circuit. The consistent functional changes across the 5 cognitive domains were related to symptom severity. Overall, these findings provide insights into biomarkers associated with multiple cognitive domains in major depressive disorder. These results may contribute to the development of effective treatment targeting cognitive deficits and social function.

Gray matters: ViT-GAN framework for identifying schizophrenia biomarkers linking structural MRI and functional network connectivity.

Brain disorders are often associated with changes in brain structure and function, where functional changes may be due to underlying structural variations. Gray matter (GM) volume segmentation from 3D structural MRI offers vital structural information for brain disorders like schizophrenia, as it encompasses essential brain tissues such as neuronal cell bodies, dendrites, and synapses, which are crucial for neural signal processing and transmission; changes in GM volume can thus indicate alterations in these tissues, reflecting underlying pathological conditions. In addition, the use of the ICA algorithm to transform high-dimensional fMRI data into functional network connectivity (FNC) matrices serves as an effective carrier of functional information. In our study, we introduce a new generative deep learning architecture, the conditional efficient vision transformer generative adversarial network (cEViT-GAN), which adeptly generates FNC matrices conditioned on GM to facilitate the exploration of potential connections between brain structure and function. We developed a new, lightweight self-attention mechanism for our ViT-based generator, enhancing the generation of refined attention maps critical for identifying structural biomarkers based on GM. Our approach not only generates high quality FNC matrices with a Pearson correlation of 0.74 compared to real FNC data, but also uses attention map technology to identify potential biomarkers in GM structure that could lead to functional abnormalities in schizophrenia patients. Visualization experiments within our study have highlighted these structural biomarkers, including the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (DL-PFC), and cerebellum. In addition, through cross-domain analysis comparing generated and real FNC matrices, we have identified functional connections with the highest correlations to structural information, further validating the structure-function connections. This comprehensive analysis helps to understand the intricate relationship between brain structure and its functional manifestations, providing a more refined insight into the neurobiological research of schizophrenia.

Searching Reproducible Brain Features using NeuroMark: Templates for Different Age Populations and Imaging Modalities.

A primary challenge to the data-driven analysis is the balance between poor generalizability of population-based research and characterizing more subject-, study- and population-specific variability. We previously introduced a fully automated spatially constrained independent component analysis (ICA) framework called NeuroMark and its functional MRI (fMRI) template. NeuroMark has been successfully applied in numerous studies, identifying brain markers reproducible across datasets and disorders. The first NeuroMark template was constructed based on young adult cohorts. We recently expanded on this initiative by creating a standardized normative multi-spatial-scale functional template using over 100,000 subjects, aiming to improve generalizability and comparability across studies involving diverse cohorts. While a unified template across the lifespan is desirable, a comprehensive investigation of the similarities and differences between components from different age populations might help systematically transform our understanding of the human brain by revealing the most well-replicated and variable network features throughout the lifespan. In this work, we introduced two significant expansions of NeuroMark templates first by generating replicable fMRI templates for infants, adolescents, and aging cohorts, and second by incorporating structural MRI (sMRI) and diffusion MRI (dMRI) modalities. Specifically, we built spatiotemporal fMRI templates based on 6,000 resting-state scans from four datasets. This is the first attempt to create robust ICA templates covering dynamic brain development across the lifespan. For the sMRI and dMRI data, we used two large publicly available datasets including more than 30,000 scans to build reliable templates. We employed a spatial similarity analysis to identify replicable templates and investigate the degree to which unique and similar patterns are reflective in different age populations. Our results suggest remarkably high similarity of the resulting adapted components, even across extreme age differences. With the new templates, the NeuroMark framework allows us to perform age-specific adaptations and to capture features adaptable to each modality, therefore facilitating biomarker identification across brain disorders. In sum, the present work demonstrates the generalizability of NeuroMark templates and suggests the potential of new templates to boost accuracy in mental health research and advance our understanding of lifespan and cross-modal alterations.

Common and unique brain aging patterns between females and males quantified by large-scale deep learning.

There has been extensive evidence that aging affects human brain function. However, there is no complete picture of what brain functional changes are mostly related to normal aging and how aging affects brain function similarly and differently between males and females. Based on resting-state brain functional connectivity (FC) of 25,582 healthy participants (13,373 females) aged 49-76 years from the UK Biobank project, we employ deep learning with explainable AI to discover primary FCs related to progressive aging and reveal similarity and difference between females and males in brain aging. Using a nested cross-validation scheme, we conduct 4200 deep learning models to classify all paired age groups on the main data for females and males separately and then extract gender-common and gender-specific aging-related FCs. Next, we validate those FCs using additional 21,000 classifiers on the independent data. Our results support that aging results in reduced brain functional interactions for both females and males, primarily relating to the positive connectivity within the same functional domain and the negative connectivity between different functional domains. Regions linked to cognitive control show the most significant age-related changes in both genders. Unique aging effects in males and females mainly involve the interaction between cognitive control and the default mode, vision, auditory, and frontoparietal domains. Results also indicate females exhibit faster brain functional changes than males. Overall, our study provides new evidence about common and unique patterns of brain aging in females and males.

Time-restricted eating with or without a low-carbohydrate diet improved myocardial status and thyroid function in individuals with metabolic syndrome: secondary analysis of a randomized clinical trial.

BACKGROUND: Obesity and metabolic syndrome (MetS) have become urgent worldwide health problems, predisposing patients to unfavorable myocardial status and thyroid dysfunction. Low-carbohydrate diet (LCD) and time-restricted eating (TRE) have been confirmed to be effective methods for weight management and improving MetS, but their effects on the myocardium and thyroid are unclear. METHODS: We conducted a secondary analysis in a randomized clinical diet-induced weight-loss trial. Participants (N = 169) diagnosed with MetS were randomized to the LCD group, the 8 h TRE group, or the combination of the LCD and TRE group for 3 months. Myocardial enzymes and thyroid function were tested before and after the intervention. Pearson's or Spearman's correlation was assessed between functions of the myocardium and thyroid and cardiometabolic parameters at baseline. RESULTS: A total of 162 participants who began the trial were included in the intention-to-treat (ITT) analysis, and 57 participants who adhered to their assigned protocol were involved in the per-protocol (PP) analysis. Relative to baseline, lactate dehydrogenase, creatine kinase MB, hydroxybutyrate dehydrogenase, and free triiodothyronine (FT3) declined, and free thyroxine (FT4) increased after all 3 interventions (both analyses). Creatine kinase (CK) decreased only in the TRE (- 18 [44] U/L, P < 0.001) and combination (- 22 [64] U/L, P = 0.003) groups (PP analysis). Thyrotropin (- 0.24 [0.83] µIU/mL, P = 0.011) and T3 (- 0.10 ± 0.04 ng/mL, P = 0.011) decreased in the combination group (ITT analysis). T4 (0.82 ± 0.39 µg/dL, P = 0.046), thyroglobulin antibodies (TgAb, 2 [1] %, P = 0.021), and thyroid microsomal antibodies (TMAb, 2 [2] %, P < 0.001) increased, while the T3/T4 ratio (- 0.01 ± 0.01, P = 0.020) decreased only in the TRE group (PP analysis). However, no significant difference between groups was observed in either analysis. At baseline, CK was positively correlated with the visceral fat area. FT3 was positively associated with triglycerides and total cholesterol. FT4 was negatively related to insulin and C-peptide levels. TgAb and TMAb were negatively correlated with the waist-to-hip ratio. CONCLUSIONS: TRE with or without LCD confers remarkable metabolic benefits on myocardial status and thyroid function in subjects with MetS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475822.

Lipidomic studies revealing serological markers associated with the occurrence of retinopathy in type 2 diabetes.

PURPOSE: The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. METHODS: A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi'an JiaoTong University were selected as the discovery set. One-to-one case-control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography-mass spectrometry (LC-MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. RESULTS: The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. CONCLUSION: Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Common and distinct functional brain network abnormalities in adolescent, early-middle adult, and late adult major depressive disorders.

BACKGROUND: The age-related heterogeneity in major depressive disorder (MDD) has received significant attention. However, the neural mechanisms underlying such heterogeneity still need further investigation. This study aimed to explore the common and distinct functional brain abnormalities across different age groups of MDD patients from a large-sample, multicenter analysis. METHODS: The analyzed sample consisted of a total of 1238 individuals including 617 MDD patients (108 adolescents, 12-17 years old; 411 early-middle adults, 18-54 years old; and 98 late adults, > = 55 years old) and 621 demographically matched healthy controls (60 adolescents, 449 early-middle adults, and 112 late adults). MDD-related abnormalities in brain functional connectivity (FC) patterns were investigated in each age group separately and using the whole pooled sample, respectively. RESULTS: We found shared FC reductions among the sensorimotor, visual, and auditory networks across all three age groups of MDD patients. Furthermore, adolescent patients uniquely exhibited increased sensorimotor-subcortical FC; early-middle adult patients uniquely exhibited decreased visual-subcortical FC; and late adult patients uniquely exhibited wide FC reductions within the subcortical, default-mode, cingulo-opercular, and attention networks. Analysis of covariance models using the whole pooled sample further revealed: (1) significant main effects of age group on FCs within most brain networks, suggesting that they are decreased with aging; and (2) a significant age group × MDD diagnosis interaction on FC within the default-mode network, which may be reflective of an accelerated aging-related decline in default-mode FCs. CONCLUSIONS: To summarize, these findings may deepen our understanding of the age-related biological and clinical heterogeneity in MDD.

Determining four confounding factors in individual cognitive traits prediction with functional connectivity: an exploratory study.

Resting-state functional connectivity (RSFC) has been widely adopted for individualized trait prediction. However, multiple confounding factors may impact the predicted brain-behavior relationships. In this study, we investigated the impact of 4 confounding factors including time series length, functional connectivity (FC) type, brain parcellation choice, and variance of the predicted target. The data from Human Connectome Project including 1,206 healthy subjects were employed, with 3 cognitive traits including fluid intelligence, working memory, and picture vocabulary ability as the prediction targets. We compared the prediction performance under different settings of these 4 factors using partial least square regression. Results demonstrated appropriate time series length (300 time points) and brain parcellation (independent component analysis, ICA100/200) can achieve better prediction performance without too much time consumption. FC calculated by Pearson, Spearman, and Partial correlation achieves higher accuracy and lower time cost than mutual information and coherence. Cognitive traits with larger variance among subjects can be better predicted due to the well elaboration of individual variability. In addition, the beneficial effects of increasing scan duration to prediction partially arise from the improved test-retest reliability of RSFC. Taken together, the study highlights the importance of determining these factors in RSFC-based prediction, which can facilitate standardization of RSFC-based prediction pipelines going forward.

Two subtypes of schizophrenia identified by an individual-level atypical pattern of tensor-based morphometric measurement.

Difficulties in parsing the multiaspect heterogeneity of schizophrenia (SCZ) based on current nosology highlight the need to subtype SCZ using objective biomarkers. Here, utilizing a large-scale multisite SCZ dataset, we identified and validated 2 neuroanatomical subtypes with individual-level abnormal patterns of the tensor-based morphometric measurement. Remarkably, compared with subtype 1, which showed moderate deficits of some subcortical nuclei and an enlarged striatum and cerebellum, subtype 2, which showed cerebellar atrophy and more severe subcortical nuclei atrophy, had a higher subscale score of negative symptoms, which is considered to be a core aspect of SCZ and is associated with functional outcome. Moreover, with the neuroimaging-clinic association analysis, we explored the detailed relationship between the heterogeneity of clinical symptoms and the heterogeneous abnormal neuroanatomical patterns with respect to the 2 subtypes. And the neuroimaging-transcription association analysis highlighted several potential heterogeneous biological factors that may underlie the subtypes. Our work provided an effective framework for investigating the heterogeneity of SCZ from multilevel aspects and may provide new insights for precision psychiatry.

Sex differences and dietary patterns in the association of air pollutants and hypertension.

BACKGROUND: Hypertension is one of the major public health problems in China. Limited evidence exists regarding sex differences in the association between hypertension and air pollutants, as well as the impact of dietary factors on the relationship between air pollutants and hypertension. The aim of this study was to investigate the sex-specific effects of dietary patterns on the association between fine particulate matter (PM2.5), ozone(O3) and hypertension in adults residing in Jiangsu Province of China. METHODS: A total of 3189 adults from the 2015 China Adult Chronic Disease and Nutrition Surveillance in Jiangsu Province were included in this study. PM2.5 and O3 concentrations were estimated using satellite space-time models and assigned to each participant. Dietary patterns were determined by reduced rank regression (RRR), and multivariate logistic regression was used to assess the associations of the obtained dietary patterns with air pollutants and hypertension risk. RESULTS: After adjusting for confounding variables, we found that males were more sensitive to long-term exposure to PM2.5 (Odds ratio (OR) = 1.42 95%CI:1.08,1.87), and females were more sensitive to long-term exposure to O3 (OR = 1.61 95%CI:1.15,2.23). Traditional southern pattern identified through RRR exhibited a protective effect against hypertension in males (OR = 0.73 95%CI: 0.56,1.00). The results of the interaction between dietary pattern score and PM2.5 revealed that adherence to traditional southern pattern was significantly associated with a decreased risk of hypertension in males (P < 0.05), while no significant association was observed among females. CONCLUSIONS: Our findings suggested that sex differences existed in the association between dietary patterns, air pollutants and hypertension. Furthermore, we found that adherence to traditional southern pattern may mitigate the risk of long-term PM2.5 exposure-induced hypertension in males.

[Genetic analysis of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 due to variant of PIGN gene].

OBJECTIVE: To analyze the clinical phenotype and genetic etiology of a child with Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1). METHODS: Clinical data of a 2-year-old boy who had presented at the Affiliated Hospital of Qingdao University in March 2023 for "intermittent limb twitching for 2 years" was collected. Peripheral blood samples were collected from the child and his parents for whole-exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child had manifested with distinctive facial features, limb deformities, hypotonia, motor and intellectual delays, and epileptic seizures. WES revealed that he has harbored compound heterozygous variants of the PIGN gene, namely c.963G>A (p.Q321=) and c.994A>T (p.I332F), which were inherited from his phenotypically normal mother and father, respectively. Based on the ACMG guidelines, the c.963G>A was classified as a pathogenic variant (PVS1+PM2_Supporting+PM3), whilst the c.994A>T was classified as a variant of uncertain significance (PM2_Supporting+PP3). CONCLUSION: Above discovery has expanded the mutational spectrum of the PIGN gene variants associated with MCAHS1, which may facilitate delineation of its genotype-phenotype correlation.

Multimodal fusion of multiple rest fMRI networks and MRI gray matter via parallel multilink joint ICA reveals highly significant function/structure coupling in Alzheimer's disease.

In this article, we focus on estimating the joint relationship between structural magnetic resonance imaging (sMRI) gray matter (GM), and multiple functional MRI (fMRI) intrinsic connectivity networks (ICNs). To achieve this, we propose a multilink joint independent component analysis (ml-jICA) method using the same core algorithm as jICA. To relax the jICA assumption, we propose another extension called parallel multilink jICA (pml-jICA) that allows for a more balanced weight distribution over ml-jICA/jICA. We assume a shared mixing matrix for both the sMRI and fMRI modalities, while allowing for different mixing matrices linking the sMRI data to the different ICNs. We introduce the model and then apply this approach to study the differences in resting fMRI and sMRI data from patients with Alzheimer's disease (AD) versus controls. The results of the pml-jICA yield significant differences with large effect sizes that include regions in overlapping portions of default mode network, and also hippocampus and thalamus. Importantly, we identify two joint components with partially overlapping regions which show opposite effects for AD versus controls, but were able to be separated due to being linked to distinct functional and structural patterns. This highlights the unique strength of our approach and multimodal fusion approaches generally in revealing potentially biomarkers of brain disorders that would likely be missed by a unimodal approach. These results represent the first work linking multiple fMRI ICNs to GM components within a multimodal data fusion model and challenges the typical view that brain structure is more sensitive to AD than fMRI.

Stage-Specific Brain Aging in First-Episode Schizophrenia and Treatment-Resistant Schizophrenia.

BACKGROUND: Brain age is a popular brain-based biomarker that offers a powerful strategy for using neuroscience in clinical practice. We investigated the brain-predicted age difference (PAD) in patients with schizophrenia (SCZ), first-episode schizophrenia spectrum disorders (FE-SSDs), and treatment-resistant schizophrenia (TRS) using structural magnetic resonance imaging data. The association between brain-PAD and clinical parameters was also assessed. METHODS: We developed brain age prediction models for the association between 77 average structural brain measures and age in a training sample of controls (HCs) using ridge regression, support vector regression, and relevance vector regression. The trained models in the controls were applied to the test samples of the controls and 3 patient groups to obtain brain-based age estimates. The correlations were tested between the brain PAD and clinical measures in the patient groups. RESULTS: Model performance indicated that, regardless of the type of regression metric, the best model was support vector regression and the worst model was relevance vector regression for the training HCs. Accelerated brain aging was identified in patients with SCZ, FE-SSDs, and TRS compared with the HCs. A significant difference in brain PAD was observed between FE-SSDs and TRS using the ridge regression algorithm. Symptom severity, the Social and Occupational Functioning Assessment Scale, chlorpromazine equivalents, and cognitive function were correlated with the brain PAD in the patient groups. CONCLUSIONS: These findings suggest additional progressive neuronal changes in the brain after SCZ onset. Therefore, pharmacological or psychosocial interventions targeting brain health should be developed and provided during the early course of SCZ.

Symptom-guided multimodal neuroimage fusion patterns in children with attention-deficit/hyperactivity disorder and its potential "brain structure-function-cognition-behavior" pathological pathways.

The "brain-cognition-behavior" process is an important pathological pathway in children with attention-deficit/hyperactivity disorder (ADHD). Symptom guided multimodal neuroimaging fusion can capture behaviorally relevant and intrinsically linked structural and functional features, which can help to construct a systematic model of the pathology. Analyzing the multimodal neuroimage fusion pattern and exploring how these brain features affect executive function (EF) and leads to behavioral impairment is the focus of this study. Based on gray matter volume (GMV) and fractional amplitude of low frequency fluctuation (fALFF) for 152 ADHD and 102 healthy controls (HC), the total symptom score (TO) was set as a reference to identify co-varying components. Based on the correlation between the identified co-varying components and EF, further mediation analysis was used to explore the relationship between brain image features, EF and clinical symptoms. This study found that the abnormalities of GMV and fALFF in ADHD are mainly located in the default mode network (DMN) and prefrontal-striatal-cerebellar circuits, respectively. GMV in ADHD influences the TO through Metacognition Index, while fALFF in HC mediates the TO through behavior regulation index (BRI). Further analysis revealed that GMV in HC influences fALFF, which further modulates BRI and subsequently affects hyperactivity-impulsivity score. To conclude, structural brain abnormalities in the DMN in ADHD may affect local brain function in the prefrontal-striatal-cerebellar circuit, making it difficult to regulate EF in terms of inhibit, shift, and emotional control, and ultimately leading to hyperactive-impulsive behavior.

Aberrant brain dynamics and spectral power in children with ADHD and its subtypes.

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children, usually categorized as three subtypes, predominant inattention (ADHD-I), predominant hyperactivity-impulsivity (ADHD-HI), and a combined subtype (ADHD-C). Yet, common and unique abnormalities of electroencephalogram (EEG) across different subtypes remain poorly understood. Here, we leveraged microstate characteristics and power features to investigate temporal and frequency abnormalities in ADHD and its subtypes using high-density EEG on 161 participants (54 ADHD-Is and 53 ADHD-Cs and 54 healthy controls). Four EEG microstates were identified. The coverage of salience network (state C) were decreased in ADHD compared to HC (p = 1.46e-3), while the duration and contribution of frontal-parietal network (state D) were increased (p = 1.57e-3; p = 1.26e-4). Frequency power analysis also indicated that higher delta power in the fronto-central area (p = 6.75e-4) and higher power of theta/beta ratio in the bilateral fronto-temporal area (p = 3.05e-3) were observed in ADHD. By contrast, remarkable subtype differences were found primarily on the visual network (state B), of which ADHD-C have higher occurrence and coverage than ADHD-I (p = 9.35e-5; p = 1.51e-8), suggesting that children with ADHD-C might exhibit impulsivity of opening their eyes in an eye-closed experiment, leading to hyper-activated visual network. Moreover, the top discriminative features selected from support vector machine model with recursive feature elimination (SVM-RFE) well replicated the above results, which achieved an accuracy of 72.7% and 73.8% separately in classifying ADHD and two subtypes. To conclude, this study highlights EEG microstate dynamics and frequency features may serve as sensitive measurements to detect the subtle differences in ADHD and its subtypes, providing a new window for better diagnosis of ADHD.

Aberrant brain functional and structural developments in MECP2 duplication rats.

Transgenic animal models with homologous etiology provide a promising way to pursue the neurobiological substrates of the behavioral deficits in autism spectrum disorder (ASD). Gain-of-function mutations of MECP2 cause MECP2 duplication syndrome, a severe neurological disorder with core symptoms of ASD. However, abnormal brain developments underlying the autistic-like behavioral deficits of MECP2 duplication syndrome are rarely investigated. To this end, a human MECP2 duplication (MECP2-DP) rat model was created by the bacterial artificial chromosome transgenic method. Functional and structural magnetic resonance imaging (MRI) with high-field were performed on 16 male MECP2-DP rats and 15 male wildtype rats at postnatal 28 days, 42 days, and 56 days old. Multimodal fusion analyses guided by locomotor-relevant metrics and social novelty time separately were applied to identify abnormal brain networks associated with diverse behavioral deficits induced by MECP2 duplication. Aberrant functional developments of a core network primarily composed of the dorsal medial prefrontal cortex (dmPFC) and retrosplenial cortex (RSP) were detected to associate with diverse behavioral phenotypes in MECP2-DP rats. Altered developments of gray matter volume were detected in the hippocampus and thalamus. We conclude that gain-of-function mutations of MECP2 induce aberrant functional activities in the default-mode-like network and aberrant volumetric changes in the brain, resulting in autistic-like behavioral deficits. Our results gain critical insights into the biomarker of MECP2 duplication syndrome and the neurobiological underpinnings of the behavioral deficits in ASD.

Three-way parallel group independent component analysis: Fusion of spatial and spatiotemporal magnetic resonance imaging data.

Advances in imaging acquisition techniques allow multiple imaging modalities to be collected from the same subject. Each individual modality offers limited yet unique views of the functional, structural, or dynamic temporal features of the brain. Multimodal fusion provides effective ways to leverage these complementary perspectives from multiple modalities. However, the majority of current multimodal fusion approaches involving functional magnetic resonance imaging (fMRI) are limited to 3D feature summaries that do not incorporate its rich temporal information. Thus, we propose a novel three-way parallel group independent component analysis (pGICA) fusion method that incorporates the first-level 4D fMRI data (temporal information included) by parallelizing group ICA into parallel ICA via a unified optimization framework. A new variability matrix was defined to capture subject-wise functional variability and then link it to the mixing matrices of the other two modalities. Simulation results show that the three-way pGICA provides highly accurate cross-modality linkage estimation under both weakly and strongly correlated conditions, as well as comparable source estimation under different noise levels. Results using real brain imaging data identified one linked functional-structural-diffusion component associated to differences between schizophrenia and controls. This was replicated in an independent cohort, and the identified components were also correlated with major cognitive domains. Functional network connectivity revealed visual-subcortical and default mode-cerebellum pairs that discriminate between schizophrenia and controls. Overall, both simulation and real data results support the use of three-way pGICA to identify multimodal spatiotemporal links and to pursue the study of brain disorders under a single unifying multimodal framework.

Multimodal brain deficits shared in early-onset and adult-onset schizophrenia predict positive symptoms regardless of illness stage.

Incidence of schizophrenia (SZ) has two predominant peaks, in adolescent and young adult. Early-onset schizophrenia provides an opportunity to explore the neuropathology of SZ early in the disorder and without the confound of antipsychotic mediation. However, it remains unexplored what deficits are shared or differ between adolescent early-onset (EOS) and adult-onset schizophrenia (AOS) patients. Here, based on 529 participants recruited from three independent cohorts, we explored AOS and EOS common and unique co-varying patterns by jointly analyzing three MRI features: fractional amplitude of low-frequency fluctuations (fALFF), gray matter (GM), and functional network connectivity (FNC). Furthermore, a prediction model was built to evaluate whether the common deficits in drug-naive SZ could be replicated in chronic patients. Results demonstrated that (1) both EOS and AOS patients showed decreased fALFF and GM in default mode network, increased fALFF and GM in the sub-cortical network, and aberrant FNC primarily related to middle temporal gyrus; (2) the commonly identified regions in drug-naive SZ correlate with PANSS positive significantly, which can also predict PANSS positive in chronic SZ with longer duration of illness. Collectively, results suggest that multimodal imaging signatures shared by two types of drug-naive SZ are also associated with positive symptom severity in chronic SZ and may be vital for understanding the progressive schizophrenic brain structural and functional deficits.

Associations between grip strength, brain structure, and mental health in > 40,000 participants from the UK Biobank.

BACKGROUND: Grip strength is a widely used and well-validated measure of overall health that is increasingly understood to index risk for psychiatric illness and neurodegeneration in older adults. However, existing work has not examined how grip strength relates to a comprehensive set of mental health outcomes, which can detect early signs of cognitive decline. Furthermore, whether brain structure mediates associations between grip strength and cognition remains unknown. METHODS: Based on cross-sectional and longitudinal data from over 40,000 participants in the UK Biobank, this study investigated the behavioral and neural correlates of handgrip strength using a linear mixed effect model and mediation analysis. RESULTS: In cross-sectional analysis, we found that greater grip strength was associated with better cognitive functioning, higher life satisfaction, greater subjective well-being, and reduced depression and anxiety symptoms while controlling for numerous demographic, anthropometric, and socioeconomic confounders. Further, grip strength of females showed stronger associations with most behavioral outcomes than males. In longitudinal analysis, baseline grip strength was related to cognitive performance at ~9 years follow-up, while the reverse effect was much weaker. Further, baseline neuroticism, health, and financial satisfaction were longitudinally associated with subsequent grip strength. The results revealed widespread associations between stronger grip strength and increased grey matter volume, especially in subcortical regions and temporal cortices. Moreover, grey matter volume of these regions also correlated with better mental health and considerably mediated their relationship with grip strength. CONCLUSIONS: Overall, using the largest population-scale neuroimaging dataset currently available, our findings provide the most well-powered characterization of interplay between grip strength, mental health, and brain structure, which may facilitate the discovery of possible interventions to mitigate cognitive decline during aging.