Effects of blood-processing protocols on cell-free DNA fragmentomics in plasma: Comparisons of one- and two-step centrifugations.

BACKGROUND: Cell-free DNA (cfDNA) fragmentomic characteristics are promising analytes with abundant physiological signals for non-invasive disease diagnosis and monitoring. Previous studies on plasma cfDNA fragmentomics commonly employed a two-step centrifugation process for removing cell debris, involving a low-speed centrifugation followed by a high-speed centrifugation. However, the effects of centrifugation conditions on the analysis of cfDNA fragmentome remain uncertain. METHODS: We collected blood samples from 10 healthy individuals and divided each sample into two aliquots for plasma preparation with one- and two-step centrifugation processes. We performed whole genome sequencing (WGS) of the plasma cfDNA in the two groups and comprehensively compared the cfDNA fragmentomic features. Additionally, we reanalyzed the fragmentomic features of cfDNA from 16 healthy individuals and 16 COVID-19 patients, processed through one- and two-step centrifugation in our previous study, to investigate the impact of centrifugation on disease signals. RESULTS: Our results showed that there were no significant differences observed in the characteristics of nuclear cfDNA, including size, motif diversity score (MDS) of end motifs, and genome distribution, between plasma samples treated with one- and two-step centrifugation. The cfDNA size shortening in COVID-19 patients was observed in plasma samples with one- and two-step centrifugation methods. However, we observed a significantly higher relative abundance and longer size of cell-free mitochondrial DNA (mtDNA) in the one-step samples compared to the two-step samples. This difference in mtDNA caused by the one- and two-step centrifugation methods surpasses the pathological difference between COVID-19 patients and healthy individuals. CONCLUSIONS: Our findings indicate that one-step low-speed centrifugation is a simple and potentially suitable method for analyzing nuclear cfDNA fragmentation characteristics. These results offer valuable guidance for cfDNA research in various clinical scenarios.

Task sub-type states decoding via group deep bidirectional recurrent neural network.

Decoding brain states under different cognitive tasks from functional magnetic resonance imaging (fMRI) data has attracted great attention in the neuroimaging filed. However, the well-known temporal dependency in fMRI sequences has not been fully exploited in existing studies, due to the limited temporal-modeling capacity of the backbone machine learning algorithms and rigid training sample organization strategies upon which the brain decoding methods are built. To address these limitations, we propose a novel method for fine-grain brain state decoding, namely, group deep bidirectional recurrent neural network (Group-DBRNN) model. We first propose a training sample organization strategy that consists of a group-task sample generation module and a multiple-scale random fragment strategy (MRFS) module to collect training samples that contain rich task-relevant brain activity contrast (i.e., the comparison of neural activity patterns between different tasks) and maintain the temporal dependency. We then develop a novel decoding model by replacing the unidirectional RNNs that are widely used in existing brain state decoding studies with bidirectional stacked RNNs to better capture the temporal dependency, and by introducing a multi-task interaction layer (MTIL) module to effectively model the task-relevant brain activity contrast. Our experimental results on the Human Connectome Project task fMRI dataset (7 tasks consisting of 23 task sub-type states) show that the proposed model achieves an average decoding accuracy of 94.7% over the 23 fine-grain sub-type states. Meanwhile, our extensive interpretations of the intermediate features learned in the proposed model via visualizations and quantitative assessments of their discriminability and inter-subject alignment evidence that the proposed model can effectively capture the temporal dependency and task-relevant contrast.

Mapping dynamic spatial patterns of brain function with spatial-wise attention.

Objective: Using functional magnetic resonance imaging (fMRI) and deep learning to discover the spatial pattern of brain function, or functional brain networks (FBNs) has been attracted many reseachers. Most existing works focus on static FBNs or dynamic functional connectivity among fixed spatial network nodes, but ignore the potential dynamic/time-varying characteristics of the spatial networks themselves. And most of works based on the assumption of linearity and independence, that oversimplify the relationship between blood-oxygen level dependence signal changes and the heterogeneity of neuronal activity within voxels.Approach: To overcome these problems, we proposed a novel spatial-wise attention (SA) based method called Spatial and Channel-wise Attention Autoencoder (SCAAE) to discover the dynamic FBNs without the assumptions of linearity or independence. The core idea of SCAAE is to apply the SA to generate FBNs directly, relying solely on the spatial information present in fMRI volumes. Specifically, we trained the SCAAE in a self-supervised manner, using the autoencoder to guide the SA to focus on the activation regions. Experimental results show that the SA can generate multiple meaningful FBNs at each fMRI time point, which spatial similarity are close to the FBNs derived by known classical methods, such as independent component analysis.Main results: To validate the generalization of the method, we evaluate the approach on HCP-rest, HCP-task and ADHD-200 dataset. The results demonstrate that SA mechanism can be used to discover time-varying FBNs, and the identified dynamic FBNs over time clearly show the process of time-varying spatial patterns fading in and out.Significance: Thus we provide a novel method to understand human brain better. Code is available athttps://github.com/WhatAboutMyStar/SCAAE.

Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine.

BACKGROUND: MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated approximately 50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting that efforts to improve this vaccine design might yield a vaccine suitable for licensure. METHODS: A messenger RNA (mRNA)-based vaccine candidate encoding HCMV gB and pentameric complex (PC), mRNA-1647, is currently in late-stage efficacy trials. However, its immunogenicity has not been compared to the partially effective gB/MF59 vaccine. We assessed neutralizing and Fc-mediated immunoglobulin G (IgG) effector antibody responses induced by mRNA-1647 in both HCMV-seropositive and -seronegative vaccinees from a first-in-human clinical trial through 1 year following third vaccination using a systems serology approach. Furthermore, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative gB/MF59 vaccine recipients. RESULTS: mRNA-1647 vaccination elicited and boosted HCMV-specific IgG responses in seronegative and seropositive vaccinees, respectively, including neutralizing and Fc-mediated effector antibody responses. gB-specific IgG responses were lower than PC-specific IgG responses. gB-specific IgG and antibody-dependent cellular phagocytosis responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited higher neutralization and antibody-dependent cellular cytotoxicity (ADCC) responses. CONCLUSIONS: Overall, mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses, with lower gB-specific IgG responses but higher neutralization and ADCC responses compared to the gB/MF59 vaccine. CLINICAL TRIALS REGISTRATION: NCT03382405 (mRNA-1647) and NCT00133497 (gB/MF59).

Frequency-specific functional difference between gyri and sulci in naturalistic paradigm fMRI.

Disentangling functional difference between cortical folding patterns of gyri and sulci provides novel insights into the relationship between brain structure and function. Previous studies using resting-state functional magnetic resonance imaging (rsfMRI) have revealed that sulcal signals exhibit stronger high-frequency but weaker low-frequency components compared to gyral ones, suggesting that gyri may serve as functional integration centers while sulci are segregated local processing units. In this study, we utilize naturalistic paradigm fMRI (nfMRI) to explore the functional difference between gyri and sulci as it has proven to record stronger functional integrations compared to rsfMRI. We adopt a convolutional neural network (CNN) to classify gyral and sulcal fMRI signals in the whole brain (the global model) and within functional brain networks (the local models). The frequency-specific difference between gyri and sulci is then inferred from the power spectral density (PSD) profiles of the learned filters in the CNN model. Our experimental results show that nfMRI shows higher gyral-sulcal PSD contrast effect sizes in the global model compared to rsfMRI. In the local models, the effect sizes are either increased or decreased depending on frequency bands and functional complexity of the FBNs. This study highlights the advantages of nfMRI in depicting the functional difference between gyri and sulci, and provides novel insights into unraveling the relationship between brain structure and function.

Investigating mental workload caused by NDRTs in highly automated driving with deep learning.

OBJECTIVE: This study aimed to examine the impact of non-driving-related tasks (NDRTs) on drivers in highly automated driving scenarios and sought to develop a deep learning model for classifying mental workload using electroencephalography (EEG) signals. METHODS: The experiment involved recruiting 28 participants who engaged in simulations within a driving simulator while exposed to 4 distinct NDRTs: (1) reading, (2) listening to radio news, (3) watching videos, and (4) texting. EEG data collected during NDRTs were categorized into 3 levels of mental workload, high, medium, and low, based on the NASA Task Load Index (NASA-TLX) scores. Two deep learning methods, namely, long short-term memory (LSTM) and bidirectional long short-term memory (BLSTM), were employed to develop the classification model. RESULTS: A series of correlation analyses revealed that the channels and frequency bands are linearly correlated with mental workload. The comparative analysis of classification results demonstrates that EEG data featuring significantly correlated frequency bands exhibit superior classification accuracy compared to the raw EEG data. CONCLUSIONS: This research offers a reference for assessing mental workload resulting from NDRTs in the context of highly automated driving. Additionally, it delves into the development of deep learning classifiers for EEG signals with heightened accuracy.

A Unified and Biologically Plausible Relational Graph Representation of Vision Transformers.

Vision transformer (ViT) and its variants have achieved remarkable success in various tasks. The key characteristic of these ViT models is to adopt different aggregation strategies of spatial patch information within the artificial neural networks (ANNs). However, there is still a key lack of unified representation of different ViT architectures for systematic understanding and assessment of model representation performance. Moreover, how those well-performing ViT ANNs are similar to real biological neural networks (BNNs) is largely unexplored. To answer these fundamental questions, we, for the first time, propose a unified and biologically plausible relational graph representation of ViT models. Specifically, the proposed relational graph representation consists of two key subgraphs: an aggregation graph and an affine graph. The former considers ViT tokens as nodes and describes their spatial interaction, while the latter regards network channels as nodes and reflects the information communication between channels. Using this unified relational graph representation, we found that: 1) model performance was closely related to graph measures; 2) the proposed relational graph representation of ViT has high similarity with real BNNs; and 3) there was a further improvement in model performance when training with a superior model to constrain the aggregation graph.

Regularity and variability of functional brain connectivity characteristics between gyri and sulci under naturalistic stimulus.

The human cerebral cortex is folded into two fundamentally anatomical units: gyri and sulci. Previous studies have demonstrated the genetical, structural, and functional differences between gyri and sulci, providing a unique perspective for revealing the relationship among brain function, cognition, and behavior. While previous studies mainly focus on the functional differences between gyri and sulci under resting or task-evoked state, such characteristics under naturalistic stimulus (NS) which reflects real-world dynamic environments are largely unknown. To address this question, this study systematically investigates spatio-temporal functional connectivity (FC) characteristics between gyri and sulci under NS using a spatio-temporal graph convolutional network model. Based on the public Human Connectome Project dataset of 174 subjects with four different runs of both movie-watching NS and resting state 7T functional MRI data, we successfully identify unique FC features under NS, which are mainly involved in visual, auditory, emotional and cognitive control, and achieve high discriminative accuracy 93.06 % to resting state. Moreover, gyral regions as well as gyro-gyral connections consistently participate more as functional information exchange hubs than sulcal ones among these networks. This study provides novel insights into the functional brain mechanism under NS and lays a solid foundation for accurately mapping the brain anatomy-function relationship.

MEET: A Multi-Band EEG Transformer for Brain States Decoding.

OBJECTIVE: Electroencephalography (EEG) is among the most widely used and inexpensive neuroimaging techniques. Compared to the CNN or RNN based models, Transformer can better capture the temporal information in EEG signals and focus more on global features of the brain's functional activities. Importantly, according to the multiscale nature of EEG signals, it is crucial to consider the multi-band concept into the design of EEG Transformer architecture. METHODS: We propose a novel Multi-band EEG Transformer (MEET) to represent and analyze the multiscale temporal time series of human brain EEG signals. MEET mainly includes three parts: 1) transform the EEG signals into multi-band images, and preserve the 3D spatial information between electrodes; 2) design a Band Attention Block to compute the attention maps of the stacked multi-band images and infer the fused feature maps; 3) apply the Temporal Self-Attention and Spatial Self-Attention modules to extract the spatiotemporal features for the characterization and differentiation of multi-frame dynamic brain states. RESULTS: The experimental results show that: 1) MEET outperforms state-of-the-art methods on multiple open EEG datasets (SEED, SEED-IV, WM) for brain states classification; 2) MEET demonstrates that 5-bands fusion is the best integration strategy; and 3) MEET identifies interpretable brain attention regions. SIGNIFICANCE: MEET is an interpretable and universal model based on the multiband-multiscale characteristics of EEG. CONCLUSION: The innovative combination of band attention and temporal/spatial self-attention mechanisms in MEET achieves promising data-driven learning of the temporal dependencies and spatial relationships of EEG signals across the entire brain in a holistic and comprehensive fashion.

Rectify ViT Shortcut Learning by Visual Saliency.

Shortcut learning in deep learning models occurs when unintended features are prioritized, resulting in degenerated feature representations and reduced generalizability and interpretability. However, shortcut learning in the widely used vision transformer (ViT) framework is largely unknown. Meanwhile, introducing domain-specific knowledge is a major approach to rectifying the shortcuts that are predominated by background-related factors. For example, eye-gaze data from radiologists are effective human visual prior knowledge that has the great potential to guide the deep learning models to focus on meaningful foreground regions. However, obtaining eye-gaze data can still sometimes be time-consuming, labor-intensive, and even impractical. In this work, we propose a novel and effective saliency-guided ViT (SGT) model to rectify shortcut learning in ViT with the absence of eye-gaze data. Specifically, a computational visual saliency model (either pretrained or fine-tuned) is adopted to predict saliency maps for input image samples. Then, the saliency maps are used to filter the most informative image patches. Considering that this filter operation may lead to global information loss, we further introduce a residual connection that calculates the self-attention across all the image patches. The experiment results on natural and medical image datasets show that our SGT framework can effectively learn and leverage human prior knowledge without eye-gaze data and achieves much better performance than baselines. Meanwhile, it successfully rectifies the harmful shortcut learning and significantly improves the interpretability of the ViT model, demonstrating the promise of transferring human prior knowledge derived visual saliency in rectifying shortcut learning.

Energy Prediction Models and Distributed Analysis of the Grinding Process of Sustainable Manufacturing.

Grinding is a critical surface-finishing process in the manufacturing industry. One of the challenging problems is that the specific grinding energy is greater than in ordinary procedures, while energy efficiency is lower. However, an integrated energy model and analysis of energy distribution during grinding is still lacking. To bridge this gap, the grinding time history is first built to describe the cyclic movement during air-cuttings, feedings, and cuttings. Steady and transient power features during high-speed rotations along the spindle and repeated intermittent feeding movements along the x-, y-, and z-axes are also analysed. Energy prediction models, which include specific movement stages such as cutting-in, stable cutting, and cutting-out along the spindle, as well as infeed and turning along the three infeed axes, are then established. To investigate model parameters, 10 experimental groups were analysed using the Gauss-Newton gradient method. Four testing trials demonstrate that the accuracy of the suggested model is acceptable, with errors of 5%. Energy efficiency and energy distributions for various components and motion stages are also analysed. Low-power chip design, lightweight worktable utilization, and minimal lubricant quantities are advised. Furthermore, it is an excellent choice for optimizing grinding parameters in current equipment.

Arousal modulates the amygdala-insula reciprocal connectivity during naturalistic emotional movie watching.

Emotional arousal is a complex state recruiting distributed cortical and subcortical structures, in which the amygdala and insula play an important role. Although previous neuroimaging studies have showed that the amygdala and insula manifest reciprocal connectivity, the effective connectivities and modulatory patterns on the amygdala-insula interactions underpinning arousal are still largely unknown. One of the reasons may be attributed to static and discrete laboratory brain imaging paradigms used in most existing studies. In this study, by integrating naturalistic-paradigm (i.e., movie watching) functional magnetic resonance imaging (fMRI) with a computational affective model that predicts dynamic arousal for the movie stimuli, we investigated the effective amygdala-insula interactions and the modulatory effect of the input arousal on the effective connections. Specifically, the predicted dynamic arousal of the movie served as regressors in general linear model (GLM) analysis and brain activations were identified accordingly. The regions of interest (i.e., the bilateral amygdala and insula) were localized according to the GLM activation map. The effective connectivity and modulatory effect were then inferred by using dynamic causal modeling (DCM). Our experimental results demonstrated that amygdala was the site of driving arousal input and arousal had a modulatory effect on the reciprocal connections between amygdala and insula. Our study provides novel evidence to the underlying neural mechanisms of arousal in a dynamical naturalistic setting.

China's dietary changes would increase agricultural blue and green water footprint.

Agriculture accounts for 61 % of fresh water consumption in China. Although population and diet have a significant impact on water consumption, little is known about the reasons for and extent of their influence. Changes in the blue and green water footprint of 20 agricultural sectors in 31 Chinese provinces were estimated in 5 scenarios by applying the environmentally expanded multi-regional input-output model. The water footprint network is strongly interconnected, with over 50 % of the provinces characterized as net importers of the blue water footprint, 70 % of the total blue and green water footprint imports in developed provinces, and 65 % of the total blue and green water footprint exports in developing provinces, with the flow distribution driven and dominated by economically developed provinces. The findings also highlighted that the impact of population change on the water footprint is insignificant, contributing 0.51 % and 5.78 % to the reduction of the water footprint in 2030 and 2050, respectively. The impact of simultaneous changes in the population and dietary structure on the water footprint was higher than population changes and lower than dietary structure changes. The main force driving changes in the water footprint was changes in the dietary structure, which resulted in a two-fold effect on the water footprint. First, it has increased the blue and green water footprint by 33 % and 12 %, respectively, thus aggravating the coercive impact on water resources on the production side. Second, it has led to a change in the main contributing sectors for the blue and green water footprint from cereals to fruits, vegetables, and potatoes. Therefore, when the population is changing and optimizing its dietary structures, a greater focus must be placed on threats and pressures to water resources. This will result in better scientific management and more efficient use of water resources.

A generic framework for embedding human brain function with temporally correlated autoencoder.

Learning an effective and compact representation of human brain function from high-dimensional fMRI data is crucial for studying the brain's functional organization. Traditional representation methods such as independent component analysis (ICA) and sparse dictionary learning (SDL) mainly rely on matrix decomposition which represents the brain function as spatial brain networks and the corresponding temporal patterns. The correspondence of those brain networks across individuals are built by viewing them as one-hot vectors and then performing the matching. However, those one-hot vectors do not encode the regularity and/or variability of different brains very well, and thus are limited in effectively representing the functional brain activities across individuals and among different time points. To address this problem, in this paper, we formulate the human brain functional representation as an embedding problem, and propose a novel embedding framework based on the Transformer model to encode the brain function in a compact, stereotyped and comparable latent space where the brain activities are represented as dense embedding vectors. We evaluate the proposed embedding framework on the publicly available Human Connectome Project (HCP) task fMRI dataset. The experiments on brain state prediction task indicate the effectiveness and generalizability of the learned embedding. We also explore the interpretability of the learned embedding from both spatial and temporal perspective. In general, our approach provides novel insights on representing the regularity and variability of human brain function in a general, comparable, and stereotyped latent space.

Characterization of a VRC01-like antibody lineage with immature VL from an HIV-1 infected Chinese donor.

Because of the broadly neutralizing activity, VRC01-class antibodies are attractive templates for HIV-1 vaccine development and suitable candidates for HIV-1 therapy. Although we previously revealed that glycans in gp120 may have a role in the uneven evolution of the VH and the VL of a VRC01-class antibody, DRVIA7, which was isolated from an elite neutralizer, it is unknown whether the immature VH or VL of VRC01-class antibodies are also present in the non-neutralizer. We identified a CD4bs-directed antibody - 263A9 - with low neutralizing activity from a donor whose plasma had a moderate neutralizing spectrum in this study. The 263A9 antibody, in particular, was a VRC01-like antibody whose VH and VL were derived from IGHV1-2 * 04 and IGKV1-33 * 01, respectively, and both had significant SHM rates. Surprisingly, we discovered that the VL of 263A9 hindered the neutralizing activity of the antibody, and that replacing its LCDR1 and LCDR3 with VRC01 increased the neutralizing breadth of the chimeric antibodies. Following that, an antibodyomics research revealed that the VL of 263A9 lineage was remote from VRC01-class antibodies. We also looked at the envelope sequence characteristics of donor CBJC263 and discovered that N276 in the D loop and N460/N463 glycans in the V5 region of gp120 potentially interact with VL of 263A9 at the structural level. This study will provide valuable information for immunogen screening and vaccine development for eliciting VRC01-class antibodies. DATA AVAILABILITY STATEMENT: The original data presented in the study are included in the article or Supplementary materials. Further inquiries can be directed to the corresponding author. HIV Env sequences in the manuscript had been deposited into the GenBank with the accession numbers from OL466822 to OL466859.

Differentiate preterm and term infant brains and characterize the corresponding biomarkers via DICCCOL-based multi-modality graph neural networks.

Preterm birth is a worldwide problem that affects infants throughout their lives significantly. Therefore, differentiating brain disorders, and further identifying and characterizing the corresponding biomarkers are key issues to investigate the effects of preterm birth, which facilitates the interventions for neuroprotection and improves outcomes of prematurity. Until now, many efforts have been made to study the effects of preterm birth; however, most of the studies merely focus on either functional or structural perspective. In addition, an effective framework not only jointly studies the brain function and structure at a group-level, but also retains the individual differences among the subjects. In this study, a novel dense individualized and common connectivity-based cortical landmarks (DICCCOL)-based multi-modality graph neural networks (DM-GNN) framework is proposed to differentiate preterm and term infant brains and characterize the corresponding biomarkers. This framework adopts the DICCCOL system as the initialized graph node of GNN for each subject, utilizing both functional and structural profiles and effectively retaining the individual differences. To be specific, functional magnetic resonance imaging (fMRI) of the brain provides the features for the graph nodes, and brain fiber connectivity is utilized as the structural representation of the graph edges. Self-attention graph pooling (SAGPOOL)-based GNN is then applied to jointly study the function and structure of the brain and identify the biomarkers. Our results successfully demonstrate that the proposed framework can effectively differentiate the preterm and term infant brains. Furthermore, the self-attention-based mechanism can accurately calculate the attention score and recognize the most significant biomarkers. In this study, not only 87.6% classification accuracy is observed for the developing Human Connectome Project (dHCP) dataset, but also distinguishing features are explored and extracted. Our study provides a novel and uniform framework to differentiate brain disorders and characterize the corresponding biomarkers.

Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development.

Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in infants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to a significant disease burden in immunocompromised individuals. Hence, an effective HCMV vaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, despite more than five decades of vaccine development, no successful HCMV vaccine is available. This review summarizes what we have learned from acquired natural immunity, including innate and adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the progress in related animal models; and the analysis of protective immune responses during natural infection and vaccination settings. Finally, we propose novel vaccine strategies that will harness the knowledge of protective immunity and employ new technology and vaccine concepts to inform next-generation HCMV vaccine development.

Exploring Hierarchical Auditory Representation via a Neural Encoding Model.

By integrating hierarchical feature modeling of auditory information using deep neural networks (DNNs), recent functional magnetic resonance imaging (fMRI) encoding studies have revealed the hierarchical neural auditory representation in the superior temporal gyrus (STG). Most of these studies adopted supervised DNNs (e.g., for audio classification) to derive the hierarchical feature representation of external auditory stimuli. One possible limitation is that the extracted features could be biased toward discriminative features while ignoring general attributes shared by auditory information in multiple categories. Consequently, the hierarchy of neural acoustic processing revealed by the encoding model might be biased toward classification. In this study, we explored the hierarchical neural auditory representation via an fMRI encoding framework in which an unsupervised deep convolutional auto-encoder (DCAE) model was adopted to derive the hierarchical feature representations of the stimuli (naturalistic auditory excerpts in different categories) in fMRI acquisition. The experimental results showed that the neural representation of hierarchical auditory features is not limited to previously reported STG, but also involves the bilateral insula, ventral visual cortex, and thalamus. The current study may provide complementary evidence to understand the hierarchical auditory processing in the human brain.

Test-retest reliability of dynamic functional connectivity in naturalistic paradigm functional magnetic resonance imaging.

Dynamic functional connectivity (dFC) has been increasingly used to characterize the brain transient temporal functional patterns and their alterations in diseased brains. Meanwhile, naturalistic neuroimaging paradigms have been an emerging approach for cognitive neuroscience with high ecological validity. However, the test-retest reliability of dFC in naturalistic paradigm neuroimaging is largely unknown. To address this issue, we examined the test-retest reliability of dFC in functional magnetic resonance imaging (fMRI) under natural viewing condition. The intraclass correlation coefficients (ICC) of four dFC statistics including standard deviation (Std), coefficient of variation (COV), amplitude of low frequency fluctuation (ALFF), and excursion (Excursion) were used to measure the test-retest reliability. The test-retest reliability of dFC in naturalistic viewing condition was then compared with that under resting state. Our experimental results showed that: (a) Global test-retest reliability of dFC was much lower than that of static functional connectivity (sFC) in both resting-state and naturalistic viewing conditions; (b) Both global and local (including visual, limbic and default mode networks) test-retest reliability of dFC could be significantly improved in naturalistic viewing condition compared to that in resting state; (c) There existed strong negative correlation between sFC and dFC, weak negative correlation between dFC and dFC-ICC (i.e., ICC of dFC), as well as weak positive correlation between dFC-ICC and sFC-ICC (i.e., ICC of sFC). The present study provides novel evidence for the promotion of naturalistic paradigm fMRI in functional brain network studies.