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•Patients with KOA have altered static and dynamic functional network connectivity.•KOA have abnormal pain-related information processing of the default mode network, sensorimotor network, cognitive control network.•Although abnormalities in dFNCs of KOA patients have been found using the common window size, but the results were not robust. This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

This study aimed to investigate altered static and dynamic functional network connectivity (FNC) and its correlation with clinical symptoms in patients with knee osteoarthritis (KOA). One hundred and fifty-nine patients with KOA and 73 age- and gender-matched healthy subjects (HS) underwent resting-state functional magnetic resonance imaging (rs-fMRI) and clinical evaluations. Group independent component analysis (GICA) was applied, and seven resting-state networks were identified. Patients with KOA had decreased static FNC within the default mode network (DM), visual network (VS), and cerebellar network (CB) and increased static FNC between the subcortical network (SC) and VS (p < 0.05, FDR corrected). Four reoccurring FNC states were identified using k-means clustering analysis. Although abnormalities in dynamic FNCs of KOA patients have been found using the common window size (22 TR, 44 s), but the results of the clustering analysis were inconsistent when using different window sizes, suggesting dynamic FNCs might be an unstable method to compare brain function between KOA patients and HS. These recent findings illustrate that patients with KOA have a wide range of abnormalities in the static and dynamic FNCs, which provided a reference for the identification of potential central nervous therapeutic targets for KOA treatment and might shed light on the other musculoskeletal pain neuroimaging studies.

In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a technique using normalized mutual information (NMI) that calculates the nonlinear relationship between different brain regions. We demonstrate our proposed approach using simulated data and then apply it to a dataset previously studied by Damaraju et al. This resting‐state fMRI data included 151 schizophrenia patients and 163 age‐ and gender‐matched healthy controls. We first decomposed these data using group independent component analysis (ICA) and yielded 47 functionally relevant intrinsic connectivity networks. Our analysis showed a modularized nonlinear relationship among brain functional networks that was particularly noticeable in the sensory and visual cortex. Interestingly, the modularity appears both meaningful and distinct from that revealed by the linear approach. Group analysis identified significant differences in explicitly nonlinear functional network connectivity (FNC) between schizophrenia patients and healthy controls, particularly in the visual cortex, with controls showing more nonlinearity (i.e., higher normalized mutual information between time courses with linear relationships removed) in most cases. Certain domains, including subcortical and auditory, showed relatively less nonlinear FNC (i.e., lower normalized mutual information), whereas links between the visual and other domains showed evidence of substantial nonlinear and modular properties. Overall, these results suggest that quantifying nonlinear dependencies of functional connectivity may provide a complementary and potentially important tool for studying brain function by exposing relevant variation that is typically ignored. Beyond this, we propose a method that captures both linear and nonlinear effects in a “boosted” approach. This method increases the sensitivity to group differences compared to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects. In this work, we focus on explicitly nonlinear relationships in functional networks. We introduce a normalized mutual information (NMI) technique that calculates the nonlinear relationship between different brain regions. Also, we propose a method that captures both linear and nonlinear effects in a “boosted” approach. This method increases the sensitivity to group differences compared to the standard linear approach, at the cost of being unable to separate linear and nonlinear effects.

•The alterations in dFC and SC networks unveil distinct characteristics associated with cLBP.•The enhanced connectivity between the FPN, SMN and thalamus signifies the most relevant changes in brain networks associated with cLBP.•The integration of different features effectively enhances the classification accuracy between cLBP patients and HC. The prolonged duration of chronic low back pain (cLBP) inevitably leads to changes in the cognitive, attentional, sensory and emotional processing brain regions. Currently, it remains unclear how these alterations are manifested in the interplay between brain functional and structural networks. This study aimed to predict the Oswestry Disability Index (ODI) in cLBP patients using multimodal brain magnetic resonance imaging (MRI) data and identified the most significant features within the multimodal networks to aid in distinguishing patients from healthy controls (HCs). We constructed dynamic functional connectivity (dFC) and structural connectivity (SC) networks for all participants (n = 112) and employed the Connectome-based Predictive Modeling (CPM) approach to predict ODI scores, utilizing various feature selection thresholds to identify the most significant network change features in dFC and SC outcomes. Subsequently, we utilized these significant features for optimal classifier selection and the integration of multimodal features. The results revealed enhanced connectivity among the frontoparietal network (FPN), somatomotor network (SMN) and thalamus in cLBP patients compared to HCs. The thalamus transmits pain-related sensations and emotions to the cortical areas through the dorsolateral prefrontal cortex (dlPFC) and primary somatosensory cortex (SI), leading to alterations in whole-brain network functionality and structure. Regarding the model selection for the classifier, we found that Support Vector Machine (SVM) best fit these significant network features. The combined model based on dFC and SC features significantly improved classification performance between cLBP patients and HCs (AUC=0.9772). Finally, the results from an external validation set support our hypotheses and provide insights into the potential applicability of the model in real-world scenarios. Our discovery of enhanced connectivity between the thalamus and both the dlPFC (FPN) and SI (SMN) provides a valuable supplement to prior research on cLBP.

Late-onset depression (LOD) is featured by disrupted cognitive performance, which is refractory to conventional treatments and increases the risk of dementia. Aberrant functional connectivity among various brain regions has been reported in LOD, but their abnormal patterns of functional network connectivity remain unclear in LOD. A total of 82 LOD and 101 healthy older adults (HOA) accepted functional magnetic resonance imaging scanning and a battery of neuropsychological tests. Static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) were analyzed using independent component analysis, with dFNC assessed via a sliding window approach. Both sFNC and dFNC contributions were classified using a support vector machine. LOD exhibited decreased sFNC among the default mode network (DMN), salience network (SN), sensorimotor network (SMN), and language network (LAN), along with reduced dFNC of DMN-SN and SN-SMN. The sFNC of SMN-LAN and dFNC of DMN-SN contributed the most in differentiating LOD and HOA by support vector machine. Additionally, abnormal sFNC of DMN-SN and DMN-SMN both correlated with working memory, with DMN-SMN mediating the relationship between depression and working memory. The dFNC of SN-SMN was associated with depressive severity and multiple domains of cognition, and mediated the impact of depression on memory and semantic function. This study displayed the abnormal connectivity among DMN, SN, and SMN that involved the relationship between depression and cognition in LOD, which might reveal mutual biomarkers between depression and cognitive decline in LOD.

Catatonia is a transnosologic psychomotor syndrome with high prevalence in schizophrenia spectrum disorders (SSD). There is mounting neuroimaging evidence that catatonia is associated with aberrant frontoparietal, thalamic and cerebellar regions. Large‐scale brain network dynamics in catatonia have not been investigated so far. In this study, resting‐state fMRI data from 58 right‐handed SSD patients were considered. Catatonic symptoms were examined on the Northoff Catatonia Rating Scale (NCRS). Group spatial independent component analysis was carried out with a multiple analysis of covariance (MANCOVA) approach to estimate and test the underlying intrinsic components (ICs) in SSD patients with (NCRS total score ≥ 3; n = 30) and without (NCRS total score = 0; n = 28) catatonia. Functional network connectivity (FNC) during rest was calculated between pairs of ICs and transient changes in connectivity were estimated using sliding windowing and clustering (to capture both static and dynamic FNC). Catatonic patients showed increased static FNC in cerebellar networks along with decreased low frequency oscillations in basal ganglia (BG) networks. Catatonic patients had reduced state changes and dwelled more in a state characterized by high within‐network correlation of the sensorimotor, visual, and default‐mode network with respect to noncatatonic patients. Finally, in catatonic patients according to DSM‐IV‐TR (n = 44), there was a significant correlation between increased within FNC in cortico‐striatal state and NCRS motor scores. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states. The data support a neuromechanistic model of catatonia that emphasizes a key role of disrupted sensorimotor network control during distinct functional states.

Resting‐state functional network connectivity (rsFNC) has shown utility for identifying characteristic functional brain patterns in individuals with psychiatric and mood disorders, providing a promising avenue for biomarker development. However, several factors have precluded widespread clinical adoption of rsFNC diagnostics, namely a lack of standardized approaches for capturing comparable and reproducible imaging markers across individuals, as well as the disagreement on the amount of data required to robustly detect intrinsic connectivity networks (ICNs) and diagnostically relevant patterns of rsFNC at the individual subject level. Recently, spatially constrained independent component analysis (scICA) has been proposed as an automated method for extracting ICNs standardized to a chosen network template while still preserving individual variation. Leveraging the scICA methodology, which solves the former challenge of standardized neuroimaging markers, we investigate the latter challenge of identifying a minimally sufficient data length for clinical applications of resting‐state fMRI (rsfMRI). Using a dataset containing rsfMRI scans of individuals with schizophrenia and controls (M = 310) as well as simulated rsfMRI, we evaluated the robustness of ICN and rsFNC estimates at both the subject‐ and group‐level, as well as the performance of diagnostic classification, with respect to the length of the rsfMRI time course. We found individual estimates of ICNs and rsFNC from the full‐length (5 min) reference time course were sufficiently approximated with just 3–3.5 min of data (r = 0.85, 0.88, respectively), and significant differences in group‐average rsFNC could be sufficiently approximated with even less data, just 2 min (r = 0.86). These results from the shorter clinical data were largely consistent with the results from validation experiments using longer time series from both simulated (30 min) and real‐world (14 min) datasets, in which estimates of subject‐level FNC were reliably estimated with 3–5 min of data. Moreover, in the real‐world data we found rsFNC and ICN estimates generated across the full range of data lengths (0.5–14 min) more reliably matched those generated from the first 5 min of scan time than those generated from the last 5 min, suggesting increased influence of “late scan” noise factors such as fatigue or drowsiness may limit the reliability of FNC from data collected after 10+ min of scan time, further supporting the notion of shorter scans. Lastly, a diagnostic classification model trained on just 2 min of data retained 97%–98% classification accuracy relative to that of the full‐length reference model. Our results suggest that, when decomposed with scICA, rsfMRI scans of just 2–5 min show good clinical utility without significant loss of individual FNC information of longer scan lengths. Here, we test the reliability (both in general and in the context of identifying schizophrenia) of intrinsic connectivity networks and functional connectivity patterns estimated via spatially constrained ICA with respect to data length for short (5 min), medium (15 min) and long (30 min) resting‐state fMRI scans. Our results suggest that, when decomposed with spatially constrained ICA, resting‐state fMRI scans of just 2–5 min show good clinical utility without significant loss of individual functional connectivity information or diagnostic accuracy of longer scan lengths.

Dynamic functional network connectivity (dFNC) analysis is a widely used approach for studying brain function and offering insight into how brain networks evolve over time. Typically, dFNC studies utilize fixed spatial maps and evaluate transient changes in coupling among time courses estimated from independent component analysis (ICA). This manuscript presents a complementary approach that relaxes this assumption by spatially reordering the components dynamically at each time point to optimize for a smooth gradient in the FNC (i.e., a smooth gradient among ICA connectivity values). Several methods are presented to summarize dynamic FNC gradients (dFNGs) over time, starting with static FNC gradients (sFNGs), then exploring the reordering properties as well as the dynamics of the gradients themselves. We then apply this approach to a dataset of schizophrenia (SZ) patients and healthy controls (HCs). Functional dysconnectivity between different brain regions has been reported in SZ, yet the neural mechanisms behind it remain elusive. Using resting‐state fMRI and ICA on a dataset consisting of 151 SZ patients and 160 age and gender‐matched HCs, we extracted 53 intrinsic connectivity networks (ICNs) for each subject using a fully automated spatially constrained ICA approach. We develop several summaries of our functional network connectivity gradient analysis, both in a static sense, computed as the Pearson correlation coefficient between full time series, and a dynamic sense, computed using a sliding window approach followed by reordering based on the computed gradient, and evaluate group differences. Static connectivity analysis revealed significantly stronger connectivity between subcortical (SC), auditory (AUD), and visual (VIS) networks in patients, as well as hypoconnectivity in the sensorimotor (SM) network relative to controls. sFNG analysis highlighted distinctive clustering patterns in patients and HCs along cognitive control (CC)/default mode network (DMN), as well as SC/AUD/SM/cerebellar (CB) and VIS gradients. Furthermore, we observed significant differences in the sFNGs between groups in SC and CB domains. dFNG analysis suggested that SZ patients spend significantly more time in a SC/CB state based on the first gradient, while HCs favor the SM/DMN state. For the second gradient, however, patients exhibited significantly higher activity in CB domains, contrasting with HCs' DMN engagement. The gradient synchrony analysis conveyed more shifts between SM/SC networks and transmodal CC/DMN networks in patients. In addition, the dFNG coupling revealed distinct connectivity patterns between SC, SM, and CB domains in SZ patients compared to HCs. To recap, our results advance our understanding of brain network modulation by examining smooth connectivity trajectories. This provides a more complete spatiotemporal summary of the data, contributing to the growing body of current literature regarding the functional dysconnectivity in SZ patients. By employing dFNG, we highlight a new perspective to capture large‐scale fluctuations across the brain while maintaining the convenience of brain networks and low‐dimensional summary measures. The resting‐state functional magnetic resonance imaging (fMRI) data were preprocessed using standard procedures, and then spatially constrained independent component analysis (ICA) was run on the data using the Neuromark fMRI 1.0 template, resulting in 53 intrinsic connectivity networks (ICNs). Next, functional network connectivity (FNC) was calculated both in static and dynamic sense. A diffusion map (gradients) was computed for each static and windowed‐FNC, and each matrix was reordered based on its gradient, followed by k‐means clustering of the reordered dynamic functional network connectivity (dFNCs). This resulted in five dynamic FNC gradients (dFNGs). By employing dFNG, we highlight a new perspective to capture large‐scale fluctuations across the brain while maintaining the convenience of brain networks and low‐dimensional summary measures.

To explore altered patterns of static and dynamic functional brain network connectivity (sFNC and dFNC) in Primary angle-closure glaucoma (PACG) patients. Clinically confirmed 34 PACG patients and 33 age- and gender-matched healthy controls (HCs) underwent evaluation using T1 anatomical and functional MRI on a 3 T scanner. Independent component analysis, sliding window, and the K-means clustering method were employed to investigate the functional network connectivity (FNC) and temporal metrics based on eight resting-state networks. Differences in FNC and temporal metrics were identified and subsequently correlated with clinical variables. For sFNC, compared with HCs, PACG patients showed three decreased interactions, including SMN-AN, SMN-VN and VN-AN pairs. For dFNC, we derived four highly structured states of FC that occurred repeatedly between individual scans and subjects, and the results are highly congruent with sFNC. In addition, PACG patients had a decreased fraction of time in state 3 and negatively correlated with IOP (p < 0.05). PACG patients exhibit abnormalities in both sFNC and dFNC. The high degree of overlap between static and dynamic results suggests the stability of functional connectivity networks in PACG patients, which provide a new perspective to understand the neuropathological mechanisms of optic nerve damage in PACG patients.

The sliding-window-based dynamic functional connectivity network (D-FCN) has been becoming an increasingly useful tool for understanding the changes of brain connectivity patterns and the association of neurological diseases with these dynamic variations. However, conventional D-FCN is essentially low-order network, which only reflects the pairwise interaction pattern between brain regions and thus overlooking the high-order interactions among multiple brain regions. In addition, D-FCN is innate with temporal sensitivity issue, i.e., D-FCN is sensitive to the chronological order of its subnetworks. To deal with the above issues, we propose a novel high-order functional connectivity network framework based on the central moment feature of D-FCN. Specifically, we firstly adopt a central moment approach to extract multiple central moment feature matrices from D-FCN. Furthermore, we regard the matrices as the profiles to build multiple high-order functional connectivity networks which further capture the higher level and more complex interaction relationships among multiple brain regions. Finally, we use the voting strategy to combine the high-order networks with D-FCN for autism spectrum disorder diagnosis. Experimental results show that the combination of multiple functional connectivity networks achieves accuracy of 88.06%, and the best single network achieves accuracy of 79.5%.