Machine learning with multitype functional connectivity uncovers whole-brain network disruption in primary angle-closure glaucoma.

Dynamic functional connectivity (DFC) obtained from resting state functional magnetic resonance imaging (fMRI) data has been shown to provide novel insights into brain function which may be obscured by static functional connectivity (SFC). Further, DFC, and by implication how different brain regions may engage or disengage with each other over time, has been shown to be behaviorally relevant and more predictive than SFC of behavioral performance and/or diagnostic status. DFC is not a directional entity and may capture neural synchronization. However, directional interactions between different brain regions is another putative mechanism by which neural populations communicate. Accordingly, static effective connectivity (SEC) has been explored as a means of characterizing such directional interactions. But investigation of its dynamic counterpart, i.e., dynamic effective connectivity (DEC), is still in its infancy. Of particular note are methodological insufficiencies in identifying DEC configurations that are reproducible across time and subjects as well as a lack of understanding of the behavioral relevance of DEC obtained from resting state fMRI. In order to address these issues, we employed a dynamic multivariate autoregressive (MVAR) model to estimate DEC. The method was first validated using simulations and then applied to resting state fMRI data obtained in-house (N = 21), wherein we performed dynamic clustering of DEC matrices across multiple levels [using adaptive evolutionary clustering (AEC)] – spatial location, time, and subjects. We observed a small number of directional brain network configurations alternating between each other over time in a quasi-stable manner akin to brain microstates. The dominant and consistent DEC network patterns involved several regions including inferior and mid temporal cortex, motor and parietal cortex, occipital cortex, as well as part of frontal cortex. The functional relevance of these DEC states were determined using meta-analyses and pertained mainly to memory and emotion, but also involved execution and language. Finally, a larger cohort of resting-state fMRI and behavioral data from the Human Connectome Project (HCP) (N = 232, Q1–Q3 release) was used to demonstrate that metrics derived from DEC can explain larger variance in 70 behaviors across different domains (alertness, cognition, emotion, and personality traits) compared to SEC in healthy individuals.

Previous neuroimaging studies have identified significant alterations in brain functional activity in retinal detachment (RD) patients, these investigations predominantly concentrated on local functional activity changes. The potential directional alterations in functional connectivity within the primary visual cortex (V1) in RD patients remain to be elucidated. In this study, we employed seed-based functional connectivity analysis along with Granger causality analysis to examine the directional alterations in dynamic functional connectivity (dFC) within the V1 region of patients diagnosed with RD. Finally, a support vector machine algorithm was utilized to classify patients with RD and healthy controls (HCs). RD patients exhibited heightened dynamic functional connectivity (dFC) and dynamic effective connectivity (dEC) between the Visual Network (VN) and default mode network (DMN), as well as within the VN, compared to HCs. Conversely, dFC between VN and auditory network (AN) decreased, and dEC between VN and sensorimotor network (SMN) significantly reduced. In state 4, RD patients had higher frequency. Notably, variations in dFC originating from the left V1 region proved diagnostically effective, achieving an AUC of 0.786. This study reveals significant alterations in the connectivity between the VN and the default mode network in patients with RD. These changes may disrupt visual information processing and higher cognitive integration in RD patients. Additionally, alterations in the left V1 region and whole-brain dFC show promising potential in aiding the diagnosis of RD. These findings offer valuable insights into the neural mechanisms underlying visual and cognitive impairments associated with RD.

Brain connectivity is highly dynamic, but functional connectivity (FC) studies using resting-state functional magnetic resonance imaging (rs-fMRI) assume it to be static. This study assessed differences in dynamic FC between young healthy adults (YH) and elderly healthy adults (EH) compared to static FC. Using rs-fMRI data from 12 YH and 31 EH, FC was assessed in six functional regions (subcortical, auditory [AUD], sensorimotor [SM], visuospatial [VS], cognitive control [CC], and default mode network [DMN]). Static FC was calculated as Fisher's z-transformed correlation coefficient. The sliding time window correlation (window size 30s, step size 3s) was applied for dynamic FC, and the standard deviation across sliding windows was calculated. Differences in static and dynamic FC between EH and YH were calculated and compared by region. EH showed decreased static FC in the subcortical, CC, and DMN regions (FDR corrected p=0.0013; 74 regions), with no regions showing static FC higher than that in YH. EH showed increased dynamic FC in the subcortical, CC, and DMN regions, whereas decreased dynamic FC in CC and DMN regions (p<0.01). However, the regions showing differences between EH and YH did not overlap between static and dynamic FC. Dynamic FC exhibited differences from static FC in EH and YH, mainly in regions involved in cognitive control and the DMN. Altered dynamic FC demonstrated both qualitatively and quantitatively distinct patterns of transient brain activity and needs to be studied as an imaging biomarker in the aging process.

A long-haul flight across more than five time zones may produce a circadian rhythm sleep disorder known as jet lag. Little is known about the effect of jet lag on white matter (WM) functional connectivity (FC). The present study is to investigate changes in WM FC in subjects due to recovery from jet lag after flying across six time zones. Here, resting-state functional magnetic resonance imaging was performed in 23 participants within 24 hours of flying and again 50 days later. Gray matter (GM) and WM networks were identified by k-means clustering. WM FC and functional covariance connectivity (FCC) were analyzed. Next, a sliding window method was used to establish dynamic WM FC. WM static and dynamic FC and FCC were compared between when participants had initially completed their journey and 50 days later. Emotion was assessed using the Positive and Negative Affect Schedule and the State Anxiety Inventory. All participants were confirmed to have jet lag symptoms by the Columbian Jet Lag Scale. The static FC strengthes of cingulate network (WM7)- sensorimotor network and ventral frontal network- visual network were lower after the long-haul flight compared with recovery. Corresponding results were obtained for the dynamic FC analysis. The analysis of FCC revealed weakened connections between the WM7 and several other brain networks, especially the precentral/postcentral network. Moreover, a negative correlation was found between emotion scores and the FC between the WM7 and sensorimotor related regions. The results of this study provide further evidence for the existence of WM networks and show that jet lag is associated with alterations in static and dynamic WM FC and FCC, especially in sensorimotor networks. Jet lag is a complex problem that not only is related to sleep rhythm but also influences emotion.

Altered dynamic large-scale brain networks and combined machine learning in primary angle-closure glaucoma

Background and purposeAsymptomatic carotid stenosis (ACS) is an independent risk factor for ischemic stroke and vascular cognitive impairment, affecting cognitive function across multiple domains. This study aimed to explore differences in static and dynamic intrinsic functional connectivity and temporal dynamics between patients with ACS and those without carotid stenosis.MethodsWe recruited 30 patients with unilateral moderate-to-severe (stenosis ≥ 50%) ACS and 30 demographically-matched healthy controls. All participants underwent neuropsychological testing and 3.0T brain MRI scans. Resting-state functional MRI (rs-fMRI) was used to calculate both static and dynamic functional connectivity. Dynamic independent component analysis (dICA) was employed to extract independent circuits/networks and to detect time-frequency modulation at the circuit level. Further imaging-behavior associations identified static and dynamic functional connectivity patterns that reflect cognitive decline.ResultsACS patients showed altered functional connectivity in multiple brain regions and networks compared to controls. Increased connectivity was observed in the inferior parietal lobule, frontal lobe, and temporal lobe. dICA further revealed changes in the temporal frequency of connectivity in the salience network. Significant differences in the temporal variability of connectivity were found in the fronto-parietal network, dorsal attention network, sensory-motor network, language network, and visual network. The temporal parameters of these brain networks were also related to overall cognition and memory.ConclusionsThese results suggest that ACS involves not only changes in the static large-scale brain network connectivity but also dynamic temporal variations, which parallel overall cognition and memory recall.

This study investigates abnormalities in cerebellar-cerebral static and dynamic functional connectivity among patients with acute pontine infarction, examining the relationship between these connectivity changes and behavioral dysfunction. Resting-state functional magnetic resonance imaging was utilized to collect data from 45 patients within seven days post-pontine infarction and 34 normal controls. Seed-based static and dynamic functional connectivity analyses identified divergences in cerebellar-cerebral connectivity features between pontine infarction patients and normal controls. Correlations between abnormal functional connectivity features and behavioral scores were explored. Compared to normal controls, left pontine infarction patients exhibited significantly increased static functional connectivity within the executive, affective-limbic, and motor networks. Conversely, right pontine infarction patients demonstrated decreased static functional connectivity in the executive, affective-limbic, and default mode networks, alongside an increase in the executive and motor networks. Decreased temporal variability of dynamic functional connectivity was observed in the executive and default mode networks among left pontine infarction patients. Furthermore, abnormalities in static and dynamic functional connectivity within the executive network correlated with motor and working memory performance in patients. These findings suggest that alterations in cerebellar-cerebral static and dynamic functional connectivity could underpin the behavioral dysfunctions observed in acute pontine infarction patients.

Thyroid-associated ophthalmopathy (TAO) is a prevalent autoimmune disease characterized by ocular symptoms like eyelid retraction and exophthalmos. Prior neuroimaging studies have revealed structural and functional brain abnormalities in TAO patients, along with central nervous system symptoms such as cognitive deficits. Nonetheless, the changes in the static and dynamic functional network connectivity of the brain in TAO patients are currently unknown. This study delved into the modifications in static functional network connectivity (sFNC) and dynamic functional network connectivity (dFNC) among thyroid-associated ophthalmopathy patients using independent component analysis (ICA). Thirty-two patients diagnosed with thyroid-associated ophthalmopathy and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. ICA method was utilized to extract the sFNC and dFNC changes of both groups. In comparison to the HC group, the TAO group exhibited significantly increased intra-network functional connectivity (FC) in the right inferior temporal gyrus of the executive control network (ECN) and the visual network (VN), along with significantly decreased intra-network FC in the dorsal attentional network (DAN), the default mode network (DMN), and the left middle cingulum of the ECN. On the other hand, FNC analysis revealed substantially reduced connectivity intra- VN and inter- cerebellum network (CN) and high-level cognitive networks (DAN, DMN, and ECN) in the TAO group compared to the HC group. Regarding dFNC, TAO patients displayed abnormal connectivity across all five states, characterized by notably reduced intra-VN connectivity and CN connectivity with high-level cognitive networks (DAN, DMN, and ECN), alongside compensatory increased connectivity between DMN and low-level perceptual networks (VN and basal ganglia network). No significant differences were observed between the two groups for the three dynamic temporal metrics. Furthermore, excluding the classification outcomes of FC within VN (with an accuracy of 51.61% and area under the curve of 0.35208), the FC-based support vector machine (SVM) model demonstrated improved performance in distinguishing between TAO and HC, achieving accuracies ranging from 69.35 to 77.42% and areas under the curve from 0.68229 to 0.81667. The FNC-based SVM classification yielded an accuracy of 61.29% and an area under the curve of 0.57292. In summary, our study revealed that significant alterations in the visual network and high-level cognitive networks. These discoveries contribute to our understanding of the neural mechanisms in individuals with TAO, offering a valuable target for exploring future central nervous system changes in thyroid-associated eye diseases.

Alterations of static and dynamic brain functional network connectivity in preschool children with autism spectrum disorder.

Stroke is a condition characterized by damage to the cerebral vasculature from various causes, resulting in focal or widespread brain tissue damage. Prior neuroimaging research has demonstrated that individuals with stroke present structural and functional brain abnormalities, evident through disruptions in motor, cognitive, and other vital functions. Nevertheless, there is a lack of studies on alterations in static and dynamic functional network connectivity in the brains of stroke patients. Fifty stroke patients and 50 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning. Initially, the independent component analysis (ICA) method was utilized to extract the resting-state network (RSN). Subsequently, the disparities in static functional network connectivity both within and between networks among the two groups were computed and juxtaposed. Following this, five consistent and robust dynamic functional network connectivity (dFNC) states were derived by integrating the sliding time window method with k-means cluster analysis, and the distinctions in dFNC between the groups across different states, along with the intergroup variations in three dynamic temporal metrics, were assessed. Finally, a support vector machine (SVM) approach was employed to discriminate stroke patients from HCs using FC and FNC as classification features. Comparing the stroke group to the healthy control (HC) group, the stroke group exhibited reduced intra-network functional connectivity (FC) in the right superior temporal gyrus of the ventral attention network (VAN), the left calcarine of the visual network (VN), and the left precuneus of the default mode network (DMN). Regarding static functional network connectivity (FNC), we identified increased connectivity between the executive control network (ECN) and dorsal attention network (DAN), salience network (SN) and DMN, SN-ECN, and VN-ECN, along with decreased connectivity between DAN-DAN, ECN-SN, SN-SN, and DAN-VN between the two groups. Noteworthy differences in dynamic FNC (dFNC) were observed between the groups in states 3 to 5. Moreover, stroke patients demonstrated a significantly higher proportion of time and longer mean dwell time in state 4, alongside a decreased proportion of time in state 5 compared to HC. Finally, utilizing FC and FNC as features, stroke patients could be distinguished from HC with an accuracy exceeding 70% and an area under the curve ranging from 0.8284 to 0.9364. In conclusion, our study reveals static and dynamic changes in large-scale brain networks in stroke patients, potentially linked to abnormalities in visual, cognitive, and motor functions. This investigation offers valuable insights into the neural mechanisms underpinning the functional deficits observed in stroke, thereby aiding in the diagnosis and development of targeted therapeutic interventions for affected individuals.

Resting-state functional MRI (fMRI) has revealed functional changes at the cortical level in degenerative cervical myelopathy (DCM) patients. The aim of this study was to systematically integrate static and dynamic functional connectivity (FC) to unveil abnormalities of functional networks of DCM patients and to analyze the prognostic value of these abnormalities for patients using resting-state fMRI. In this study, we collected clinical data and fMRI data from 44 DCM patients and 39 healthy controls (HC). Independent component analysis (ICA) was performed to investigate the group differences of intra-network FC. Subsequently, both static and dynamic FC were calculated to investigate the inter-network FC alterations in DCM patients. k-means clustering was conducted to assess temporal properties for comparison between groups. Finally, the support vector machine (SVM) approach was performed to predict the prognosis of DCM patients based on static FC, dynamic FC, and fusion of these two metrics. Relative to HC, DCM patients exhibited lower intra-network FC and higher inter-network FC. DCM patients spent more time than HC in the state in which both patients and HC were characterized by strong inter-network FC. Both static and dynamic FC could successfully classify DCM patients with different surgical outcomes. The classification accuracy further improved after fusing the dynamic and static FC for model training. In conclusion, our findings provide valuable insights into the brain mechanisms underlying DCM neuropathology on the network level.

Background and HypothesisAltered functional connectivity (FC) has been frequently reported in psychosis. Studying FC and its time-varying patterns in early-stage psychosis allows the investigation of the neural mechanisms of this disorder without the confounding effects of drug treatment or illness-related factors.Study DesignWe employed resting-state functional magnetic resonance imaging (rs-fMRI) to explore FC in individuals with early psychosis (EP), who also underwent clinical and neuropsychological assessments. 96 EP and 56 demographically matched healthy controls (HC) from the Human Connectome Project for Early Psychosis database were included. Multivariate analyses using spatial group independent component analysis were used to compute static FC and dynamic functional network connectivity (dFNC). Partial correlations between FC measures and clinical and cognitive variables were performed to test brain-behavior associations.Study ResultsCompared to HC, EP showed higher static FC in the striatum and temporal, frontal, and parietal cortex, as well as lower FC in the frontal, parietal, and occipital gyrus. We found a negative correlation in EP between cognitive function and FC in the right striatum FC (pFWE = 0.009). All dFNC parameters, including dynamism and fluidity measures, were altered in EP, and positive symptoms were negatively correlated with the meta-state changes and the total distance (pFWE = 0.040 and pFWE = 0.049).ConclusionsOur findings support the view that psychosis is characterized from the early stages by complex alterations in intrinsic static and dynamic FC, that may ultimately result in positive symptoms and cognitive deficits.

To investigate the specific features of static functional connectivity (SFC) and dynamic functional connectivity (DFC) of networks related to cognition in patients with subcortical ischemic vascular disease (SIVD). In this retrospective study, resting-state functional MRI data and a series of cognitive scores were obtained from 38 patients with SIVD and 23 normal controls. Independent component analysis, sliding window method, k-means clustering analysis and graph theory method were used to examine FC between the default mode network (DMN), dorsal attention network (DAN), frontoparietal network (FPN), salience network (SN) and executive control network (ECN) in patients with SIVD. Then, correlations between abnormal FC features and cognition were assessed. Compared with normal controls, SFC within the DMN significantly increased and SFC between the DMN and DAN significantly decreased in patients with SIVD. The decreased DFC mainly occurred in weakly connected states, especially the DFC of the SN; but the increased DFC, global network efficiency and local network efficiency and the decreased mean dwell time (MDT) and frequency mainly occurred in strongly connected states in SIVD patients. Moreover, aberrant SFC, DFC and MDT were significantly correlated with patients' cognitive scores. The overall results are suggestive of abnormal functional segregation and integration of SFC and DFC among networks related to cognition, especially in the SN. This may advance our comprehensive understanding of the abnormal changes in brain network connectivity in patients with SIVD. Our findings also highlight DFC may be an effective neuroimaging marker for the clinical diagnosis of SIVD.

Background: A long haul flight across more than five time zones may produce a circadian rhythm sleep disorder known as Jet Lag. Little is know about the effect of Jet Lag on white matter (WM) functional connectivity (FC). Methods: Resting-state functional Magnetic Resonance Imaging was performed in 23 participants within 24 hours of flying and again 50-days later. Gray (GM) and WM networks were identified by K-means clustering. WM FC and Functional Covariance Connectivity (FCC) analyzed. Next, a sliding window method was used to establish dynamic WM FC. WM static and dynamic FC and FCC were compared between when participants had initially completed their journey and 50-days later. Emotion was assessed by using the Positive and Negative Affect Schedule and the State Anxiety Inventory. All subjects were confirmed to have experienced Jet Lag by the Columbian Jet Lag Scale. Findings: The static FC of WM7-GM7, and WM14-GM4, were lower after the long haul flight compared with recovery. Corresponding results were obtained for the dynamic FC analysis. FCC between the cingulate network (WM7) and several brain networks was weaken and especially precentral/postcentral network. Emotion scores were negatively correlated with the FC between the WM7 and sensorimotor related regions. Interpretation: The results of this study provide further evidence for the existence of WM networks and show that Jet Lag is associated with alterations in static and dynamic WM FC and FCC especially in sensori-motor networks. Jet Lag is a complex problem which not only related with sleep rhythm but also influence emotion. Funding Statement: This study was supported by the National Natural Science Foundation (Grant Nos. 81971595, 81771812, 81761128023 and 81621003). Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, Grant No. IRT16R52) of China, and the Science and Technology Department of Sichuan Province (2018SZ0391) and the Innovation Spark Project of Sichuan University (No. 2019SCUH0003). Declaration of Interests: The authors have no conflict of interest to declare. Ethics Approval Statement: The study was approved by the West China Hospital Ethics Committee of Sichuan University and prior to any investigations being performed each subject gave fully informed written consent of their willingness to participate.

BackgroundAlterations in static and dynamic functional connectivity during resting state have been widely reported in major depressive disorder (MDD). The objective of this study was to compare the performances of whole-brain dynamic and static functional connectivity combined with machine learning approach in differentiating MDD patients from healthy controls at the individual subject level. Given the dynamic nature of brain activity, we hypothesized that dynamic connectivity would outperform static connectivity in the classification.MethodsSeventy-one MDD patients and seventy-one well-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Whole-brain dynamic and static functional connectivity patterns were calculated and utilized as classification features. Linear kernel support vector machine was employed to design the classifier and a leave-one-out cross-validation strategy was used to assess classifier performance.ResultsExperimental results of dynamic functional connectivity-based classification showed that MDD patients could be discriminated from healthy controls with an excellent accuracy of 100% irrespective of whether or not global signal regression (GSR) was performed (permutation test with P < 0.0002). Brain regions with the most discriminating dynamic connectivity were mainly and reliably located within the default mode network, cerebellum, and subcortical network. In contrast, the static functional connectivity-based classifiers exhibited unstable classification performances, i.e., a low accuracy of 38.0% without GSR (P = 0.9926) while a high accuracy of 96.5% with GSR (P < 0.0002); moreover, there was a considerable variability in the distribution of brain regions with static connectivity most informative for classification.ConclusionThese findings suggest the superiority of dynamic functional connectivity in machine learning-based classification of depression, which may be helpful for a better understanding of the neural basis of MDD as well as for the development of effective computer-aided diagnosis tools in clinical settings.