Acupuncture Alters Brain's Dynamic Functional Network Connectivity in Stroke Patients with Motor Dysfunction: A Randomised Controlled Neuroimaging Trial.

Low back pain (LBP) is a prevalent pain condition whose persistence can lead to changes in the brain regions responsible for sensory, cognitive, attentional, and emotional processing. Previous neuroimaging studies have identified various structural and functional abnormalities in patients with LBP; however, how the static and dynamic large-scale functional network connectivity (FNC) of the brain is affected in these patients remains unclear. Forty-one patients with chronic low back pain (cLBP) and 42 healthy controls underwent resting-state functional MRI scanning. The independent component analysis method was employed to extract the resting-state networks. Subsequently, we calculate and compare between groups for static intra- and inter-network functional connectivity. In addition, we investigated the differences between dynamic functional network connectivity and dynamic temporal metrics between cLBP patients and healthy controls. Finally, we tried to distinguish cLBP patients from healthy controls by support vector machine method. The results showed that significant reductions in functional connectivity within the network were found within the DMN,DAN, and ECN in cLBP patients. Significant between-group differences were also found in static FNC and in each state of dynamic FNC. In addition, in terms of dynamic temporal metrics, fraction time and mean dwell time were significantly altered in cLBP patients. In conclusion, our study suggests the existence of static and dynamic large-scale brain network alterations in patients with cLBP. The findings provide insights into the neural mechanisms underlying various brain function abnormalities and altered pain experiences in patients with cLBP.

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.

BackgroundExcessive daytime sleepiness (EDS) is a frequent nonmotor symptoms of Parkinson’s disease (PD), which seriously affects the quality of life of PD patients and exacerbates other nonmotor symptoms. Previous studies have used static analyses of these resting-state functional magnetic resonance imaging (rs-fMRI) data were measured under the assumption that the intrinsic fluctuations during MRI scans are stationary. However, dynamic functional network connectivity (dFNC) analysis captures time-varying connectivity over short time scales and may reveal complex functional tissues in the brain.PurposeTo identify dynamic functional connectivity characteristics in PD-EDS patients in order to explain the underlying neuropathological mechanisms.MethodsBased on rs-fMRI data from 16 PD patients with EDS and 41 PD patients without EDS, we applied the sliding window approach, k-means clustering and independent component analysis to estimate the inherent dynamic connectivity states associated with EDS in PD patients and investigated the differences between groups. Furthermore, to assess the correlations between the altered temporal properties and the Epworth sleepiness scale (ESS) scores.ResultsWe found four distinct functional connectivity states in PD patients. The patients in the PD-EDS group showed increased fractional time and mean dwell time in state IV, which was characterized by strong connectivity in the sensorimotor (SMN) and visual (VIS) networks, and reduced fractional time in state I, which was characterized by strong positive connectivity intranetwork of the default mode network (DMN) and VIS, while negative connectivity internetwork between the DMN and VIS. Moreover, the ESS scores were positively correlated with fraction time in state IV.ConclusionOur results indicated that the strong connectivity within and between the SMN and VIS was characteristic of EDS in PD patients, which may be a potential marker of pathophysiological features related to EDS in PD patients.

Temporal lobe epilepsy (TLE) is a common type of epilepsy, with seizures primarily originating in the deep temporal lobe. This condition results in changes in connectivity across gray matter (GM), and white matter (WM) regions. This altered connectivity categorizes TLE as a network disorder, highlighting the need to investigate functional network connectivity (FNC) in WM areas. Dynamic functional connectivity (dFC) measures time-varying correlations between two or multiple regions of interest and derives clusters highlighting functional networks (FNs) where connectivity among regions behaves in a similar fashion. In this study, we included a total of 103 subjects from the Epilepsy Connectome Project, comprising 51 healthy controls (HC), and 52 subjects with TLE. We obtained static FNs (sFNs) and dynamic FNs (dFNs) using K-means clustering on ROI-based static functional connectivity (sFC) and dFC, respectively. Both static and dynamic FNCs were then separately investigated in HC and TLE subjects, with the latter demonstrating significant differences in WM networks. The static FNC was significantly decreased between the Forceps minor-Anterior corona radiata (ACR) - genu and left inferior longitudinal fasciculus (ILF) in TLE. Dynamic FNC significantly decreased between the corpus callosum (CC) (body) - superior corona radiata - right superior longitudinal fasciculus network and the Forceps minor - ACR - medial frontal gyrus network in subjects with TLE. This result implies that this WM connection changes with lower variability in TLE. On the other hand, the dynamic connections between the left temporal sub gyral - left thalamus - left pallidus - left hippocampus and right thalamus - right putamen - right temporal sub gyral - right pallidus network and the connections between the cingulum network and right thalamus - right putamen - right temporal sub gyral - right pallidus network significantly increased. These results indicate that these two GM subcortical connections change with higher variability in TLE. The study also demonstrates that the static functional connectivity strength (FCS) of the left ILF decreased significantly in subjects with TLE. However, the dynamic FCS of the splenium and brain stem were altered significantly in TLE, implying that the total dynamic connections of this network with all other networks experienced greater changes. Furthermore, the FNC suggests that the WM regions - ILF, superior and ACR, and CC exhibit connectivity changes related to the clinical features.

Individual large-scale functional network mapping for major depressive disorder with electroconvulsive therapy

Reconfigurations of dynamic functional network connectivity after 1HZ repetitive transcranial magnetic stimulation in insomnia disorder.

Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people’s health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks that represents a powerful tool for gaining novel insight into neurological diseases. To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function. We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI (rs-fMRI) with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the functional connectivity (FC) strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance. A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse FC both inter-network and intra-networks. Additionally, the CSVD group had a reduced number of windows and shorter mean dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state 2 and state 3 and between state 3 and state 4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a significant difference in the FC strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance. Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC alterations could help us to better understand the progressive dysfunction of networks in CSVD patients.

Dynamic Functional Network Connectivity in Acute Incomplete Cervical Cord Injury Patients and Its Associations With Sensorimotor Dysfunction Measures

<bold>Objective</bold> To observe the differences in brain network activation and functional connectivity of patients with post-stroke cognitive impairment (PSCI) of different severity using functional near-infrared spectroscopy (fNIRS). <bold>Methods</bold> A total of 40 stroke patients in the outpatient and inpatient Rehabilitation Department in the Pudong District of Huashan Hospital, Fudan University from April to November 2020 were recruited and divided into normal group (<italic>n</italic>=14), mild to moderate group (<italic>n</italic>=11) and severe group (<italic>n</italic>=15) according to the mini-mental state examination (MMSE) score. Fugl-Meyer assessment scale (FMA) and functional comprehensive assessment (FCA) were used to evaluate the motor function of upper and lower limbs; 64-channel fNIRS functional imaging device was used to collect the resting-state brain network data of patients. The whole brain functional connectivity was analyzed based on oxyhemoglobin (HbO₂) and deoxyhemoglobin (HbR). Differences in functional connectivity strengths between homologous and heterologous brain networks in dorsal attention network (DAN), sensorimotor network (SEN), ventral attention network (VAN), frontoparietal network (FPN), default mode network (DMN) and visual network (VIS) regions were analyzed. <bold>Results</bold> (1) Motor function: there was no significant difference in FMA and FCA scores in three groups (<italic>P</italic>&gt;0.05). (2) Whole brain functional connectivity and strength of homologous brain network functional connectivity: there was no significant difference in whole brain functional connectivity based on HbO₂ and HbR in three groups (<italic>P</italic>&gt;0.05). Compared with the normal group, there were significant differences in the strength of functional connectivity of the in the SEN and FPN regions of the HbO₂-based homologous brain network in the severe group (<italic>P</italic>&lt;0.05), but there were no significant differences in the regions of interest of the HbR-based homologous brain network in the three groups (<italic>P</italic>&gt;0.05). (3) Functional connectivity strength of heterologous brain networks: compared with the normal group, the functional connectivity of SEN-VAN, SEN-DMN, SEN-FPN, VAN-FPN and DMN-FPN in the severe group decreased significantly, and the differences were statistically significant (<italic>P</italic>&lt;0.05). Compared with the mild to moderate group, the functional connectivity of SEN-DAN and SEN-FPN in the severe group decreased significantly, and the differences were statistically significant (<italic>P</italic>&lt;0.05). There was no significant difference of strength of functional connectivity based on HbR in the three groups (<italic>P</italic>&gt;0.05). (4) Correlation analysis between SEN-FPN heterologous functional connectivity and MMSE, FCA scores: MMSE score (<italic>r</italic>=0.32, <italic>P</italic>&lt;0.05) and FCA score (<italic>r</italic>=0.38, <italic>P</italic>&lt;0.05) were positively correlated with SEN-FPN functional connectivity. <bold>Conclusion</bold> The SEN-FPN functional connectivity may play an important role in the cognitive function of stroke patients. Altered functional connectivity patterns of SEN-FPN may be closely related to the occurrence and progression of PSCI, and changes in functional connectivity strength of SEN-FPN may be a potential imaging indicator of PSCI.

The pathogenesis of autism spectrum disorder (ASD) remains unclear. Diagnosis relies on symptoms and relevant scales, which are highly subjective. Moreover, most diagnoses are made after the age of 3, delaying treatment opportunities. This study aimed to explore dynamic functional network connectivity (dFNC) in toddlers with ASD aged 1-3 years, to identify group-level differences in dynamic functional connectivity (FC) patterns and investigate their associations with autistic symptoms, with the goal of providing preliminary neuroimaging insights into the neural mechanisms underlying ASD during this critical developmental window. Magnetic resonance imaging (MRI) data of 41 toddlers diagnosed with ASD and 23 age- and sex-matched normal development control (NC) individuals were collected. We examined group differences in dFNC properties, including temporal characteristics of brain states, mean dwell time (MDT), state occurrence rate (OR), and state transition frequency. Correlation analyses were performed to assess the relationships between these dFNC metrics and the severity of autistic symptoms. Compared with the NC group, toddlers with ASD spent more time in a brain state characterized by globally weak connectivity and a notable lack of between-network functional connectivity, with a significantly higher OR and nominally longer MDT. They also showed a nominally reduced MDT in a brain state marked by strong within-network connectivity and enhanced modular organization across multiple functional networks. Exploratory correlation analyses between autism metrics and dFC measures suggested several nominal associations (uncorrected p < 0.05). Toddlers with ASD exhibit abnormal dFNC patterns, characterized by altered temporal properties of brain states and disrupted state-related connectivity profiles. These results provide empirical evidence for altered dynamic brain organization in early ASD, contributing to a better understanding of its neural underpinnings during this critical developmental window.

Background: Alzheimer's disease (AD) is the most common age-related dementia that promotes a decline in memory, thinking, and social skills. The initial stages of dementia can be associated with mild symptoms, and symptom progression to a more severe state is heterogeneous across patients. Recent work has demonstrated the potential for functional network mapping to assist in the prediction of symptomatic progression. However, this work has primarily used static functional connectivity (sFC) from resting-state functional magnetic resonance imaging. Recently, dynamic functional connectivity (dFC) has been recognized as a powerful advance in functional connectivity methodology to differentiate brain network dynamics between healthy and diseased populations. Methods: Group independent component analysis was applied to extract 17 components within the cognitive control network (CCN) from 1385 individuals across varying stages of AD symptomology. We estimated dFC among 17 components within the CCN, followed by clustering the dFCs into 3 recurring brain states, and then estimated a hidden Markov model and the occupancy rate for each subject. Then, we investigated the link between CCN dFC features and AD progression. Also, we investigated the link between sFC and AD progression and compared its results with dFC results. Results: Progression of AD symptoms was associated with increases in connectivity within the middle frontal gyrus. Also, the very mild AD (vmAD) showed less connectivity within the inferior parietal lobule (in both sFC and dFC) and between this region and the rest of CCN (in dFC analysis). Also, we found that within-middle frontal gyrus connectivity increases with AD progression in both sFC and dFC results. Finally, comparing with vmAD, we found that the normal brain spends significantly more time in a state with lower within-middle frontal gyrus connectivity and higher connectivity between the hippocampus and the rest of CCN, highlighting the importance of assessing the dynamics of brain connectivity in this disease. Conclusion: Our results suggest that AD progress not only alters the CCN connectivity strength but also changes the temporal properties in this brain network. This suggests the temporal and spatial pattern of CCN as a biomarker that differentiates different stages of AD.

Recently, much attention has been devoted to examining time-varying changes in functional connectivity to understand the network structure in the human brain. Most studies, however, analyze the time-varying functional connectivity but ignore the time-varying spatial information. In this paper, we propose a method based on independent vector analysis (IVA) to study dynamic functional network connectivity (dFNC) as well as dynamic spatial functional network connectivity (dsFNC) in fMRI data. Though IVA allows one to effectively capture both, its performance degrades with the increase in the number of datasets. Hence, we propose an effective scheme to bypass this limitation followed by graph theoretical analysis to study both inter-network dynamics and intra-network stationarity. We observe higher dFNC fluctuations for patients with schizophrenia in the default-mode (DM)-salience network and cerebellum with associated connections. dsFNC analysis indicates higher inter-network fluctuation in patients while DM, anterior DM and frontal networks demonstrate significant intra-network fluctuation in controls.

Idiopathic Normal pressure hydrocephalus (iNPH) is a neurodegenerative disease characterized by gait disturbance, dementia, and urinary dysfunction. The neural network mechanisms underlying this phenomenon is currently unknown. To investigate the resting-state functional connectivity (rs-FC) abnormalities of iNPH-related brain connectivity from static and dynamic perspectives and the correlation of these abnormalities with clinical symptoms before and 3-month after shunt. We investigated both static and dynamic functional network connectivity (sFNC and dFNC, respectively) in 33 iNPH patients and 23 healthy controls (HCs). The sFNC and dFNC of networks were generally decreased in iNPH patients. The reduction in sFNC within the default mode network (DMN) and between the somatomotor network (SMN) and visual network (VN) were related to symptoms. The temporal properties of dFNC and its temporal variability in state-4 were sensitive to the identification of iNPH and were correlated with symptoms. The temporal variability in the dorsal attention network (DAN) increased, and the average instantaneous FC was altered among networks in iNPH. These features were partially associated with clinical symptoms. The dFNC may be a more sensitive biomarker for altered network function in iNPH, providing us with extra information on the mechanisms of iNPH.

In functional magnetic resonance imaging (fMRI), spatial smoothing procedure is generally a stable step in the preprocessing stream. Previous research (including ours) suggested dependency of the static functional connectivity on the size of the spatial smoothing kernel size. But its impact on the time-varying patterns of functional connectivity has not been investigated. Here, we sought to identify the effects of spatial smoothing on brain dynamics by performing dynamic functional network connectivity (dFNC) and meta-state analysis, a unique approach capable of examining a higher-dimensional temporal dynamism of whole-brain functional connectivity. Gaussian smoothing kernel with different widths at half of the maximum of the height of the Gaussian (4, 8, and 12 mm FWHM) were used during preprocessing prior to the group independent component analysis (ICA) with a relatively high model order of 75. dFNC was conducted using the sliding-time window approach and k-means clustering algorithm. Meta-state dynamics method was performed by reducing the number of windowed FNC correlations using principal components analysis (PCA), temporal and spatial ICA and k-means. Results revealed robust effects of spatial smoothing on the connectivity dynamics of several network pairs including a variety of cognitive/attention networks in a connectivity state with the highest occurrence (FDR corrected-p < 0.01). Meta-state analyses indicated significant changes in meta-state metrics including the number of meta-states, meta-state changes, meta-state span, and the total distance. These changes were particularly pronounced when we compared resting state data smoothed with 8 vs. 12 mm FWHM. Our preliminary findings give insights into the effects of spatial smoothing kernel size on the dynamics of functional connectivity and its consequences on meta-state parameters. It also provides further indication of the importance of evaluating variance associated with preprocessing steps on analysis outcomes.

Dynamic functional network connectivity (dFNC) is an expansion of static FNC (sFNC) that reflects connectivity variations among brain networks. This study aimed to investigate changes in sFNC and dFNC strength and temporal properties in individuals with subthreshold depression (StD). Forty-two individuals with subthreshold depression and 38 healthy controls (HCs) were included in this study. Group independent component analysis (GICA) was used to determine target resting-state networks, namely, executive control network (ECN), default mode network (DMN), sensorimotor network (SMN) and dorsal attentional network (DAN). Sliding window and k-means clustering analyses were used to identify dFNC patterns and temporal properties in each subject. We compared sFNC and dFNC differences between the StD and HCs groups. Relationships between changes in FNC strength, temporal properties, and neurophysiological score were evaluated by Spearman's correlation analysis. The sFNC analysis revealed decreased FNC strength in StD individuals, including the DMN-CEN, DMN-SMN, SMN-CEN, and SMN-DAN. In the dFNC analysis, 4 reoccurring FNC patterns were identified. Compared to HCs, individuals with StD had increased mean dwell time and fraction time in a weakly connected state (state 4), which is associated with self-focused thinking status. In addition, the StD group demonstrated decreased dFNC strength between the DMN-DAN in state 2. sFNC strength (DMN-ECN) and temporal properties were correlated with HAMD-17 score in StD individuals (all p < 0.01). Our study provides new evidence on aberrant time-varying brain activity and large-scale network interaction disruptions in StD individuals, which may provide novel insight to better understand the underlying neuropathological mechanisms.