Whole-brain Functional Networks Research Articles

Analyzing the topological properties of resting-state brain function network connectivity based on graph theoretical methods in patients with high myopia

AimRecent imaging studies have found significant abnormalities in the brain’s functional or structural connectivity among patients with high myopia (HM), indicating a heightened risk of cognitive impairment and other behavioral changes. However, there is a lack of research on the topological characteristics and connectivity changes of the functional networks in HM patients. In this study, we employed graph theoretical analysis to investigate the topological structure and regional connectivity of the brain function network in HM patients.MethodsWe conducted rs-fMRI scans on 82 individuals with HM and 59 healthy controls (HC), ensuring that the two groups were matched for age and education level. Through graph theoretical analysis, we studied the topological structure of whole-brain functional networks among participants, exploring the topological properties and differences between the two groups.ResultsIn the range of 0.05 to 0.50 of sparsity, both groups demonstrated a small-world architecture of the brain network. Compared to the control group, HM patients showed significantly lower values of normalized clustering coefficient (γ) (P = 0.0101) and small-worldness (σ) (P = 0.0168). Additionally, the HM group showed lower nodal centrality in the right Amygdala (P < 0.001, Bonferroni-corrected). Notably, there is an increase in functional connectivity (FC) between the saliency network (SN) and Sensorimotor Network (SMN) in the HM group, while the strength of FC between the basal ganglia is relatively weaker (P < 0.01).ConclusionHM Patients exhibit reduced small-world characteristics in their brain networks, with significant drops in γ and σ values indicating weakened global interregional information transfer ability. Not only that, the topological properties of the amygdala nodes in HM patients significantly decline, indicating dysfunction within the brain network. In addition, there are abnormalities in the FC between the SN, SMN, and basal ganglia networks in HM patients, which is related to attention regulation, motor impairment, emotions, and cognitive performance. These findings may provide a new mechanism for central pathology in HM patients.

Characteristics of pain empathic networks in healthy and primary dysmenorrhea women: an fMRI study.

Pain empathy enables us to understand and share how others feel pain. Few studies have investigated pain empathy-related functional interactions at the whole-brain level across all networks. Additionally, women with primary dysmenorrhea (PDM) have abnormal pain empathy, and the association among the whole-brain functional network, pain, and pain empathy remain unclear. Using resting-state functional magnetic resonance imaging (fMRI) and machine learning analysis, we identified the brain functional network connectivity (FNC)-based features that are associated with pain empathy in two studies. Specifically, Study 1 examined 41 healthy controls (HCs), while Study 2 investigated 45 women with PDM. Additionally, in Study 3, a classification analysis was performed to examine the differences in FNC between HCs and women with PDM. Pain empathy was evaluated using a visual stimuli experiment, and trait and state of menstrual pain were recorded. In Study 1, the results showed that pain empathy in HCs relied on dynamic interactions across whole-brain networks and was not concentrated in a single or two brain networks, suggesting the dynamic cooperation of networks for pain empathy in HCs. In Study 2, PDM exhibited a distinctive network for pain empathy. The features associated with pain empathy were concentrated in the sensorimotor network (SMN). In Study 3, the SMN-related dynamic FNC could accurately distinguish women with PDM from HCs and exhibited a significant association with trait menstrual pain. This study may deepen our understanding of the neural mechanisms underpinning pain empathy and suggest that menstrual pain may affect pain empathy through maladaptive dynamic interaction between brain networks.

Sex-related patterns of functional brain networks in children and adolescents with autism spectrum disorder.

Although numerous studies have emphasized the male predominance in autism spectrum disorder (ASD), how sex differences are related to the topological organization of functional networks remains unclear. This study utilized imaging data from 86 ASD (43 females, aged 7-18 years) and 86 typically developing controls (TCs) (43 females, aged 7-18 years) obtained from Autism Brain Imaging Data Exchange databases, constructed individual whole-brain functional networks, used a graph theory analysis to compute topological metrics, and assessed sex-related differences in topological metrics using a 2 × 2 factorial design. At the global level, females with ASD exhibited significantly higher cluster coefficient and local efficiency than female TCs, while no significant difference was observed between males with ASD and male TCs. Meanwhile, the neurotypical sex differences in cluster coefficient and local efficiency observed in TCs were not present in ASD. At the nodal level, ASD exhibited abnormal nodal centrality in the left middle temporal gyrus.

STDCformer: Spatial-temporal dual-path cross-attention model for fMRI-based autism spectrum disorder identification

Resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive neuroimaging technique widely utilized in the research of Autism Spectrum Disorder (ASD), providing preliminary insights into the potential biological mechanisms underlying ASD. Deep learning techniques have demonstrated significant potential in the analysis of rs-fMRI. However, accurately distinguishing between healthy control group and ASD has been a longstanding challenge. In this regard, this work proposes a model featuring a dual-path cross-attention framework for spatial and temporal patterns, named STDCformer, aiming to enhance the accuracy of ASD identification. STDCformer can preserve both temporal-specific patterns and spatial-specific patterns while explicitly interacting spatiotemporal information in depth. The embedding layer of the STDCformer embeds temporal and spatial patterns in dual paths. For the temporal path, we introduce a perturbation positional encoding to improve the issue of signal misalignment caused by individual differences. For the spatial path, we propose a correlation metric based on Gramian angular field similarity to establish a more specific whole-brain functional network. Subsequently, we interleave the query and key vectors of dual paths to interact spatial and temporal information. We further propose integrating the dual-path attention into a tensor that retains spatiotemporal dimensions and utilizing 2D convolution for feed-forward processing. Our attention layer allows the model to represent spatiotemporal correlations of signals at multiple scales to alleviate issues of information distortion and loss. Our STDCformer demonstrates competitive results compared to state-of-the-art methods on the ABIDE dataset. Additionally, we conducted interpretative analyses of the model to preliminarily discuss the potential physiological mechanisms of ASD. This work once again demonstrates the potential of deep learning technology in identifying ASD and developing neuroimaging biomarkers for ASD.

Adoption of deep learning-based magnetic resonance image information diagnosis in brain function network analysis of Parkinson’s disease patients with end-of-dose wearing-off

Objectivethis study was to analyze the brain functional network of end-of-dose wearing-off (EODWO) in patients with Parkinson’s disease (PD) using a convolutional neural network (CNN)-based functional magnetic resonance imaging (fMRI) data classification model. Methodsone hundred PD patients were recruited and assigned to control (Ctrl) group (39 cases without EODWO) and experimental (Exp) group (61 cases with EODWO). The data classification model based on a CNN was employed to assist the analysis of the changes in brain functional network structure in the two groups. The CNN-based fMRI data classification model was primarily based on a CNN architecture, with improvements made to the initialization of convolutional kernel parameters. Firstly, a structure based on restricted Boltzmann machine (RBM) was constructed, followed by the initialization of convolutional kernel parameters. Subsequently, the model underwent training. Utilizing the data analysis module within the GRETNA toolbox, extracted feature sets were analyzed, including local measures such as betweenness centrality (BC) and degree centrality (DC), as well as global measures such as global efficiency (Eg) and local efficiency (Eloc). Resultsas sparsity increased, there was a gradual upward trend observed in Eg; however, the values of Eg in both brain functional networks remained relatively stable within the range of 0.2–0.5. The Eg value of the Ctrl group’s whole-brain functional network was 0.17 ± 0.02, while that of the Exp group’s whole-brain functional network was 0.17 ± 0.03, with no significant difference between them (P>0.05). The functional DC value of the superior frontal gyrus in the Exp group (8.71 ± 2.56) was significantly lower than that of the Ctrl group (13.32 ± 3.22), whereas the functional DC value of the anterior cingulate gyrus in the Exp group (19.33 ± 4.78) was significantly higher than that of the Ctrl group (15.21 ± 4.02) (P<0.05). There was no significant correlation observed between the functional DC value and levodopa or dopamine agonist therapy (DDT) in the Exp group, whereas the Ctrl group exhibited a significant positive correlation. Conclusionanalysis conducted via a CNN-based fMRI data classification model revealed a correlation between the occurrence of EODWO in PD patients and functional impairments in the left precuneus. Additionally, the occurrence of EODWO may potentially diminish the plasticity of the central prefrontal dopamine.

Local and global effects of sedation in resting-state fMRI: a randomized, placebo-controlled comparison between etifoxine and alprazolam.

TSPO ligands are promising alternatives to benzodiazepines in the treatment of anxiety, as they display less pronounced side effects such as sedation, cognitive impairment, tolerance development and abuse potential. In a randomized double-blind repeated-measures study we compare a benzodiazepine (alprazolam) to a TSPO ligand (etifoxine) by assessing side effects and acquiring resting-state fMRI data from 34 healthy participants after 5 days of taking alprazolam, etifoxine or a placebo. To study the effects of the pharmacological interventions in fMRI in detail and across different scales, we combine in our study complementary analysis strategies related to whole-brain functional network connectivity, local connectivity analysis expressed in regional homogeneity, fluctuations in low-frequency BOLD amplitudes and coherency of independent resting-state networks. Participants reported considerable adverse effects such as fatigue, sleepiness and concentration impairments, related to the administration of alprazolam compared to placebo. In resting-state fMRI we found a significant decrease in functional connection density, network efficiency and a decrease in the networks rich-club coefficient related to alprazolam. While observing a general decrease in regional homogeneity in high-level brain networks in the alprazolam condition, we simultaneously could detect an increase in regional homogeneity and resting-state network coherence in low-level sensory regions. Further we found a general increase in the low-frequency compartment of the BOLD signal. In the etifoxine condition, participants did not report any significant side effects compared to the placebo, and we did not observe any corresponding modulations in our fMRI metrics. Our results are consistent with the idea that sedation globally disconnects low-level functional networks, but simultaneously increases their within-connectivity. Further, our results point towards the potential of TSPO ligands in the treatment of anxiety and depression.

Rich-club organization of whole-brain spatio-temporal multilayer functional connectivity networks

ObjectiveIn this work, we propose a novel method for constructing whole-brain spatio-temporal multilayer functional connectivity networks (FCNs) and four innovative rich-club metrics.MethodsSpatio-temporal multilayer FCNs achieve a high-order representation of the spatio-temporal dynamic characteristics of brain networks by combining the sliding time window method with graph theory and hypergraph theory. The four proposed rich-club scales are based on the dynamic changes in rich-club node identity, providing a parameterized description of the topological dynamic characteristics of brain networks from both temporal and spatial perspectives. The proposed method was validated in three independent differential analysis experiments: male–female gender difference analysis, analysis of abnormality in patients with autism spectrum disorders (ASD), and individual difference analysis.ResultsThe proposed method yielded results consistent with previous relevant studies and revealed some innovative findings. For instance, the dynamic topological characteristics of specific white matter regions effectively reflected individual differences. The increased abnormality in internal functional connectivity within the basal ganglia may be a contributing factor to the occurrence of repetitive or restrictive behaviors in ASD patients.ConclusionThe proposed methodology provides an efficacious approach for constructing whole-brain spatio-temporal multilayer FCNs and conducting analysis of their dynamic topological structures. The dynamic topological characteristics of spatio-temporal multilayer FCNs may offer new insights into physiological variations and pathological abnormalities in neuroscience.

Brain functional network changes in patients with juvenile myoclonic epilepsy: a study based on graph theory and Granger causality analysis.

Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have shown that the brain networks are disrupted in adolescent patients with juvenile myoclonic epilepsy (JME). However, previous studies have mainly focused on investigating brain connectivity disruptions from the perspective of static functional connections, overlooking the dynamic causal characteristics between brain network connections. In our study involving 37 JME patients and 35 Healthy Controls (HC), we utilized rs-fMRI to construct whole-brain functional connectivity network. By applying graph theory, we delved into the altered topological structures of the brain functional connectivity network in JME patients and identified abnormal regions as key regions of interest (ROIs). A novel aspect of our research was the application of a combined approach using the sliding window technique and Granger causality analysis (GCA). This method allowed us to delve into the dynamic causal relationships between these ROIs and uncover the intricate patterns of dynamic effective connectivity (DEC) that pervade various brain functional networks. Graph theory analysis revealed significant deviations in JME patients, characterized by abnormal increases or decreases in metrics such as nodal betweenness centrality, degree centrality, and efficiency. These findings underscore the presence of widespread disruptions in the topological features of the brain. Further, clustering analysis of the time series data from abnormal brain regions distinguished two distinct states indicative of DEC patterns: a state of strong connectivity at a lower frequency (State 1) and a state of weak connectivity at a higher frequency (State 2). Notably, both states were associated with connectivity abnormalities across different ROIs, suggesting the disruption of local properties within the brain functional connectivity network and the existence of widespread multi-functional brain functional networks damage in JME patients. Our findings elucidate significant disruptions in the local properties of whole-brain functional connectivity network in patients with JME, revealing causal impairments across multiple functional networks. These findings collectively suggest that JME is a generalized epilepsy with localized abnormalities. Such insights highlight the intricate network dysfunctions characteristic of JME, thereby enriching our understanding of its pathophysiological features.

Modular organization of functional brain networks in patients with degenerative cervical myelopathy

Previous studies have indicated that brain functional plasticity and reorganization in patients with degenerative cervical myelopathy (DCM). However, the effects of cervical cord compression on the functional integration and separation between and/or within modules remain unclear. This study aimed to address these questions using graph theory. Functional MRI was conducted on 46 DCM patients and 35 healthy controls (HCs). The intra- and inter-modular connectivity properties of the whole-brain functional network and nodal topological properties were then calculated using theoretical graph analysis. The difference in categorical variables between groups was compared using a chi-squared test, while that between continuous variables was evaluated using a two-sample t-test. Correlation analysis was conducted between modular connectivity properties and clinical parameters. Modules interaction analyses showed that the DCM group had significantly greater inter-module connections than the HCs group (DMN-FPN: t = 2.38, p = 0.02); inversely, the DCM group had significantly lower intra-module connections than the HCs group (SMN: t = − 2.13, p = 0.036). Compared to HCs, DCM patients exhibited higher nodal topological properties in the default-mode network and frontal–parietal network. In contrast, DCM patients exhibited lower nodal topological properties in the sensorimotor network. The Japanese Orthopedic Association (JOA) score was positively correlated with inter-module connections (r = 0.330, FDR p = 0.029) but not correlated with intra-module connections. This study reported alterations in modular connections and nodal centralities in DCM patients. Decreased nodal topological properties and intra-modular connection in the sensory-motor regions may indicate sensory-motor dysfunction. Additionally, increased nodal topological properties and inter-modular connection in the default mode network and frontal-parietal network may serve as a compensatory mechanism for sensory-motor dysfunction in DCM patients. This could provide an implicative neural basis to better understand alterations in brain networks and the patterns of changes in brain plasticity in DCM patients.

Evaluating the Effect of Alzheimer's Disease-Related Biomarker Change in Corticobasal Syndrome and Progressive Supranuclear Palsy.

To evaluate the effect of Alzheimer's disease (AD) -related biomarker change on clinical features, brain atrophy and functional connectivity of patients with corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP). Data from patients with a clinical diagnosis of CBS, PSP, and AD and healthy controls were obtained from the 4-R-Tauopathy Neuroimaging Initiative 1 and 2, the Alzheimer's Disease Neuroimaging Initiative, and a local cohort from the Toronto Western Hospital. Patients with CBS and PSP were divided into AD-positive (CBS/PSP-AD) and AD-negative (CBS/PSP-noAD) groups based on fluid biomarkers and amyloid PET scans. Cognitive, motor, and depression scores; AD fluid biomarkers (cerebrospinal p-tau, t-tau, and amyloid-beta, and plasma ptau-217); and neuroimaging data (amyloid PET, MRI and fMRI) were collected. Clinical features, whole-brain gray matter volume and functional networks connectivity were compared across groups. Data were analyzed from 87 CBS/PSP-noAD and 23 CBS/PSP-AD, 18 AD, and 30 healthy controls. CBS/PSP-noAD showed worse performance in comparison to CBS/PSP-AD in the PSPRS [mean(SD): 34.8(15.8) vs 23.3(11.6)] and the UPDRS scores [mean(SD): 34.2(17.0) vs 21.8(13.3)]. CBS/PSP-AD demonstrated atrophy in AD signature areas and brainstem, while CBS/PSP-noAD patients displayed atrophy in frontal and temporal areas, globus pallidus, and brainstem compared to healthy controls. The default mode network showed greatest disconnection in CBS/PSP-AD compared with CBS/PSP-no AD and controls. The thalamic network connectivity was most affected in CBS/PSP-noAD. AD biomarker positivity may modulate the clinical presentation of CBS/PSP, with evidence of distinctive structural and functional brain changes associated with the AD pathology/co-pathology. ANN NEUROL 2024;96:99-109.

Whole-brain dynamics across the menstrual cycle: the role of hormonal fluctuations and age in healthy women

Recent neuroimaging research suggests that female sex hormone fluctuations modulate brain activity. Nevertheless, how brain network dynamics change across the female menstrual cycle remains largely unknown. Here, we investigated the dynamical complexity underlying three menstrual cycle phases (i.e., early follicular, pre-ovulatory, and mid-luteal) in 60 healthy naturally-cycling women scanned using resting-state fMRI. Our results revealed that the pre-ovulatory phase exhibited the highest dynamical complexity (variability over time) across the whole-brain functional network compared to the early follicular and mid-luteal phases, while the early follicular showed the lowest. Furthermore, we found that large-scale resting-state networks reconfigure along menstrual cycle phases. Multilevel mixed-effects models revealed age-related changes in the whole-brain, control, and dorsal attention networks, while estradiol and progesterone influenced the whole-brain, DMN, limbic, dorsal attention, somatomotor, and subcortical networks. Overall, these findings evidence that age and ovarian hormones modulate brain network dynamics along the menstrual cycle.

The brain entropy dynamics in resting state.

As a novel measure for irregularity and complexity of the spontaneous fluctuations of brain activities, brain entropy (BEN) has attracted much attention in resting-state functional magnetic resonance imaging (rs-fMRI) studies during the last decade. Previous studies have shown its associations with cognitive and mental functions. While most previous research assumes BEN is approximately stationary during scan sessions, the brain, even at its resting state, is a highly dynamic system. Such dynamics could be characterized by a series of reoccurring whole-brain patterns related to cognitive and mental processes. The present study aims to explore the time-varying feature of BEN and its potential links with general cognitive ability. We adopted a sliding window approach to derive the dynamical brain entropy (dBEN) of the whole-brain functional networks from the HCP (Human Connectome Project) rs-fMRI dataset that includes 812 young healthy adults. The dBEN was further clustered into 4 reoccurring BEN states by the k-means clustering method. The fraction window (FW) and mean dwell time (MDT) of one BEN state, characterized by the extremely low overall BEN, were found to be negatively correlated with general cognitive abilities (i.e., cognitive flexibility, inhibitory control, and processing speed). Another BEN state, characterized by intermediate overall BEN and low within-state BEN located in DMN, ECN, and part of SAN, its FW, and MDT were positively correlated with the above cognitive abilities. The results of our study advance our understanding of the underlying mechanism of BEN dynamics and provide a potential framework for future investigations in clinical populations.

Temporal and topological properties of dynamic networks reflect disability in patients with neuromyelitis optica spectrum disorders

Approximately 36% of patients with neuromyelitis optica spectrum disorders (NMOSD) suffer from severe visual and motor disability (blindness or light perception or unable to walk) with abnormalities of whole-brain functional networks. However, it remains unclear how whole-brain functional networks and their dynamic properties are related to clinical disability in patients with NMOSD. Our study recruited 30 NMOSD patients (37.70 ± 11.99 years) and 45 healthy controls (HC, 41.84 ± 11.23 years). The independent component analysis, sliding-window approach and graph theory analysis were used to explore the static strength, time-varying and topological properties of large-scale functional networks and their associations with disability in NMOSD. Compared to HC, NMOSD patients showed significant alterations in dynamic networks rather than static networks. Specifically, NMOSD patients showed increased occurrence (fractional occupancy; P < 0.001) and more dwell times of the low-connectivity state (P < 0.001) with fewer transitions (P = 0.028) between states than HC, and higher fractional occupancy, increased dwell times of the low-connectivity state and lower transitions were related to more severe disability. Moreover, NMOSD patients exhibited altered small-worldness, decreased degree centrality and reduced clustering coefficients of hub nodes in dynamic networks, related to clinical disability. NMOSD patients exhibited higher occurrence and more dwell time in low-connectivity states, along with fewer transitions between states and decreased topological organizations, revealing the disrupted communication and coordination among brain networks over time. Our findings could provide new perspective to help us better understand the neuropathological mechanism of the clinical disability in NMOSD.

Uncovering brain functional connectivity disruption patterns of lung cancer-related pain.

Pain is a pervasive symptom in lung cancer patients during the onset of the disease. This study aims to investigate the connectivity disruption patterns of the whole-brain functional network in lung cancer patients with cancer pain (CP+). We constructed individual whole-brain, region of interest (ROI)-level functional connectivity (FC) networks for 50 CP+ patients, 34 lung cancer patients without pain-related complaints (CP-), and 31 matched healthy controls (HC). Then, a ROI-based FC analysis was used to determine the disruptions of FC among the three groups. The relationships between aberrant FCs and clinical parameters were also characterized. The ROI-based FC analysis demonstrated that hypo-connectivity was present both in CP+ and CP- patients compared to HC, which were particularly clustered in the somatomotor and ventral attention, frontoparietal control, and default mode modules. Notably, compared to CP- patients, CP+ patients had hyper-connectivity in several brain regions mainly distributed in the somatomotor and visual modules, suggesting these abnormal FC patterns may be significant for cancer pain. Moreover, CP+ patients also showed increased intramodular and intermodular connectivity strength of the functional network, which could be replicated in cancer stage IV and lung adenocarcinoma. Finally, abnormal FCs within the prefrontal cortex and somatomotor cortex were positively correlated with pain intensity and pain duration, respectively. These findings suggested that lung cancer patients with cancer pain had disrupted connectivity in the intrinsic brain functional network, which may be the underlying neuroimaging mechanisms.

A Method to Estimate Longitudinal Change Patterns in Functional Network Connectivity of the Developing Brain Relevant to Psychiatric Problems, Cognition, and Age.

Aim: To develop an approach to evaluate multiple overlapping brain functional change patterns (FCPs) in functional network connectivity (FNC) and apply to study developmental changes in brain function. Introduction: FNC, the network analog of functional connectivity (FC), is commonly used to capture the intrinsic functional relationships among brain networks. Ongoing research on longitudinal changes of intrinsic FC across whole-brain functional networks has proven useful for characterizing age-related changes, but to date, there has been little focus on capturing multivariate patterns of FNC change with brain development. Methods: In this article, we introduce a novel approach to evaluate multiple overlapping FCPs by utilizing FNC matrices. We computed FNC matrices from the large-scale Adolescent Brain Cognitive Development data using fully automated spatially constrained independent component analysis (ICA). We next evaluated changes in these patterns for a 2-year period using a second-level ICA on the FNC change maps. Results: Our proposed approach reveals several highly structured (modular) FCPs and significant results including strong brain FC between visual and sensorimotor domains that increase with age. We also find several FCPs that are associated with longitudinal changes of psychiatric problems, cognition, and age in the developing brain. Interestingly, FCP cross-covariation, reflecting coupling between maximally independent FCPs, also shows significant differences between upper and lower quartile loadings for longitudinal changes in age, psychiatric problems, and cognition scores, as well as baseline age in the developing brain. FCP patterns and results were also found to be highly reliable based on analysis of data collected in a separate scan session. Conclusion: In sum, our results show evidence of consistent multivariate patterns of functional change in emerging adolescents and the proposed approach provides a useful and general tool to evaluate covarying patterns of whole-brain functional changes in longitudinal data. Impact statement In this article, we introduce a novel approach utilizing functional network connectivity (FNC) matrices to estimate multiple overlapping brain functional change patterns (FCPs). The findings demonstrate several well-structured FCPs that exhibit significant changes for a 2-year period, particularly in the functional connectivity between the visual and sensorimotor domains. In addition, we discover several FCPs that are associated with psychopathology, cognition, and age. Finally, our proposed approach for studying age-related FCPs represents a pioneering method that provides a valuable tool for assessing interconnected patterns of whole-brain functional changes in longitudinal data and may be useful to study change over time with applicability to many other areas, including the study of longitudinal changes within diagnostic groups, treatment effects, aging effects, and more.

Altered whole-brain functional network in patients with frontal low-grade gliomas: a resting-state functional MRI study.

Gliomas are the most common primary brain tumor. Currently, topological alterations of whole-brain functional network caused by gliomas are not fully understood. The work here clarified the topological reorganization of the functional network in patients with unilateral frontal low-grade gliomas (LGGs). A total of 45 patients with left frontal LGGs, 19 with right frontal LGGs, and 25 healthy controls (HCs) were enrolled. All the resting-state functional MRI (rs-fMRI) images of the subjects were preprocessed to construct the functional network matrix, which was used for graph theoretical analysis. A two-sample t-test was conducted to clarify the differences in global and nodal network metrics between patients and HCs. A network-based statistic approach was used to identify the altered specific pairs of regions in which functional connectivity in patients with LGGs. The local efficiency, clustering coefficient, characteristic path length, and normalized characteristic path length of patients with unilateral frontal LGGs were significantly lower than HCs, while there were no significant differences of global efficiency and small-worldness between patients and HCs. Compared with the HCs, betweenness centrality, degree centrality, and nodal efficiency of several brain nodes were changed significantly in patients. Around the tumor and its adjacent areas, the inter- and intra-hemispheric connections were significantly decreased in patients with left frontal LGGs. The patients with unilateral frontal LGGs have altered global and nodal network metrics and decreased inter- and intra-hemispheric connectivity. These topological alterations may be involved in functional impairment and compensation of patients.

Individual variability in functional connectivity of human auditory cortex.

Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.

Reorganization of intrinsic functional connectivity in early-stage Parkinson’s disease patients with probable REM sleep behavior disorder

REM sleep behavior disorder (RBD) symptoms in Parkinson’s disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

Transcriptional signatures of the whole-brain voxel-wise resting-state functional network centrality alterations in schizophrenia

Neuroimaging studies have revealed that patients with schizophrenia exhibit disrupted resting-state functional connectivity. However, the inconsistent findings across these studies have hindered our comprehensive understanding of the functional connectivity changes associated with schizophrenia, and the molecular mechanisms associated with these alterations remain largely unclear. A quantitative meta-analysis was first conducted on 21 datasets, involving 1057 patients and 1186 healthy controls, to examine disrupted resting-state functional connectivity in schizophrenia, as measured by whole-brain voxel-wise functional network centrality (FNC). Subsequently, partial least squares regression analysis was employed to investigate the relationship between FNC changes and gene expression profiles obtained from the Allen Human Brain Atlas database. Finally, gene enrichment analysis was performed to unveil the biological significance of the altered FNC-related genes. Compared with healthy controls, patients with schizophrenia show consistently increased FNC in the right inferior parietal cortex extending to the supramarginal gyrus, angular gyrus, bilateral medial prefrontal cortex, and right dorsolateral prefrontal cortex, while decreased FNC in the bilateral insula, bilateral postcentral gyrus, and right inferior temporal gyrus. Meta-regression analysis revealed that increased FNC in the right inferior parietal cortex was positively correlated with clinical score. In addition, these observed functional connectivity changes were found to be spatially associated with the brain-wide expression of specific genes, which were enriched in diverse biological pathways and cell types. These findings highlight the aberrant functional connectivity observed in schizophrenia and its potential molecular underpinnings, providing valuable insights into the neuropathology of dysconnectivity associated with this disorder.

Higher-order sensorimotor circuit of the whole-brain functional network involved in pruritus regulation in atopic dermatitis.

Little is known about the neural mechanisms underlying pruritus regulation in Atopic dermatitis (AD). To investigate the functional changes of the resting-state whole brain network of AD participants and the mechanisms by which they were involved in pruritus regulation. Based on the functional magnetic resonance imaging data from 19 AD participants and 37 healthy controls (HC), a graph-theoretical measure of degree centrality (DC) conjoined with a voxel-level seed-based functional connectivity (FC) method was used to identify abnormal higher-order nodes and the functionally relevant circuit in AD participants compared to healthy controls (HC). Of 64 participants screened, 19 AD participants (12M/7F, median [IQR] age, 27 [14] years) and 36 HCs (13M/23F, median [IQR] age, 20 [1] years) were enrolled. DC values of the left superior frontal gyrus (LSFG) increased in AD participants and exhibited a negative correlation with the SCORAD score (r = -0.561, p = 0.012) compared with HC. In the FC analysis with LSFG as the seed, FC values of several sensory and motor regions increased in AD participants, highly overlapping with the anatomical distribution of the inferior fronto-occipital fascicle (IFOF). AD participants with severe pruritus exhibited lower levels of DC (T = -2.316, p = 0.033) and FC between the LSFG and left insula (T = -2.203, p = 0.042) than those with mild-to- moderate pruritus. LSFG was involved in pruritus regulation in AD by forming a high-order sensorimotor circuit through the IFOF, a white matter fascicle that proved to provide multimodal integration in motor control and sensory information processing. These results offer more mechanism-guided treatment targets for severe pruritus in AD.