Functional Network Hubs Research Articles

Machine learning analysis reveals abnormal functional network hubs in the primary angle-closure glaucoma patients.

BackgroundPrimary angle-closure glaucoma (PACG) is a serious and irreversible blinding eye disease. Growing studies demonstrated that PACG patients were accompanied by vision and vision-related brain region changes. However, whether the whole-brain functional network hub changes occur in PACG patients remains unknown.PurposeThe purpose of the study was to investigate the brain function network hub changes in PACG patients using the voxel-wise degree centrality (DC) method.Materials and methodsThirty-one PACG patients (21 male and 10 female) and 31 healthy controls (HCs) (21 male and 10 female) closely matched in age, sex, and education were enrolled in the study. The DC method was applied to investigate the brain function network hub changes in PACG patients. Moreover, the support vector machine (SVM) method was applied to distinguish PACG patients from HC patients.ResultsCompared with HC, PACG patients had significantly higher DC values in the right fusiform, left middle temporal gyrus, and left cerebelum_4_5. Meanwhile, PACG patients had significantly lower DC values in the right calcarine, right postcentral gyrus, left precuneus gyrus, and left postcentral gyrus. Furthermore, the SVM classification reaches a total accuracy of 72.58%, and the ROC curve of the SVM classifier has an AUC value of 0.85 (r = 0.25).ConclusionOur results showed that PACG patients showed widespread brain functional network hub dysfunction relative to the visual network, auditory network, default mode network, and cerebellum network, which might shed new light on the neural mechanism of optic atrophy in PACG patients.

Altered voxel-wise degree centrality associated with patients with comitant exotropia.

Objective of the study is to investigate the altered intrinsic functional hubs in patients with comitant exotropia (CE) using the voxel-wise degree centrality (DC) analysis method. A total of 28 CE patients and 28 healthy controls (HCs) similarly matched in sex, age, and education level were recruited in this study. All subjects underwent a resting-state functional MRI scan, the voxel-wise DC method was applied to evaluate brain network hubs alterations in CE patients. Then, the DC maps between two groups were chosen to be classification features to distinguish patients with CE from HCs based on the support vector machine (SVM) model. The algorithm performance was evaluated by a permutation test. Compared with HCs, CE patients exhibited significant enhanced DC value in the left cerebelum 8 and the right cerebelum 3; and remarkably decreased DC value in the right precentral gyrus, right anterior cingulated, and paracingulate gyri (two-tailed, voxel level: P < 0.01; GRF correction, cluster level: P < 0.05). However, no relationship was found between the observed average DC of the different brain regions and the clinical features ( P > 0.05). In addition, the SVM model showed an accuracy of 83.93% to clarify CE patients from HCs using the DC maps as a classification feature. CE patients displayed altered functional network hubs in multiple brain areas associated with cognition and motor control, and the DC variability could classify patients from HCs with high accuracy. These findings may assist to understand the neuropathological mechanism for the disease.

Cognitive impairment after focal brain lesions is better predicted by damage to structural than functional network hubs

Hubs are highly connected brain regions important for coordinating processing in brain networks. It is unclear, however, which measures of network "hubness" are most useful in identifying brain regions critical to human cognition. We tested how closely two measures of hubness-edge density and participation coefficient, derived from white and gray matter, respectively-were associated with general cognitive impairment after brain damage in two large cohorts of patients with focal brain lesions (N = 402 and 102, respectively) using cognitive tests spanning multiple cognitive domains. Lesions disrupting white matter regions with high edge density were associated with cognitive impairment, whereas lesions damaging gray matter regions with high participation coefficient had a weaker, less consistent association with cognitive outcomes. Similar results were observed with six other gray matter hubness measures. This suggests that damage to densely connected white matter regions is more cognitively impairing than similar damage to gray matter hubs, helping to explain interindividual differences in cognitive outcomes after brain damage.

Abnormal intrinsic functional network hubs in diabetic retinopathy patients.

However, whether the whole-brain functional network hub changes occur in diabetic retinopathy patients remains unknown. The purpose of the study was to investigate the function network centrality and connectivity changes in diabetic retinopathy patients using the voxel-wise degree centrality method. Thirty-four diabetic retinopathy patients (18 male and 16 female) and 38 healthy controls (18 male and 20 female) closely matched in age, sex, and education were enrolled in the study. Graph theory-based network analysis was performed to investigate the degree centrality between two groups. Compared with healthy controls, diabetic retinopathy patients had significantly higher degree centrality values in the pons and bilateral caudate and had significantly lower degree centrality values in the left lingual and right lingual, and right angular/middle occipital gyrus (MOG). Moreover, diabetic retinopathy patients exhibited increased functional connectivity between the bilateral lingual and right cerebellum lobe and right fusiform/bilateral caudate and increased functional connectivity between the right angular/MOG and bilateral anterior cingulum and right cuneus/bilateral precuneus and increased functional connectivity between the bilateral caudate and right lingual and right superior occipital gyrus. In contrast, diabetic retinopathy patients showed decreased functional connectivity between bilateral lingual and left lingual and right lingual and left superior occipital gyrus and decreased functional connectivity between the angular/MOG and right inferior occipital gyrus/right fusiform and left MOG/inferior occipital gyrus and decreased functional connectivity between the bilateral caudate and bilateral cerebellum crus1. Our results highlight that reorganization of the hierarchy of the cortical connectivity network related to visual network.

Abnormal intrinsic functional network hubs and connectivity following peripheral visual loss because of inherited retinal degeneration.

Previous neuroimaging studies have shown that the long-term effects of peripheral vision loss lead to functional and morphological reorganization in visual cortices. However, it has not been determined whether whole-brain functional network centrality changes occur during peripheral vision loss. This study aimed to investigate functional network centrality and connectivity changes in individuals with peripheral vision loss because of retinitis pigmentosa (RP) by using voxel-wise degree centrality (DC) and seed-based resting-state functional connectivity (rsFC) methods. In total, 30 RP patients (18 men and 12 women, mean age: 38.77±14.44 years) and 30 healthy controls (HCs) (18 men and 12 women, mean age: 34.57±10.70 years) matched for age, sex, cognition, education, and visual expertise underwent resting-state magnetic resonance imaging scans. Graph theory-based network analysis was carried out to investigate DC between the two groups. A seed-based rsFC analysis was then carried out to further reveal the abnormal functional connectivity of the altered DC brain region. Pearson's correlation was used to analyze the relationships of DC and rsFC index with the clinical variables in RP patients: visual function (best-corrected visual acuity and visual field, VF) and optical coherence tomography testing (mean retinal nerve fiber layer). Compared with HCs, RP patients had significantly lower DC values in the bilateral cuneus/calcarine/precuneus (CUN/CAL/PreCUN) [Brodmann's area (BA) 17/18/19/30/31]. In addition, RP patients showed decreased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral lingual/cuneus/calcarine (LIG/CUN/CAL) (BA 18/19/30) and the bilateral postcentral gyrus/superior parietal lobule (BA 3/5/7/40). In contrast, RP patients showed increased rsFC index, relative to that of HCs, from bilateral CUN/CAL/PreCUN to bilateral thalamus/caudate (voxel-level P<0.01; Gaussian random-field correction, cluster-level P<0.05). Moreover, the course of RP showed a negative correlation with the mean DC values of the bilateral CUN/CAL/PreCUN (r=-0.480; P=0.007) and the mean FC values of the bilateral LIG/CUN/CAL (r=-0.484; P=0.007); the mean DC values of the bilateral CUN/CAL/PreCUN in RP showed a negative correlation with the right eye VF (r=-0.411; P=0.024) and left eye VF (r=-0.426; P=0.019). Our results showed that RP patients showed abnormal function network hubs in various brain regions related to visual, thalamocortical, and sensorimotor networks; these might reflect impaired top-down modulations, visual imagery, and visuomotor coordination in RP patients. Moreover, the DC index can be used as a biomarker to indicate the severity of visual loss in RP patients.

Changed hub and functional connectivity patterns of the posterior fusiform gyrus in chess experts.

The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, the effects of long-term practice on functional network hubs in chess experts are largely undefined. Here, we investigated whether alterations of hubs can be detected in chess experts using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods. We first mapped the whole-brain voxel-wise functional connectivity and calculated the functional connectivity strength (FCS) map in each of the 28 chess players and 27 gender- and age-matched healthy novice players. Whole-brain resting-state functional connectivity analyses for the changed hub areas were conducted to further elucidate the corresponding changes of functional connectivity patterns in chess players. The hub analysis revealed increased FCS in the right posterior fusiform gyrus of the chess players, which was supported by analyses of this area's regional homogeneity (ReHo), amplitude of low frequency fluctuations (ALFF), and fractional amplitude of low frequency fluctuations (fALFF). The following functional connectivity analyses revealed increased functional connectivities between the right posterior fusiform gyrus and the visuospatial attention and motor networks in chess players. These findings demonstrate that cognitive expertise has a positive influence on the functions of the brain regions associated with the chess expertise and that increased functional connections might in turn facilitate within and between networks communication for expert behavior to get superior performance.

The effects of cognitive behavioral therapy on resting-state functional brain network in drug-naive patients with obsessive-compulsive disorder.

ObjectivesAlthough cognitive behavioral therapy (CBT) is an effective treatment for obsessive–compulsive disorder (OCD), the treatment mechanisms remain poorly understood. This study aimed to investigate the effects of CBT on changes in the intrinsic whole‐brain functional network of OCD patients.Materials and MethodsTwenty drug‐naive and noncomorbid OCD patients were recruited, and resting‐state functional magnetic resonance imaging was performed before and after 12 weeks of CBT. Moreover, 20 healthy controls were scanned twice with a 12‐week interval. A graph‐theory degree centrality (DC) approach and functional connectivity method were used to analyze the whole‐brain functional network hub and connectivity changes in OCD patients before and after CBT treatment.ResultsA significant group × time interaction on DC was found in the left dorsolateral prefrontal cortex (DLPFC); the DC in the left DLPFC was significantly reduced after CBT treatment. Resting‐state functional connectivity (RSFC) between the left DLPFC and right orbitofrontal cortex was increased in the OCD patients at baseline, and normalized after CBT treatment. RSFC changes between the left DLPFC and default mode network (DMN) positively correlated with changes in clinical symptoms in OCD patients.ConclusionsThese findings suggest that CBT can modulate changes in intrinsic functional network hubs in the cortico–striato–thalamo‐cortical circuit in OCD patients. Cognitive control network and DMN connectivity may be a potential imaging biomarker for evaluating CBT treatment for OCD.

Mapping the changed hubs and corresponding functional connectivity in idiopathic restless legs syndrome

ObjectiveThe hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of leg discomfort symptoms in restless legs syndrome (RLS) patients remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in RLS. MethodsFirst, we constructed the whole-brain voxelwise functional connectivity and calculated a functional connectivity strength (FCS) map in each of 16 drug-naive idiopathic RLS patients and 26 gender- and age-matched healthy control (HC) subjects. Next, a two-sample t test was applied to compare the FCS maps between HC and RLS patients, and to identify significant changes in FCS in RLS patients. To further elucidate the corresponding changes in the functional connectivity patterns of the aberrant hubs in RLS patients, whole-brain resting-state functional connectivity analyses for the hub areas were performed. ResultsThe hub analysis revealed decreased FCS in the cuneus, fusiform gyrus, paracentral lobe, and precuneus, and increased FCS in the superior frontal gyrus and thalamus in idiopathic drug-naive RLS patients. Subsequent functional connectivity analyses revealed decreased functional connectivity in sensorimotor and visual processing networks and increased functional connectivity in the affective cognitive network and cerebellar–thalamic circuit. Furthermore, the mean FCS value in the superior frontal gyrus was significantly correlated with Hamilton Anxiety Rating Scale scores in RLS patients, and the mean FCS value in the fusiform gyrus was significantly correlated with Hamilton Depression Rating Scale scores. ConclusionsThese findings may provide novel insight into the pathophysiology of RLS.

Mapping the structural and functional network architecture of the medial temporal lobe using 7T MRI.

Medial temporal lobe (MTL) subregions play integral roles in memory function and are differentially affected in various neurological and psychiatric disorders. The ability to structurally and functionally characterize these subregions may be important to understanding MTL physiology and diagnosing diseases involving the MTL. In this study, we characterized network architecture of the MTL in healthy subjects (n = 31) using both resting state functional MRI and MTL-focused T2-weighted structural MRI at 7 tesla. Ten MTL subregions per hemisphere, including hippocampal subfields and cortical regions of the parahippocampal gyrus, were segmented for each subject using a multi-atlas algorithm. Both structural covariance matrices from correlations of subregion volumes across subjects, and functional connectivity matrices from correlations between subregion BOLD time series were generated. We found a moderate structural and strong functional inter-hemispheric symmetry. Several bilateral hippocampal subregions (CA1, dentate gyrus, and subiculum) emerged as functional network hubs. We also observed that the structural and functional networks naturally separated into two modules closely corresponding to (a) bilateral hippocampal formations, and (b) bilateral extra-hippocampal structures. Finally, we found a significant correlation in structural and functional connectivity (r = 0.25). Our findings represent a comprehensive analysis of network topology of the MTL at the subregion level. We share our data, methods, and findings as a reference for imaging methods and disease-based research.

Changed Hub and Corresponding Functional Connectivity of Subgenual Anterior Cingulate Cortex in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD.

Altered cortical hubs in functional brain networks in amyotrophic lateral sclerosis.

Cortical hubs are highly connected nodes in functional brain networks that play vital roles in the efficient transfer of information across brain regions. Although altered functional connectivity has been found in amyotrophic lateral sclerosis (ALS), the changing pattern in functional network hubs in ALS remains unknown. In this study, we applied a voxel-wise method to investigate the changing pattern of cortical hubs in ALS. Through resting-state fMRI, we constructed whole-brain voxel-wise functional networks by measuring the temporal correlations of each pair of brain voxels and identified hubs using the graph theory method. Specifically, a functional connectivity strength (FCS) map was derived from the data on 20 patients with ALS and 20 healthy controls. The brain regions with high FCS values were regarded as functional network hubs. Functional hubs were found mainly in the bilateral precuneus, parietal cortex, medial prefrontal cortex, and in several visual regions and temporal areas in both groups. Within the hub regions, the ALS patients exhibited higher FCS in the prefrontal cortex compared with the healthy controls. The FCS value in the significantly abnormal hub regions was correlated with clinical variables. Results indicated the presence of altered cortical hubs in the ALS patients and could therefore shed light on the pathophysiology mechanisms underlying ALS.

Disrupted cortical hubs in functional brain networks in social anxiety disorder

ObjectiveThe network hubs, characterized by the large number of connections to other regions, play important roles in the proper and effective transfer of information. Previous functional neuroimaging studies have demonstrated that patients with social anxiety disorder (SAD) have aberrant functional connectivity. The changing pattern in functional network hubs in SAD, however, remains incompletely understood. MethodsTwenty SAD patients and 20 matched healthy controls were recruited. Resting-state fMRI data were obtained using a gradient-recalled echo-planar imaging sequence. Whole-brain voxel-wise functional networks were constructed by measuring the temporal correlations of each pair of brain voxels and then hubs were identified by using the graph theory method. Specifically, a functional connectivity strength (FCS) map was computed in each subject and the regions with higher FCS value were considered as functional network hubs. ResultsCompared with healthy controls, SAD patients showed significantly decreased FCS in the bilateral precuneus and significantly increased FCS in the right fusiform gyrus. Furthermore, a significantly negative correlation was observed between the FCS value in the precuneus and the illness duration. ConclusionThe present study demonstrated for the first time that disrupted cortical hubs existed in patients with SAD during resting state. SignificanceThese findings may provide novel insight into understanding of pathophysiological mechanisms underlying SAD.

Gray matter and intrinsic network changes in the posterior cingulate cortex after selective serotonin reuptake inhibitor intake

Preclinical studies have demonstrated that serotonin (5-HT) challenge changes neuronal circuitries and microarchitecture. However, evidence in human subjects is missing. Pharmacologic magnetic resonance imaging (phMRI) applying selective 5-HT reuptake inhibitors (SSRIs) and high-resolution structural and functional brain assessment is able to demonstrate the impact of 5-HT challenge on neuronal network morphology and functional activity. To determine how SSRIs induce changes in gray matter and neuronal activity, we conducted a longitudinal study using citalopram and escitalopram. Seventeen healthy subjects completed a structural and functional phMRI study with randomized, cross-over, placebo-controlled, double-blind design. Significant gray matter increases were observed (among other regions) in the posterior cingulate cortex (PCC) and the ventral precuneus after SSRI intake of 10days, while decreases were observed within the pre- and postcentral gyri (all P<0.05, family-wise error [FWE] corrected). Furthermore, enhanced resting functional connectivity (rFC) within the ventral precuneus and PCC was associated with gray matter increases in the PCC (all FWE Pcorr<0.05). Corroborating these results, whole-brain connectivity density, measuring the brain's functional network hubs, was significantly increased after SSRI-intake in the ventral precuneus and PCC (all FWE Pcorr<0.05). Short-term administration of SSRIs changes gray matter structures, consistent with previous work reporting enhancement of neuroplasticity by serotonergic neurotransmission. Furthermore, increased gray matter in the PCC is associated with increased functional connectivity in one of the brain's metabolically most active regions. Our novel findings provide convergent evidence for dynamic alterations of brain structure and function associated with SSRI pharmacotherapy.