Organization Of Whole-brain Functional Networks Research Articles

Functional disruptions of the brain network in low back pain: a graph-theoretical study.

The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches.

Abnormal intrinsic brain functional network dynamics in patients with cervical spondylotic myelopathy

The specific topological changes in dynamic functional networks and their role in cervical spondylotic myelopathy (CSM) brain function reorganization remain unclear. This study aimed to investigate the dynamic functional connection (dFC) of patients with CSM, focusing on the temporal characteristics of the functional connection state patterns and the variability of network topological organization. Eighty-eight patients with CSM and 77 healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. We applied the sliding time window analysis method and K-means clustering analysis to capture the dFC variability patterns of the two groups. The graph-theoretical approach was used to investigate the variance in the topological organization of whole-brain functional networks. All participants showed four types of dynamic functional connection states. The mean dwell time in state 2 was significantly different between the two groups. Particularly, the mean dwell time in state 2 was significantly longer in the CSM group than in the healthy control group. Among the four states, switching of relative brain networks mainly included the executive control network (ECN), salience network (SN), default mode network (DMN), language network (LN), visual network (VN), auditory network (AN), precuneus network (PN), and sensorimotor network (SMN). Additionally, the topological properties of the dynamic network were variable in patients with CSM. Dynamic functional connection states may offer new insights into intrinsic functional activities in CSM brain networks. The variance of topological organization may suggest instability of the brain networks in patients with CSM.

Improved Functional Organization in Patients With Primary Insomnia After Individually-Targeted Transcranial Magnetic Stimulation.

Primary insomnia (PI) is among the most prevalent sleep-related disorders and has a far-reaching impact on daytime functioning. Repetitive transcranial magnetic stimulation (rTMS) has drawn attention because of its effectiveness and safety. The purpose of the current study was to detect changes in the topological organization of whole-brain functional networks and to determine their associations with the clinical treatment effects of rTMS. Resting-state functional magnetic resonance imaging (rsfMRI) data from 32 patients with PI were collected and compared with findings from 32 age- and gender-matched healthy controls (HCs). The patients were treated with Stanford accelerated intelligent neuromodulation therapy, which is a recently validated neuroscience-informed accelerated intermittent theta-burst stimulation protocol. Graph theoretical analysis was used to construct functional connectivity matrices and to extract the attribute features of small-world networks in insomnia. Scores on the Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the associations between these clinical characteristics and functional metrics, were the primary outcomes. At baseline, the patients with PI showed inefficient small-world property and aberrant functional segregation and functional integration compared with the HCs. These properties showed renormalization after individualized rTMS treatment. Furthermore, low functional connectivity between the right insula and left medial frontal gyrus correlated with improvement in ISI scores. We highlight functional network dysfunctions in PI patients and provide evidence into the pathophysiological mechanisms involved and the possible mode of action of rTMS.

Brain network topology and future development of freezing of gait in Parkinson's disease: a longitudinal study.

Freezing of gait (FOG) is a common disabling gait disturbance in Parkinson's disease (PD). The objectives of this study were to explore alterations in the topological organization of whole-brain functional networks in patients with PD who will develop FOG. We recruited 20 patients with PD who developed FOG (PD-FOGt) during a 5-year follow-up period, 20 patients with PD who did not developed FOG (PD-FOGn) within the follow-up period, and 20 healthy control subjects. Using graph theory approaches, we performed a comparative analysis of the topological organization of whole-brain functional networks among the groups, and further explored their potential relationships with latency to develop FOG. At baseline, the global topological properties of functional brain networks in PD-FOGt and PD-FOGn showed no abnormalities. Additionally, regarding regional topological properties, compared with PD-FOGn patients, PD-FOGt patients exhibited decreased nodal centrality in the left middle frontal gyrus (MFG). Although there were no significant differences compared with PD-FOGn patients, the PD-FOGt group exhibited the lowest nodal centrality values in the frontal cortex (left gyrus rectus), and visual cortex (bilateral inferior occipital gyrus and left fusiform gyrus), and the highest nodal centrality values in the cerebellum (vermis_6) among the three groups. However, no relationship was found between the nodal centrality in above brain regions and latency to develop FOG. This study demonstrates the disrupted regional topological organization might contribute to the future development of FOG in PD patients, especially associated with damage to the left MFG.

Disrupted functional brain network topology in Parkinson’s disease patients with freezing of gait

BackgroundFreezing of gait (FOG) is a common and debilitating gait disturbance in patients with Parkinson’s disease (PD), but the potential mechanisms are still unclear. This study aimed to explore alterations in the topological organization of whole-brain functional networks in PD patients with FOG. MethodsWe recruited 75 patients with PD, 37 patients with FOG and 38 patients without FOG, to undergo resting-state functional magnetic resonance imaging (fMRI). The whole-brain functional networks were constructed, and the topological properties at three (global, nodal, and connectional) levels were analyzed using graph theory approaches. ResultsCompared with patients without FOG, patients with FOG exhibited altered global topological properties (a significant decrease in the normalized clustering coefficient and small-worldness), implying a shift toward randomization in their functional brain networks. At the node and connectional levels, patients with FOG showed increased nodal centralities and functional connectivity in the sensorimotor network, frontoparietal network, visual network, subcortical and limbic regions, and decreased nodal centralities in the frontoparietal network and the cerebellum. Furthermore, the altered nodal centralities in the right hippocampus (HIP) were positively correlated with FOG severity. ConclusionsThis study suggests that FOG in PD is associated with disrupted topological organization of whole-brain functional networks, involving dysfunction of the multiple networks.

Reconfiguration of functional brain networks and metabolic cost converge during task performance.

The ability to solve cognitive tasks depends upon adaptive changes in the organization of whole-brain functional networks. However, the link between task-induced network reconfigurations and their underlying energy demands is poorly understood. We address this by multimodal network analyses integrating functional and molecular neuroimaging acquired concurrently during a complex cognitive task. Task engagement elicited a marked increase in the association between glucose consumption and functional brain network reorganization. This convergence between metabolic and neural processes was specific to feedforward connections linking the visual and dorsal attention networks, in accordance with task requirements of visuo-spatial reasoning. Further increases in cognitive load above initial task engagement did not affect the relationship between metabolism and network reorganization but only modulated existing interactions. Our findings show how the upregulation of key computational mechanisms to support cognitive performance unveils the complex, interdependent changes in neural metabolism and neuro-vascular responses.

A preliminary study of disrupted functional network in individuals with Internet gaming disorder: Evidence from the comparison with recreational game users

Although online gaming may lead to Internet gaming disorder (IGD), most players are recreational game users (RGU) who do not develop IGD. So far, the topological organization of whole-brain functional networks in IGD remains poorly understood. The inclusion of RGU as a control group could minimize the potential effects of gaming experience and gaming-related cue familiarity on the neural characteristics of IGD subjects. In the present study, we applied graph theoretical analysis to preliminarily explore the topological organization of intrinsic functional brain networks in IGD. 61 IGD participants and 61 matched RGU participants were recruited to undergo a resting-state functional magnetic resonance imaging scan. The whole-brain functional networks were constructed by thresholding partial correlation matrices of 90 brain regions, and graph-based approaches were applied to analysis their topological attributes, including small-world, efficiency, and nodal centralities. Both of IGD and RGU groups showed efficient and economic small-world topology in brain functional networks. Although there was no significant group difference in global properties, subjects with IGD as compared to those with RGU showed increased nodal centralities in the reward, craving, emotional memory and sensory-motor processing regions. These results suggest that the functional network dysfunction, characterizing by heightened incentive motivation and sensory-motor coordination, may provide a new perspective for understanding the neural characteristics underlying IGD.

Disrupted Functional Network Topology in Children and Adolescents With Post-traumatic Stress Disorder.

Neuroimaging studies in children and adolescents with post-traumatic stress disorder (PTSD) have focused on abnormal structures and the functionality of a few individual brain regions. However, little is known about alterations to the topological organization of whole-brain functional networks in children and adolescents with PTSD. To this end, we investigated the topological properties of brain functional networks derived from resting-state functional magnetic resonance imaging (r-fMRI) in patients suffering from PTSD. The r-fMRI data were obtained from 10 PTSD patients and 16 trauma-exposed non-PTSD subjects. Graph theory analysis was used to investigate the topological properties of the two groups, and group comparisons of topological metrics were performed using nonparametric permutation tests. Both the PTSD and non-PTSD groups showed the functional brain network to have a small-world architecture. However, the PTSD group exhibited alterations in global properties characterized by higher global efficiency, lower clustering coefficient, and characteristic path length, implying a shift toward randomization of the networks. The PTSD group also showed increased nodal centralities, predominately in the left middle frontal gyrus, caudate nucleus, and hippocampus, and decreased nodal centralities in the left anterior cingulate cortex, left paracentral lobule, and bilateral thalami. In addition, the clustering coefficient and nodal betweenness of the left paracentral lobule were found to be negatively and positively correlated with the re-experiencing and hyper-arousal symptoms of PTSD respectively. The findings of disrupted topological properties of functional brain networks may help to better understand the pathophysiological mechanism of PTSD in children and adolescents.

Convergence and Divergence of Brain Network Dysfunction in Deficit and Non-deficit Schizophrenia.

Deficit schizophrenia (DS), characterized by primary and enduring negative symptoms, has been considered as a pathophysiologically distinct schizophrenic subgroup. Neuroimaging characteristics of DS, especially functional brain network architecture, remain largely unknown. Resting-state functional magnetic resonance imaging and graph theory approaches were employed to investigate the topological organization of whole-brain functional networks of 114 male participants including 33 DS, 41 non-deficit schizophrenia (NDS) and 40 healthy controls (HCs). At the whole-brain level, both the NDS and DS group exhibited lower local efficiency (Eloc) than the HC group, implying the reduction of local specialization of brain information processing (reduced functional segregation). The DS, but not NDS group, exhibited enhanced parallel information transfer (enhanced functional integration) as determined by smaller characteristic path length (Lp) and higher global efficiency (Eglob). The Lp and Eglob presented significant correlations with Brief Psychiatric Rating Scale (BPRS) total score in the DS group. At the nodal level, both the NDS and DS groups showed higher functional connectivity in the inferior frontal gyrus and hippocampus, and lower connectivity in the visual areas and striatum than the controls. The DS group exhibited higher nodal connectivity in the right inferior temporal gyrus than the NDS and HC group. The diminished expression of Scale for the Assessment of Negative Symptoms (SANS) subfactors negatively correlated with nodal connectivity of right putamen, while asociality/amotivation positively correlated with right hippocampus across whole patients. We highlighted the convergence and divergence of brain functional network dysfunctions in patients with DS and NDS, which provides crucial insights into pathophysiological mechanisms of the 2 schizophrenic subtypes.

Functional connectome assessed using graph theory in drug-naive Parkinson's disease.

The purpose of this study is to investigate whether the topological organization of whole-brain functional network is disrupted in patients with Parkinson's disease (PD). We employed resting-state functional MRI (R-fMRI) and graph theory to investigate the topological organization of the functional connectome in 47 early-stage drug-naïve PD patients and 47 healthy control subjects. Correlations between network properties and clinical variables were tested. Both the PD and control groups showed small-world architecture in brain functional networks. However, the PD patients had lower clustering coefficient and local efficiency relative to control subjects, indicating disrupted topologic organization and a shift toward randomization in their functional brain network. At node and connection level, reduced node centralities and connectivity strength were found mainly in temporal-occipital regions and also in sensorimotor regions of PD patients. In PD patients, altered global network properties correlated with cognitive function, while motor impairment was correlated with local connection changes. This study demonstrates a disruption of whole-brain topological organization of the functional brain networks in early-stage drug-naïve PD patients and this disruption might contribute to preclinical changes in cognitive process in these patients.

Apolipoprotein E ε4 modulates functional brain connectome in Alzheimer's disease.

The apolipoprotein E (APOE) ɛ4 allele is a well-established genetic risk factor for Alzheimer's disease (AD). Recent research has demonstrated an APOE ɛ4-mediated modulation of intrinsic functional brain networks in cognitively normal individuals. However, it remains largely unknown whether and how APOE ɛ4 affects the brain's functional network architecture in patients with AD. Using resting-state functional MRI and graph-theory approaches, we systematically investigated the topological organization of whole-brain functional networks in 16 APOE ɛ4 carriers and 26 matched noncarriers with AD at three levels: global whole-brain, intermediate module, and regional node/connection. Neuropsychological analysis showed that the APOE ɛ4 carriers performed worse on delayed memory but better on a late item generation of a verbal fluency task (associated with executive function) than noncarriers. Whole-brain graph analyses revealed that APOE ɛ4 significantly disrupted whole-brain topological organization as characterized by (i) reduced parallel information transformation efficiency; (ii) decreased intramodular connectivity within the posterior default mode network (pDMN) and intermodular connectivity of the pDMN and executive control network (ECN) with other neuroanatomical systems; and (iii) impaired functional hubs and their rich-club connectivities that primarily involve the pDMN, ECN, and sensorimotor systems. Further simulation analysis indicated that these altered connectivity profiles of the pDMN and ECN largely accounted for the abnormal global network topology. Finally, the changes in network topology exhibited significant correlations with the patients' cognitive performances. Together, our findings suggest that the APOE genotype modulates large-scale brain networks in AD and shed new light on the gene-connectome interaction in this disease.

Disrupted Topological Organization in Whole-Brain Functional Networks of Heroin-Dependent Individuals: A Resting-State fMRI Study

Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

Exploring the brains of Baduk (Go) experts: gray matter morphometry, resting-state functional connectivity, and graph theoretical analysis

One major characteristic of experts is intuitive judgment, which is an automatic process whereby patterns stored in memory through long-term training are recognized. Indeed, long-term training may influence brain structure and function. A recent study revealed that chess experts at rest showed differences in structure and functional connectivity (FC) in the head of caudate, which is associated with rapid best next-move generation. However, less is known about the structure and function of the brains of Baduk experts (BEs) compared with those of experts in other strategy games. Therefore, we performed voxel-based morphometry (VBM) and FC analyses in BEs to investigate structural brain differences and to clarify the influence of these differences on functional interactions. We also conducted graph theoretical analysis (GTA) to explore the topological organization of whole-brain functional networks. Compared to novices, BEs exhibited decreased and increased gray matter volume (GMV) in the amygdala and nucleus accumbens (NA), respectively. We also found increased FC between the amygdala and medial orbitofrontal cortex (mOFC) and decreased FC between the NA and medial prefrontal cortex (mPFC). Further GTA revealed differences in measures of the integration of the network and in the regional nodal characteristics of various brain regions activated during Baduk. This study provides evidence for structural and functional differences as well as altered topological organization of the whole-brain functional networks in BEs. Our findings also offer novel suggestions about the cognitive mechanisms behind Baduk expertise, which involves intuitive decision-making mediated by somatic marker circuitry and visuospatial processing.