Hemispheric Networks Research Articles

Development and emergence of functional network asymmetry in 3- to 9-month-old infants

Cerebral asymmetry is a cardinal feature of functional organization in the human brain and an important biomarker of successful brain development. Studies have demonstrated that functional network asymmetries across hemispheres undergo significant development through childhood and adulthood. However, it remains unknown when such asymmetries of functional networks emerge and how they develop across the early months of infancy. To address this issue, we used multiple-channel functional near-infrared spectroscopy (fNIRS) imaging to record spontaneous brain activity in 66 healthy infants aged 3–9 months. We then adopted a graph-theory analysis approach to quantify the topological characteristics of hemispheric networks in each participant. Our results showed that infants aged 3 to 6 months old exhibited leftward asymmetries in local network efficiency, while infants aged 6 to 9 months old exhibited leftward asymmetries in global network efficiency. Importantly, the degree of leftward asymmetry in global network efficiency was increased over development from 3 to 9 months old, with a faster increase in the left hemisphere than in the right hemisphere. At the regional level, 3- to 6-month-old infants exhibited leftward asymmetries in functional connectivity strength (FCS) in the temporal cortex, whereas the FCS asymmetries were located in the temporal, frontal, and occipital cortexes for 6- to 9-month-old infants. Furthermore, the 6- to 9-month-old infants also exhibited leftward asymmetries in nodal efficiency around the frontal cortex. These combined findings demonstrate that functional asymmetric organization has emerged in early infancy, which could lay a critical foundation for the development of brain functions (e.g., language and social cognition functions) later in life.

Brain Functional Connectivity in Low- and High-Grade Gliomas: Differences in Network Dynamics Associated with Tumor Grade and Location.

Simple SummaryThis study investigates brain network modifications related to tumor grade and location using resting-state functional magnetic resonance imaging and graph theory. We demonstrated that low-grade gliomas (LGG) lead to increased efficiency of the surrounding functional network, while high-grade gliomas (HGG) seem to disrupt brain connectivity in remote areas. Tumor location appears to influence the pattern of reorganization, including the recruitment of the contralateral hemisphere. Overall, LGG may show more favorable connectivity changes than HGG. If confirmed by future studies, the ability to discriminate between ‘maladaptive’ (detrimental) and ‘adaptive’ (beneficial) functional reorganization based on graph theory metrics may provide biomarkers to select patients for surgery and monitor recovery. Brain tumors lead to modifications of brain networks. Graph theory plays an important role in clarifying the principles of brain connectivity. Our objective was to investigate network modifications related to tumor grade and location using resting-state functional magnetic resonance imaging (fMRI) and graph theory. We retrospectively studied 30 low-grade (LGG), 30 high-grade (HGG) left-hemispheric glioma patients and 20 healthy controls (HC) with rs-fMRI. Tumor location was labeled as: frontal, temporal, parietal, insular or occipital. We collected patients’ clinical data from records. We analyzed whole-brain and hemispheric networks in all patients and HC. Subsequently, we studied lobar networks in subgroups of patients divided by tumor location. Seven graph-theoretical metrics were calculated (FDR p < 0.05). Connectograms were computed for significant nodes. The two-tailed Student t-test or Mann–Whitney U-test (p < 0.05) were used to compare graph metrics and clinical data. The hemispheric network analysis showed increased ipsilateral connectivity for LGG (global efficiency p = 0.03) and decreased contralateral connectivity for HGG (degree/cost p = 0.028). Frontal and temporal tumors showed bilateral modifications; parietal and insular tumors showed only local effects. Temporal tumors led to a bilateral decrease in all graph metrics. Tumor grade and location influence the pattern of network reorganization. LGG may show more favorable network changes than HGG, reflecting fewer clinical deficits.

Gender effects on the controllability of hemispheric white matter networks.

Male and female adults exhibited significant group differences in brain white matter (WM) asymmetry and WM network controllability. However, gender differences in controllability of hemispheric WM networks between males and females remain to be determined. Based on 1 principal atlas and 1 replication atlas, this work characterized the average controllability (AC) and modal controllability (MC) of hemispheric WM network based on 1 principal dataset and 2 replication datasets. All results showed that males had higher AC of left hemispheric networks than females. And significant hemispheric asymmetry was revealed in regional AC and MC. Furthermore, significant gender differences in the AC asymmetry were mainly found in regions lie in the frontoparietal network, and the MC asymmetry was found in regions involving auditory and emotion process. Finally, we found significant associations between regional controllability and cognitive features. Taken together, this work could provide a novel perspective for understanding gender differences in hemispheric WM asymmetry and cognitive function between males and females.

Network analysis shows decreased ipsilesional structural connectivity in glioma patients

Gliomas that infiltrate networks and systems, such as the motor system, often lead to substantial functional impairment in multiple systems. Network-based statistics (NBS) allow to assess local network differences and graph theoretical analyses enable investigation of global and local network properties. Here, we used network measures to characterize glioma-related decreases in structural connectivity by comparing the ipsi- with the contralesional hemispheres of patients and correlated findings with neurological assessment. We found that lesion location resulted in differential impairment of both short and long connectivity patterns. Network analysis showed reduced global and local efficiency in the ipsilesional hemisphere compared to the contralesional hemispheric networks, which reflect the impairment of information transfer across different regions of a network.

Elucidating the structural–functional connectome of language in glioma‐induced aphasia using nTMS and DTI

Glioma‐induced aphasia (GIA) is frequently observed in patients with newly diagnosed gliomas. Previous studies showed an impact of gliomas not only on local brain regions but also on the functionality and structure of brain networks. The current study used navigated transcranial magnetic stimulation (nTMS) to localize language‐related regions and to explore language function at the network level in combination with connectome analysis. Thirty glioma patients without aphasia (NA) and 30 patients with GIA were prospectively enrolled. Tumors were located in the vicinity of arcuate fasciculus‐related cortical and subcortical regions. The visualized ratio (VR) of each tract was calculated based on their respective fractional anisotropy (FA) and maximal FA. Using a thresholding method of each tract at 25% VR and 50% VR, DTI‐based tractography was performed to construct structural brain networks for graph‐based connectome analysis, containing functional data acquired by nTMS. The average degree of left hemispheric networks (M left) was higher in the NA group than in the GIA group for both VR thresholds. Differences of global and local efficiency between 25% and 50% VR thresholds were significantly lower in the NA group than in the GIA group. Aphasia levels correlated with connectome properties in M left and networks based on positive nTMS mapping regions (M pos). A more substantial relation to language performance was found in M pos and M left compared to the network of negative mapping regions (M neg). Gliomas causing deterioration of language are related to various cerebral networks. In NA patients, mainly M neg was impacted, while M pos was impacted in GIA patients.

The Allocation of Vertical Attention in Patients with End-Stage Renal Disease Receiving Dialysis.

Objectives: Alterations of spatial attention can have adverse effects, such a greater probability of accidents. Patients with end-stage renal disease (ESRD) receiving dialysis have stronger left-sided spatial attentional bias, suggesting that this disorder or treatment alters the brain networks that mediate spatial attention. The hemispheric networks that mediate the allocation of horizontal attention may also influence the allocation of vertical attention. However, the allocation of vertical spatial attention has not been studied in ESRD patients. Methods: Twenty-three ESRD patients receiving dialysis and 23 healthy right-handed controls performed line bisections using 24 vertical lines (24 cm long and 2 mm thick) aligned with the intersection of their midsagittal and coronal planes. Results: Hemodialyzed ESRD patients had a significantly greater upward bias than healthy controls. The magnitude of this bias was correlated with the duration of the kidney disease. Conclusions: The reason why upward attentional bias is increased in hemodialyzed ESRD patients is not known. Further research is needed to better understand the brain mechanism that might account for this bias, as well as its treatment. However, hemodialyzed ESRD patients and their families-caregivers should be made aware of this disorder to avoid accidents such as tripping.

The neural control of volitional vocal production-from speech to identity, from social meaning to song.

The networks of cortical and subcortical fields that contribute to speech production have benefitted from many years of detailed study, and have been used as a framework for human volitional vocal production more generally. In this article, I will argue that we need to consider speech production as an expression of the human voice in a more general sense. I will also argue that the neural control of the voice can and should be considered to be a flexible system, into which more right hemispheric networks are differentially recruited, based on the factors that are modulating vocal production. I will explore how this flexible network is recruited to express aspects of non-verbal information in the voice, such as identity and social traits. Finally, I will argue that we need to widen out the kinds of vocal behaviours that we explore, if we want to understand the neural underpinnings of the true range of sound-making capabilities of the human voice. This article is part of the theme issue 'Voice modulation: from origin and mechanism to social impact (Part II)'.

Structural connectivity changes in the motor execution network after stroke rehabilitation.

Background:Although quite a very few studies have tested structural connectivity changes following an intervention, it reflects only selected key brain regions in the motor network. Thus, the understanding of structural connectivity changes related to the motor recovery process remains unclear.Objective:This study investigated structural connectivity changes of the motor execution network following a combined intervention of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) and intensive occupational therapy (OT) after a stroke using graph theory approach.Methods:Fifty-six stroke patients underwent Fugl-Meyer Assessment (FMA), Wolf Motor Function Test-Functional Ability Scale (WMFT-FAS), diffusion tensor imaging (DTI), and T1 weighted imaging before and after the intervention. We examined graph theory measures related to twenty brain regions using structural connectomes.Results:The ipsilesional and contralesional hemisphere showed structural connectivity changes post-intervention after stroke. We found significantly increased regional centralities and nodal efficiency within the frontal pole and decreased degree centrality and nodal efficiency in the ipsilesional thalamus. Correlations were found between network measures and clinical assessments in the cuneus, postcentral gyrus, precentral gyrus, and putamen of the ipsilesional hemisphere. The contralesional areas such as the caudate, cerebellum, and frontal pole also showed significant correlations.Conclusions:This study was helpful to expand the understanding of structural connectivity changes in both hemispheric networks during the motor recovery process following LF-rTMS and intensive OT after stroke.

Hemispheric Asymmetry of Functional Brain Networks under Different Emotions Using EEG Data.

Despite many studies reporting hemispheric asymmetry in the representation and processing of emotions, the essence of the asymmetry remains controversial. Brain network analysis based on electroencephalography (EEG) is a useful biological method to study brain function. Here, EEG data were recorded while participants watched different emotional videos. According to the videos’ emotional categories, the data were divided into four categories: high arousal high valence (HAHV), low arousal high valence (LAHV), low arousal low valence (LALV) and high arousal low valence (HALV). The phase lag index as a connectivity index was calculated in theta (4–7 Hz), alpha (8–13 Hz), beta (14–30 Hz) and gamma (31–45 Hz) bands. Hemispheric networks were constructed for each trial, and graph theory was applied to quantify the hemispheric networks’ topological properties. Statistical analyses showed significant topological differences in the gamma band. The left hemispheric network showed significantly higher clustering coefficient (Cp), global efficiency (Eg) and local efficiency (Eloc) and lower characteristic path length (Lp) under HAHV emotion. The right hemispheric network showed significantly higher Cp and Eloc and lower Lp under HALV emotion. The results showed that the left hemisphere was dominant for HAHV emotion, while the right hemisphere was dominant for HALV emotion. The research revealed the relationship between emotion and hemispheric asymmetry from the perspective of brain networks.

Abnormalities in hemispheric lateralization of intra- and inter-hemispheric white matter connections in schizophrenia.

Hemispheric lateralization is a prominent feature of the human brain and is grounded into intra- and inter-hemispheric white matter (WM) connections. However, disruptions in hemispheric lateralization involving both intra- and inter-hemispheric WM connections in schizophrenia is still unclear. Hence, a quantitative measure of the hemispheric lateralization of intra- and inter-hemispheric WM connections could provide new insights into schizophrenia. This work performed diffusion tensor imaging on 50 patients and 58 matched healthy controls. Using graph theory, the global and nodal efficiencies were computed for both intra- and inter-hemispheric networks. We found that patients with schizophrenia showed significantly decrease in both global and nodal efficiency of hemispheric networks relative to healthy controls. Specially, deficits in intra-hemispheric integration and inter-hemispheric communication were revealed in frontal and temporal regions for schizophrenia. We also found disrupted hemispheric asymmetries in brain regions associated with emotion, memory, and visual processes for schizophrenia. Moreover, abnormal hemispheric asymmetry of nodal efficiency was significantly correlated with the symptom of the patients. Our finding indicated that the hemispheric WM lateralization of intra- and inter-hemispheric connections could serve as a potential imaging biomarker for schizophrenia.

Functional near-infrared spectroscopy evidence for the development of topological asymmetry between hemispheric brain networks from childhood to adulthood.

Cerebral asymmetry is considered an important marker of the successful development of the human brain. Recent studies have demonstrated topological asymmetries between structurally hemispheric networks in the human brain. However, it remains largely unknown whether and how the functionally topological asymmetries evolve from childhood to adulthood, a critical period that constitutes the primary peak of human brain and cognitive development. Here, we adopted resting-state functional near-infrared spectroscopy imaging data to construct hemispheric functional networks and then applied graph theory analysis to quantify the topological characteristics of the hemispheric networks. We found that the adult group exhibited consistent leftward hemispheric asymmetries in both global and local network efficiency, and the degree of leftward asymmetry in local network efficiency was significantly increased with development from childhood to adulthood. At the nodal level, the degree of leftward asymmetry in nodal efficiency, mainly involving the frontal, parietal-occipital junction, and occipital regions, increased with development. These developmental patterns of topological asymmetries suggest that the protracted maturation of functional segregation in the left hemisphere could underlie language development from childhood to adulthood and provide insight into the development of human brain functional networks.

Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional–structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.

Hemispheric Module-Specific Influence of the X Chromosome on White Matter Connectivity: Evidence from Girls with Turner Syndrome.

Turner syndrome (TS) is caused by the congenital absence of all or part of one of the X chromosomes in females, offering a valuable human "knockout model" to study the functioning patterns of the X chromosome in the human brain. Little is known about whether and how the loss of the X chromosome influences the brain structural wiring patterns in human. We acquired a multimodal MRI dataset and cognitive assessments from 22 girls with TS and 21 age-matched control girls to address these questions. Hemispheric white matter (WM) networks and modules were derived using refined diffusion MRI tractography. Statistical comparisons revealed a reduced topological efficiency of both hemispheric networks and bilateral parietal modules in TS girls. Specifically, the efficiency of right parietal module significantly mediated the effect of the X chromosome on working memory performance, indicating that X chromosome loss impairs working memory performance by disrupting this module. Additionally, TS girls showed structural and functional connectivity decoupling across specific within- and between-modular connections, predominantly in the right hemisphere. These findings provide novel insights into the functional pathways in the brain that are regulated by the X chromosome and highlight a module-specific genetic contribution to WM connectivity in the human brain.

The Abnormality of Topological Asymmetry in Hemispheric Brain Anatomical Networks in Bipolar Disorder.

Convergent evidences have demonstrated a variety of regional abnormalities of asymmetry in bipolar disorder (BD). However, little is known about the alterations in hemispheric topological asymmetries. In this study, we used diffusion tensor imaging to construct the hemispheric brain anatomical network of 49 patients with BD and 61 matched normal controls. Graph theory was then applied to quantify topological properties of the hemispheric networks. Although small-world properties were preserved in the hemispheric networks of BD, the degrees of the asymmetry in global efficiency, characteristic path length, and small-world property were significantly decreased. More changes in topological properties of the right hemisphere than those of left hemisphere were found in patients compared with normal controls. Consistent with such changes, the nodal efficiency in patients with BD also showed less rightward asymmetry mainly in the frontal, occipital, parietal, and temporal lobes. In contrast to leftward asymmetry, significant rightward asymmetry was found in supplementary motor area of BD, and attributed to more deficits in nodal efficiency of the left hemisphere. Finally, these asymmetry score of nodal efficiency in the inferior parietal lobule and rolandic operculum were significantly associated with symptom severity of BD. Our results suggested that abnormal hemispheric asymmetries in brain anatomical networks were associated with aberrant neurodevelopment, and providing insights into the potential neural biomarkers of BD by measuring the topological asymmetry in hemispheric brain anatomical networks.

Altered intra- and inter-hemispheric functional dysconnectivity in schizophrenia.

Despite convergent evidence suggesting that schizophrenia is a disorder of brain dysconnectivity, it remains unclear whether intra- or inter-hemispheric deficits or their combination underlie the dysconnection. This study examined the source of the functional dysconnection in schizophrenia. Resting-state fMRI was performed in 66 patients with schizophrenia and 73 matched healthy controls. Functional brain networks were constructed for each participant and further partitioned into intra- and inter-hemispheric connections. We examined how schizophrenia altered the intra-hemispheric topological properties and the inter-hemispheric nodal strength. Although several subcortical and cingulate regions exhibited hemispheric-independent aberrations of regional efficiency, the optimal small-world properties in the hemispheric networks and their lateralization were preserved in patients. A significant deficit in the inter-hemispheric connectivity was revealed in most of the hub regions, leading to an inter-hemispheric hypo-connectivity pattern in patients. These abnormal intra- and inter-hemispheric network organizations were associated with the clinical features of schizophrenia. The patients in the present study received different medications. These findings provide new insights into the nature of dysconnectivity in schizophrenia, highlighting the dissociable processes between the preserved intra-hemispheric network topology and altered inter-hemispheric functional connectivity.

Longitudinal fMRI study of language recovery after a left hemispheric ischemic stroke.

Recovery from stroke-induced aphasia is typically protracted and involves complex functional reorganization. The relative contributions of the lesioned and non-lesioned hemispheres to this process have been examined in several cross-sectional studies but longitudinal studies involving several time-points and large numbers of subjects are scarce. The aim of this study was to address the gaps in the literature by longitudinally studying the evolution of post-stroke lateralization and localization of language-related fMRI activation in the first year after single left hemispheric ischemic stroke. Seventeen patients with stroke-induced aphasia were enrolled to undergo detailed behavioral testing and fMRI at 2, 6, 12, 26, and 52 weeks post-stroke. Matched for age, handedness and sex participants were also enrolled to visualize canonical language regions. Behavioral results showed improvements over time for all but one of the behavioral scores (Semantic Fluency Test). FMRI results showed that the left temporal area participates in compensation for language deficits in the first year after stroke, that there is a correlation between behavioral improvement and the left cerebellar activation over time, and that there is a shift towards stronger frontal left-lateralization of the fMRI activation over the first year post-stroke. Temporary compensation observed in the initial phases of post-stroke recovery that involves the non-lesioned hemisphere may not be as important as previously postulated, since in this study the recovery was driven by activations in the left fronto-temporal regions. Language recovery after left hemispheric ischemic stroke is likely driven by the previously involved in language and attention left hemispheric networks.

Aberrant development of the asymmetry between hemispheric brain white matter networks in autism spectrum disorder

Atypical brain asymmetry/lateralization has long been hypothesized for autism spectrum disorder (ASD), and this model has been repeatedly supported by various neuroimaging studies. Recently, hemispheric network topologies have been found to be asymmetric, thereby providing a new avenue for investigating brain asymmetries under various conditions. To date, however, how network topological asymmetries are altered in ASD remains largely unexplored. To clarify this, the present study included ASD individuals from the newly released Autism Brain Imaging Data Exchange II database (58 right-handed male ASD individuals aged 5 to 26 years and 70 age- and IQ-matched typically developing (TD) individuals). Diffusion and structural magnetic resonance imaging were used to construct hemispheric white matter networks, and graph-theory approaches were applied to quantify topological efficiencies for hemispheric networks. Statistical analyses revealed a decreased rightward asymmetry of network efficiencies with increasing age in the TD group, but not in the ASD group. More specifically, the TD group did not exhibit an age-related increase in network efficiency in the right hemisphere, but the ASD group did. For the left hemisphere, no difference between the groups was observed for the developmental trajectory of network efficiencies. Intriguingly, within the ASD group, more severe restricted and repetitive behavior in ASD was found to be correlated with less rightward asymmetry of network local efficiency. These findings provide suggestive evidence of atypical network topological asymmetries and offer important insights into the abnormal development of ASD brains.

Asymmetry of Hemispheric Network Topology Reveals Dissociable Processes between Functional and Structural Brain Connectome in Community-Living Elders.

Human brain is structurally and functionally asymmetrical and the asymmetries of brain phenotypes have been shown to change in normal aging. Recent advances in graph theoretical analysis have showed topological lateralization between hemispheric networks in the human brain throughout the lifespan. Nevertheless, apparent discrepancies of hemispheric asymmetry were reported between the structural and functional brain networks, indicating the potentially complex asymmetry patterns between structural and functional networks in aging population. In this study, using multimodal neuroimaging (resting-state fMRI and structural diffusion tensor imaging), we investigated the characteristics of hemispheric network topology in 76 (male/female = 15/61, age = 70.08 ± 5.30 years) community-dwelling older adults. Hemispheric functional and structural brain networks were obtained for each participant. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that the optimal small-world properties were preserved in both structural and functional hemispheric networks in older adults. Moreover, a leftward asymmetry in both global and local levels were observed in structural brain networks in comparison with a symmetric pattern in functional brain network, suggesting a dissociable process of hemispheric asymmetry between structural and functional connectome in healthy older adults. Finally, the scores of hemispheric asymmetry in both structural and functional networks were associated with behavioral performance in various cognitive domains. Taken together, these findings provide new insights into the lateralized nature of multimodal brain connectivity, highlight the potentially complex relationship between structural and functional brain network alterations, and augment our understanding of asymmetric structural and functional specializations in normal aging.

Altered topology of structural brain networks in patients with Gilles de la Tourette syndrome

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by tics. Abnormal neuronal circuits in a wide-spread structural and functional network involved in planning, execution and control of motor functions are thought to represent the underlying pathology. We therefore studied changes of structural brain networks in 13 adult GTS patients reconstructed by diffusion tensor imaging and probabilistic tractography. Structural connectivity and network topology were characterized by graph theoretical measures and compared to 13 age-matched controls. In GTS patients, significantly reduced connectivity was detected in right hemispheric networks. These were furthermore characterized by significantly reduced local graph parameters (local clustering, efficiency and strength) indicating decreased structural segregation of local subnetworks. Contrasting these results, whole brain and right hemispheric networks of GTS patients showed significantly increased normalized global efficiency indicating an overall increase of structural integration among distributed areas. Higher global efficiency was associated with tic severity (R = 0.63, p = 0.022) suggesting the clinical relevance of altered network topology. Our findings reflect an imbalance between structural integration and segregation in right hemispheric structural connectome of patients with GTS. These changes might be related to an underlying pathology of impaired neuronal development, but could also indicate potential adaptive plasticity.

Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia

Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level.