Hemisphere- and gender-related differences in small-world brain networks: A resting-state functional MRI study
Research Highlights
►We employed resting-state fMRI (R-fMRI) and graph theoretical approaches to investigate hemisphere- and gender-related differences in the topological organization of human brain functional networks. ►We found that compared with females, males have a higher normalized clustering coefficient in the right hemispheric network but a lower clustering coefficient in the left hemispheric network, suggesting a hemisphere–gender interaction. ►We observed significant hemisphere-related differences in the regional nodal characteristics in various brain regions, such as the frontal and occipital regions (leftward asymmetry) and the temporal regions (rightward asymmetry).
Introduction
The human brain is asymmetric in terms of structure and function (for a review, see Toga and Thompson, 2003). The structural asymmetries of the brain have been well-documented. For example, besides the well-known frontal (right > left) and occipital (left > right) petalias (Watkins et al., 2001, Lancaster et al., 2003, Narr et al., 2007), leftward volume asymmetries have been consistently observed in brain regions specialized for language (Good et al., 2001, Pujol et al., 2002). Functional asymmetries of the brain have been repeatedly reported to exist in a variety of functions such as language, motor, and visuospatial processing (for a review, see Toga and Thompson, 2003). It has been suggested that alterations of brain asymmetries are associated with behavior changes in normal aging (Kovalev et al., 2003, Bergerbest et al., 2009) and in various neuropsychiatric and neurological diseases such as schizophrenia (Bilder et al., 1999, Niznikiewicz et al., 2000, Sommer et al., 2001, Narr et al., 2001, Bleich-Cohen et al., 2009), stroke (Liepert et al., 2000, Tecchio et al., 2006a, Tecchio et al., 2006b, Tecchio et al., 2007) and dyslexia (Leonard et al., 2001, Heim et al., 2003, Leonard and Eckert, 2008).
Some aspects of brain asymmetries also interact with gender. Research in gender-related differences in brain asymmetries began several decades ago. Kulynych et al. (1994) reported that males have a greater structural asymmetry of the plenum temporal than females. Hiscock et al., 1994, Hiscock et al., 1995 demonstrated that the male brain is more functionally lateralized or asymmetric in visual and auditory areas than the female brain. Shaywitz et al. (1995) observed that phonological processing aroused activation in the left inferior frontal gyrus (IFG) in males, but the bilateral IFG was activated in females. Closely related to these results, gender differences have also been demonstrated in behaviors. Statistically, males perform better in right-lateralized visuospatial perception processing, whereas females have advantages in the left-lateralized language processing (Hamilton, 2008). The gender differences in brain asymmetries have been suggested as the underlying origin of gender differences in lateralized behaviors (Kimura, 1999).
Despite the advances in brain asymmetry research, however, little is known about whether there are differences in the topological organization of brain networks between the hemispheres and whether those differences are related to gender. Graph theoretical analysis provides a powerful tool to characterize the topological organization of complex networks, and it has recently been applied to the study of human brain networks in health and disease (for reviews, see Bullmore and Sporns, 2009, Bassett and Bullmore, 2009, He et al., 2009a, He and Evans, 2010). Using graph theoretical approaches, researchers have demonstrated that the structural and functional networks of the human brain constructed by a variety of neuroimaging modalities (e.g., structural MRI, functional MRI, and diffusion MRI) have non-trivial topological attributes such as the small-world property (high clustering and short path lengths linking different nodes [Watts and Strogatz, 1998]) (Salvador et al., 2005, Achard et al., 2006, Hagmann et al., 2007, He et al., 2007), high network efficiency at a low wiring cost (Achard et al., 2006, He et al., 2009b), and highly connected network hubs (Achard et al., 2006, He et al., 2007, Bassett et al., 2008, Hagmann et al., 2008, Gong et al., 2009a, He et al., 2009c). It is noteworthy that almost all of these previous studies of brain networks focused on whole-brain level graphic analyses. To date only one study examined hemisphere-related differences in the topological organization of structural brain networks in right-handed subjects using diffusion-weighted MRI tractography; it was found that the right hemisphere is more efficient and interconnected than the left hemisphere (Iturria-Medina et al., in press). However, no study has reported hemisphere-related differences in the topological organization of brain functional networks. Moreover, very little is known about whether the topological organization is associated with gender.
Here, we utilized resting-state functional MRI (R-fMRI) to investigate hemisphere- and gender-related differences in the organizational patterns of functional networks in the human brain. R-fMRI has recently attracted considerable attention as a novel, non-invasive way to measure intrinsic or spontaneous activity in the brain (Biswal et al., 1995; for reviews, see Fox and Raichle, 2007, Zhang and Raichle, 2010). Advances in graph theoretical analysis of R-fMRI data have allowed us to map the topological organization of brain functional networks under normal and pathological conditions (for reviews, see Bullmore and Sporns, 2009, He et al., 2009a, Bassett and Bullmore, 2009, He and Evans, 2010, Wang et al., 2010). In this study, we sought to determine whether there are small-world attributes and high network efficiency within each hemisphere and whether these topological properties show hemisphere- or gender-related differences. To address these issues, we acquired R-fMRI data of 86 young, healthy, right-handed adults, and parcellated the brain into 90 cortical and subcortical regions according to a prior brain atlas (Tzourio-Mazoyer et al., 2002). Then we constructed brain functional networks by thresholding temporal correlations of spontaneous activity between any pairs of brain areas within each hemisphere and calculated the global and regional nodal parameters, as well as the asymmetries of these parameters. Finally, hemisphere- and gender-related differences in these network parameters were statistically evaluated.
Section snippets
Subjects
Data were selected from a large sample resting-state fMRI dataset of our group, which has been publicly released in the “1000 Functional Connectomes” Project (http://www.nitrc.org/projects/fcon_1000/) (Biswal et al., 2010). We selected 86 young healthy volunteers (48 females: 20.8 ± 1.6 years old, range 18–25; and 38 males: 20.7 ± 1.7 years old, range 17–25) with head motion less than 2.0 mm displacement in any of the x, y, or z directions or 2.0° of any angular motion throughout the resting-state
Small-worldness and efficiency
In this study we constructed functional networks based on separate hemispheres rather than on the whole brain. We found that over the sparsity range of 10%~46%, the γ were larger than 1 (i.e., the Cp for these networks were larger than those of their matched random networks) and the λ were nearly 1 (i.e., the Lp for these networks were comparable to those of their matched random networks) for four subgroups (2 hemispheres × 2 genders) of functional networks (Fig. 1). When evaluating the global
Discussion
In this study we utilized R-fMRI and graph theoretical approaches to investigate the hemisphere- and gender-related differences in brain functional networks. The main findings are as follows: 1) the hemispheric networks exhibited small-world attributes (high clustering and short paths); 2) males tended to be more locally efficient in their right hemispheric networks, but females tended to be more locally efficient in their left hemispheric networks; 3) significant hemisphere-related differences
Conclusion
To summarize, we evaluated the hemisphere- and gender-related differences in human brain functional networks based on R-fMRI. We observed that males and females have quite different asymmetric patterns in their network local efficiencies and suggest that these differences are closely related to the behavioral differences. Most regions that exhibited significant hemisphere-related differences in the present study have formerly been observed to be structurally or functionally asymmetric. Overall
Acknowledgments
The authors thank Dr. Yufeng Zang for kindly providing the dataset. This work was supported by the National Natural Science Foundation of China (grant nos. 30870667 and 30800249), Beijing Natural Science Foundation (grant no. 7102090), and the Scientific Research Foundation for the Returned Overseas Chinese Scholars (State Education Ministry, YH).
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