Small-world and scale-free organization of voxel-based resting-state functional connectivity in the human brain

Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Department of Psychiatry, Utrecht, The Netherlands.
NeuroImage (Impact Factor: 6.36). 09/2008; 43(3):528-39. DOI: 10.1016/j.neuroimage.2008.08.010
Source: PubMed


The brain is a complex dynamic system of functionally connected regions. Graph theory has been successfully used to describe the organization of such dynamic systems. Recent resting-state fMRI studies have suggested that inter-regional functional connectivity shows a small-world topology, indicating an organization of the brain in highly clustered sub-networks, combined with a high level of global connectivity. In addition, a few studies have investigated a possible scale-free topology of the human brain, but the results of these studies have been inconclusive. These studies have mainly focused on inter-regional connectivity, representing the brain as a network of brain regions, requiring an arbitrary definition of such regions. However, using a voxel-wise approach allows for the model-free examination of both inter-regional as well as intra-regional connectivity and might reveal new information on network organization. Especially, a voxel-based study could give information about a possible scale-free organization of functional connectivity in the human brain. Resting-state 3 Tesla fMRI recordings of 28 healthy subjects were acquired and individual connectivity graphs were formed out of all cortical and sub-cortical voxels with connections reflecting inter-voxel functional connectivity. Graph characteristics from these connectivity networks were computed. The clustering-coefficient of these networks turned out to be much higher than the clustering-coefficient of comparable random graphs, together with a short average path length, indicating a small-world organization. Furthermore, the connectivity distribution of the number of inter-voxel connections followed a power-law scaling with an exponent close to 2, suggesting a scale-free network topology. Our findings suggest a combined small-world and scale-free organization of the functionally connected human brain. The results are interpreted as evidence for a highly efficient organization of the functionally connected brain, in which voxels are mostly connected with their direct neighbors forming clustered sub-networks, which are held together by a small number of highly connected hub-voxels that ensure a high level of overall connectivity.

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    • "These two metrics could also be unified as one metric, called small-worldness, i.e., σ=γ/λ. A real network is considered as small-world network if it meets the criteria: C≫C rand and L≈L rand , or σ>1 [18] "
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    • "A region-specific analysis of the lateral prefrontal cortex, part of the fronto-parietal network, found that its global connectivity predicted working memory performance and fluid intelligence (Cole et al., 2012). Two studies have reported an association between efficiency of global communication and intellectual performance, suggesting that individuals with higher intelligence have a more organized brain network overall (Van den Heuvel et al., 2008; Song et al., 2009). However, the relationships between brain functional connectivity and psychological measures such as intelligence are not fully defined. "
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