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

Neuroimage. 2008 Nov 15;43(3):528-39. doi: 10.1016/j.neuroimage.2008.08.010. Epub 2008 Aug 22.


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.

MeSH terms

  • Adult
  • Brain / physiology*
  • Brain Mapping / methods*
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / physiology*