Computational and Mathematical Methods in Medicine
Volume 2012 (2012), Article ID 615709, 15 pages
Research Article

Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

1Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline Medicines Research Centre, via Fleming 4, 37135 Verona, Italy
2Translational Medicine, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
3Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Piazza San Silvestro 12, 56127 Pisa, Italy
4Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche e Dipartimento di Fisica, Università “Sapienza”, Piazzale A. Moro 2, 00185 Rome, Italy
5Linkalab, Complex Systems Computational Laboratory, 09129 Cagliari, Italy

Received 27 March 2012; Revised 21 May 2012; Accepted 25 May 2012

Academic Editor: Fabrizio De Vico Fallani

Copyright © 2012 Adam J. Schwarz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine) to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.