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

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.