Structural connectivity in schizophrenia and its impact on the dynamics of spontaneous functional networks

Abstract

The neuropathology of schizophrenia remains unclear. Some insight has come from modern/nneuroimaging techniques, which offer an unparalleled opportunity to explore/nin vivo/nthe structure/nand function of the brain. Using functional magnetic resonance imaging, it has been found that the/nlarge-scale resting-state functional connectivity (rsFC) in schizophrenia — measured as the/ntemporal correlations of the blood-oxygen-level-dependent (BOLD) signal — exhibit altered/nnetwork topology, with lower small-world index. The origin of these rsFC alterations and link with/nthe underlying structural connectivity remain unclear. In this work, we used a computational model/nof spontaneous large-scale brain activity to explore the role of the structural connectivity in the/nlarge-scale dynamics of the brain in health and schizophrenia. The structural connectomes from 15/nadolescent patients with early-onset schizophrenia and 15 age- and gender-matched controls were/nbuilt from diffusion tensor imaging data to detect the white matter tracts between 90 brain areas./nBrain areas, simulated using a reduced dynamic mean-field model, receive excitatory input from/nother areas in proportion to the number of fibre tracts between them. The simulated mean field/nactivity was transformed into BOLD signal, and the properties of the simulated functional networks/nwere analyzed. Our results suggest that the functional alterations observed in schizophrenia are not/ndirectly linked to alterations in the structural topology. Instead, subtly randomized and less/nsmall-world functional networks appear when the brain operates with lower global coupling, which/nshifts the dynamics from the optimal healthy regime.

The research reported herein was supported by the ERC/nAdvanced Grant DYSTRUCTURE (No. 295129), by the/nFET Flagship Human Brain Project, by the Spanish Research/nProject SAF2010-16085, by the CONSOLIDER-INGENIO/n2010 Programme CSD2007-00012, by the Brain Network/nRecovery Group through the James S. McDonnell/nFoundation, by the FP7-ICT BrainScales, and by the/nTrygFonden Charitable Foundation. Funding for the scan-/nning was supported by the MRC (G0500092).