ORIGINAL RESEARCH Increased cortico-subcortical functional connectivity in schizophrenia Degang Zhang & Lei Guo & Xintao Hu & Kaiming Li & Qun Zhao & Tianming Liu Published online: 15 October 2011 # Springer Science+Business Media, LLC 2011 Abstract It has been widely reported that structural and functional connectivities are disturbed in cortical networks in schizophrenia (SZ). However, much less is known about the structural and functional connectivities between cortical and subcortical regions in SZ. Here, diffusion tensor imaging (DTI) data was used to identify consistent cortico-subcortical structural connection patterns across SZ patients and controls, and thus 13 common cortical Regions of Interest (ROIs) were determined. DTI and resting state fMRI (R-fMRI) datasets were used to assess the structural and functional connectivities between the 13 cortical ROIs and 12 subcortical regions in 8 SZ patients and 10 normal controls. It was found that there are significantly increased functional connectivities for 7 cortico-subcortical connections between the 13 cortical ROIs and 12 subcortical regions. Among most of these connections, the functional connectivity strength was doubled in SZ in comparison to controls. The cortical ROIs with functional hyper-connectivities to subcortical regions are localized in frontal and parietal lobes. However, no significant difference in the structural connectivity between these cortical and subcortical regions was found between SZ and controls. Additional analysis results showed 4 significantly increased and 2 significantly decreased cortico-cortical connections. Our study results suggest the functional hyper-connectivity between cortical and subcortical regions, adding further evidence to litera- ture findings that SZ is a disorder of connectivity between components of large-scale brain networks. The result of either increased or decreased functional connectivities among cortical ROIs exhibits the complex pattern of disturbance of brain networks in SZ. Keywords Resting state fMRI . Diffusion tensor imaging (DTI) . Subcortical . Connectivity . Schizophrenia Introduction Schizophrenia (SZ) has been widely conceived as a disorder of connectivity between components of large- scale brain networks (Lynall et al. 2010; Bassett et al. 2008). It was widely reported that functional connectivity strength in SZ was significantly decreased, whereas diversity of functional connections was increased (Lynall et al. 2010; Bassett et al. 2008; Meyer-Lindenberg et al. 2001; Minzenberg et al. 2009). For instance, a variety of publications reported the disruption of the working memory network in SZ (Meyer-Lindenberg et al. 2001; Minzenberg et al. 2009; Camchong et al. 2008). However, most previous studies focused on the structural and/or functional connectivities in cortical networks in SZ, and thus much less is known about the structural and/or functional connectivities between cortical and subcortical regions in SZ. A recent study by (Salvador et al. 2010) reported a cortical region located frontally in medial and orbital D. Zhang : L. Guo : X. Hu : K. Li School of Automation, Northwestern Polytechnic University, Xian, China D. Zhang : Q. Zhao Department of Physics, The University of Georgia, Athens, GA, USA T. Liu (*) Department of Computer Science, The University of Georgia, Athens, GA, USA e-mail: tliu@cs.uga.edu K. Li : Q. Zhao : T. Liu BioImaging Research Center, The University of Georgia, Athens, GA, USA Brain Imaging and Behavior (2012) 6:27–35 DOI 10.1007/s11682-011-9138-z