a | Seed-based structural co-variance networks (green) and intrinsic functional connectivity networks (yellow) in healthy individuals, using, as seed regions, the foci of grey matter loss in different samples of patients with five neurodegenerative diseases (blue). These include the right angular gyrus (R ANG) in Alzheimer’s disease (AD); right frontal insula (R FI) in behavioural variant frontotemporal dementia (bvFTD); left temporal pole (L TPO) in semantic dementia (SD); left inferior frontal gyrus (L IFG) in progressive non-fluent aphasia (PNFA); and the right premotor cortex (R PMC) in corticobasal syndrome (CBS). The pattern of grey matter loss in patients recapitulates the patterns of structural co-variance and functional MRI functional connectivity in healthy individuals. This suggests that these diseases may target structural co-variance networks and that these structural co-variance networks are also functionally significant in the healthy brain. b | Structural co-variance alterations in AD. The brain map (left) shows specific regions whose structural correlations are higher (red lines) or lower (blue lines) in patients with AD compared with control subjects. These regions include the paracentral lobule (PCL), superior parietal gyrus (SPG), posterior cingulate gyrus (PCG), anterior cingulate gyrus (ACG), olfactory cortex (OLF), inferior orbital cortex (ORBinf), superior medial orbital cortex (ORBsupmed), fusiform gyrus (FFG), parahippocampal gyrus (PHG), superior temporal pole (TPOsup) and middle temporal pole (TPOmid). At the network level (right), the AD network shows abnormally high clustering, indicating greater local agglomeration of connected nodes. c | Structural co-variance alterations in schizophrenia. The brain map (left) illustrates specific regions in which structural correlations are higher (red lines) or lower (blue lines) in patients with schizophrenia compared with control subjects. These regions include the postcentral cortex (PoC); supramarginal cortex (SM); inferior frontal cortex, orbital part (IFor); inferior frontal cortex, opercular part (IFop); caudal anterior cingulate (CAC); pallidum (Pal); and thalamus (Tha). At the network level (right), the average distance between connected nodes is longer in schizophrenia, suggesting that pairs of regions with the strongest structural co-variance are less close to each other in the patient group. Results are shown across a range of network ‘density’, which indicates the proportion of the strongest pairwise correlations included as edges in the graph models. Part a is modified, with permission, from REF. © (2009) Cell Press. Part b (left) is modified from REF. . Part b (right) is modified, with permission, from REF. © (2008) Society for Neuroscience. Part c (left) is modified, with permission, from REF. © (2012) Elsevier. Part c (right) is modified, with permission, from REF. © (2008) Society for Neuroscience.