Emerging Evidence of Connectomic Abnormalities in Schizophrenia
Journal of Neuroscience
Review of van den Heuvel et al. Schizophrenia is an etiologically and clinically heterogeneous psychiatric disorder, characterized by psychotic symptoms, motivational disturbances, and cognitive disorganization. Pioneers of neuropathology such as Meynert and Wernicke proposed in the late 19th century that schizophrenia is associated with abnormalities in anatomical connectivity between specialized brain regions. Over the last 30 years, neuroimaging studies have provided general evidence for the
... al evidence for the existence of such anatomical dysconnectivity. For instance, functional neuroimaging studies in schizophrenia show abnormal integration between multiple cortical and subcortical regions (Friston and Frith, 1995; Gur and Gur, 2010) , implying the presence of underlying anatomical connection abnormalities. Structural neuroimaging studies show deep white-matter abnormalities in frontal and temporal regions and gray-matter reductions in frontal, temporal, limbic, and thalamic regions Bullmore, 2009, 2010). However, the precise location of affected anatomical connections in schizophrenia and the relationship between these connectivity abnormalities and emergent functional deficits remain unknown. Recent advances in diffusion magnetic resonance imaging (MRI) technology and white-matter fiber reconstruction algorithms make it increasingly possible to assemble high-resolution large-scale anatomical connectivity maps of the human brain. Such "connectomic" maps allow researchers to characterize the organization of anatomical brain networks and to identify the anatomical correlates of functional abnormalities in brain disorders (Sporns et al., 2005) . One of the first diffusion MRI connectomic studies of schizophrenia was recently described by van den Heuvel et al. (2010). The authors characterized large-scale anatomical brain networks extracted from diffusion imaging data acquired from 40 healthy people and 40 people with schizophrenia. The location, direction, and length of white matter fiber tracts in these networks were inferred from diffusion of water molecules in brain tissue, using a white-matter fiber reconstruction algorithm. The connectivity strength of white matter tracts was inferred from the level of tract myelination, which was estimated using magnetization transfer imaging, a technique that quantifies the amount of macromolecules (including myelin) in the tracts. The tracts were combined with a parcellation of the brain into 108 regions of interest to construct whole-brain anatomical networks. The regional and global properties of these networks were then characterized as described below and compared between healthy and schizophrenia groups. van den Heuvel et al. (2010) characterized the properties of anatomical brain networks with statistical measures of network topology. The authors used four complementary network measures to assess the structural organization and infer the potential functional role of individual brain regions. First, the measure of regional connectivity, based on the total number of connections associated with each region, was used to assess the strength of direct regional communication. Second, the measure of clustering, based on the density of connections surrounding each region, was used to assess the regional capacity for functional specialization. Third, the measure of path length, based on the average length of shortest network paths between the region and all other regions, was used to assess the regional capacity for functional integration. Fourth, the measure of betweenness centrality, based on the proportion of regional participation in shortest network paths, was used to assess regional importance, by inferring the capacity for participation in distributed information processing.