Abstract

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 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 (Ellison-Wright and 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.