Through a Glass Darkly: Schizophrenia and Functional Brain Imaging

Functional neuroimaging frequently assumes anatomically and functionally specific "modules" in the brain. Schizophrenia, which is challenging in many ways, also challenges modularity. A prominent example of a modular hypothesis links working memory (WM) deficits in schizophrenia with decreased function in the prefrontal cortex, a result confirmed in several studies. Nonetheless, these studies are systematically blind to the alternative possibility that schizophrenia reflects dysfunction in broader, more distributed systems of the brain. However, to establish hypotheses about distributed cognition in health and illness requires new interpretations of functional neuroimaging. Modularity can be assessed by large-scale meta-analyses of neuroimaging studies, illustrated here through the on-line database, Brainmap (www.brainmap.org). The apparent association of WM and prefrontal cortex fades when one considers all areas engaged in WM, and all tasks associated with prefrontal cortex. In addition, several global measures of connectivity based in functional neuroimaging may provide measures of distributed dysfunction. For example, Independent Component Analysis reveals unusual oscillations in distributed networks in patients with schizophrenia.