ABSTRACT
Schizophrenia is a common and devastating mental illness that affects approximately 1% of the population worldwide. Neuroimaging findings now form part of the bedrock of clinical investigation into this disorder. Following on the heels of structural imaging findings of increased ventricular spaces and reduced brain volumes, decreased dorsolateral prefrontal cortex (DLPFC) activity or hypofrontality helped to establish schizophrenia as biological in origin, to encourage a dialogue between basic and clinical scientists regarding neurochemistry, neuronal pathology, and molecular biology within DLPFC, and to foster a keener interest in cognitive dysfunction and its potential pharmacological remediation. However, as the methodology has matured, the essential questions regarding brain dysfunction in schizophrenia have changed as well. Some questions have been altered as a result of new neuroimaging findings. For example, decreased DLPFC activity is not the sole signature of dysfunction in schizophrenia. Some questions have been changed in scope. Instead of an exclusive focus on isolated regions of dysfunction, experiments and analyses are increasingly aimed at networks and interactions within them. Finally, some questions have been changed in kind as the result of rapid advances in other research disciplines. Elucidating the relationship between genetic variation and regional brain activation is a challenge that did not exist in the pregenomic era. This chapter will address recent findings relevant to each of these issues, since
new answers may ultimately drive the field in unexpected directions as further improvements in diagnosis and treatment are still desperately needed.
