Sensitivity and specificity of hypoactivations and failure of de-activation in schizophrenia

Brain functional changes reported in schizophrenia include reduced prefrontal cortex activation (hypofrontality), increased frontal activation (hyperfrontality) and failure of de-activation in the medial frontal cortex. The relative importance of these changes is unestablished. A ‘discovery’ sample of 32 schizophrenic patients and 32 controls was used to establish regions of altered activation and de-activation in the patients. The discriminatory power of these regions was examined using receiver-operator characteristics (ROC) analysis in two ‘test’ samples, one of 83 patients with chronic schizophrenia and 83 healthy controls, and the other of 31 first-episode patients and 31 healthy controls. The discovery sample revealed reduced activation in the prefrontal cortex and other regions, and failure of de-activation in the medial frontal cortex. Failure of de-activation had significantly greater power to distinguish the chronic patients from the healthy controls than hypoactivation. The pattern was similar in the first-episode patients, where additionally the discriminatory power of hypoactivation was poor. Controlling for the effects of n-back task performance tended to reduce discriminatory power overall, but this persisted for failure of de-activation in the chronic test sample. Both hypoactivation and failure of de-activation can distinguish patients with chronic schizophrenia from healthy subjects, but the latter abnormality has more power. Failure of de-activation cannot be construed simply as a passive consequence of reduced prefrontal activation in the disorder.