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

Abstract

BackgroundBrain 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. MethodsA ‘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. ResultsThe 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. ConclusionsBoth 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.