Functional Magnetic Resonance Imaging Study of Cognitive Control in the Healthy Relatives of Schizophrenia Patients

Background: The predisposition, or diathesis, to schizophrenia is highly heritable. The manner in which this genetic diathesis is manifest in the central nervous system is largely unknown, although healthy relatives of schizophrenia patients show executive processing deficits associated with prefrontal cortical impairments. Methods: The current study evaluated brain activity in 21 healthy relatives of schizophrenia patients and 20 demographically similar control subjects during correct trials on a stimulus-response incompatibility task. During the first part of each trial, participants represented and maintained the instruction for that trial; during the second part, participants used the instruction either to make an automatic response or to overcome this prepotent response. Results: Behaviorally, relatives were slower when overcoming the prepotent response. Analyses focused on the first part of the trial indicated that both groups showed activity in middle frontal (Brodmann areas 46 and 9) and anterior cingulate (Brodmann area 32) gyri. However, control subjects showed significantly greater activity in dorsal prefrontal cortex (Brodmann areas 9, 8, and 6) when preparing to overcome the prepotent response, whereas patients' relatives showed prefrontal activity later, when making the response. Conclusions: Using an event-related design showed distinct prefrontal brain abnormalities associated with the genetic diathesis to schizophrenia.