Feature uncertainty: a novel test to probe prefrontal dysfunction in unaffected siblings of schizophrenia patients

Previous studies indicated that neuropsychological impairments are potential endophenotypes of schizophrenia. However, the sensitivity of these procedures is not sufficient and their brain substrates are poorly defined. The aim of this study was to measure the behavioral performance of siblings of schizophrenia patients and controls on a novel feature uncertainty (FU) task that selectively activates dorsal anterior cingulate cortex relative to orientation (OR) and spatial frequency (SF) discrimination. During the FU task, two subsequent sinusoidal gratings are presented and participants are asked to remember both the OR and SF of the gratings. After the disappearance of the gratings, a color cue signifies the perceptual dimension (OR or SF) to discriminate. Results revealed that the siblings of schizophrenia patients (n = 25) showed a selective deficit on the FU task as compared with controls (n = 20). The FU deficit was more severe than that found on neuropsychological tests of executive functions, psychomotor speed, and verbal memory. These results suggest that anterior cingulate dysfunction is a potential endophenotype of schizophrenia.