| Individuals with schizophrenia show deficits in working memory and attentional function as well as neurobiological abnormalities including volume reductions in various brain structures and abnormal-brain activation while performing certain tasks. Data have indicated that non-psychotic, biological relatives of individuals with schizophrenia show some of the same deficits in cognitive function, though to a lesser degree, as well as volume abnormalities in many of the same brain structures affected by the disease. The question is raised as to whether biological relatives produce abnormally activated cerebral networks when vulnerable cognitive systems are engaged. The present study investigated a sample of siblings of schizophrenic individuals from primarily multiplex families (Relatives, N = 11) and a sample of Control participants (N = 15) matched on age, male:female ratio, handedness, reading level, estimated IQ and parental education. A battery of task variants of the auditory continuous performance test (CPT) was designed to engage working memory and attention by adding interference suppression and short-term memory demands to the baseline CPT. While participants performed the CPT tasks, wholebrain activation was measured with BOLD functional magnetic resonance imaging (fMRI) using a 1.5T General Electric Signa echo-planar device. Data analysis focused on a comparison of the most effortful CPT variant to the baseline CPT, and included construction of group average statistical activation maps and between group comparisons of activation in anatomically defined regions of interest (ROIs). A network of structures possibly involved in working memory and attention was targeted, including the pulvinar, dorsolateral prefrontal cortex (DLPFC), and parietal and anterior cingulate cortices. In the statistical maps, both groups activated a wide network including prefrontal, temporal and parietal cortices, the left cuneus and cerebellum. Different patterns of cortical activation were seen in the two groups. In the ROI analysis, Relatives tended to activate bilateral superior parietal cortex more than Control participants, whereas Control participants activated right DLPFC and left pulvinar more than Relatives. In Relatives, strong correlations were seen between task performance and DLPFC activity. These results suggest that physiological consequences of carrying genes involved in schizophrenia are present even if individuals do not exhibit the defining symptoms of the disease. |
