212. Task-independent and task-dependent disturbances in functional connectivity in schizophrenia: pet studies

Abstract

The present study investigated functional connectivity, operationally defined by (intravoxel) correlations in blood flow measured using H2150 PET. Recent research supports the notion that altered cortico-cortical connectivity may be an important factor underlying schizophrenia. A group of 13 medication-free patients and 13 age and sex-matched controls was studied during a working memory task and a matched control. The functional connectivity patterns that differed most between groups were extracted. Three patterns were found significant at the p < 0.00001 level. The first pattern explained more than 50% of the variance. The blood flow pattern of patients was characterized by relatively more temporal and cerebellar and less frontal and anterior cingulate contributions than controls. The difference was accentuated in the left superior anterior temporal lobe and right hippocampus (increase in patients) and the dorsolateral prefrontal cortex bilaterally (decreased). Expression of this pattern differentiated perfectly between the patient and the control group, regardless of whether subjects performed the working memory or the control task. The second pattern (explaining 19% of variance) corresponded to the activation-deactivation seen during the working memory task and its control. Expression of this pattern during the task was significantly more variable in patients, possibly indicating a failure to sustain a task-adequate working memory network. These results raised the possibility that the relatively task-independent, hypofrontal-hyperhippocampal pattern might be a trait-marker for schizophrenia. To further investigate this possibility, we used this pattern to classify 100 resting scans obtained from the same population. 96% of these scans could be classified correctly as being either from a schizophrenic or a control subject.