Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings.

Impaired working memory and functional brain activation deficits within prefrontal cortex (PFC) may be associated with vulnerability to schizophrenia. This study compared working memory and PFC activation in individuals with schizophrenia, their unaffected siblings and healthy comparison participants. We administered a "2back" version of the "nback" task. Functional MRI (fMRI) was used to measure brain activity. Nineteen individuals with DSM-IV schizophrenia, 18 of their siblings, and 72 healthy comparison participants underwent fMRI scans while performing word and face "nback" working memory tasks. Repeated trials (items whose prior presentation was not in the correct nback position) allowed us to assess group differences in the ability to code the temporal order of items. Individuals with schizophrenia and their siblings performed worse than controls on repeated lure trials, suggesting an association between schizophrenia and impairments in the coding of temporal order within working memory. Both individuals with schizophrenia and their siblings also demonstrated abnormal brain activation in PFC, such that both groups had hyperactivation in response to word stimuli and hypoactivation in response to face stimuli. These results provide further evidence that individuals with schizophrenia and their siblings are impaired in their ability to encode the temporal order of items within working memory and that disturbances in working memory and PFC activation may be genetic markers of the vulnerability to schizophrenia.