Behavioral and neural correlates of spatial working memory dysfunction in schizophrenia

Schizophrenia is a severe mental disorder involving a complex, multi-factorial etiology and disruption of multiple brain systems. There is growing evidence that dysfunctional spatial working memory abilities may be linked to many of the cognitive impairments, clinical symptoms and aberrant neural physiology found in schizophrenia. Yet, several basic questions remain concerning the nature of spatial working memory deficits in schizophrenia, including whether aberrant physiologic activity in the dorsolateral prefrontal cortex (DLPFC) is detectable when task conditions are optimized to allow isolation of maintenance processes. This ambiguity remains because patients with schizophrenia have deficits in both maintenance and non-mnemonic (i.e., strategic) processes that are likely to be mediated in part by prefrontal cortex, and because prior functional neuroimaging studies with schizophrenic patients have used tasks that tax both kinds of processes. Here we assessed the neural correlates of impaired maintenance in schizophrenia by administering a spatial delay response task (DRT), designed to minimize non-mnemonic processing while parametrically increasing memory set size, during neuropsychological and fMRI evaluations. Patients with schizophrenia (n = 9) were less accurate and had longer reaction times than matched healthy participants (n = 9) on each level of the spatial DRT. However, the extent of this impairment did not increase with increasing memory load. This study is the first to provide direct neurophysiologic evidence of schizophrenic hypoactivation in DLPFC and parietal regions during the short-term maintenance of spatial information. We interpret this reduced activation as neurophysiologic evidence for the corruption of maintenance processing in schizophrenia. In addition, patients with schizophrenia showed significantly less covariance in activation between DLPFC and parietal regions than healthy participants, an index that was significantly correlated with task performance. Thus, the current results confirm prior reports of performance deficits in patients with schizophrenia on spatial DRT and extend those findings by demonstrating that patients exhibited less activation in DLPFC and parietal regions and less covariation of activation between those regions, relative to healthy subjects, while engaged in the maintenance of spatial information