The primary goal of the proposed study is to determine whether acute cocaine administration will improve dorsolateral prefrontal cortex (DLPFC) function in schizophrenic subjects who abuse cocaine and are maintained on typical antipsychotic medications. The hypothesized mechanism for improvement is enhanced dopamine neurotransmission in prefrontal cortex. We will investigate the effect of low dose cocaine on working memory performance and concurrent fMRI DLPFC signal changes in co-morbid cocaine-abusing schizophrenic subjects and cocaine-abusing controls. Functional magnetic resonance imaging (fMRI) technology is ideally suited for the study of cocaine effects because it is safe, permits repeated investigations within the same subject, offers high spatial and temporal resolution and allows the identification of significant changes both within single subjects and between groups. This collaborative proposal will extend the investigators' previous work in fMRI which has included validating the proposed working memory paradigm, the Sternberg Item Recognition subjects Paradigm (SIRP) as a sensitive and stable probe of DLPFC function in both normal and schizophrenic subjects and investigating the effects of acute cocaine infusions in cocaine-dependent subjects. We predict that cocaine will result in improved working memory performance and a corresponding change in DLPFC task-related activation. We expect that these effects will be more pronounced in our schizophrenic versus our non-schizophrenic subjects. Within our schizophrenic group, we expect that subjects with more severe negative symptoms and poorer performance on prefrontally-mediated cognitive tests will show greater cocaine-induced improvement. We present the results of a pilot study demonstrating the feasibility of this proposal and supporting the hypothesis that cocaine will enhance performance on the proposed working memory paradigm. We expect that our findings will lead to the development of more effective pharmacotherapies for disabling prefrontally-mediated cognitive deficits that are not ameliorated by available medications and for co-morbid cocaine-abuse.
| Kong, Jian; White, Nathan S; Kwong, Kenneth K et al. (2006) Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity. Hum Brain Mapp 27:715-21 |
