Cognitive dysfunctions are major and debilitating features of schizophrenia and schizoaffective disorder (scz-sza). Even after clinical symptom remission, persistent cognitive deficits limit school and work performance and response to behavioral treatments. Some of the most prominent and problematic of these dysfunctions, those in working memory and certain types of problem solving, are thought to reflect frontal lobe dysfunction. Since frontal lobe dysfunction is central in current models of the pathophysiology of scz-sza, cognitive deficits are of relevance both to patient quality of life and to the pathophysiology of the illness. Because of this, new efforts to understand and treat the cognitive deficits of scz-sza are significant for both understanding and for treating the disorders. Most currently available treatments are of limited benefit for the cognitive deficits of scz-sza. One possible, promising exception are new behavioral treatments developed specifically to address the cognitive deficits with varying mixes of instructions and drill and practice. We have been leaders in the development and evaluation of these treatments, and have provided preliminary evidence of substantial and enduring improvements in cognitive function. At this early state in the research, there are several important questions about the relationship between the observed improvements in cognitive function and possible changes in underlying brain dysfunctions. Answers to these questions are important for understanding the nature of the treatments, optimizing further development of the treatments and assessing the potential of the treatments to fundamentally alter the course of illness. An R-0l funded evaluation of behavioral effects of cognitive treatment is ongoing in our laboratory. R-21 support is requested to support exploratory and developmental fMRI studies that will provide preliminary data on changes in regional brain activation associated with behavioral treatment of cognitive dysfunctions, and develop methods for fuller study of these changes.
