Project Summary

J. Daniel Ragland, Ph.D. (Independent Investigator 2004) of University of Pennsylvania, will use a form of classical conditioning to test if schizophrenia disrupts hippocampally mediated trace conditioning, and leaves non-declarative delay conditioning relatively intact. Delay conditioning is a non-declarative associative learning task in which a previously neutral stimulus (CS) elicits an emotional physiologic response through repeated timed pairing with an aversive unconditioned stimulus (US). In trace conditioning there is a stimulus-free interval between the CS and US, which forces the subject to form a mental representation of the association for conditioning to occur. Forming and maintaining this association invokes declarative memory and makes trace conditioning differentially sensitive to hippocampal function. Using functional magnetic resonance imaging (fMRI) while contrasting trace with delay conditioning will allow Dr. Ragland to test his hypothesis that schizophrenia disrupts hippocampally mediated trace conditioning, and leaves non-declarative delay conditioning relatively intact. He will first study the protocol without fMRI in healthy volunteers, and will then obtain fMRI images of delay and trace conditioning in 15 patients with schizophrenia and 15 controls. Establishing that hippocampal dysfunction occurs in early stages of declarative memory has clear implications for the development of treatment and remediation strategies.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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