This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Patients with schizophrenia are impaired in their ability to make perceptually ambiguous recognitions and often respond poorly to training programs designed to improve the precision of their judgments. This research program is designed to illuminate the physiological mechanisms associated with learning and memory in this impaired group. In particular it will provide information specifically concerning the relationship between a person's symptoms and his capacity to change brain activity patterns and brain chemistry associated with learning and practice. The principal objectives of the study include finding out: a) what brain structures are associated with encoding initial presentations of visual stimuli that are to be remembered versus those that are not targets of memory; b) how does visual learning and training alter the neural pathways associated with encoding; c) to what extent do all volunteers with schizophrenia differ from normal healthy volunteers in their functional neural architecture associated with encoding before and after training; d) to what extent does a schizophrenic patient's symptoms (especially psychosis) determine the activation of neural systems associated with encoding, before and after training; e) will extended visual training 'normalize' the neural activity patterns in those with schizophrenia; f) the relation of neurochemistry to neural activity associated with learning before and after training. We will assess performance improvement on a visual Delayed Match to Sample Task (DMST) in normal volunteers (NV) and schizophrenia volunteers (SZ). We propose to recruit 30 SZ. A total of 25 NV will be matched with SZ on age, sex, and familial socioeconomic class (SES). There will be an initial screening of all. The neuropsychological task for the imaging experiment is the visual Delayed Match to Sample Task (DMST). NV and SZ will receive a pre-training fMRI and their performance on the visual DMST will be quantified. A training period of 4 sessions over two weeks on the DMST will be provided for all volunteers. After training, NV and SZ will receive a post-training fMRI and an MRS study. SZ, after the initial fMRI, four training sessions and second, post-training fMRI, will participate in a longer and more intensive practice over the subsequent one month. Two sessions weekly over 4 weeks will produce an over-trained condition. We will contrast the scans, fMRI and MRS (Scan 2 versus Scan 3) collected at the end of the one-month extension period between the two symptom groups.
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