Project Summary

Dara S. Manoach, Ph.D., (Independent Investigator 2006) of Massachusetts General Hospital, Harvard University, is studying how the brain mediates cognitive processes that are essential to adaptive, flexible behavior and which processes are preserved, and which are impaired in schizophrenia. To perform well on any challenging task, it is first necessary to free the mind from distractions to focus on the task at hand, evaluate performance to learn from errors, and finally, if an error was made, be more careful on the next try. These three distinct processes, 1) task preparation, 2) performance evaluation, and 3) remedial performance adjustments in the subsequent trial (i.e., slowing down after you have made an error), are mediated by separate networks in the brain and occur at different times during task performance. They can be studied while subjects perform a single task, and their anatomical underpinnings can be identified using methods that have high spatial and temporal resolution. Dr. Manoach proposes to study the brain networks involved in both healthy individuals and patients with schizophrenia using complementary neuroimaging techniques, functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) and will use an eye movement paradigm. Prior work suggests that task preparation and performance evaluation are impaired in schizophrenia, while remedial adjustment is intact. Because task preparation and performance evaluation are essential to optimal performance across such a broad range of tasks, deficits in these functions could lead to widespread cognitive impairments and provide an account for the seeming generality of cognitive dysfunction in schizophrenia. Impaired preparation would result in slower and more error prone performance, while abnormal performance evaluation could compromise the process of learning from one’s mistakes and consequently contribute to behavior that is rigid, stereotyped, and perseverative. Revealing the neural basis of these fundamental and disabling cognitive deficits in schizophrenia will illuminate the brain basis of schizophrenia and provide targets for treatment to improve cognition.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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