This is a application in response to RFA-MH-08-090, titled """"""""Adapting Basic Cognitive Measures for Clinical Assessment of Schizophrenia."""""""" Over the past decade there has been a growing awareness of the disabling effects of impaired cognition in individuals with schizophrenia. Along with this new awareness has come an increasing emphasis on the importance of developing new treatments that may positively impact these cognitive deficits. During this same period, the cognitive neuroscience field has seen an explosion of technical advances and new knowledge regarding the neural basis of cognition. Sadly, the translation and application of this cutting edge knowledge and paradigm development to new drug development in schizophrenia has lagged significantly behind the overall progress in the cognitive neuroscience field. The MATRICS initiative identified that the major barrier to this translation is a lack of data on the measurement properties of the behavioral tasks used in cognitive neuroscience. This concern spawned the Cognitive Neuroscience Research To Improve Cognition in Schizophrenia (CNTRICS) initiative, which conducted a series of conferences designed to bring together basic and clinical cognitive neuroscientists to develop consensus on the constructs and paradigms from cognitive neuroscience that are ripe for translation, and the validation and psychometric goals when translating such tasks for use in clinical trials contexts. The current application is a logical and much needed extension of the CNTRICS initiative that will begin the translation process for paradigms designed to assess four of the constructs identified as being ripe for translation in the first CNTRICS meeting. We have brought together a collaborative """"""""translation"""""""" team that represents significant expertise from the many fields necessary for the success of this endeavor, including basic cognitive neuroscientists, clinical cognitive neuroscientists, psychometricians, statisticians, and clinical trials specialists. We have chosen to focus on four constructs that that allow us to illustrate the translation process with mechanisms that operate both early (e.g., gain control and visual integration in perception) and later (goal maintenance, relational encoding and retrieval) in human cognitive processing. By examining multiple mechanisms, we will be able to establish the generality of the translational approach we propose across different levels and types of cognitive mechanisms.
Specific Aim 1 for this application is to validate (in both individuals with schizophrenia and comparison participants) optimized versions of the paradigms that assess our four constructs of interest (gain control, visual integration, goal maintenance and relational encoding/retrieval). By optimization, we mean examining modifications on already validated paradigms that are designed to: 1) minimize task length; 2) simplify task administration across multiple sites; 3) maximize sensitivity and selectivity in assessing the specific cognitive mechanisms of interesting; and 4) enhance reliability and minimize floor and ceiling effects. By validation, we mean ensuring that such optimizations designed to enhance the psychometric properties of the task do not alter its construct validity.
Specific Aim 2 will be to assess and optimize test-retest reliability and practice effects for the task versions validated in Specific Aim 1. Project Narrative: This project has high relevance for public health by significantly improving our ability to translate paradigms developed into the basic cognitive neuroscience literature for use in clinical trials aimed at improving cognition in schizophrenia. Cognitive deficits in schizophrenia are a major predictor of functional outcome in this debilitating illness. Thus, we need to improve our methods for detecting and enhancing cognitive function in schizophrenia in order to help individuals with this illness lead more productive and fulfilling lives. ? ? ?
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