Over the past decade there has been a growing awareness of the treatment refractory cognitive deficits that are present in schizophrenia and strongly and consistently related to poor functional outcome and behavioral disorganization. This has been accompanied by an increasing emphasis on the importance of developing new treatments that may positively impact these deficits, culminating in the recent MATRICS meetings. Over this same period there has been an explosion of technical advances and new knowledge regarding the neural basis of cognition. Converging data from animal and human research has led to an unparalleled expansion of knowledge of the mechanisms of normal cognition and its underlying neuropharmacology, and cognition related brain activity in humans may now readily be obtained using measures such as functional MRI. The application of this cutting edge knowledge and technology to new drug development has lagged significantly behind the overall progress in the field. Generally, the methodology for measuring the effects of drugs on cognition in schizophrenia has relied on measures from clinical neuropsychology whose development pre-dates the cognitive neuroscience era. During the final, """"""""new approaches"""""""" MATRICS meeting it was broadly agreed that the major barrier to bridging the gulf between the new neuroscience and drug development is a lack of data on the measurement properties of the behavioral tasks used in cognitive neuroscience. In this R13 application we propose to maintain the momentum created by the MATRICS New Approaches meeting and take a step closer to a brain based approach to measuring the effects of treatments on impaired cognition in schizophrenia. To accomplish this goal we organize three conferences over an 18 month period. The first conference will develop a consensus on the key component processes related to a subset of the higher cognitive functions that are affected in schizophrenia, related to poor outcome and measurable in animal models. The second conference will clarify the psychometric issues relevant to translating tasks from cognitive psychology and neuroscience into useful measures for drug development, and establish benchmarks against which the psychometric properties of candidate tasks can be compared. The third meeting will develop a set of candidate tasks which measure key component processes of the cognitive systems impaired in schizophrenia which 1) can be linked to animal models and 2) are amenable to incorporation into neuroimaging studies of the underlying brain circuitry. These meetings and their published products will take the field a step closer to having a new set of brain based tools that can be used at both early and later stages of the drug development process to enhance the translation of new knowledge regarding the neuroscience of cognition into effective treatments for cognitive impairments in schizophrenia. ? ? ?
