Prefrontal Cortex Dysfunction as a Risk Factor for the Development of Schizophrenia
A growing body of research suggests that disturbances in prefrontal cortex (PFC) function and particular cognitive processes, such as working memory, are present in individuals who suffer from schizophrenia. Further, prior high-risk research suggests that at least some cognitive deficits are present before the onset of the illness and may predict who will develop schizophrenia. This prior high-risk research has generated tantalizing hints about potential cognitive and neurobiological mechanisms that may play a role in the development of schizophrenia, but has not generated probes or markers that either: (1) adequately discriminate groups of individuals thought to be at risk for schizophrenia; or 2) demonstrate adequate sensitivity or specificity for determining precisely who will develop schizophrenia from among individuals in high-risk groups. In prior work, we have used detailed neural networks and behavioral paradigms to demonstrate that schizophrenic deficits in several cognitive domains (i.e., selective attention, working memory) can be explained by a disturbance in a particular function of PFC: the ability to represent and maintain context information necessary to guide appropriate task behavior (e.g., a specific component of working memory). Further, we have shown that the representation and maintenance of context is supported by PFC function, and that deficits in the processing of context are associated with a failure to activate PFC among first episode, medication-naive patients with schizophrenia. The purpose of this project is to expand upon prior research by examining brain activity during cognitive processing, using carefully controlled tasks designed to measure context processing and novel functional magnetic resonance imaging (fMRI) methods, to study individuals at risk for the development of schizophrenia. We will study 40 individuals with Schizotypal Personality Disorder, a group of individuals known to be at heightened risk for the development of schizophrenia, as well as 40 control subjects. We will have all participants perform a task specifically designed to assess context processing (an AX version of the Continuous Performance task) as well as tasks used in prior high risk research (CPT-IP and degraded CPT). In addition, we will ask everyone to participate in a fMRI session, allowing us to determine the integrity of PFC function while these individuals perform cognitive tasks. Results from this initial cross-sectional study will provide a starting point for follow-up longitudinal studies to further establish the causal and developmental relationships among PFC dysfunction, cognitive deficits, and symptoms in schizophrenia, and their ability to predict risk for this debilitating disease.
A growing body of research suggests that disturbances in prefrontal cortex (PFC) function and particular cognitive processes, such as working memory, are present in individuals who suffer from schizophrenia. Further, prior high-risk research suggests that at least some cognitive deficits are present before the onset of the illness and may predict who will develop schizophrenia. This prior high-risk research has generated tantalizing hints about potential cognitive and neurobiological mechanisms that may play a role in the development of schizophrenia, but has not generated probes or markers that either: (1) adequately discriminate groups of individuals thought to be at risk for schizophrenia; or 2) demonstrate adequate sensitivity or specificity for determining precisely who will develop schizophrenia from among individuals in high-risk groups. In prior work, we have used detailed neural networks and behavioral paradigms to demonstrate that schizophrenic deficits in several cognitive domains (i.e., selective attention, working memory) can be explained by a disturbance in a particular function of PFC: the ability to represent and maintain context information necessary to guide appropriate task behavior (e.g., a specific component of working memory). Further, we have shown that the representation and maintenance of context is supported by PFC function, and that deficits in the processing of context are associated with a failure to activate PFC among first episode, medication-naive patients with schizophrenia. The purpose of this project is to expand upon prior research by examining brain activity during cognitive processing, using carefully controlled tasks designed to measure context processing and novel functional magnetic resonance imaging (fMRI) methods, to study individuals at risk for the development of schizophrenia. We will study 40 individuals with Schizotypal Personality Disorder, a group of individuals known to be at heightened risk for the development of schizophrenia, as well as 40 control subjects. We will have all participants perform a task specifically designed to assess context processing (an AX version of the Continuous Performance task) as well as tasks used in prior high risk research (CPT-IP and degraded CPT). In addition, we will ask everyone to participate in a fMRI session, allowing us to determine the integrity of PFC function while these individuals perform cognitive tasks. Results from this initial cross-sectional study will provide a starting point for follow-up longitudinal studies to further establish the causal and developmental relationships among PFC dysfunction, cognitive deficits, and symptoms in schizophrenia, and their ability to predict risk for this debilitating disease.
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