Within-individual variability (WIV), or fluctuations, in behavioral performance is common in many psychiatric disorders, and is predictive of clinical outcome. Higher neurocognitive WIV is found in patients with schizophrenia and their relatives, however, this area in understudied in individuals at clinical risk for psychosis. Clinical signs of psychosis, including cognitive dysfunction, often begin in adolescence. However, the neural origins of these deficits are still unknown, and little is understood about how cognitive variabiliy manifests in adolescents who are at risk for psychosis. Therefore, the identification of neural mechanisms underlying cognitive variability is crucial for advances in identification of youths at risk and eventual treatment of psychosis. Here, I propose to address this crucial need by measuring neurocognitive WIV and its relationship to brain structure and neurochemistry in patients with schizophrenia, youths at risk for developing psychosis, and in healthy youths. Specialized behavioral measures, dedicated structural imaging of the prefrontal cortex, and spectroscopic analysis of key brain structures will be applied. Through this work, I expect to demonstrate that the presence of WIV is related to disrupted organization and altered neuronal integrity of the prefrontal cortex. The proposed work will produce novel scientific results that hold the potential to effect understanding and treatment of mental disorders within the medical and scientific communities. This work will additionally provide me with critical training as I finih prepare for a career as a cognitive neuroscientist. The proposal builds upon my established interest in cognitive dysfunction and significant experience in neuroimaging. The mentors I have selected are highly experienced and committed to my success. Lead mentor Dr. Ruben Gur, Ph.D. is a renowned expert in cognitive neuroscience and is an expert in investigations of the biological basis of psychopathology. The guidance of Dr. Gur, along with the other mentors, will assure that the training plan outlined here leads me to establish an independent research program in the neuroscience of cognitive dysfunction in neuropsychiatric disorders.

Public Health Relevance

Schizophrenia is a complex brain disorder that often develops in adolescence or early adulthood. Cognitive variability is common and signifies poor outcome. The work proposed integrates brain and behavior measures aimed at understanding the deficits in cognitive variability in patients with schizophrenia and individuals at clinical risk for develoing psychosis. Greater understanding of how cognitive variability manifests during adolescence and it relation to structural and neurochemical alterations within the prefrontal cortex will be criticl for the identification of clinically risk individuals and for the development of earlier and more effective treatments.

National Institute of Health (NIH)
Research Scientist Development Award - Research & Training (K01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Sarampote, Christopher S
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University of Pennsylvania
Schools of Medicine
United States
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