This is a request for 5 years of funding through the """"""""Mentored Quantitative Research Career Award"""""""" (K25) mechanism. The applicant, a biophysicist/electrical engineer, proposes a program of training in neuroscience and pharmacology. The long term goal of the applicant is to become an independent and interdisciplinary investigator, skilled in the application of magnetic resonance methods for the study of substance abuse research. The research component of this award will develop and improve functional magnetic resonance imaging (fMRI) techniques for the study of substance abuse and addiction in human subjects. These techniques will be applied to study the effects of cocaine administration in humans. Cocaine abuse is a serious public health problem having important psychiatric, medical, and drug abuse policy implications. Acute administration of cocaine alters central nervous system (CNS) neuronal activity and cerebral blood flow; chronic use of cocaine can lead to long term neuronal and behavioral changes, as well as to alterations in cerebral vascular function. fMRI uses blood oxygenation changes to estimate neuronal activity, with a temporal resolution of several seconds and spatial resolution of a few millimeters. However, signal to noise ratio (SNR) and temporal resolution limits put constraints on the parameters that can currently be measured in vivo. Three separate technical development efforts are proposed. First, a phased array echoplanar imaging system, optimized for the study of brain regions which may mediate the rewarding effects of cocaine, will be implemented on a 4 Tesla MR scanner. This system will significantly increase the SNR of fMRI, and allow the detection of cocaine-induced alterations in neuronal activity in ventral striatum, thalamus, and posterior neocortex in individual subjects. Second, a method for rapidly and simultaneously assessing the relative BOLD activation resulting from blue and red light will be developed with a time resolution of at least one multicolor measurement per minute to determine the relationship between cocaine's effects on color visual processing (a proxy for dopaminergic alterations) and activation in other brain regions. Third, a set of experimental studies will be conducted to determine the relationship between EEG alpha activity (a surrogate marker for drug-induced euphoria) and the BOLD photic response. This study may aid in the development of magnetic resonance methods for assessing EEG alpha activity, giving an objective measure of the euphorigenic effects of various drugs. The long term goals of this research are to provide a better understanding of the phenomenon of cocaine abuse so that better prevention and treatment strategies can be developed and evaluated.
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