This revised NIDA Mentored Research Scientist Development (K01) Award application will support Dr. James Eliassen's long-term career objective of developing an independent substance abuse research program that examines the link between learning and memory functions, monoaminergic transmitter systems and substance abuse. Specifically, Dr. Eliassen will examine the effect of human recreational MDMA use on learning and memory and the link between cognitive and serotonergic function with electroencephalography techniques (EEG) and simultaneous functional magnetic resonance imaging (fMRI). MDMA is the second most widely used illicit substance after marijuana, and animal research indicates that MDMA damages serotonergic neurons and chronically impairs behavior. Since the effects in humans appear to be similar and up to 10% of young adults have tried MDMA any negative consequences constitute a significant public health concern. Some ambiguity exists in the link between human MDMA use, serotonergic dysfunction, and memory impairment, and this issue needs to be clarified through further research so that the dangers of MDMA use can be clearly appreciated by the public. Specifically, in order to substantiate the claim that MDMA impairs learning and memory through neurotoxic sequelae Dr. Eliassen will record evoked and event- related potential EEG (EP, ERP) simultaneously with fMRI in MDMA users. He will examine whether the EEG and fMRI markers of learning and memory processes are altered by MDMA use in correspondence to changes in serotonergic function, as measured by the loudness dependence of the late auditory evoked potential N1 (LDAEP). Additionally, Dr. Eliassen will combine EEG and fMRI data into multi-modal dynamic brain activity maps in order to confirm that mnemonic and serotonergic dysfunction arise from the same temporal and spatial neural sources in the brain. We predict that if MDMA's neurotoxic actions are responsible for learning and memory impairments we will observe corresponding changes in the electrophysiological, fMRI, and behavioral measures of cognition and the LDAEP measure of serotonin function in recreational MDMA users but not controls. This research will help confirm and further characterize the mechanism by which MDMA ostensibly causes learning and memory impairments due to its neurotoxic actions on the serotonin system. The proposed research and training plan and the productive research environment of the University of Cincinnati Center for Imaging Research will enable the candidate to develop an independent substance abuse research career that examines the link between learning and memory, monoaminergic transmitters (e.g., serotonin), and substance abuse. ? ? ?
