Multi-parametric MRI Assessment of Brain Connectivity and Spectroscopic Biomarkers in Patients with a Substance Use Disorder

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Opioid use disorder (OUD) has been declared as a public health emergency in the United States. Data from the Centers for Disease Control and Prevention indicate a fivefold increase in the number of deaths due to opioids from 1999 to 2016. Neuroimaging is a powerful tool in understanding the neurocircuitry and physiology of OUD in order to target treatments for patients suffering from this disorder. This K23 application presents a training program for a board-certified clinical medical physicist, who specializes in magnetic resonance imaging (MRI), in order to receive training in the neuroscience of substance use disorders and to become an independent investigator. The goals set in this application will build on the candidate’s imaging physics background by (1) developing a foundational knowledge of brain function and neurocircuitry in substance use disorders in order to design, optimize, and interpret advanced neuroimaging techniques for addiction research; (2) acquiring training in professional development to become an independent investigator, mentor and educator; and (3) receiving additional training in the responsible and ethical conduct of scientific research. The overall training program will involve a research study focused on (1) brain effective connectivity (i.e., directional connectivity) of neural circuits in OUD, and (2) magnetic resonance spectroscopic quantification of neurotransmitters related to these circuits. In this proposed work, we will employ fMRI-based dynamic causal modeling of effective connectivity with guided expertise from mentors in order to identify neurocircuits underlying drug craving and attentional bias to dug cues. In addition, we will use MR spectroscopy to investigate the neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in OUD and their relation to drug craving and attentional bias, and to explore the association of these neurotransmitters with brain effective connectivity.