Grant: Discovery Grants Program - Individual

My research program develops improved methods to better understand the function of the neurotransmitter dopamine in the human brain. My recent work has validated a specialized magnetic resonance imaging (MRI) method, neuromelanin-sensitive MRI (NM-MRI) as a measure of dopamine function, not only as a marker of damage to the dopamine system, as previously used. This discovery allows more advanced development work and investigation of novel applications for this technology, including many where knowledge has been limited by the lack of practical tools to use in living human brain. Importantly, NM-MRI is non-invasive, unlike traditional dopamine PET imaging. Thus, NM-MRI can be used for applications not accessible to PET imaging, such as studies in youth or longitudinal studies with repeated assessment over time. NM-MRI has high anatomical resolution, revealing distinct groups of dopamine neurons involved in emotional, cognitive, and motor behaviors. Neuromelanin (NM), the compound detected by NM-MRI, is a dark pigment created from the breakdown of dopamine. It is absent at birth and progressively accumulates in dopamine neurons over the lifespan, providing a permanent record of the history of dopamine activity. We propose to examine for the first time the NM-MRI signal in children and adolescents: to measure the signal longitudinally and investigate its relevance to experience-dependent brain development via its relationship to behavior and environmental conditions. We will acquire NM-MRI scans and behavioral and environmental measures at multiple time points in children and adolescents and also in young and older adults for comparison. One component of the research program will test the pattern of NM-MRI signal changes over time during early and later life stages and compare these dynamics in males and females. Another component of the proposed research will investigate the relationship of the NM-signal to behavior, cognitive performance, and environmental conditions known to be regulated by dopamine. To support this work the research program will further refine the methods used for NM-MRI. This includes methods to acquire and analyze NM-MRI scans, validation work examining its relationship to the chemical content of the brain (using post-mortem tissue), and developing improved methods to separate dopamine neurons, visualized with NM-MRI, into emotional, cognitive, and motor subgroups using personalized information based on individual patterns of brain connectivity. NM-MRI is on the path to becoming a standard neuroimaging tool in neuroscience and experimental psychology. The proposed research will support further refinement of the method and discovery of novel applications for this new method, particularly in regards to human brain development, where few tools exist to investigate the influence of key neurotransmitters such as dopamine.