Grant: Discovery Grants Program - Individual

Adolescence is a period of pronounced change in reward, attention, learning, and motor processes that has been linked to the development of the dopamine system, a complex set of circuits comprised of midbrain projection nuclei, the striatum, and regions of frontal, and cingulate cortices. The system is highly attuned to variations in the quality of the environment and is therefore increasingly recognized as a "plasticity system" whose development can be shaped by positive and negative experiences. Advancing our understanding of the development of this system is therefore an important priority in developmental cognitive neuroscience. Progress on this issue is however hampered by the fact that studying the development of the dopamine system in humans is very challenging. Histological methods rely on post-mortem tissue which is exceedingly rare, and gold-standard imaging techniques like positron emission tomography are not viable for individuals younger than 18-years because of their reliance on radioactive tracers. The proposed research program will therefore study the development of the nigrostriatal pathway using high field strength (7-Tesla) magnetic resonance imaging (MRI). The nigrostriatal pathway originates in the substantia nigra (SN), a small midbrain nucleus that produces dopamine. Although the SN has historically considered motoric in function given links between SN pathology and Parkinson's disease, more recent evidence suggest structurally and functionally distinct subregions. MRI provides a powerful means of imaging the SN and the nigrostriatal pathway. The SN produces a paramagnetic pigment called neuromelanin as a by-product of dopamine metabolism, and therefore can be imaged by means of MRI. Resulting images create a high-resolution image of the SN and predict molecular and functional measures related to dopamine metabolism and neurotransmission. We have adapted this recently validated method, called neuromelanin MRI, or nmMRI, for use at 7-Tesla, creating a range of new possibilities for imaging developmental changes in this part of the dopamine system. The proposed research program will capitalize on this opportunity by combining high-field strength nmMRI with standard structural and functional imaging methods. These methods will allow my research team to address the following foundational questions concerning the development of the nigrostriatal pathway and its relationship with cognitive and behavioural change during adolescence. 1.Are there age-related changes in the volume and neuromelanin content of the SN during adolescence? 2.Are structurally distinct subdivisions of the SN a starting point or an end point of adolescent development? 3.Do fibre tracts connecting the SN to the striatum show age-related change during adolescence? 4.Does age-related variability in the structure and function of nigrostriatal pathways predict differences in broader measures of attention, decision, and motor processes?