Connectomic Analysis of Substantia Nigra Pars Compacta and Ventral Tegmental Area Projections to the Striatum and Cortex

We investigated the connectivity of dopamine (DA) neurons emerging from the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) and targeting the dorsal striatum (DS), ventral striatum (VS), and prefrontal cortex (PFC). We used diffusion magnetic resonance imaging (dMRI) probabilistic tractography on human connectome project MRI data. We found that unlike conventional descriptions of DA pathways (i.e., nigrostriatal, mesolimbic, mesocortical), connectivity from both SNc and VTA each targeted DS, VS, and PFC. We also found that from the DS, VS, and PFC, a greater proportion of connections targeted the SNc as compared to the VTA. These findings suggest that DA pathways are more complex than conventionally described. In a follow-up dMRI experiment, we found reduced connectivity from the SNc/VTA complex to the caudal motor region of the striatum in patients with Parkinson\u27s disease, indicating a potential role of dMRI to measure DA connectivity changes in patients with DA-mediated diseases