Structural Connectivity of the Substantia Nigra: A Comprehensive Review of Diffusion Imaging and Tractography Studies

The substantia nigra (SN) has historically been regarded as a pivotal element of the brain’s motor circuits, notably within the context of the nigrostriatal pathway and Parkinson’s disease. However, recent advancements in neuroimaging techniques, particularly tractography, have facilitated the delineation of its anatomical projections. These techniques have revealed the involvement of the SN in a more extensive array of functional networks encompassing cognitive, emotional, and motivational domains. This paper reviews the current knowledge on the structural connectivity of the SN in humans based on diffusion tensor imaging and tractography. It summarizes the main projection pathways, including classical and newly described connections, such as the direct SN pars compacta connections to the thalamus, cortico–neural inputs, and connections to limbic regions and the hippocampus. Furthermore, the text delves into the distinctions between the SN pars compacta and SN pars reticulata subregions, exploring their parcellation based on connectivity. The paper demonstrates that the SN is a functionally diversified nucleus, the implications of which are significant for the understanding of both motor and neuropsychiatric disorders. The present study addresses the paucity of comprehensive treatment in this area and provides a framework for further research on dopaminergic circuits.