The rationale for examining the matrix and nigrosome 1 subdivisions arose from earlier demonstrations by Damier and colleagues that human substantia nigra is compartmentalized into distinct zones termed nigrosomes 1–5 (calbindin poor) and matrix (calbindin rich) [22] and that the nigrosome 1 is the site of the earliest loss of dopamine neurons in Parkinson’s [23]. This evidence concerns the gene CALB1 and Parkinsonism.