• calcium binding proteins;
  • immunohistochemistry;
  • interneurons;
  • motor cortices;
  • non-phosphorylated neurofilament;
  • pyramidal neurons


The nonprimary motor cortices have not previously been studied in Parkinson's disease, despite the selective pattern of dysfunction observed in these regions. In particular, the pre-supplementary motor region is consistently underactive, with successful treatments correlating with increased excitatory drive to nonprimary motor regions. This finding could suggest a primary cortical abnormality in the pre-supplementary motor area (pre-SMA) in Parkinson's disease. We analysed and compared neuronal number in the pre-SMA and dorsolateral premotor cortical regions in 5 cases of Parkinson's disease and 5 controls. For each cortical region, the total neuronal number as well as the estimated numbers of subpopulations of interneurons and pyramidal neurons was quantified using previously published unbiased techniques. The results showed a significant loss of cortico–cortical projecting pyramidal neurons in the pre-SMA with no loss of other pyramidal neurons or interneurons either in this region or in the dorsolateral premotor region. These findings indicate a highly selective loss of pyramidal cells in the pre-SMA in Parkinson's disease, consistent with previous imaging findings in this disease. Our results implicate the degeneration of the premotor projection from the pre-SMA, along with dopaminergic basal ganglia dysfunction, in the pathogenesis of Parkinson's disease. © 2002 Movement Disorder Society