Pathophysiological brain mapping in Parkinson's disease

Abstract

Malfunctions of the dopaminergic system in Parkinson's disease are thought to affect motion, behavior, and cognition through the neural loops connecting the basal ganglia and the cerebral cortices. We investigated the pathophysiology using [F-18]FDOPA (fluorodopa) and [F-18]FDG (fluorodeoxyglucose) positron emission tomography (PET) in Parkinson's disease patients without apparent dementia (PD), PD patients with dementia (PDD), and age-matched normal control subjects (NC). PD patients showed significant declines of influx rate (Ki) values of [F-18]FDOPA in the bilateral striatum (dominant in the posterior and dorsal putamen) and substantia nigra. On the other hand, the PDD patients showed declines of Ki in the extrastriatal regions such as the medial frontal lobe and the hippocampus in addition to the striatum. Multi-volume projection (MVP) displayed that the decline of Ki was more widespread to the medial part of the midbrain in PDD than in PD. This area showing slight decrease of Ki was thought to correspond to the ventral tegmental area. The Ki value in the caudate head correlated with the glucose metabolism in the posterior cingulate, precuneus, and the parietotemporal area. The Ki value in the anterior cingulate correlated with the glucose metabolism in the anterior cingulate and left frontal association area. The results suggest that cerebral cortical functions are influenced by dopaminergic activities depending on its pathway. Cognitive disorder may be caused by the impaired mesolimbic dopaminergic system in Parkinson's disease.