The Metabolic Substrates of Bradykinesia and Tremor in Uncomplicated Parkinson's Disease

Abstract

The pathophysiological mechanisms of bradykinesia and resting tremor, i.e., two major features of Parkinson's disease (PD), remain incompletely understood despite extensive studies, including functional imaging investigations. Using high-resolution positron emission tomography (PET) and [ 18 F]fluoro-2-deoxyglucose (FDG) in 17 nondemented patients with uncomplicated PD on a stable therapeutic regimen, we measured the resting-state cerebral metabolic rate of glucose (CMRGlc), a validated marker of synaptic density/activity. Following formulation of distinct a priori hypotheses about potentially involved brain regions based on previous experimental and clinical literature, correlations between CMRGlc and objective scores of bradykinesia and tremor were searched in a voxel-based fashion using SPM99. Bradykinesia scores were significantly positively correlated with bilateral putamen and globus pallidum CMRGlc, while tremor scores were negatively correlated with bilateral putamen and cerebellar vermis CMRGlc. There was a large overlap of putamenal voxels significantly but inversely correlated with both extrapyramidal features. For both bradykinesia and tremor, the observed patterns of subcortical correlations largely concurred with our a priori hypotheses, and point to the major role of disruption of the striatofrontal and corticocerebellar pathways in the genesis of these extrapyramidal features. The direction of these correlations was not entirely expected, however, which may be due to the patients' being studied on medication, contrary to most studies performed to date. The observation that overlapping portions of the putamen inversely correlated with bradykinesia and tremor was a novel and striking finding which points to the complexity of the underlying pathophysiology of PD. Because it allows greater control of the neurological status, studying patients on medication may partly explain our findings. Voxel-based analysis of resting FDG-PET holds considerable potential for assessing the neural substrates of motor impairment in PD.