Focusing effects of L-dopa in Parkinson's disease.

Previous fMRI motor studies in Parkinson's disease (PD) have suggested that L-dopa may "normalize" areas of hypo- and hyperactivity. However, results from these studies, which were largely based on analyzing BOLD signal amplitude, have been conflicting. Examining only amplitude changes at distinct loci may thus be inadequate in fully capturing the activation changes induced by L-dopa. In this article, we extended prior analyses on the effects of L-dopa by investigating both amplitude and spatial changes of brain activation before and after L-dopa. Ten subjects with PD, both on and off medication, and ten healthy, age-matched controls performed a visuo-motor tracking task in which they sinusoidally squeezed a bulb at 0.25, 0.5, and 0.75 Hz. This task was contrasted with static squeezing to generate fMRI activation maps. To investigate the effects of L-dopa, we examined the amplitude and spatial variance of the BOLD response within anatomically-defined regions of interest (ROIs). L-dopa had significant main effects on the amplitude of BOLD signal in bilateral primary motor cortex and left SMA. In contrast, L-dopa-mediated spatial changes were apparent in bilateral cerebellar hemispheres, M1, SMA, and right prefrontal cortex. Moreover, L-dopa appeared to normalize the spatial distribution of ROI activation in PD to that of the controls. Specifically, L-dopa had a "focusing" effect on activity-an effect more pronounced than the typically-measured fMRI amplitude changes. This observation is consistent with modeling studies, which demonstrated that dopamine increases the signal-to-noise ratio at the neuronal level with a resultant focusing of representations at the macroscopic level.