New perspectives on the pathophysiology of Parkinson's disease as assessed by saccade performance: a clinical review.

We reviewed basal ganglia (BG) dysfunction in Parkinson's disease (PD) based on recent findings on saccade performance. Hypometria in all saccade paradigms and impaired initiation of internally triggered saccades such as memory guided saccades (MGS) are reported, whereas visually guided saccades (VGS) are relatively spared, although they are also mildly affected. The ability to inhibit unwanted saccades is also impaired. We propose that three major drives converges on SC to determine the saccade abnormalities. The impairment in VGS may be caused by the excessive inhibition of SC due to the increased BG output, whereas for MGS, decreased activity of the frontal cortex-BG circuit may also be involved. The impaired suppression of unwanted saccades may result from the "leaky" inhibition of SC. When PD patients inspect pictures, they end up exploring a smaller area of them with smaller saccades compared to normal subjects. Levodopa slightly prolongs VGS latency and shortens MGS latency, by altering the balance between the direct and indirect pathways of the BG circuit. In contrast, deep brain stimulation of the subthalamic nucleus improves saccade hypometria in both VGS and MGS, presumably by acting relatively directly on the SC-substantia nigra pars reticulata pathway to remove the excessive SC inhibition.