Abstract
Inhibiting inappropriate actions in a context is an important part of the human cognitive repertoire, and deficiencies in this ability are common in neurological and psychiatric disorders. An anti-saccade is a simple oculomotor task that tests this ability by requiring inhibition of saccades to peripheral targets (pro-saccade) and producing voluntary eye movements toward the mirror position (anti-saccades). Previous studies provide evidence for a possible contribution from the basal ganglia in anti-saccade behavior, but the precise role of different components is still unclear. Parkinson’s disease patients with implanted deep brain stimulators (DBS) in subthalamic nucleus (STN) provide a unique opportunity to investigate the role of the STN in anti-saccade behavior. Previous attempts to show the effect of STN DBS on anti-saccades have produced conflicting observations. For example, the effect of STN DBS on anti-saccade error rate is not yet clear. Part of this inconsistency may be related to differences in dopaminergic states in different studies. Here, we tested Parkinson’s disease patients on anti- and pro-saccade tasks ON and OFF STN DBS, in ON and OFF dopaminergic medication states. First, STN DBS increases anti-saccade error rate while patients are OFF dopamine replacement therapy. Second, dopamine replacement therapy and STN DBS interact: L-dopa reduces the effect of STN DBS on anti-saccade error rate. Third, STN DBS induces different effects on pro- and anti-saccades in different patients. These observations provide evidence for an important role for the STN in the circuitry underlying context-dependent modulation of visuomotor action selection.
Highlights
Our tremor measurements indicate that both L-dopa and deep brain stimulators (DBS) have a significant effect in decreasing tremor amplitude (t-stat = 2.15, p-value = 0.03 for L-dopa, and t-stat = 3.04, p-value = 0.004 for DBS), confirming that effective subthalamic nucleus (STN) DBS and L-dopa treatment was delivered during the oculomotor task
We draw three important conclusions based on our results: first, pro-saccades and anti-saccades are driven by partially independent mechanisms, and DBS and L-dopa can modulate the two systems independently
As pro-saccades are mainly generated faster than anti-saccades, the DBS effect is relatively more pronounced on pro-saccades than anti-saccades, and the action facilitation caused by STN DBS leads to higher anti-saccade error rate
Summary
Patients first received a general introduction to different steps of the protocol that covered the whole day They were instructed on the eye movement tasks and went through the first block of tests in the OFF L-dopa – ON stimulation condition. Patients had a one minute break between the blocks, and a two minute break between pro-saccade and anti-saccade trials For both tasks, the fixation target, a green circle subtending 1.5 visual degrees (luminance 55.2 cd/m2), appeared on the center of the screen at the beginning of each trial. For GLME models to fit the data probability distribution, for all the measurements, the Akaike Information Criterion (AIC) was used to compare between different models with different output distributions: Normal, Gamma, and Inverse Gaussian Based on these model comparisons, for the error rate and latencies, we used normal and inverse gamma distributions, respectively. In the cases where the structure of the GLME model needed to be determined based on the data (e.g. adding or removing an interaction term, or a random-effect), we used AIC to compare between different model structures
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