Computational models to delineate 3D gaze-shift strategies in Parkinson's disease

Objective: Parkinson's disease (PD) frequently affects vergence eye movements interfering with the perception of depth and dimensionality critical for mitigating falls. We examined neural strategies that compensate for abnormal vergence and their mechanistic underpinning in PD. Approach: The a priori hypothesis was that impaired vergence is compensated by incorporating rapid eye movements (saccades) to accomplish gaze shifts at different depths. Our experiments examined the hypothesis by simulating biologically plausible computational models of saccade-vergence interactions in PD and validating predictions in the actual patient data. Main results: We found four strategies to accomplish 3D gaze shift; pure vergence eye movements, pure saccadic eye movements, combinations of vergence followed by a saccade, and combination of saccade followed by vergence. The gaze shifting strategy of the two eyes was incongruent in PD. The latency of vergence was prolonged, and it was more so when the saccades preceded the vergence or when the saccades only made 3D gaze shift. Computational models predicted at least two possible mechanisms triggering saccades along with vergence. One is based on the lack of foveal accuracy when the vergence gain is suboptimal. The second mechanism reflects the noise in the gating mechanism, the omnipause neurons, for vergence and saccades. None of the two model predictions alone were completely supported by the patient data. However, a combined model incorporating both abnormal vergence velocity gain and impaired gating accurately simulated the results from PD patients. Significance: The combined strategy is biologically plausible for two reasons: (a) The basal ganglia that is prominently affected in PD projects to the vergence velocity neurons in the midbrain via the cerebellum. The projection directly affects the vergence velocity gain. (b) The basal ganglia, via superior colliculus, influences the pattern of omnipause neuronal activity. Abnormal basal ganglia activity may introduce noise in the omnipause neurons.