Role of anticipation and prediction in smooth pursuit eye movement control in Parkinson's disease

Abstract

Patients with Parkinson's disease (PD) have difficulties in the control of self-guided (i.e., internally driven) movements. The basal ganglia provide a nonspecific internal cue for the development of a preparatory activity for a given movement in the sequence of repetitive movements. Controversy surrounds the question of whether PD patients are capable of (1) anticipating (before an external trigger appears; i.e., anticipation) and (2) predicting movement velocity once a moving target shortly disappears from the visual scene (i.e., prediction). To dissociate between these two components, we examined internally driven (extraretinal generated) smooth pursuit eye movements in PD patients and age-matched healthy controls by systematically varying target blanking periods of a trapezoidally moving target in four paradigms (initial blanking, midramp blanking, blanking after a short ramp, and no blanking). Compared to controls, PD patients showed (1) decreased smooth pursuit gain (without blanking), (2) deficient anticipatory pursuit (prolonged pursuit initiation latency; reduced eye velocity before target onset in the early onset blanking paradigm), and (3) preserved extraretinal predictive pursuit velocity (midramp target blanking). Deficient anticipation of future target motion was not related to either disease duration or the general motor impairment (UPDRS). We conclude that PD patients have difficulties in anticipating future target motion, which may play a role for the mechanisms involved in deficient gait initiation and termination of PD. In contrast, they remain unimpaired in their capacity of building up an internal representation of continuous target motion. This may explain the clinical advantage of medical devices that use visual motion to improve gait initiation (e.g., "PD glasses").

The association between alterations of eye movement control and cerebral intrinsic functional connectivity in Parkinson’s disease

“…Altered oculomotor performance in PD Significant differences between PD patients and controls were demonstrated for all of the investigated eye movement parameters (Table 2), in agreement with previous studies (Helmchen et al 2012;Mosimann et al 2005;Pinkhardt et al 2012;Terao et al 2011). The only exception was peak eye velocity.…”

“…2a, left panels). Notably, patients with severely impaired pursuit eye movements were fairly able to track the target smoothly for at least small periods in time, as previously reported (Helmchen et al 2012;Pinkhardt et al 2012). The reduced accuracy gain during the performance of reactive saccades resulted from predominantly 'hypometric saccades'.…”

Association of variants in DRD2 and GRM3 with motor and cognitive function in first-episode psychosis

“…The present candidate gene study of discrete oculomotor phenotypes demonstrates for the first time that pursuit initiation and sustained pursuit maintenance have distinct associations with genes regulating dopamine and glutamate systems respectively in untreated patients with psychotic disorders. Specifically, DRD2 was associated with pursuit initiation ability, consistent with the role of dopaminergic neurotransmission in the striatum regulating speed of motor response initiation as demonstrated in preclinical studies and in patients with Parkinson's disease [24]. This association was also modulated by antipsychotic treatment highlighting the importance of studying the genotype-phenotype associations of interest in untreated patients and offering indirect support for the proposed role of D2 receptor activity and motor response initiation.…”

“…First, slowed pursuit initiation in response to the onset of target motion represents an abnormality in motor function. Dopamine modulation in the basal ganglia is crucial for motor response initiation generally and pursuit initiation specifically [24]. Second, deficits in maintaining accurate sustained pursuit reflect altered use of higher-order predictive mechanisms and perceptual analysis of performance that are dependent on corticocortical connectivity across specific well-characterized regions of association cortex [25,26].…”

Alterations of Eye Movement Control in Neurodegenerative Movement Disorders

“…In this paradigm, subjects are asked to track a randomly “jumping” target as quickly and as accurately as possible. Smooth pursuit eye movements are elicited by requiring the subjects either to track a continuously moving target [36] or to track a sinusoidally oscillating target [37]. In order to assess attentional eye movement control as a correlate of the cognitive (cortical) top-down oculomotor pathway, delayed saccades and antisaccades are executed.…”