Saccadic latency distributions in Parkinson’s disease and the effects of l-dopa

Abstract

Parkinson's disease (PD) is associated with a loss of central dopaminergic pathways in the brain leading to an abnormality of movement, including saccades. In PD, analysis of saccadic latency distributions, rather than mean latencies, can provide much more information about how the neural decision process that precedes movement is affected by disease or medication. Subject to the constraints of intersubject variation and reproducibility, latency distribution may represent an attractive potential biomarker of PD. Here we report two studies that provide information about these parameters, and demonstrate a novel effect of dopamine on saccadic latency, implying that it influences the neural decision process itself. We performed a detailed cross-sectional study of saccadic latency distributions during a simple step task in 22 medicated patients and 27 agematched controls. This revealed high intersubject variability and an overlap of PD and control distributions. A second study was undertaken on a different population specifically to investigate the effects of dopamine on saccadic latency distributions in 15 PD patients. L-dopa was found to prolong latency, although the magnitude of the effect varied between subjects. The implications of these observations for the use of saccadic latency distributions as a potential biomarker of PD are discussed, as are the effects of L-dopa on neural decision making, where it is postulated to increase the criterion level of evidence required before the decision to move is made.

Ocular motor abnormalities in neurodegenerative disorders

“…A few studies have shown beneficial effects on the parameters of voluntary saccades, 39,42 and on the ability to perform sequences of MGS, 49 but none has ever demonstrated any improvement in the most characteristic abnormality in PD, the hypometria of MGS. Recent studies have agreed that L-dopa and dopamine agonists shorten the latency of these voluntary saccades, 62,63 whereas they prolong the latency of both externally guided or triggered saccades. 64 Several studies have examined the effect of STN stimulation on saccades.…”

Levodopa slows prosaccades and improves antisaccades: an eye movement study in Parkinson's disease

“…There is only one other report of slowed reflexive saccades with medication in PD, but those patients had early stage disease. 25 Some previous PD studies reported patients with hyperreflexive (faster than controls) baseline orienting. 12 15 26 Hence, in those studies, a levodopa slowing effect might have been beneficial for patients' reflexive responding.…”

Delayed saccadic eye movements in glaucoma

“…Normal saccade reaction times in control subjects in our study are consistent with previous work. 25,27,34 The fact that other saccade parameters such as duration, amplitude, and peak velocity are not altered suggests that patients were able to detect the targets located at 10° to the right and to the left of the fixation point, and that once the saccades were initiated, the accuracy and the motor characteristics of the saccades were not significantly affected. Therefore, the glaucomatous pathological process seems to alter mainly the initiation of saccades that involve visual input as well as a complex saccade-generation network.…”

“…Trials with saccade reaction times between 50 ms and 600 ms were analyzed, removing anticipatory saccades (,50 ms) and latencies due to inattention (.600 ms). 22,[24][25][26] Trials with saccade reaction times between 50 ms and 100 ms were defined as express saccades, 19,[32][33][34][35][36] and their frequency was counted. Trials with direction error were analyzed separately.…”

“…21,22 Dovepress submit your manuscript | www.dovepress.com Studies of these saccade parameters are used to assess the integrity of the saccade-generating neural network in various brain diseases. [23][24][25][26][27][28] In addition, saccade parameters such as increased saccade reaction time are altered in various optic nerve pathologies affecting the nerve fibers that convey visual signals to the saccade-generating network. 29,30 We hypothesize that eye movements may provide another functional marker of injury in glaucoma.…”