Time Distortion in Parkinsonism

Abstract

Although animal studies and studies on Parkinson's disease (PD) suggest that dopamine deficiency slows the pace of the internal clock, which is corrected by dopaminergic medication, timing deficits in parkinsonism remain to be characterized with diverse findings. Here we studied patients with PD and progressive supranuclear palsy (PSP), 3-4 h after drug intake, and normal age-matched subjects. We contrasted perceptual (temporal bisection, duration comparison) and motor timing tasks (time production/reproduction) in supra- and sub-second time domains, and automatic versus cognitive/short-term memory-related tasks. Subjects were allowed to count during supra-second production and reproduction tasks. In the time production task, linearly correlating the produced time with the instructed time showed that the "subjective sense" of 1 s is slightly longer in PD and shorter in PSP than in normals. This was superposed on a prominent trend of underestimation of longer (supra-second) durations, common to all groups, suggesting that the pace of the internal clock changed from fast to slow as time went by. In the time reproduction task, PD and, more prominently, PSP patients over-reproduced shorter durations and under-reproduced longer durations at extremes of the time range studied, with intermediate durations reproduced veridically, with a shallower slope of linear correlation between the presented and produced time. In the duration comparison task, PD patients overestimated the second presented duration relative to the first with shorter but not longer standard durations. In the bisection task, PD and PSP patients estimated the bisection point (BP50) between the two supra-second but not sub-second standards to be longer than normal subjects. Thus, perceptual timing tasks showed changes in opposite directions to motor timing tasks: underestimating shorter durations and overestimating longer durations. In PD, correlation of the mini-mental state examination score with supra-second BP50 and the slope of linear correlation in the reproduction task suggested involvement of short-term memory in these tasks. Dopamine deficiency didn't correlate significantly with timing performances, suggesting that the slowed clock hypothesis cannot explain the entire results. Timing performance in PD may be determined by complex interactions among time scales on the motor and sensory sides, and by their distortion in memory.

Keywords: Parkinson’s disease; basal ganglia; dopamine; progressive supranuclear palsy; time perception.

FIGURE 1

Duration comparison task. (A) The subjects compared time durations (S1, S2) presented successively with an interval of 2.0–2.5 s and judged which of the two durations was longer. Subjects responded by pressing one of two buttons, corresponding to long or short responses. The proportion of trials in which subjects judged S2 duration to be longer than S1 duration was plotted as a function of S1 (standard) duration, separately in the (B) S1 = 700 ms, (D) S1 = 2100 ms, and (F) S1 = 3500 ms standard tasks. Red dots: PD patients, Black dots: normal subjects. The scattergrams were fitted to a logistic function. The horizontal dashed lines indicate the 50% level on the ordinate. The cross-point with the curve corresponds to the point of subjective equality (PSE). The PSE was compared between normal subjects and PD patients. (C) S1 = 700 ms, (E) S1 = 2100 ms, (G) S1 = 3500 ms. Error bars give standard errors.

FIGURE 2

Temporal bisection task. (A) In the training phase, subjects were presented with standard durations of short and long durations until they learned the durations. In the test phase, subjects were required to judge whether the presented test duration was closer to the shorter or longer standard durations. (B) In the 400 versus 1600 ms task, the proportion of test trials in which subjects responded “long” was plotted as a function of test stimulus duration for each subject group (normal subjects, PD patients, and PSP patients). Error bars give standard errors. (C) Comparison of the bisection point at which subjects responded “long” with a probability of 50% (BP50) was compared among different subject groups in the 400 ms versus 1600 ms task. (D) A plot similar to B made for the 2 s versus 8 s bisection task. (E) A plot similar to (C) for the 2 s versus 8 s bisection task.

FIGURE 3

Time production task. (A) In the time production task, subjects were required to produce the time presented on the monitor screen in number of seconds. When the subjects press a button, a filled circle appears in the center of the screen. The subjects press the button again when they consider the time to be produced has elapsed, when the circle disappears and a cross reappears instead. The interval between the two button presses corresponds to the produced time. (B) The time produced was plotted as a function of the time instructed to produce for a normal subject. The dashed line indicates the line of unison on which the produced time equals the instructed time. (C) Comparison of the slopes of linear correlation among the three subject groups. (D) The time produced was plotted as a function of the time instructed to produce for the average of all subjects within each group. Error bars indicate standard errors. The dashed line indicates the line of unison as in (B). Blue curve: normal subject, red curve: PD patients, green curve: PSP curve.

FIGURE 4

Time reproduction task. (A) Subjects were required to reproduce the time duration indicated by the presentation of a visual stimuli (circle) by making two button presses and making the interval between them equal to the presented duration. (B) The time reproduced was plotted as a function of the presented time duration in a subject. Dots represent data for individual trials. The dashed line indicates the line of unison over which the produced time equals the instructed time. (C) The slope of linear correlation was compared among the three subject groups. (D) A similar plot depicting the averaged group data. Error bars indicate standard errors. Dashed lines indicate the line of unison over which the produced time equals the instructed time. Blue curve: normal subjects, red curve: PD patients, green curve: PSP patients. (E) Subjects (normal subjects, PD patients) were required to reproduce the presented time duration ranging from 0.5 to 10 s similarly as above. Blue curve: normal subjects, red curve: PD patients.