Table 1 Summaries of the main methodologies and their results

Silva et al., 2015 [18]

Experimental Study

2 experiments were performed with young, healthy elderly and PD participants. In the 1st experiment, the task consisted of temporal order intervals and in the second experiment, it required precision in the PSE.

In Experiment 1, patients with PD were less accurate than healthy and young adults, while healthy elderly subjects were less precise than young ones. In Experiment 2, PSE was 29 ms for young, 121 ms for healthy elderly and 283 ms for PD patients.

Wiener et al., 2014 [69]

Experimental Study

25 participants underwent fMRI while performing a task of temporal discrimination and color. In addition, the polymorphisms of DRD2/ANKK1-Taq1a.SE genes were genotyped.

Better performance on time discrimination versus color was associated with a greater activation in prefrontal and subcortical regions associated with time. A1 carriers of the Taq1a polymorphism showed relatively poorer performance on time discrimination, but not on color. However, in the fMRI greater activation in the striatum and in the right dorsolateral prefrontal cortex and smaller volume in the cerebellum. These results suggest that performance differences in a time discrimination task are attributable to the DRD2/ANKK1 genotype.

Lake and Meck, 2013 [51]

Experimental Study

22 healthy volunteers were tested in peak interval timing procedures, followed by treatment with d-amphetamine, haloperidol and placebo.

Drug effects were observed, so were encountered two different patterns of timing behavior. In the first standard, d-amphetamines produced shifts to the left in the timing, while haloperidol produced shifts to the right. The second pattern was the opposite of the first pattern.

Balci et al., 2013 [67]

Experimental Study

Participants performed the task of modified interval peak and genotyping of three different gene polymorphisms (COMT Val158Met, DRD2/ANKK1-Taq1a and SLC6A3 3 ‘VNTR).

Participants anticipated the timed response when a higher reward was expected in the absence of changes in decision time or perceived time. The results showed that the reward alters the decision limits rather than the clock speed and that these effects are specific for COMT and DRD2, which constitute a balanced transmission of prefrontal and striatal dopamine.

Miller et al., 2013 [130]

Experimental Study

28 PD patients performed the finger beats synchronized with tone sequences at time intervals of 500 ms, 1000 ms or 1500 ms, when “ON” for levodopa or the placebo pill.

Patients were less synchronized with the target time interval of 500 ms compared to the larger ones, however, neither the medication status, the affected hand nor the time affected the accuracy and variability of the synchronization.

Wiener et al. 2011 [9]

Experimental Study

65 people performed the temporal discrimination task with intervals of 500 and 2000 ms, spontaneous motor timing task. Genotyping was performed for the DRD2/ANKK1-Taq1a, COMT Val158Met and BDNF Val66Met polymorphisms.

A double dissociation for time discrimination: the DRD2/ANKK1-Taq1a (A1+ allele) polymorphism was associated with significantly greater variability over 500 s, while the COMT Val158Met (Val/Val homozygotes) polymorphism was significantly associated with greater variability only for the duration of 2000 ms. In addition, the DRD2/ANKK1-Taq1a polymorphism was associated with a significantly slower motor timing.

Harrington et al., 2011 [131]

Experimental Study

The subjects composed the control and PD groups on “ON” and “OFF” therapy for DA, under evaluation of fMRI when performing a time perception task.

The results indicated the impaired timing of PD due to nigrostriatal and mesocortical dysfunction in systems that measure timing processes and non-temporal activities. However, perceived deficits in time were not improved by DA treatment, probably due to an inadequate restoration of effective corticostriatal connectivity.

Lewis and Miall. 2009 [102]

Experimental Study

5 participants estimated the time in a range of intervals (68 ms to 16.7 min), where he CV was examined.

Evidence shows a continued logarithmic decrease in CV as the intervals increase. This context, along with other reports demonstrates a scalar property violation in timing data.

Rakitin et al., 2006 [76]

Experimental Study

32 elderly and 32 healthy young people divided into placebo or levodopa groups. They trained to produce two target time slots (6 and 17 s). In addition, participants performed an accelerated reaction time task.

The results indicate that elderly participants show duration-dependent timing errors that are greater than in young people. The Levodopa use produced elongated time perception of both intervals. The aging and effects of levodopa did not interact. And aging retarded RT and increased the variability of RT, but levodopa had no effect on RT.

Lustig and Meck, 2005 [57]

Experimental Study

10 volunteers divided into 2 groups with 5 participants. In the control group, there was no drug exposure. Haloperidol group received doses of haloperidol before and during the experiment. Participants were tested for peak intervals of 7 and 14 s.

There was a deviation to the right at peak time, which increased because of feedback and was reinforced by chronic treatment with haloperidol. These data suggested a shift in the underlying signal duration representation as a function of the feedback spacing that depends on both changes in working memory and the internal clock speed.

Haslinger et al., 2001 [74]

Experimental Study

8 PD patients and 8 healthy participants underwent three fMRI executions while performing movements with joystick in free movement chosen every 7–15 s. The joystick was monitored for the online record of performance parameters, along with pacing tone time and fMRI acquisition parameters.

The control group compared to patients with and without levodopa showed impaired activation related to movement in the supplemental motor area and hyperactivation in the primary motor cortex and the lateral premotor cortex bilaterally. In this context, levodopa improved the motor initiation impairment in the supplemental motor area and decreased the hyperfunction of the lateral premotor and M1 found in Parkinson’s disease.