In this study we investigated whether an accurate assessment of oculomotor changes in PD patients - subdivided in a group with oral dopaminergic medication and a group of STN-DBS patients in the DBS "on" and "off" condition with additional oral dopaminergic medication - may allow a conclusion as to the pathomechanism of oculomotor dysfunction in PD. With regard to oculomotor function, we observed a reduced SPEM gain (typically caused by the release of predictive saccades, cf. Figure 1 in ), increased latency of RS (in PD-DA only) and a decreased number and gain of AVGS in all patient groups in comparison to controls. These results are in general agreement with the literature on oculomotor dysfunction in PD (i.e. ). However, none of the investigated oculomotor parameters exhibited significant differences between patients treated with dopamine only (group PD-DA) and those receiving STN-DBS (group PD-DBS-on). In DBS patients, the only effect of stimulation withdrawal was a just significant reduction of N30 whereas all other examined oculomotor parameters did not differ.
STN-DBS has been reported to significantly reduce the latency of visually triggered saccades [2, 7, 8], and to increase their gain [7, 8]. Similar to the present study, Rivaud-Péchoux et al. observed an only non-significant shortening of latency by STN-DBS but a reduction of errors in an antisaccades task. A convincing mechanistic explanation for the observed improvements does not seem to exist, so far. Since STN neurones are thought to excite crossed nigro-collicular cells, it is difficult to understand how a supposedly elevated STN activity in PD could facilitate (instead of prevent) the release of inappropriate saccades by the colliculus observed in many studies [4, 6] or how a reduction of STN overactivity by DBS could lead to the reduction of inappropriate saccades noted in other studies . Sauleau et al.  invoke an altered control of the interaction between STN and substantia nigra pars reticulata (SNpr) in advanced PD which would be restored to normal via improved functioning of the parieto-collicular pathway. Temel et al.  suggest that the reduction of STN activity by DBS enhances the facilitation of the colliculus by interacting with the cortico-basal-collicular pathway. Yugeta et al.  invoke the more recent finding that PD pathology may be linked to the occurrence of abnormal oscillatory β-activity in STN. Similar to skeleto-motor performance , desynchronisation of this activity by STN-DBS would also be beneficial for oculomotor behaviour although its differential effect on reactive and unsolicited saccades remains to be explained.
Why do our measurements of saccadic latency not reproduce the beneficial effect of STN-DBS reported by others? With regard to latency and saccadic gain, the majority of our STN-DBS patients appear to have been too close to normal to exhibit any sizeable effect of STN-DBS. Moreover, the tendency for longer saccade latencies in PD as compared to CTL may in part have resulted from their dopaminergic medication that had been received two hours before eye movement recording .
We are unaware of studies that would have examined the effect of STN-DBS on the SPEM gain. The lack of a significant SPEM gain amelioration by STN-DBS in our patients suggests that the stimulation does not improve the inhibitory control of unwarranted saccades during pursuit (a main cause of SPEM gain reduction, [18, 21–26]). Experimental evidence for an amelioration of inhibitory control from previous studies by STN-DBS is mixed, at best. STN-DBS was found ineffective at reducing antisaccade errors [8, 9], but reportedly diminishes the frequency of premature saccades during a memory saccade task .
As a further paradigm which has not been studied during STN-DBS, we have examined the ability to rapidly saccade back and forth between two fixed targets. This paradigm was the only one to reveal a significant but small improvement under STN-DBS. This result is in line with the notion of the basal ganglia being particularly important for voluntary, endogenous saccades  in PD. In summary, our data suggest that STN-DBS can increase the frequency of voluntary saccades but does not improve SPEM gain in PD.
In contrast to the investigated eye movement parameters, the patients' skeletomotor system (UPDRS III scores) clearly improved with STN-DBS. The beneficial effect of STN-DBS on motor function is well established . Nevertheless, if the observed eye movement alterations in PD resulted from a dysfunction of mainly dopamine-mediated mechanisms that can be relieved by STN-DBS, there should exist a correlation between STN-DBS-related improvement in UPDRS III and eye movement performance. We observed no such correlation, in particular when comparing the only eye movement parameter improving with DBS-STN (N30) to a skeletomotor analogue (UPDRS III subscore for rapid alternating hand movements). However, also authors who noted a SPEM improvement with dopamine agonists point out that this effect is much smaller than the concurrent UPDRS III improvement .
Also studies addressing the effect of dopamine on eye movements have produced ambiguous results (i.e. [4–6, 23]). Some of these studies warrant methodological concerns such as different medication and withdrawal regimes (for a review, ). Moreover, the long half-value period of the ubiquitously applied dopamine agonists makes it difficult to examine patients in a true medication-off state since the medication-free time has to be limited for ethical reasons and because it is unclear whether there is a direct link between the plasma level of medication and possible influences on oculomotor function.
Compared with skeleto-motor function, there may be not an as clear a link between pathologic STN oscillations and eye movement alterations as these oscillations mainly affect dorsal STN and less so the ventral, eye movement related STN  Therefore, the effect of STN-DBS on eye movement alterations may be limited. Taken all together, the above considerations are in line with growing evidence that pathologies outside the dopaminergic nigrostriatal pathway may also be responsible for oculomotor deficits in PD (i.e. ). In view of the occurrence of frontal lobe pathology in PD , an impact of non-dopaminergic alterations in frontal cortical areas on eye movement control in PD is conceivable . In this regard Rieger et al.  have found the frontal eye field itself to be hypoactive when performing horizontal voluntary saccades in an fMRI study. This study  as well as data showing a statistically significant correlation between the impairment of smooth pursuit and premature saccades in a delayed saccade task in PD  strongly support for the assumption of a top-down frontostriatal pathomechanism of saccadic dysfunction in PD..