The finding that the

PD group initiated voluntary saccades at abnormally long latencies in the baseline condition is consistent with many previous reports (Kennard & Lueck, 1989; Kitagawa et al., 1994; Amador et al., 2006). It is also consistent with the premise PLX3397 mouse that saccade initiation in PD is impaired due to over-activity of inhibitory outputs from the basal ganglia via the substantia nigra pars reticulata (SNr) projection to the SC (Albin et al., 1995; Mink, 1996; Hikosaka et al., 2000). The tonic inhibitory output to the SC must be selectively released to allow burst firing of saccade-triggering cells (Hikosaka & Wurtz, 1985). Nigral dopaminergic innervation of the striatum is crucially involved in generating the signal that suppresses the tonic inhibitory output from the SNr to the SC when a saccade is to be made (Hikosaka et al., 2000; Nakamura & Hikosaka,

2006). Thus, in PD, degeneration of nigral dopamine cells may result in over-activity of the inhibitory output from the SNr, thereby affecting the build-up of neural activity in the SC and delaying the triggering of saccades. In the PD group, latencies were abnormally reduced by (pre-saccadic) peripheral symbol changes when voluntary saccades were performed without the discrimination task. Olaparib This observation is consistent with other studies showing that exogenous stimuli can facilitate endogenous saccades (Shepherd et al., 1986). We suggest that peripheral visual events (i.e. the symbol changes in this paradigm) might 4-Aminobutyrate aminotransferase accelerate saccade initiation in PD by boosting the build-up of neural activity in saccade neurons. This exogenous boost might reduce the delay in the build-up of neural activity in the SC in PD. The PD group exhibited an abnormally large latency reduction when voluntary saccades were made in conjunction with the discrimination task. We suggest that the

intention to perform the discrimination task promotes the release and shift of attention away from the central fixation point, in preparation for the impending appearance of the discrimination symbol at the peripheral saccade target location. This effect supports and facilitates saccade planning and can thereby reduce saccade latencies (Montagnini & Chelazzi, 2005; Trottier & Pratt, 2005). Previously, we reported that the concurrent performance of a discrimination task abnormally reduced latencies of visually guided (or reflexive) saccades in the same PD group (van Stockum et al., 2011b). Especially in overlap trials, the continued presence of the fixation point apparently did not exert the same inhibitory effect in the PD group as in the control group. We proposed that the abnormal endogenous facilitation of visually guided saccades observed in PD may be associated with a decrease in the inhibition of saccade cells during fixation.