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passages: Discussion
  Our results indicate beneficial effects of motivational incentives on cognitive performance and alleviating effects on cognitive decline. These beneficial effects were evident in healthy young and older adults and in patients with Parkinson's disease. Young adults showed improved antisaccade preparation when a reward was at stake; older adults and PD patients could utilize reward prospect to improve their impaired antisaccade preparation. Elderly participants and PD patients were not only better prepared by means of commonly used preparatory aids (i.e., more preparation time and advance information on the upcoming response) but also by means of motivational incentives. These beneficial effects of motivational incentives on cognitive action preparation in healthy and pathological aging further support views that question the notion of monotonic deterioration of cognitive function with age (Allen et al., 2001). They indicate that age-related declines can be modulated by emotion-cognition interactions.
  In line with the predominant view that cognitive control deteriorates in aging and Parkinson's disease, and in line with previous findings on age-related changes in antisaccade control specifically (Eenshuistra et al., 2004; Chan et al., 2005; Amador et al., 2006; Abel and Douglas, 2007), the current results showed decline in antisaccade preparation in PD patients with severe motor symptoms as compared to healthy seniors. Mild-symptom patients and healthy elderly did not differ in antisaccade preparation. Healthy seniors showed declining antisaccade preparation as compared to young adults. Decline was evident on several oculomotor parameters and most pronounced on antisaccade onset latencies. In line with the notion that in general, elderly tend to prefer accuracy over speed, elderly showed no decreased antisaccade accuracy as compared to young adults. As compared to the young group, elderly and PD patients exhibited slightly, but not significantly more premature eye movements. Premature eye movements, however significantly increased in elderly and PD patients but only slightly in the young, when more specific information on the upcoming movement was available in advance. Presumably, this increase in premature eye movements reflects difficulties with the inhibition of externally guided movement and/or the suppression of strongly activated prepotent action plans. On the one hand, the choice for medicated PD patients represents a limitation of the current study as we cannot exclude differential effects of medication on behavior. On the other hand, PD patients generally take medication in their daily routine, such that the results can be generalized to clinical practice. Exploratory analysis within the PD patient group revealed that patients with more severe motoric symptoms (as indexed by their motoric subscore on the UPDRS) displayed more signs of antisaccade decline, such as longer antisaccade latencies and lower accuracy compared to mildly affected patients, who initiated saccades equally fast as healthy adults. This suggests that dopaminergic medication was not sufficient to raise the patient's antisaccadic preparation up to the level of the healthy older adults.
  One intriguing observation was that despite the different extents of observed antisaccade performance decline in elderly and PD patients, reward prospect led to beneficial effects on antisaccade latency and accuracy in young, elderly, and PD patients alike. Young, elderly and PD patients benefited from reward prospect to the same extent, confirming that the expectancy of reward is a powerful mediator of cognitive control, even if cognitive control suffers from decline. The expectation of rewarding incentives thus seems to support older adults' and PD patients' ability to anticipate, prepare and initiate goal-directed behavior.
  These findings imply that despite a general decline in the action preparation system as indexed by increased antisaccade latency, action preparation processes remain susceptible to the prospect of future reward. It could thus be argued that the neural representations of upcoming rewards influence neural systems concerned with action preparation and oculomotor control. Although the current behavioral results cannot exclude or confirm neural links between reward anticipation and action preparation systems in the brain, they suggest intact cross-talk among subcortical circuits that allow goal-directed action to be modified by motivational factors. The motivational neural reward anticipation signal presumably activates the reward network including the amygdala, orbitofrontal cortex, the more ventral and dorsal striatum (nucleus accumbens, putamen, and caudate), leading to an release of caudate/SNr inhibition on the executive oculomotor structure superior colliculus. This transiently decreased inhibitory force on superior colliculus may improve goal-directed oculomotor control. Thus reward anticipation might compensate for the age- and disease-related dopaminergic loss in the SNc projections to the caudate/SNr and may thus play a compensatory role in "boosting" the efficiency of interactions between motivational and impaired cognitive control processes.
  However the reward-related modulation of the oculomotor control system may not only apply to the basal ganglia part of the oculomotor network. Although speculative, it could extend to the cortical eyefields (frontal, supplementary, and parietal eyefields) and to parts of the visual cortex. Human research shows that more preparatory activation in the frontal eyefields leads to a faster antisaccade latency (Connolly et al., 2002, 2005). The compensatory effect on the antisaccade latency, therefore, could theoretically stem from a propagation of reward anticipation signal in the caudate to the frontal eyefields. Complex structural connections enable the striatum to exert a controlling influence over the cerebral cortex via a series of reentrant corticobasal ganglia circuits. Thus reward anticipation may increase the level of preparation in the intact cortical eyefields and thereby compensate for age- and disease-related subcortical decrements in the oculomotor network.
  Taken together, it seems plausible that motivational reward processes in the caudate enhance preparatory activation in subcortical as well as in cortical nodes of the oculomotor network. Several neurotransmission mechanisms may underlie the remedial effect of positive incentives on declining antisaccadic control. Given the convergence of dopamine and glutamate inputs at the spiny projection neurons in the striatum (Burns et al., 1994), an interaction between dopamine and glutamate might underlie striatal processes of reward anticipation and action preparation. However, it cannot be fully excluded that alterations in other neurotransmitter systems may also have an effect on declining oculomotor control and on remediating incentive effects. Non-dopaminergic changes such as noradrenergic, serotonergic, and cholinergic deafferentation of the cortex also occur in PD and can inflict cognitive deficits (Agid et al., 1987). Evidence from non-human primates suggests that basal ganglia dopamine acts to speed motor responding in response to rewarding cues (Niv, 2007; Niv et al., 2007). Among at least five types of DA receptors, mainly D1 and D2 receptors are expressed in caudate projection neurons (Nakamura and Hikosaka, 2006). Tendencies to speed responses to obtain large rewards have been found to be dependent on striatal D1 receptors (Dalley et al., 2005; Berridge, 2007). In contrast to this D1 modulated speeding in reward-motor tasks, evidence from saccade tasks in non-human primates suggests D2 receptor modulation of reward dependent improvements of performance (Nakamura and Hikosaka, 2006). Injections of a D1 antagonist and a D2 antagonist into the region of the caudate where saccade-related neurons are clustered while the monkey performed a reward-biased saccade task showed that D1 antagonists attenuate the reward modulation of saccade behavior whereas D2 antagonists into the same region enhanced the reward-dependent changes.
  Future studies of Parkinson patients on versus off medication, could provide some information on the role of dopaminergic mechanisms in the remedial effects on antisaccadic performance. A recent study of reward learning in Parkinson patients on/off dopaminergic medication showed that patients adapted their behavior to maximize expected reward value dependent on their medication status (Moustafa et al., 2008). Whilst off dopaminergic medication, patients slowed their responses to avoid low expected values, but succeeded less well in speeding responses when a reward was at stake. The opposite pattern emerged when the same patients were on medication; patients showed better response speeding, and worse response slowing, to maximize expected value.
  The current behavioral findings are in line with neuroimaging research showing intact neural representations of future reward in the aging striatum (Samanez-Larkin et al., 2007). The observation however that older adults and PD patients can use this intact neural representation of reward anticipation (a positive motivational incentive) to optimize their preparatory processes, cannot necessarily be generalized to cognitive contexts with negative motivational incentives. Samanez-Larkin et al.(2010) recently showed that older adults were not able to optimally use their intact neural reward anticipation system in risky financial decision making. Elderly made more suboptimal choices when they were to choose risky assets. The authors deemed it likely that these decrements in value-based decision making are explained by the fact that value-based decision making requires the weighting of behavioral alternatives, that may lead to either gain or loss. During anticipation of rewards older adults show similar neural responses as young adults but they show reduced neural activation during the anticipation of losses (Samanez-Larkin et al., 2007). The latter, together with the observation that older adults tend to shift their attention away from negative stimuli and attend to positive information instead (Mather and Carstensen, 2003, 2005), may have led to the underestimation of loss and therefore to more risky and suboptimal decisions.
  In this respect, one limitation of the current task is that it built solely on reward prospect and not on the prospect of loss, such that the question of how the anticipation of loss influences action preparation was not tested. The impact of negative incentives might be an intriguing question for future research, as due to the decreased activation of the neural loss anticipation system (Samanez-Larkin et al., 2007) together with the observed differential attentional bias for negative and positive information (Mather and Carstensen, 2003), it seems likely that negative motivational incentives, i.e., the prospect of loss, might have a different impact on action preparation in older adults than in the young. Future approaches to the effect of loss anticipation on declining antisaccade control may ideally contain a sequence of experiments, starting with a separate (punishment only) approach before moving to combined reward-punishment designs. This might be necessary as previous evidence (from healthy young adults) suggests that the reward effect on oculomotor control disappears in the presence of punishment trials. The authors deemed it likely that the participants increased caution to all incentive (reward and punishment) trials (Blaukopf and DiGirolamo, 2006).
  As of yet, age-related changes in neural reward anticipation have mainly been studied in isolation. Recently however, the interaction of neural reward processing with other cognitive functions and their underlying neural systems, such as the action control system, has gained increasing interest (Haber and Knutson, 2010). Initial evidence suggests coordinated activity between distant brain regions responsible for reward processing (Cohen et al., 2009). The current results encourage further neural network investigations on the role of coordinated brain network activity in motivated behavior. Behavioral benefits from motivation might be associated with changes in functional brain connectivity on a larger scale, e.g., between frontostriatal reward and action preparation structures.
  Another important factor that emerges from the present and previous results, is the importance of the training of the motivational aspects of the instructions that need to be kept in working memory when performing a cognitive task. Samanez-Larkin et al. (2007) found intact neural reward anticipation processes specifically in the absence of learning (after the learning process of reward cue-reward associations was completed). Therefore it might be important for researchers doing experiments with motivation based instructions to keep in mind that, compared to young adults, elderly and PD patients are generally hampered on stimulus-response learning (Shohamy et al., 2004; Marschner et al., 2005). Reward instruction cues, as they were used in the current study require participants to form reward cue-reward associations. Impairments in the learning of associations between the cue signaling reward and the actual reward might conceal intact reward anticipation processes. When the formation of associations is weakened, it could appear as a failure to capitalize on the neural reward anticipation system, whereas it represents an indirect effect of non-available reward associations in working memory when preparing the response. Hence, one might circumvent the effect of potential learning impairments on reward anticipation processes by the training of abstract reward cues (as in the current and in Samanez-Larkin's study) or by using explicit and concrete rewards. Once the learning of reward cues is accomplished the intact reward anticipation processes might become evident.
  In sum, the results confirmed that the preparation of goal-directed actions declined in PD patients compared to healthy seniors, and in healthy seniors compared to young adults. Due perhaps to deterioration in dopaminergic striatal circuitry, antisaccade performance is subject to decline in healthy seniors, and even more in individuals with Parkinson's disease. The prospect of future reward however provided a motivational incentive for optimizing oculomotor preparation in all groups alike. These results suggest that reward-processing networks and oculomotor-control networks in the brain are connected in such a way (presumably with the dorsal striatum as a common nexus) that reward anticipation can facilitate oculomotor control and alleviate the deficiencies experienced by healthy seniors and PD patients. Future investigations should examine whether the observed effects are specific for the current task or generalize to other tasks that show age- and PD-related cognitive decrements (e.g., in task switching) and have been related to dopaminergic denervation in the caudate (e.g., impaired verbal episodic memory, attention, and response inhibition; Rinne et al., 2000; Bruck et al., 2005). Future studies on network processes may help to localize the neural link between reward prospect and action preparation that enables alleviating effects of motivational incentives on cognitive decline.
  