Executive impairment in Parkinson's disease: Response automaticity and task switching
Introduction
Parkinson's disease (PD) involves the degeneration of dopamine producing cells in the substantia nigra pars compacta that input to the striatum (Betchen & Kaplitt, 2003). The consequence of this is altered neuronal firing in the two principal pathways of the basal ganglia (BG): the direct and indirect, which leads to a net increase in inhibitory output from the BG on thalamo-cortical circuits, and on the superior colliculus (Dagher and Nagano-Saito, 2007, Hikosaka et al., 2000, Mink, 1996, Schultz, 2001). This results in the hallmark motor symptoms of bradykinesia (slowed movement execution) and akinesia (impaired movement initiation), and is thought to contribute to executive dysfunction often observed in PD which resembles that following frontal lobe damage (Lewis et al., 2003, Owen, 2004). Accordingly, tasks that require both an initiation of a motor response as well as executive control over behavior unearth deficits in behavioral control in PD. In the antisaccade task, PD patients fail to suppress an automatic prosaccade to a visual stimulus more frequently than normal healthy adults, resulting in erroneous eye movements in the direction of the stimulus (Amador et al., 2006, Briand et al., 1999, Chan et al., 2005, Hood et al., 2007). PD patients are also slower to initiate an antisaccade. The antisaccade task is one of the simplest models of behavioral control, and deficits in PD suggest that deficient dopaminergic (DA) input to the BG disrupts the suppression and focusing mechanisms (Mink, 1996) of the BG on cortical (e.g., frontal eye fields, dorsolateral prefrontal cortex) signals critical to generating a voluntary saccade, and suppressing an automatic saccade (Munoz & Everling, 2004). Importantly, these antisaccade deficits highlight an asymmetric impairment in PD, in which an unimpaired automatic response interferes with the execution of an alternative, voluntary, response. Some evidence exists that this impairment might occur at a more cognitive stage, during which an antisaccade task set (a rule about how to respond) is established prior to response programming (Rivaud-Pechoux, Vidailhet, Brandel, & Gaymard, 2007). However, most previous studies have focused on the failure to suppress an automatic prosaccade to a peripheral stimulus, and on the slower programming of the voluntary antisaccade away from the stimulus in PD. More work is needed to understand how the easier prosaccade task set might compete with the more difficult antisaccade task set, setting-up a person with PD for an incorrect or impeded response before a response is programmed.
To explore this, we now draw on studies of task switching that have been more optimally designed to explore the interaction between competing task sets. Task switching experiments have also shown that PD patients have deficits in behavioral flexibility that can be explained, at least partially, by fronto-BG dysfunction. Deficits include slowed reaction times when the appropriate response changes across trials (Cools et al., 2001, Cools et al., 2003), perseveration errors in the Wisconsin Card Sorting Task (Lees and Smith, 1983, Milner, 1963) related to the inability to change task set, and impairments in working memory resulting in deficits manipulating rule representations (Lewis et al., 2005, Owen, 2004). Importantly, it has been demonstrated with functional magnetic resonance imaging (fMRI) that fronto-BG circuitry is important to task switching (Cools, Ivry, & D’Esposito, 2006) and that differences in cortical as well as BG activation are seen when comparing PD patients and control subjects performing switching tasks (Monchi et al., 2004, Monchi et al., 2007). However, unlike the antisaccade task, studies in task switching typically rely on participants to switch between stimulus–response mappings learned in a given experiment, and do not contrast highly automatic behavior to alternative, more difficult behavior to perform. An exception to this is a study by Woodward, Bub, and Hunter (2002), who showed in a Stroop paradigm that patients with PD had greater reaction time ‘costs’ than controls when they first performed the more automatic word reading response, but then subsequently performed the more difficult color naming response. Thus, deficits in task switching in PD may relate to how ‘easily’ one can switch between two behaviors that differ in automaticity.
We previously created a paradigm in which participants were prompted to plan one response (pro or antisaccade) but then switch it, unexpectedly, to the alternative on a subset of trials (Cameron, Watanabe, & Munoz, 2007). Importantly, the switching difficulty was asymmetric, meaning that subjects could be switching to a response that was either more automatic (prosaccade), or less automatic (antisaccade), to perform. Moreover, the time in a given trial in which the switch occurred varied with respect to peripheral stimulus onset, such that if the switch in instruction occurred in advance of stimulus onset, it would constitute a change of task set alone. Using a version of this paradigm, we also showed with fMRI that activation in the caudate nucleus (CN), the BG input nucleus in the oculomotor system, correlated to switching difficulty (Cameron, Coe, Watanabe, Stroman, & Munoz, 2009). A greater increase in CN activation occurred when subjects first planned a prosaccade, but then had to switch to an antisaccade, than when subjects first planned an antisaccade, but then had to switch to a prosaccade. This demonstrated that activation of the CN correlated with switching from a more automatic to a more difficult behavior. Based on previous findings from the antisaccade and task switching literature, we hypothesize that PD patients in a similar task will show greater difficulties (increased reaction time and error rates) on antisaccade trials compared to control subjects, greater difficulties in switching task, and greatest difficulties in switching from a pro to an antisaccade. We are also interested in determining if deficits exist when only task set is changed.
The results show that PD patients had an underlying bias towards the more automatic prosaccade response that interacted with their task switching behavior: patients were overall superior at prosaccade performance, but impaired at antisaccade performance. Thus, with respect to task switching, patients showed poorer performance in switching from a pro to an antisaccade in comparison to the controls, but showed superior performance in switching from an anti to a prosaccade. Interestingly, their poorer performance in switching from a pro to an antisaccade occurred only when a change in task set was required. Therefore, we suggest that enhanced biases towards more automatic or habitual behavior exist prior to programming a response in PD, and this can explain some of the deficits observed in both antisaccade and task switching experiments.
Section snippets
Participants
All experimental procedures were reviewed and approved by the Queen's University Human Research Ethics Board and adhered to the Declaration of Helsinki. 26 individuals (14 PD, 12 age-matched control participants) with normal or corrected-to-normal vision were recruited. All participants were permitted to wear corrective lenses if required, and all participants provided written informed consent and were compensated for their participation ($10/h). PD patients (mean age = 60.1, 10 males) were
Blocked design
Both PD patients and controls made more errors on antisaccade trials than on prosaccade trials, PD: Z = 3.06, P < 0.01, control: Z = 2.67, P < 0.01 (compare Fig. 2A and C). There was a greater percentage of direction errors on antisaccade trials for PD (21%) compared to controls (13%) (Fig. 2C), however this did not reach significance, Z = 1.65, P = 0.10. Both PD and control participants had greater SRTs for antisaccade trials relative to prosaccade trials, PD: t(11) = 5.65, P < 0.01, control: t(11) = 4.79, P <
Discussion
We hypothesized that if PD patients had an underlying deficit in task switching, they would have shown increased switch costs in both SRT and the occurrence of direction errors. However, PD patients only showed greater direction error switch costs when switching from the more automatic prosaccade to the less automatic antisaccade. In fact, PD patients showed an advantage over the controls in terms of fewer errors when switching towards the more automatic prosaccade. Additional analysis showed
Conclusions
We employed a saccade switching paradigm to identify an underlying bias in PD towards a more automatic prosaccade response that influenced their ability to switch task. Specifically, PD patients performed with impairment or superiority relative to controls, depending on the switch direction. Our results suggest that an underlying deficit in setting a task set towards a non-habitual and voluntary motor task can explain behavioral deficits in PD when a required voluntary behavior competes with an
Acknowledgements
We thank members of the Munoz lab for comments on earlier versions of the manuscript, and the participants for their time. This research was supported by the Canadian Institutes of Health Research grant number MOP-97741 to DPM and GP, and the Canada Research Chair Program to DPM. IGMC is the recipient of a Frederick Banting and Charles Best Canada Graduate Scholarship.
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