Stimulation of the Subthalamic Region Facilitates the Selection and Inhibition of Motor Responses in Parkinson's Disease

Wildenberg, Wery P. M. van den; Boxtel, G.J.M. van; Molen, Maurits W. van der; Bosch, Dirk; Speelman, Johannes D.; Brunia, C.H.M.

doi:10.1162/jocn.2006.18.4.626

Cited by 247 publications

(182 citation statements)

References 56 publications

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“…Following the acoustic stimulus, RT significantly decreased, whereas only a significant trend for shorter RTs appeared after the visual signal. Thus our results with both SRT paradigms support clinical and experimental findings that suggest an improved function of the basal ganglia-thalamocortical circuitry during DBS [6, 8, 13, 24, 25]. This is facilitated by the correlations that were found between computed differences of trial outcomes during the off and on conditions of the stimulator (table 3).…”

Section: Discussionsupporting

confidence: 86%

Deep Brain Stimulation Improves Performance of Complex Instrumental Paradigms

Ellrichmann¹,

Harati²,

Müller³

2008

Eur Neurol

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Patients with Parkinson’s disease (PD) show deficits of motion behaviour and cognitive function, which were assessed with various instrumental paradigms. Objectives of the present trial were to investigate the effects of bilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the performance of complex and simple movement series, on the execution of simple reaction time (SRT) paradigms following an acoustic or a visual stimulus, on scored motor symptoms and the interrelation of the various study parameters in PD patients. Motor symptoms, operation of complex movements, and the execution of SRT tasks significantly improved when the stimulator was switched on. Execution of simple movement series did not differ between the on and off conditions of the stimulator. Instrumental test results significantly correlated with scored motor symptoms in particular during the off condition. During the on state, significant correlations were found between the performance of complex motion sequences and the SRT outcomes. PD patients treated with DBS of the STN show better results for more complex instrumental paradigms with a higher need for cognitive effort during the on situation due to improvements in motor performance, function of the basal ganglia-thalamocortical circuitry and cognitive function.

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Section: Discussionsupporting

confidence: 86%

Deep Brain Stimulation Improves Performance of Complex Instrumental Paradigms

Ellrichmann¹,

Harati²,

Müller³

2008

Eur Neurol

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“…Disrupting rIFC with transcranial magnetic stimulation leads to failure of response inhibition (37), and individual differences in rIFC volume predict successful stopping (38). Similarly, DBS of the STN in patients with Parkinson's disease directly modulates stopsignal RTs (27,28). In our task, a simple inhibitory account of STN function would suggest greater activity when a difficult default is accepted (lack of action), whereas an account that emphasizes a role for the STN in controlled responding would predict greater activity when the default is rejected.…”

Section: Discussionmentioning

confidence: 99%

Overcoming status quo bias in the human brain

Fleming

Thomas

Dolan

2010

Proc. Natl. Acad. Sci. U.S.A.

147

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Humans often accept the status quo when faced with conflicting choice alternatives. However, it is unknown how neural pathways connecting cognition with action modulate this status quo acceptance. Here we developed a visual detection task in which subjects tended to favor the default when making difficult, but not easy, decisions. This bias was suboptimal in that more errors were made when the default was accepted. A selective increase in subthalamic nucleus (STN) activity was found when the status quo was rejected in the face of heightened decision difficulty. Analysis of effective connectivity showed that inferior frontal cortex, a region more active for difficult decisions, exerted an enhanced modulatory influence on the STN during switches away from the status quo. These data suggest that the neural circuits required to initiate controlled, nondefault actions are similar to those previously shown to mediate outright response suppression. We conclude that specific prefrontal-basal ganglia dynamics are involved in rejecting the default, a mechanism that may be important in a range of difficult choice scenarios.hen faced with a complex decision, people tend to accept the status quo, as reflected in the old adage, "When in doubt, do nothing." Indeed, across a range of everyday decisions, such as whether to move house or trade in a car, or even whether to flip the TV channel, there is a considerable tendency to maintain the status quo and refrain from acting (1). One factor driving this status quo bias is the difficulty of the decision process. In supermarkets, for example, there is often an overwhelming choice of different brands for the same product, and consumers may leave the store empty handed because of a difficulty-induced bias toward inaction (2, 3).Here we shed light on the brain mechanisms involved in making difficult decisions involving a status quo. We operationally define a status quo bias as suboptimal acceptance of a default choice option (Fig. 1B). The neural mechanisms involved in overcoming this bias are unknown, but informative parallels can be derived from the effects of treatments for Parkinson's disease. Akinesia, a core symptom of Parkinson's, can be alleviated by disruption of the basal ganglia either by neurosurgical lesions or deep-brain stimulation (DBS) (4, 5). Despite these beneficial therapeutic effects, it is known that DBS of the subthalamic nucleus (STN) in Parkinson's patients can lead to impairments of cognitive control (6-8), suggesting that one of the core functions of the STN is to modulate basal ganglia circuits involved in decision making (9-11). An anatomic "hyperdirect" pathway from medial and lateral prefrontal cortex, previously characterized in primates (12) and humans (13), may mediate cognitive influences on the STN (14-16). Here we tested whether interactions between the frontal cortex and basal ganglia provide candidate mechanisms for how decision difficulty modulates choices involving a status quo.We asked participants to make sensory judgments in the context of a...

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“…cocaine, amphetamine, methamphetamine), and is also seen as a useful behavioural marker of genetic risk factors (Aron 2007;Aron and Poldrack 2005;Bellgrove et al 2006;Durston et al 2008;Fillmore et al , 2006Gauggel et al 2004;Monterosso et al 2005;Nigg et al 2004;Oosterlaan et al 1998;Penades et al 2007;Rubia et al 1998Rubia et al , 2005bRubia et al , 2007Schachar et al 2007;Schachar et al 1995;van den Wildenberg et al 2006). Indeed, impaired action inhibition is often considered as the core deficit in ADHD (e.g.…”

Section: The Unitary Concept Of 'Action Inhibition'mentioning

confidence: 99%

“…For example, adult patients with basal ganglia lesions have impaired action cancellation on a stop-signal task (Rieger et al 2003) with a similar effect produced by excitotoxic lesions of the dorsomedial striatum in rats (Eagle and Robbins 2003a). In addition, SSRT deficits have been linked with abnormal subthalamic nucleus (STN) function in Parkinson's disease (Gauggel et al 2004), and stimulation within the STN, but not surrounding structures, in these patients improved SSRT (van den Wildenberg et al 2006). However, in the rat, lesions of the STN globally disrupted performance on the stop-signal task, both when the stop signal was delayed and when the stop signal was presented at the same time as the go signal, more strongly indicative of a generalised attentional or response selection (no-go-like) deficit following these lesions.…”

Section: Neural Systems Underlying Action Restraint and Action Cancelmentioning

confidence: 99%

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

2008

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Background and rationale The term 'action inhibition' encapsulates the ability to prevent any form of planned physical response. Growing evidence suggests that different 'stages' or even subtypes of action inhibition activate subtly different neuropharmacological and neuroanatomical processes. Objectives In this review, we present evidence from two commonly used and apparently similar behavioural tests, the stop-signal task and the go/no-go task, to determine if these have similar neuroanatomical and neurochemical modulation. Results Whilst performance of the stop-signal and go/no-go tasks is modulated across only subtly different anatomical networks, serotonin (5-HT) is strongly implicated in inhibitory control on the go/no-go but not the stop-signal task, whereas the stop-signal reaction time appears more sensitive to the action of noradrenaline. Conclusions There is clear neuropharmacological and neuroanatomical evidence that stop-signal and go/no-go tasks represent different forms of action inhibition. This evidence translates with remarkable consistency across species. We discuss the possible implications of this evidence with respect to the development of novel therapeutic treatments for disorders in which inhibitory deficits are prominent and debilitating.

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Stimulation of the Subthalamic Region Facilitates the Selection and Inhibition of Motor Responses in Parkinson's Disease

Cited by 247 publications

References 56 publications

Deep Brain Stimulation Improves Performance of Complex Instrumental Paradigms

Deep Brain Stimulation Improves Performance of Complex Instrumental Paradigms

Overcoming status quo bias in the human brain

The neuropsychopharmacology of action inhibition: cross-species translation of the stop-signal and go/no-go tasks

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