Dopaminergic therapy affects learning and impulsivity in Parkinson's disease

Hiebert, Nole M.; Seergobin, Ken N.; Vo, Andrew; Ganjavi, Hooman; MacDonald, Penny A.

doi:10.1002/acn3.128

Cited by 19 publications

(15 citation statements)

References 45 publications

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“…In paradigms other than the Go No-go task, there is evidence that motor impulsivity is improved by dopaminergic therapy. In a study by Hiebert et al ( 2014a ), PD patients off dopaminergic medications demonstrated greater motor impulsivity in the form of enhanced facilitation in the congruent condition of a modified Stroop task that was in fact normalized relative to performance of age-matched controls by dopaminergic treatment. This study provided an example of impulsive behavior, specifically motor impulsivity, being improved , not worsened, by dopaminergic therapy, supporting the notion that impulsivity is not a unitary construct (Antonelli et al, 2011 ).…”

Section: Discussionmentioning

confidence: 99%

“…PD patients with greater motor impulsivity are more susceptible to falls (Ahlskog, 2010 ; Wylie et al, 2012 ). In contrast to its effect of motivational/cognitive impulsivity, there is evidence that dopaminergic therapy might improve motor impulsivity in PD (Fera et al, 2007 ; Hiebert et al, 2014a ; Caillava-Santos et al, 2015 ; van Wouwe et al, 2016 ). Our aim in the current study, was therefore to investigate the effect of DA on motor rather than cognitive impulsivity using the Go No-go paradigm (Simmonds et al, 2008 ; Wright et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Pramipexole Increases Go Timeouts but Not No-go Errors in Healthy Volunteers

Yang

Glizer

et al. 2016

Front. Hum. Neurosci.

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Parkinson’s disease (PD) is characterized by motor symptoms, such as resting tremor, bradykinesia and rigidity, but also features non-motor complications. PD patients taking dopaminergic therapy, such as levodopa but especially dopamine agonists (DAs), evidence an increase in impulse control disorders (ICDs), suggesting a link between dopaminergic therapy and impulsive pursuit of pleasurable activities. However, impulsivity is a multifaceted construct. Motor impulsivity refers to the inability to overcome automatic responses or cancel pre-potent responses. Previous research has suggested that PD patients, on dopaminergic medications, have decreased motor impulsivity. Whether effects on impulsivity are main effects of dopaminergic therapies or are specific to PD is unclear. Using a Go No-go task, we investigated the effect of a single dose of the DA pramipexole on motor impulsivity in healthy participants. The Go No-go task consisted of Go trials, for which keystroke responses were made as quickly as possible, and lesser frequency No-go trials, on which motor responses were to be inhibited. We hypothesized that pramipexole would decrease motor impulsivity. This would manifest as: (a) fewer No-go errors (i.e., fewer responses on trials in which a response ought to have been inhibited); and (b) more timed-out Go trials (i.e., more trials on which the deadline elapsed before a decision to make a keystroke occurred). Healthy volunteers were treated with either 0.5 mg of pramipexole or a standard placebo (randomly determined). During the 2-h wait period, they completed demographic, cognitive, physiological and affective measures. The pramipexole group had significantly more Go timeouts (p < 0.05) compared to the placebo group though they did not differ in percent of No-go errors. In contrast to its effect on pursuit of pleasurable activities, pramipexole did not increase motor impulsivity. In fact, in line with findings in PD and addiction, dopaminergic therapy might increase motor impulse control. In these patient groups, by enhancing function of the dorsal striatum (DS) of the basal ganglia in contrast to its effect on impulsive pursuit of pleasurable activities. These findings have implications for use and effects of pramipexole in PD as well as in other conditions (e.g., restless leg, dystonia, depression, addiction-related problems).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pramipexole Increases Go Timeouts but Not No-go Errors in Healthy Volunteers

Yang

Glizer

et al. 2016

Front. Hum. Neurosci.

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“…Implicit in the reward prediction error model of dopamine function is the idea that decreased release of dopamine will track with a decreasing capability to perform stimulus‐response and reinforcement learning. In humans with PD, sometimes l ‐dopa does not improve reinforcement learning deficits (Shiner et al ) and might worsen them (Hiebert et al ; Macdonald et al ) though other experiments have shown improved reinforcement learning while on PD medication, increasing learning rates from positive, rewarded outcomes without impacting potential negative prediction errors on negative outcomes (Frank et al , ). While this outcome may call into question how reliable the RPE hypothesis of mdDA function is regarding humans, it is still difficult to account for all variables in clinical scenarios.…”

Section: Neurodevelopment Of Mesodiencephalic Dopamine Neuronsmentioning

confidence: 99%

Development and function of the midbrain dopamine system: what we know and what we need to

Bissonette

Roesch

2015

Genes Brain and Behavior

109

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The past two decades have seen an explosion in our understanding of the origin and development of the midbrain dopamine system. Much of this work has been focused on the aspects of dopamine neuron development related to the onset of movement disorders such as Parkinson’s disease, with the intent of hopefully delaying, preventing or fixing symptoms. While midbrain dopamine degeneration is a major focus for treatment and research, many other human disorders are impacted by abnormal dopamine, including drug addiction, autism and schizophrenia. Understanding dopamine neuron ontogeny and how dopamine connections and circuitry develops may provide us with key insights into potentially important avenues of research for other dopamine-related disorders. This review will provide a brief overview of the major molecular and genetic players throughout the development of midbrain dopamine neurons and what we know about the behavioral- and disease-related implications associated with perturbations to midbrain dopamine neuron development. We intend to combine the knowledge of two broad fields of neuroscience, both developmental and behavioral, with the intent on fostering greater discussion between branches of neuroscience in the service of addressing complex cognitive questions from a developmental perspective and identifying important gaps in our knowledge for future study.

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“…The DS is ascribed a role in both early, goal‐directed learning [Brovelli et al, ; O'Doherty et al, ] and late‐stage learning of stimulus–response associations to the point of automaticity [Ashby et al, ; Balleine et al, ]. Challenging this notion, however, learning is often preserved in patients [Exner et al, ; Hiebert et al, ; MacDonald et al, ; Vo et al, ] and in animals [Atallah et al, ] with DS dysfunction. Features of standard stimulus–response learning methodology potentially shed light on this controversy as detailed in the paragraphs below.…”

Section: Introductionmentioning

confidence: 99%

Dorsal striatum mediates deliberate decision making, not late‐stage, stimulus–response learning

Hiebert

Owen

Seergobin

et al. 2017

Human Brain Mapping

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We investigated a controversy regarding the role of the dorsal striatum (DS) in deliberate decision-making versus late-stage, stimulus-response learning to the point of automatization. Participants learned to associate abstract images with right or left button presses explicitly before strengthening these associations through stimulus-response trials with (i.e., Session 1) and without (i.e., Session 2) feedback. In Session 1, trials were divided into response-selection and feedback events to separately assess decision versus learning processes. Session 3 evaluated stimulus-response automaticity using a location Stroop task. DS activity correlated with response-selection and not feedback events in Phase 1 (i.e., Blocks 1-3), Session 1. Longer response times (RTs), lower accuracy, and greater intertrial variability characterized Phase 1, suggesting deliberation. DS activity extinguished in Phase 2 (i.e., Blocks 4-12), Session 1, once RTs, response variability, and accuracy stabilized, though stimulus-response automatization continued. This was signaled by persisting improvements in RT and accuracy into Session 2. Distraction between Sessions 1 and 2 briefly reintroduced response uncertainty, and correspondingly, significant DS activity reappeared in Block 1 of Session 2 only. Once stimulus-response associations were again refamiliarized and deliberation unnecessary, DS activation disappeared for Blocks 2-8, Session 2. Interference from previously learned right or left button responses with incongruent location judgments in a location Stroop task provided evidence that automaticity of stimulus-specific button-press responses had developed by the end of Session 2. These results suggest that DS mediates decision making and not late-stage learning, reconciling two, independently evolving and well-supported literatures that implicate DS in different cognitive functions. Hum Brain Mapp 38:6133-6156, 2017. © 2017 Wiley Periodicals, Inc.

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Dopaminergic therapy affects learning and impulsivity in Parkinson's disease

Cited by 19 publications

References 45 publications

Pramipexole Increases Go Timeouts but Not No-go Errors in Healthy Volunteers

Pramipexole Increases Go Timeouts but Not No-go Errors in Healthy Volunteers

Development and function of the midbrain dopamine system: what we know and what we need to

Dorsal striatum mediates deliberate decision making, not late‐stage, stimulus–response learning

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