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Penny A. Macdonald - One of the best experts on this subject based on the ideXlab platform.
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Striatum-Mediated Deficits in Stimulus-Response Learning and Decision-Making in OCD.
Frontiers in psychiatry, 2020Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Hooman Ganjavi, Marc R. Lawrence, Mark Watling, Penny A. MacdonaldAbstract:Obsessive compulsive disorder (OCD) is a prevalent psychiatric disorder characterized by obsessions and compulsions. Studies investigating symptomatology and cognitive deficits in OCD frequently implicate the striatum. The aim of this study was to explore striatum-mediated cognitive deficits in patients with OCD as they complete a stimulus-Response Learning task previously shown to differentially rely on the dorsal (DS) and ventral striatum (VS). We hypothesized that patients with OCD will show both impaired decision-making and Learning, coupled with reduced task-relevant activity in DS and VS, respectively, compared to healthy controls. We found that patients with OCD (n = 14) exhibited decision-making deficits and learned associations slower compared to healthy age-matched controls (n = 16). Along with these behavioral deficits, OCD patients had reduced task-relevant activity in DS and VS, compared to controls. This study reveals that Responses in DS and VS are altered in OCD, and sheds light on the cognitive deficits and symptoms experienced by patients with OCD.
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dorsal striatum does not mediate feedback based stimulus Response Learning an event related fmri study in patients with parkinson s disease tested on and off dopaminergic therapy
NeuroImage, 2019Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Hooman Ganjavi, Daniel Mendonca, Mary E Jenkins, Penny A. MacdonaldAbstract:Abstract Learning associations between stimuli and Responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-Response Learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-Response Learning methodology generally confounds Learning and Response selection processes. In 19 patients with Parkinson's disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-Response Learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved Response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these within-subject patterns. These double dissociations in terms of behaviour and neural activity related to VS and DS in PD and in Response to dopaminergic therapy, strongly refute the view that DS mediates stimulus-Response Learning through feedback. Our findings integrate with a growing literature favouring a role for DS in decision making rather than Learning, and unite two literature that have been evolving independently.
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Dorsal striatum mediates deliberate decision making, not late-stage, stimulus-Response Learning.
Human brain mapping, 2017Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Penny A. MacdonaldAbstract: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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Effects of levodopa on stimulus-Response Learning versus Response selection in healthy young adults.
Behavioural brain research, 2016Co-Authors: Ken N. Seergobin, Penny A. MacdonaldAbstract:Abstract Dopaminergic therapy has been shown to worsen some cognitive functions, particularly Learning, in Parkinson’s disease (PD). This has been attributed to dopamine overdose of brain regions that are relatively dopamine replete. Dopamine dosages are titrated to the severely depleted dorsal striatum (DS). According to this account, dopaminergic therapy should worsen cognitive functions in healthy young adults who have normal dopamine levels. As a critical test of the dopamine overdose hypothesis, we tested the effect of levodopa on Learning stimulus-Response associations and on performing stimulus-specific Responses once these associations were learned. In a randomized, double-blind, placebo-controlled, between-subjects design, 40 healthy young adults completed a stimulus-Response Learning task on either levodopa or placebo. Half of the participants received 100 mg of levodopa and 25 mg of carbidopa whereas the other half received an equal volume of placebo. In Session 1, participants learned to associate abstract images with specific key-press Responses through trial and error with outcome feedback. In Session 2, participants performed stimulus-specific selections to abstract images they had previously learned in Session 1. Participants treated with levodopa compared to those on placebo demonstrated unambiguously less efficient acquisition of stimulus-Response associations. The groups did not differ in their ability to enact stimulus-specific selections once they were learned, however, even though these Responses were not overlearned. This pattern of findings is entirely consistent with the effect of levodopa on cognition in PD. The deleterious effects of levodopa on Learning seem independent of PD pathology. These results have important implications for understanding mechanisms of cognitive dysfunction in PD and caution about the potential for cognitive deficits in patients treated with levodopa for other indications.
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Pramipexole Impairs Stimulus-Response Learning in Healthy Young Adults.
Frontiers in neuroscience, 2016Co-Authors: Haley Gallant, Ken N. Seergobin, Penny A. MacdonaldAbstract:Dopaminergic therapy has paradoxical effects on cognition in Parkinson’s disease (PD) patients, with some functions worsened and others improved. The dopamine overdose hypothesis is proposed as an explanation for these opposing effects of medication taking into account the varying levels of dopamine within different brain regions in PD. The detrimental effects of medication on cognition have been attributed to exogenous dopamine overdose in brain regions with spared dopamine levels in PD. It has been demonstrated that Learning is most commonly worsened by dopaminergic medication. The current study aimed to investigate whether the medication-related Learning impairment exhibited in PD patients is due to a main effect of medication by evaluating the dopamine overdose hypothesis in healthy young adults. Using a randomized, double-blind, placebo-controlled design, 40 healthy young undergraduate students completed a stimulus-Response Learning task. Half of the participants were treated with 0.5 mg of pramipexole, a dopamine agonist, whereas the other half were treated with a placebo. We found that stimulus-Response Learning was significantly impaired in participants on pramipexole relative to placebo controls. These findings are consistent with the dopamine overdose hypothesis and suggest that dopaminergic medication impairs Learning independent of PD pathology. Our results have important clinical implications for conditions treated with pramipexole, particularly PD, restless leg syndrome, some forms of dystonia, and potentially depression.
Robert J Mcdonald - One of the best experts on this subject based on the ideXlab platform.
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Dorsal striatum and stimulus-Response Learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a simple discrimination task.
Behavioural brain research, 2004Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of Response during CS+ presentations and number of CS+ trials without a Response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low Response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-Response Learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.
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dorsal striatum and stimulus Response Learning lesions of the dorsolateral but not dorsomedial striatum impair acquisition of a stimulus Response based instrumental discrimination task while sparing conditioned place preference Learning
Neuroscience, 2004Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:While some evidence suggests that the dorsal striatum is important for stimulus-Response Learning, disagreement exists about the relative contribution of the dorsolateral and dorsomedial striatum to this form of Learning. In the present experiment, the effects of lesions of the dorsolateral and dorsomedial striatum were investigated on two tasks that differentially require the development of stimulus-Response Learning. The first task utilized an operant conditional discrimination task, which is likely to rely heavily upon stimulus-Response Learning. The second task looked conditioned place preference Learning, a task that is unlikely to require the development of stimulus-Response associations. Animals with lesions of the dorsolateral striatum were impaired on the operant conditional discrimination task, but retained the ability to learn the conditioned place preference task. In contrast, animals with lesions of the dorsomedial striatum were not found to be impaired on either task used in the present experiment. These results suggest that the dorsolateral striatum is necessary for the successful acquisition of tasks that place a demand upon stimulus-Response Learning, while the dorsomedial striatum is not involved in this type of Learning.
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Dorsal striatum and stimulus–Response Learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a simple discrimination task
Behavioural Brain Research, 2003Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of Response during CS+ presentations and number of CS+ trials without a Response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low Response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-Response Learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.
Melly S. Oitzl - One of the best experts on this subject based on the ideXlab platform.
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Stress induces a shift towards striatum-dependent stimulus-Response Learning via the mineralocorticoid receptor
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016Co-Authors: Susanne Vogel, Melly S. Oitzl, Marian Joëls, Harm J. Krugers, Floris Klumpers, Tobias Navarro Schröder, Krista T Oplaat, Christian F. Doeller, Guillén FernándezAbstract:Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place Learning depending on the hippocampus whereas stimulus-Response Learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-Response Learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.
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Mineralocorticoid receptors guide spatial and stimulus-Response Learning in mice
PloS one, 2014Co-Authors: J. Marit Arp, Judith P. Ter Horst, Sofia Kanatsou, Guillén Fernández, Marian Joëls, Harm J. Krugers, Melly S. OitzlAbstract:Adrenal corticosteroid hormones act via mineralocorticoid (MR) and glucocorticoid receptors (GR) in the brain, influencing Learning and memory. MRs have been implicated in the initial behavioral Response in novel situations, which includes behavioral strategies in Learning tasks. Different strategies can be used to solve navigational tasks, for example hippocampus-dependent spatial or striatum-dependent stimulus-Response strategies. Previous studies suggested that MRs are involved in spatial Learning and induce a shift between Learning strategies when animals are allowed a choice between both strategies. In the present study, we further explored the role of MRs in spatial and stimulus-Response Learning in two separate circular holeboard tasks using female mice with forebrain-specific MR deficiency and MR overexpression and their wildtype control littermates. In addition, we studied sex-specific effects using male and female MR-deficient mice. First, we found that MR-deficient compared to control littermates and MR-overexpressing mice display altered exploratory and searching behavior indicative of impaired acquisition of novel information. Second, female (but not male) MR-deficient mice were impaired in the spatial task, while MR-overexpressing female mice showed improved performance in the spatial task. Third, MR-deficient mice were also impaired in the stimulus-Response task compared to controls and (in the case of females) MR-overexpressing mice. We conclude that MRs are important for coordinating the processing of information relevant for spatial as well as stimulus-Response Learning.
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Stress impairs spatial but not early stimulus-Response Learning.
Behavioural brain research, 2010Co-Authors: Lars Schwabe, Hartmut Schächinger, E. Ron De Kloet, Melly S. OitzlAbstract:Recent evidence indicates that stress modulates multiple memory systems, favoring caudate nucleus-based stimulus-Response Learning at the expense of hippocampus-based spatial Learning. Whether this is due to a facilitating effect of stress on stimulus-Response Learning, an impairing effect on spatial Learning, or both, is not known. To answer this question, mice were either subjected to restraint stress, injected with vehicle or corticosterone or left untreated before training in two circular hole board tasks that could discriminate spatial and stimulus-Response strategies. Stress, vehicle and corticosterone injection all impaired Learning performance in the spatial task. Conversely, performance in the stimulus-Response task was not affected by stress or corticosterone injection, although performance was generally lower than in the spatial task. Irrespective of the treatment, mice had to overcome the preference to use their spatial memory system to achieve the stimulus-Response task. These findings suggest that (i) the caudate nucleus-based memory system is less stress sensitive than the hippocampus-based system and may thus dominate behavior in situations of stress and (ii) that multiple memory systems may compete for control of behavior even in tasks that can solely be solved by one system.
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Chronic stress modulates the use of spatial and stimulus-Response Learning strategies in mice and man.
Neurobiology of learning and memory, 2008Co-Authors: Lars Schwabe, Hartmut Schächinger, Sergiu Dalm, Melly S. OitzlAbstract:Acute stress modulates multiple memory systems in favor of caudate nucleus-dependent stimulusResponse and at the expense of hippocampus-dependent spatial Learning and memory. We examined in mice and humans whether chronic stress has similar consequences. Male C57BL/6J mice that had been repeatedly exposed to rats (‘‘rat stress”) used in a circular hole board task significantly more often a stimulus-Response strategy (33%) than control mice (0%). While velocity was increased, differences in latency to exit hole, distance moved or number of holes visited were not observed. Increased velocity and performance during retention trials one day later indicates altered emotionality and motivation to explore in rat stressed mice. Forty healthy young men and women were split into ‘‘high chronic stress” and ‘‘low chronic stress” groups based on their answers in a chronic stress questionnaire (‘‘Trier Inventory of Chronic Stress”—TICS) and trained in a 2D task. A test trial immediately after training revealed that participants of the ‘‘high chronic stress” group used the S-R strategy significantly more often (94%) than participants of the ‘‘low chronic stress” group (52%). Verbal self-reports confirmed the strategy derived from participants’ choice in the test trial. Learning performance was unaffected by the chronic stress level. We conclude that one consequence of chronic stress is the shift to more rigid stimulus-Response Learning, that is accompanied by changes in motivational factors in mice.
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stress modulates the use of spatial versus stimulus Response Learning strategies in humans
Learning & Memory, 2007Co-Authors: Lars Schwabe, Melly S. Oitzl, Christine Philippsen, Steffen Richter, Andreas Bohringer, Werner Wippich, Hartmut SchächingerAbstract:Animal studies provided evidence that stress modulates multiple memory systems, favoring caudate nucleus-based “habit” memory over hippocampus-based “cognitive” memory. However, effects of stress on Learning strategy and memory consolidation were not differentiated. We specifically address the effects of psychosocial stress on the applied Learning strategy in humans. We designed a spatial Learning task that allowed differentiating spatial from stimulus-Response Learning strategies during acquisition. In 13 subsequent trials, participants (88 male and female students) had to locate a “win” card out of four placed at a fixed location in a 3D model of a room. Relocating one cue in the last trial allowed inferring the applied Learning strategy. Half of them participated first in the “Trier Social Stress Test.” Salivary cortisol and heart rate measurements were taken. Stressed participants used a stimulus-Response strategy significantly more often than controls. Subsequent verbal report revealed that spatial learners had a more complete awareness of Response options than stimulus-Response learners. Importantly, Learning performance was not affected by stress. Taken together, stress prior to Learning facilitated simple stimulus-Response Learning strategies in humans—at the expense of a more cognitive Learning strategy. Depending on the context, we consider this as an adaptive Response.
Ken N. Seergobin - One of the best experts on this subject based on the ideXlab platform.
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Striatum-Mediated Deficits in Stimulus-Response Learning and Decision-Making in OCD.
Frontiers in psychiatry, 2020Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Hooman Ganjavi, Marc R. Lawrence, Mark Watling, Penny A. MacdonaldAbstract:Obsessive compulsive disorder (OCD) is a prevalent psychiatric disorder characterized by obsessions and compulsions. Studies investigating symptomatology and cognitive deficits in OCD frequently implicate the striatum. The aim of this study was to explore striatum-mediated cognitive deficits in patients with OCD as they complete a stimulus-Response Learning task previously shown to differentially rely on the dorsal (DS) and ventral striatum (VS). We hypothesized that patients with OCD will show both impaired decision-making and Learning, coupled with reduced task-relevant activity in DS and VS, respectively, compared to healthy controls. We found that patients with OCD (n = 14) exhibited decision-making deficits and learned associations slower compared to healthy age-matched controls (n = 16). Along with these behavioral deficits, OCD patients had reduced task-relevant activity in DS and VS, compared to controls. This study reveals that Responses in DS and VS are altered in OCD, and sheds light on the cognitive deficits and symptoms experienced by patients with OCD.
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dorsal striatum does not mediate feedback based stimulus Response Learning an event related fmri study in patients with parkinson s disease tested on and off dopaminergic therapy
NeuroImage, 2019Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Hooman Ganjavi, Daniel Mendonca, Mary E Jenkins, Penny A. MacdonaldAbstract:Abstract Learning associations between stimuli and Responses is essential to everyday life. Dorsal striatum (DS) has long been implicated in stimulus-Response Learning, though recent results challenge this contention. We have proposed that discrepant findings arise because stimulus-Response Learning methodology generally confounds Learning and Response selection processes. In 19 patients with Parkinson's disease (PD) and 18 age-matched controls, we found that dopaminergic therapy decreased the efficiency of stimulus-Response Learning, with corresponding attenuation of ventral striatum (VS) activation. In contrast, exogenous dopamine improved Response selection accuracy related to enhanced DS BOLD signal. Contrasts between PD patients and controls fully support these within-subject patterns. These double dissociations in terms of behaviour and neural activity related to VS and DS in PD and in Response to dopaminergic therapy, strongly refute the view that DS mediates stimulus-Response Learning through feedback. Our findings integrate with a growing literature favouring a role for DS in decision making rather than Learning, and unite two literature that have been evolving independently.
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Dorsal striatum mediates deliberate decision making, not late-stage, stimulus-Response Learning.
Human brain mapping, 2017Co-Authors: Nole M. Hiebert, Ken N. Seergobin, Adrian M. Owen, Penny A. MacdonaldAbstract: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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Effects of levodopa on stimulus-Response Learning versus Response selection in healthy young adults.
Behavioural brain research, 2016Co-Authors: Ken N. Seergobin, Penny A. MacdonaldAbstract:Abstract Dopaminergic therapy has been shown to worsen some cognitive functions, particularly Learning, in Parkinson’s disease (PD). This has been attributed to dopamine overdose of brain regions that are relatively dopamine replete. Dopamine dosages are titrated to the severely depleted dorsal striatum (DS). According to this account, dopaminergic therapy should worsen cognitive functions in healthy young adults who have normal dopamine levels. As a critical test of the dopamine overdose hypothesis, we tested the effect of levodopa on Learning stimulus-Response associations and on performing stimulus-specific Responses once these associations were learned. In a randomized, double-blind, placebo-controlled, between-subjects design, 40 healthy young adults completed a stimulus-Response Learning task on either levodopa or placebo. Half of the participants received 100 mg of levodopa and 25 mg of carbidopa whereas the other half received an equal volume of placebo. In Session 1, participants learned to associate abstract images with specific key-press Responses through trial and error with outcome feedback. In Session 2, participants performed stimulus-specific selections to abstract images they had previously learned in Session 1. Participants treated with levodopa compared to those on placebo demonstrated unambiguously less efficient acquisition of stimulus-Response associations. The groups did not differ in their ability to enact stimulus-specific selections once they were learned, however, even though these Responses were not overlearned. This pattern of findings is entirely consistent with the effect of levodopa on cognition in PD. The deleterious effects of levodopa on Learning seem independent of PD pathology. These results have important implications for understanding mechanisms of cognitive dysfunction in PD and caution about the potential for cognitive deficits in patients treated with levodopa for other indications.
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Pramipexole Impairs Stimulus-Response Learning in Healthy Young Adults.
Frontiers in neuroscience, 2016Co-Authors: Haley Gallant, Ken N. Seergobin, Penny A. MacdonaldAbstract:Dopaminergic therapy has paradoxical effects on cognition in Parkinson’s disease (PD) patients, with some functions worsened and others improved. The dopamine overdose hypothesis is proposed as an explanation for these opposing effects of medication taking into account the varying levels of dopamine within different brain regions in PD. The detrimental effects of medication on cognition have been attributed to exogenous dopamine overdose in brain regions with spared dopamine levels in PD. It has been demonstrated that Learning is most commonly worsened by dopaminergic medication. The current study aimed to investigate whether the medication-related Learning impairment exhibited in PD patients is due to a main effect of medication by evaluating the dopamine overdose hypothesis in healthy young adults. Using a randomized, double-blind, placebo-controlled design, 40 healthy young undergraduate students completed a stimulus-Response Learning task. Half of the participants were treated with 0.5 mg of pramipexole, a dopamine agonist, whereas the other half were treated with a placebo. We found that stimulus-Response Learning was significantly impaired in participants on pramipexole relative to placebo controls. These findings are consistent with the dopamine overdose hypothesis and suggest that dopaminergic medication impairs Learning independent of PD pathology. Our results have important clinical implications for conditions treated with pramipexole, particularly PD, restless leg syndrome, some forms of dystonia, and potentially depression.
Robert E Featherstone - One of the best experts on this subject based on the ideXlab platform.
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Dorsal striatum and stimulus-Response Learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a simple discrimination task.
Behavioural brain research, 2004Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of Response during CS+ presentations and number of CS+ trials without a Response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low Response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-Response Learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.
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dorsal striatum and stimulus Response Learning lesions of the dorsolateral but not dorsomedial striatum impair acquisition of a stimulus Response based instrumental discrimination task while sparing conditioned place preference Learning
Neuroscience, 2004Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:While some evidence suggests that the dorsal striatum is important for stimulus-Response Learning, disagreement exists about the relative contribution of the dorsolateral and dorsomedial striatum to this form of Learning. In the present experiment, the effects of lesions of the dorsolateral and dorsomedial striatum were investigated on two tasks that differentially require the development of stimulus-Response Learning. The first task utilized an operant conditional discrimination task, which is likely to rely heavily upon stimulus-Response Learning. The second task looked conditioned place preference Learning, a task that is unlikely to require the development of stimulus-Response associations. Animals with lesions of the dorsolateral striatum were impaired on the operant conditional discrimination task, but retained the ability to learn the conditioned place preference task. In contrast, animals with lesions of the dorsomedial striatum were not found to be impaired on either task used in the present experiment. These results suggest that the dorsolateral striatum is necessary for the successful acquisition of tasks that place a demand upon stimulus-Response Learning, while the dorsomedial striatum is not involved in this type of Learning.
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Dorsal striatum and stimulus–Response Learning: lesions of the dorsolateral, but not dorsomedial, striatum impair acquisition of a simple discrimination task
Behavioural Brain Research, 2003Co-Authors: Robert E Featherstone, Robert J McdonaldAbstract:In the present experiment, the effects of neurotoxic lesions (quinolinic acid) of the dorsolateral or dorsomedial striatum were investigated on a simple instrumental discrimination task (CS+/CS-). Rats with lesions of the dorsolateral striatum were found to be impaired in the acquisition of this task, as compared to rats with either dorsomedial striatal or sham lesions. Furthermore, dorsolateral striatal lesioned animals had significantly lower levels of responding across the course of discrimination training, as assessed both by overall rate of Response during CS+ presentations and number of CS+ trials without a Response, despite having shown levels of responding during variable interval training that did not differ from that of sham lesioned animals. In contrast, animals with lesions of the dorsomedial striatum did not show an impairment in acquisition of the present task, but had slightly higher rates of responding during CS- presentations. It is argued that the poor acquisition and low Response rates observed in animals with dorsolateral striatal lesions reflect a failure in stimulus-Response Learning, while the performance of animals with dorsomedial striatal lesions may have been the result of an increase in overall activity rate.
