l-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction

Lange, Klaus W.; Robbins, Trevor W.; Marsden, C. D.; James, Merle; Owen, Adrian M.; Paul, Gesine

doi:10.1007/bf02245167

Cited by 565 publications

(302 citation statements)

References 31 publications

(53 reference statements)

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“…Several lines of evidence suggest that dopamine neuron activity may be reproduced more accurately by using such an extended TD model as the Critic than by using the standard TD model (Suri, 2001). This hypothesis is consistent with experimental evidence suggesting that dopamine neuron activity may not only be involved in sensorimotor learning but also in planning (Lange et al, 1992).…”

supporting

confidence: 91%

“…First, as striatal dopamine concentration is influenced by the formation of novel associative chains in the sensory preconditioning experiment (Young, Ahier, Upton, Joseph, & Gray, 1998), dopamine concentration reflects the use of an internal model, suggesting that dopamine neuron activity may be the output of an internal model. Second, since Parkinsonian patients seem to be impaired in planning tasks, dopamine may be involved in planning (Lange et al, 1992;Wallesch et al, 1990). Third, reward-specific and event-specific anticipatory neural activities in cortex and striatum represent the outcome of their actions already at the time of the behavior towards the outcome, which is typical for internal model approaches and not required for the standard TD model (Hassani et al, 2001;Schultz, 2000).…”

Section: Internal Model Approachesmentioning

confidence: 99%

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TD models of reward predictive responses in dopamine neurons

Suri

2002

Neural Networks

116

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This article focuses on recent modeling studies of dopamine neuron activity and their influence on behavior. Activity of midbrain dopamine neurons is phasically increased by stimuli that increase the animal's reward expectation and is decreased below baseline levels when the reward fails to occur. These characteristics resemble the reward prediction error signal of the temporal difference (TD) model, which is a model of reinforcement learning. Computational modeling studies show that such a dopamine-like reward prediction error can serve as a powerful teaching signal for learning with delayed reinforcement, in particular for learning of motor sequences.Several lines of evidence suggest that dopamine is also involved in 'cognitive' processes that are not addressed by standard TD models. I propose the hypothesis that dopamine neuron activity is crucial for planning processes, also referred to as 'goal-directed behavior', which select actions by evaluating predictions about their motivational outcomes. q

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supporting

confidence: 91%

Section: Internal Model Approachesmentioning

confidence: 99%

TD models of reward predictive responses in dopamine neurons

Suri

2002

Neural Networks

116

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“…Planning was simulated with Actor-Critic models for which the action selection of the Actor is guided by transient influences of the Critic (Sutton and Barto, 1981). Since dopamine bursts transiently influence striatal activity (Gonon, 1997) and dopamine is involved in planning tasks (Wallesch et al, 1990;Salamone, 1992;Lange et al, 1992;Talor and Saint-Cyr, 1995), dopamine may guide action selection in such planning tasks. To test this hypothesis, we simulate interactions between the anatomical structures shown in Fig.…”

Section: Introductionmentioning

confidence: 99%

Modeling functions of striatal dopamine modulation in learning and planning

Suri¹,

Bargas

Arbib³

2001

Neuroscience

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The activity of midbrain dopamine neurons is strikingly similar to the reward prediction error of TD reinforcement learning models. Experimental evidence and simulation studies suggest that dopamine neuron activity serves as an effective reinforcement signal for learning of sensorimotor associations in striatal matrisomes.In the current study, we simulate dopamine neuron activity with the Extended TD model (Suri and Schultz, submitted) and examine the influence of this signal on medium spiny neurons in striatal matrisomes. This model includes transient membrane effects of dopamine, dopamine-dependent longterm adaptations of corticostriatal transmission, and rhythmic fluctuations of the membrane potential between an elevated "up-state" and a hyperpolarized "down-state." The most dominant activity in the striatal matrisomes elicits behaviors via projections from the basal ganglia to the thalamus and the cortex. This "standard model" performs successfully when tested for sensorimotor learning and goaldirected behavior (planning). To investigate the contributions of these model assumptions to learning and planning, we test the performance of several model variants that lack one of these mechanisms. These simulations show that the adaptation of the dopamine-like signal is necessary for planning and for sensorimotor learning. Lack of dopamine-like novelty responses decreases the number of exploratory acts, which deteriorates planning capabilities. Sensorimotor learning requires dopamine-dependent long-term adaptation of corticostriatal transmission. The model loses its planning capabilities if the dopamine-like signal is simulated with the original TD model. The capability for planning is improved by transient dopamine membrane effects, dopamine-dependent long-term effects on corticostriatal transmission, dopamine-and input-dependent influences on the durations of membrane potential fluctuations, and manipulations that prolong the reaction time of the model. These simulation results suggest that striatal dopamine is important for sensorimotor learning, exploration, and planning.

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“…While most of the motor symptoms of PD can be related to a nigrostriatal dopaminergic defect, the relationship between the dopaminergic defect and cognitive deficits in PD is less clear. Some cognitive deficits in PD may be dopa-responsive but others are not (Cooper et al 1992;Lange et al 1992). Some cognitive problems in PD patients are even exacerbated by dopaminergic therapy (Gotham et al 1988).…”

mentioning

confidence: 99%

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

Schneider

2002

Neuropsychopharmacology

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A number of neuropeptides are affected in Parkinson's disease and the enzyme proline endopeptidase contributes to the degradation of many of these neuropeptides, some of which are linked to a variety of cognitive functions. In the present study, the effects of the highly potent proline endopeptidase inhibitor S 17092 on cognitive deficits in monkeys induced by chronic low dose 2,3, It is generally recognized that non-demented Parkinson's disease (PD) patients exhibit a number of neuropsychological deficits, some of which are present even at the earliest stages of the disease (Lees and Smith 1983;Levin et al. 1989;Owen et al. 1993). Many of these deficits are 'frontal-like' in nature and consist of problems in attentional set shifting (Owen et al. 1993), distractibility (Sharpe 1990) planning and 'executive functions ' (Morris et al. 1988) and spatial working memory ). Parkinson's disease patients also may have difficulty performing a delayed matching-to-sample shortterm visual recognition memory task, but their problems appear more related to attentional difficulties rather than to visual recognition memory problems . The neurochemical deficits underlying the cognitive disturbances in PD patients are not completely known. While most of the motor symptoms of PD can be related to a nigrostriatal dopaminergic defect, the relationship between the dopaminergic defect and cognitive deficits in PD is less clear. Some cognitive deficits in PD may be dopa-responsive but others are not (Cooper et al. 1992;Lange et al. 1992). Some cognitive problems in PD patients are even exacerbated by dopaminergic therapy (Gotham et al. 1988). These findings suggest that the cognitive deficits in PD patients most likely arise from dysfunction of several cortical and subcortical neurotransmitter systems and functional circuits that cannot be normalized by dopamine replacement therapy alone. This is supported by the recent finding that a sub-type specific neuronal nicotinic acetylcholine receptor agonist, but not levodopa, was able to improve cognitive functioning in dopamine lesioned monkeys (Schneider et al. 1999). The nicotinic receptor agonist effects on cognition were most likely related to the ability of this compound to release dopamine from striatal, limbic and frontal cortical sites, norepinephrine from hippocampal, thalamic and frontal cortical sites and acetylcholine from various cortical and subcortical sites (Menzaghi et al. 1996;Sacaan et al. 1997).In addition to deficits in levels of various neurotransmitters in PD and in animal models of PD, decreased levels of various neuropeptides may also contribute to parkinsonian symptomatology (Mauborgne et al. 1983). Several neuropeptides, particularly substance P, have been implicated in learning and memory (Huston and Hasenohrl 1995) and are present endogenously in cortex and striatum. Substance P levels are also depleted in the striatum of monkeys made parkinsonian by exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Since proline-containing neuropep...

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l-Dopa withdrawal in Parkinson's disease selectively impairs cognitive performance in tests sensitive to frontal lobe dysfunction

Cited by 565 publications

References 31 publications

TD models of reward predictive responses in dopamine neurons

TD models of reward predictive responses in dopamine neurons

Modeling functions of striatal dopamine modulation in learning and planning

Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys

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