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Patients with Parkinson's Disease Show Impaired Use of Priors in Conditions of Sensory Uncertainty.

ABSTRACT: Perceptual decisions arise after considering the available sensory evidence [1]. When sensory information is unreliable, a good strategy is to rely on previous experience in similar situations to guide decisions [2-6]. It is well known that patients with Parkinson's disease (PD) are impaired at value-based decision-making [7-11]. How patients combine past experience and sensory information to make perceptual decisions is unknown. We developed a novel, perceptual decision-making task and manipulated the statistics of the sensory stimuli presented to patients with PD and healthy participants to determine the influence of past experience on decision-making. We show that patients with PD are impaired at combining previously learned information with current sensory information to guide decisions. We modeled the results using the drift-diffusion model (DDM) and found that the impairment corresponds to a failure in adjusting the amount of sensory evidence needed to make a decision. Our modeling results also show that two complementary mechanisms operate to implement a bias when two sets of priors are learned concurrently. Asymmetric decision threshold adjustments, as reflected by changes in the starting point of evidence accumulation, are responsible for a general choice bias, whereas the adjustment of a dynamic bias that develops over the course of a trial, as reflected by a drift-rate offset, provides the stimulus-specific component of the prior. A proper interplay between these two processes is required to implement a bias based on concurrent, stimulus-specific priors in decision-making. We show here that patients with PD are impaired in these across-trial decision threshold adjustments.

SUBMITTER: Perugini A

PROVIDER: S-EPMC5633083 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Patients with Parkinson's Disease Show Impaired Use of Priors in Conditions of Sensory Uncertainty.

Perugini Alessandra A Ditterich Jochen J Basso Michele A MA

Current biology : CB 20160616 14

Perceptual decisions arise after considering the available sensory evidence [1]. When sensory information is unreliable, a good strategy is to rely on previous experience in similar situations to guide decisions [2-6]. It is well known that patients with Parkinson's disease (PD) are impaired at value-based decision-making [7-11]. How patients combine past experience and sensory information to make perceptual decisions is unknown. We developed a novel, perceptual decision-making task and manipula ...[more]

PMID: 27322000

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Project description:A full understanding of Parkinson's Disease etiopathogenesis and of the causes of the preferential vulnerability of nigrostriatal dopaminergic neurons is still an unsolved puzzle. A multiple-hit hypothesis has been proposed, which may explain the convergence of familial, environmental and idiopathic forms of the disease. Among the various determinants of the degeneration of the neurons in Substantia Nigra pars compacta, in this review we will focus on the endotoxicity associated to dopamine dyshomeostasis. In particular, we will discuss the relevance of the reactive dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) in the catechol-induced neurotoxicity. Indeed, the synergy between the catechol and the aldehyde moieties of DOPAL exacerbates its reactivity, resulting in modification of functional protein residues, protein aggregation, oxidative stress and cell death. Interestingly, αSynuclein, whose altered proteostasis is a recurrent element in Parkinson's Disease pathology, is considered a preferential target of DOPAL modification. DOPAL triggers αSynuclein oligomerization leading to synapse physiology impairment. Several factors can be responsible for DOPAL accumulation at the pre-synaptic terminals, i.e. dopamine leakage from synaptic vesicles, increased rate of dopamine conversion to DOPAL by upregulated monoamine oxidase and decreased DOPAL degradation by aldehyde dehydrogenases. Various studies report the decreased expression and activity of aldehyde dehydrogenases in parkinsonian brains, as well as genetic variants associated to increased risk in developing the pathology. Thus, we discuss how the deregulation of these enzymes might be considered a contributing element in the pathogenesis of Parkinson's Disease or a down-stream effect. Finally, we propose that a better understanding of the impaired dopamine metabolism in Parkinson's Disease would allow a more refined patients stratification and the design of more targeted and successful therapeutic strategies.

Dataset Information

Patients with Parkinson's Disease Show Impaired Use of Priors in Conditions of Sensory Uncertainty.

Publications

Patients with Parkinson's Disease Show Impaired Use of Priors in Conditions of Sensory Uncertainty.

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