Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease

Abstract

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies.

PDZ Domains as Drug Targets

“…PSD-95 and additional PDZ domain-containing proteins participating in nervous system development-gamma-2-syntrophin (SNTG2) and SRC Homology 3 Domain and multiple ankyrin repeat domains proteins 2 and 3 (SHANK2 and SHANK3)-have been linked to autism spectrum disorders, most likely by altering synaptic pathways. [99] Several PDZ-containing proteins are involved in psychiatric disorders and at least eight different PDZ-containing proteins are associated with depression and more than 20 are associated with schizophrenia (Table S3, Supporting Information). Membrane-associated guanylate kinase, WW and PDZ-containing protein 2 (MAGI2) and MAGUK p55 subfamily member 7 (MPP7), both of which participate in regulation of signaling events, are associated with Alzheimer's disease (AD) ( Table S3, Supporting Information).…”

“…A hallmark of AD is an abnormal aggregation of proteins at synapses, and several synaptic PDZ‐containing proteins might be involved in this pathological event. PDZ‐containing proteins such as connector enhancer of kinase suppressor of ras3 (CNKSR3), serine protease HTRA2, MAGUK p55 subfamily member 2 (MPP2), nitric oxide synthase (NOS1), and partitioning defective 3 homolog (PARD3) have been linked to Parkinson's disease . Several PDZ‐containing proteins are involved in psychiatric disorders and at least eight different PDZ‐containing proteins are associated with depression and more than 20 are associated with schizophrenia (Table S3, Supporting Information).…”

Phasic Dopamine Changes and Hebbian Mechanisms during Probabilistic Reversal Learning in Striatal Circuits: A Computational Study

“…While the previous deficits seem especially concerned with a malfunctioning of the ventral PFC, learning deficits in patients with Parkinson’s disease (PD) are likely to be connected with a reduction of the baseline dopamine level. Accordingly, reinforcement learning is impaired in PD subjects [ 8 , 58 ]. However, dopaminergic therapy improves some cognitive functions and worsens others in patients with PD, an apparently paradoxical result [ 9 ].…”

Cognition and motor learning in a Parkinson’s disease cohort: importance of recall in episodic memory

“…In healthy adults, both executive function and episodic memory are engaged in the acquisition phase of motor learning [2]. Hippocampus-based episodic memory is involved in the fast learning process [28], in which performance improves fast, but decays quickly, and may rely on single-cue strategies, in which individuals focus on one piece of information for accurate responses [9]. In contrast, frontostriatal circuit-based executive function is involved in the slow learning process of motor acquisition in which performance improves slowly, also decays slowly, and is better retained.…”

“…In Parkinson's disease, deficits in executive function have been proposed to underlie impairments in the skill acquisition phase of motor learning [6,7]. To compensate for impaired motor skill acquisition, evidence suggests that individuals with Parkinson's disease may implement explicit strategies including the recruitment of alternative cognitive domains to facilitate motor learning [8,9]. However, the alternative cognitive domains (attention, episodic memory, or visuospatial function) that may be recruited during motor skill acquisition in Parkinson's disease remains a gap in knowledge.…”