scholarly journals Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3422-3434
Author(s):  
Annelies J van Nuland ◽  
Rick C Helmich ◽  
Michiel F Dirkx ◽  
Heidemarie Zach ◽  
Ivan Toni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Learning Task ◽  
Learning Rate ◽  
Dopamine Depletion ◽  
Large Variability ◽  
Dopaminergic Medication ◽  
Improved Learning ◽  
Motor Phenotype

Abstract Parkinson’s disease is clinically defined by bradykinesia, along with rigidity and tremor. However, the severity of these motor signs is greatly variable between individuals, particularly the presence or absence of tremor. This variability in tremor relates to variation in cognitive/motivational impairment, as well as the spatial distribution of neurodegeneration in the midbrain and dopamine depletion in the striatum. Here we ask whether interindividual heterogeneity in tremor symptoms could account for the puzzlingly large variability in the effects of dopaminergic medication on reinforcement learning, a fundamental cognitive function known to rely on dopamine. Given that tremor-dominant and non-tremor Parkinson’s disease patients have different dopaminergic phenotypes, we hypothesized that effects of dopaminergic medication on reinforcement learning differ between tremor-dominant and non-tremor patients. Forty-three tremor-dominant and 20 non-tremor patients with Parkinson’s disease were recruited to be tested both OFF and ON dopaminergic medication (200/50 mg levodopa-benserazide), while 22 age-matched control subjects were recruited to be tested twice OFF medication. Participants performed a reinforcement learning task designed to dissociate effects on learning rate from effects on motivational choice (i.e. the tendency to ‘Go/NoGo’ in the face of reward/threat of punishment). In non-tremor patients, dopaminergic medication improved reward-based choice, replicating previous studies. In contrast, in tremor-dominant patients, dopaminergic medication improved learning from punishment. Formal modelling showed divergent computational effects of dopaminergic medication as a function of Parkinson’s disease motor phenotype, with a modulation of motivational choice bias and learning rate in non-tremor and tremor patients, respectively. This finding establishes a novel cognitive/motivational difference between tremor and non-tremor Parkinson’s disease patients, and highlights the importance of considering motor phenotype in future work.

scholarly journals Tremor in Parkinson's disease inverts the effect of dopamine on reinforcement

Brain ◽  
2020 ◽  
Vol 143 (11) ◽  
pp. 3178-3180
Author(s):  
Sanjay G Manohar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Motor Phenotype

This scientific commentary refers to ‘Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype’ by van Nuland et al. (doi:10.1093/brain/awaa335).

scholarly journals Dopaminergic medication reduces striatal sensitivity to negative outcomes in Parkinson’s disease

2018 ◽  
Author(s):  
Brónagh McCoy ◽  
Sara Jahfari ◽  
Gwenda Engels ◽  
Tomas Knapen ◽  
Jan Theeuwes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Learning Task ◽  
Dopamine Neurons ◽  
Negative Outcomes ◽  
Learning Differences ◽  
Dopaminergic Medication ◽  
Learning Rates ◽  
Approach Avoidance ◽  
Midbrain Dopamine

AbstractReduced levels of dopamine in Parkinson’s disease (PD) contribute to changes in learning, resulting from the loss of midbrain dopamine neurons that transmit a teaching signal to the striatum. Dopamine medication used by PD patients has previously been linked to either behavioral changes during learning itself or adjustments in approach and avoidance behavior after learning. To date, however, very little is known about the specific relationship between dopaminergic medication-driven differences during learning and subsequent changes in approach/avoidance tendencies in individual patients. We assessed 24 PD patients on and off dopaminergic medication and 24 healthy controls (HC) performing a probabilistic reinforcement learning task, while undergoing functional magnetic resonance imaging. During learning, medication in PD reduced an overemphasis on negative outcomes. When patients were on medication, learning rates were lower for negative (but not positive) outcomes and concurrent striatal BOLD responses showed reduced prediction error sensitivity. Medication-induced shifts in negative learning rates were predictive of changes in approach/avoidance choice patterns after learning, and these changes were accompanied by striatal BOLD response alterations. These findings highlight dopamine-driven learning differences in PD and provide new insight into how changes in learning impact the transfer of learned value to approach/avoidance responses in novel contexts.

scholarly journals Dopamine and performance in a reinforcement learning task: evidence from Parkinson’s disease

Brain ◽  
2012 ◽  
Vol 135 (6) ◽  
pp. 1871-1883 ◽  
Author(s):  
Tamara Shiner ◽  
Ben Seymour ◽  
Klaus Wunderlich ◽  
Ciaran Hill ◽  
Kailash P. Bhatia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Learning Task ◽  
And Performance

scholarly journals Attention and reinforcement learning in Parkinson’s disease

2020 ◽  
Author(s):  
Brónagh McCoy ◽  
Rebecca P. Lawson ◽  
Jan Theeuwes
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Interactive Effect ◽  
Learning Task ◽  
Brain Regions ◽  
Learning Performance ◽  
Activation Patterns ◽  
Probabilistic Classification ◽  
Dorsolateral Prefrontal

ABSTRACTDopamine is known to be involved in several important cognitive processes, most notably in learning from rewards and in the ability to attend to task-relevant aspects of the environment. Both of these features of dopaminergic signalling have been studied separately in research involving Parkinson’s disease (PD) patients, who exhibit diminished levels of dopamine. Here, we tie together some of the commonalities in the effects of dopamine on these aspects of cognition by having PD patients (ON and OFF dopaminergic medication) and healthy controls (HCs) perform two tasks that probe these processes. Within-patient behavioural measures of distractibility, from an attentional capture task, and learning performance, from a probabilistic classification reinforcement learning task, were included in one model to assess the role of distractibility during learning. Dopamine medication state and distractibility level were found to have an interactive effect on learning performance; less distractibility in PD ON was associated with higher accuracy during learning, and this was altered in PD OFF. Functional magnetic resonance imaging (fMRI) data acquired during the learning task furthermore allowed us to assess multivariate patterns of positive and negative outcomes in fronto-striatal and visual brain regions involved in both learning processes and the executive control of attention. Here, we demonstrate that while PD ON show a clearer distinction between outcomes than OFF in dorsolateral prefrontal cortex (DLPFC) and putamen, PD OFF show better distinction of activation patterns in visual regions that respond to the stimuli presented during the task. These results demonstrate that dopamine plays a key role in modulating the interaction between attention and learning at the level of both behaviour and activation patterns in the brain.

scholarly journals Effects of dopamine on reinforcement learning and consolidation in Parkinson’s disease

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
John P Grogan ◽  
Demitra Tsivos ◽  
Laura Smith ◽  
Brogan E Knight ◽  
Rafal Bogacz ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Negative Reinforcement ◽  
Control Group ◽  
Dopaminergic Medication ◽  
Matched Healthy Control ◽  
Healthy Control ◽  
Within Subjects ◽  
With Memory

Emerging evidence suggests that dopamine may modulate learning and memory with important implications for understanding the neurobiology of memory and future therapeutic targeting. An influential hypothesis posits that dopamine biases reinforcement learning. More recent data also suggest an influence during both consolidation and retrieval. Eighteen Parkinson’s disease patients learned through feedback ON or OFF medication, with memory tested 24 hr later ON or OFF medication (4 conditions, within-subjects design with matched healthy control group). Patients OFF medication during learning decreased in memory accuracy over the following 24 hr. In contrast to previous studies, however, dopaminergic medication during learning and testing did not affect expression of positive or negative reinforcement. Two further experiments were run without the 24 hr delay, but they too failed to reproduce effects of dopaminergic medication on reinforcement learning. While supportive of a dopaminergic role in consolidation, this study failed to replicate previous findings on reinforcement learning.

scholarly journals Dopamine modulates learning-related changes in dynamic striatal-cortical connectivity in Parkinson’s disease

2019 ◽  
Author(s):  
Raphael T. Gerraty ◽  
Madeleine E. Sharp ◽  
Amanda Buch ◽  
Danielle S. Bassett ◽  
Daphna Shohamy
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Reinforcement Learning ◽  
Reversal Learning ◽  
Network Dynamics ◽  
Temporal Cortex ◽  
Empirical Support ◽  
Inferior Temporal Cortex ◽  
Dopamine Depletion ◽  
Dynamic Connectivity

AbstractLearning from reinforcement is thought to depend on striatal dopamine inputs, which serve to update the value of actions by modifying connections in widespread cortico-striatal circuits. While considerable research has described the activity of individual striatal and midbrain regions in reinforcement learning, the broader role for dopamine in modulating network-level processes has been difficult to decipher. To examine whether dopamine modulates circuit-level dynamic connectivity during learning, we characterized the effects of dopamine on learning-related dynamic functional connectivity estimated from fMRI data acquired in patients with Parkinson’s disease. Patients with Parkinson’s disease have severe dopamine depletion in the striatum and are treated with dopamine replacement drugs, providing an opportunity to compare learning and network dynamics when patients are in a low dopamine state (off drugs) versus a high dopamine state (on drugs). We assessed the relationship between dopamine and dynamic connectivity while patients performed a probabilistic reversal learning task. We found that reversal learning altered dynamic network flexibility in the striatum and that this effect was dependent on dopaminergic state. We also found that dopamine modulated changes in connectivity between the striatum and specific task-relevant visual areas of inferior temporal cortex, providing empirical support for theories stipulating that value is updated through changes in cortico-striatal circuits. These results suggest that dopamine exerts a widespread effect on neural circuitry and network dynamics during reinforcement learning.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

scholarly journals Implications of dopaminergic medication withdrawal in Parkinson’s disease

2021 ◽  
Author(s):  
J. Koschel ◽  
K. Ray Chaudhuri ◽  
L. Tönges ◽  
M. Thiel ◽  
V. Raeder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Medication ◽  
Medication Withdrawal
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