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Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

ABSTRACT: 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.

SUBMITTER: Grogan JP

PROVIDER: S-EPMC5531832 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

Grogan John P JP Tsivos Demitra D Smith Laura L Knight Brogan E BE Bogacz Rafal R Whone Alan A Coulthard Elizabeth J EJ

eLife 20170710

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, withi ...[more]

PMID: 28691905

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Project description: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.

Project description:BACKGROUND AND PURPOSE:Basal ganglia play a pivotal role in procedural memory. However, the correlation between skill learning and striatal ¹²³I-ioflupane uptake in Parkinson's disease (PD) has not been reported previously. Our objective was to determine whether visuomotor skill learning is associated with striatal ¹²³I-ioflupane uptake in early PD. METHODS:We designed a case-control study to assess learning and consolidation of a visuomotor learning task (mirrored drawing of star-shaped figures) performed on two consecutive days by early-PD patients (disease duration <2 years) and age-matched healthy subjects. Outcomes were the error rate and time per trial, as well as performance indices to assess the relative improvement on the first day (learning) and the retention on the second day (consolidation). For PD patients, we evaluated the correlation of skill learning with semiquantitative ¹²³I-ioflupane uptake. RESULTS:We included 9 PD patients and 10 control subjects with the same baseline characteristics (age, male/female ratio, educational level, Mini Mental State Examination score, and Hospital Anxiety and Depression Scale score, all p>0.18) other than the score on part III of the Movement Disorders Society Unified Parkinson's Disease Rating Scale, which was higher in the PD patients (mean±SD: 15.0±10.4 vs. 1.3±1.1, p<0.001). The learning indices were the same in the two groups (p>0.5), whereas PD patients showed a lower consolidation index for the time per trial (p=0.009). Moreover, this performance was correlated with uptake in the right caudate nucleus (Spearman's rho=0.82, p=0.007) and the right striatum (Spearman's rho=0.67, p=0.049), including when multiple linear regression adjusting for the levodopa equivalent daily dose was performed (p=0.005 for the caudate nucleus and p=0.024 for the striatum). CONCLUSIONS:This study provides evidence of a correlation between procedural memory impairment and striatal dopaminergic dysfunction in early PD.

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Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

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Effects of dopamine on reinforcement learning and consolidation in Parkinson's disease.

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