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Dopamine restores reward prediction errors in old age.

Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q, Düzel E, Dolan RJ - Nat. Neurosci. (2013)

Bottom Line: Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons.The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults.Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cognitive Neuroscience, University College London, London, UK. rumana.neuro@gmail.com

ABSTRACT
Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

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Reinforcement learning model and behavioura: For young and older adults, the predicted choices from the learning model (red) closely matched subjects’ observed choices (blue). The red lines show the same time-varying probabilities, but evaluated on choices sampled from the model (see methods). Plots are shown for the two different sets of probability distributions used on the two test days.b: Older adults (n = 32) had a higher learning rate under L-DOPA compared with placebo and did not differ from young adults (n = 22). *p<0.05 two-tailed. Error bars are ±1 SEM.c: Older adults who won more on L-DOPA than placebo (‘win more on L-DOPA’, n = 15) had a significantly higher learning rate under L-DOPA than placebo, whereas learning rates did not differ between placebo and L-DOPA for older adults who won less on L-DOPA than placebo (‘win less on L-DOPA’, n = 17). *p<0.05 two-tailed. Error bars are ±1 SEM.
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Figure 2: Reinforcement learning model and behavioura: For young and older adults, the predicted choices from the learning model (red) closely matched subjects’ observed choices (blue). The red lines show the same time-varying probabilities, but evaluated on choices sampled from the model (see methods). Plots are shown for the two different sets of probability distributions used on the two test days.b: Older adults (n = 32) had a higher learning rate under L-DOPA compared with placebo and did not differ from young adults (n = 22). *p<0.05 two-tailed. Error bars are ±1 SEM.c: Older adults who won more on L-DOPA than placebo (‘win more on L-DOPA’, n = 15) had a significantly higher learning rate under L-DOPA than placebo, whereas learning rates did not differ between placebo and L-DOPA for older adults who won less on L-DOPA than placebo (‘win less on L-DOPA’, n = 17). *p<0.05 two-tailed. Error bars are ±1 SEM.

Mentions: We analysed trial-by-trial choice behaviour using a standard reinforcement learning model with a fixed β parameter (Figure 2a). Note that by using this methodological approach, the learning rate reflects a summary measure of reinforcement learning strength (see Methods). A model with a single fixed β = 1.27 across drug and placebo conditions, one single learning rate and one choice perseveration parameter provided the best model fit of older participants’ choices among the range of models that we compared, indexed by the lowest BIC values (Supplementary Table 2). When calculating the BIC, the log evidence was penalized using the number of data points associated with each parameter.


Dopamine restores reward prediction errors in old age.

Chowdhury R, Guitart-Masip M, Lambert C, Dayan P, Huys Q, Düzel E, Dolan RJ - Nat. Neurosci. (2013)

Reinforcement learning model and behavioura: For young and older adults, the predicted choices from the learning model (red) closely matched subjects’ observed choices (blue). The red lines show the same time-varying probabilities, but evaluated on choices sampled from the model (see methods). Plots are shown for the two different sets of probability distributions used on the two test days.b: Older adults (n = 32) had a higher learning rate under L-DOPA compared with placebo and did not differ from young adults (n = 22). *p<0.05 two-tailed. Error bars are ±1 SEM.c: Older adults who won more on L-DOPA than placebo (‘win more on L-DOPA’, n = 15) had a significantly higher learning rate under L-DOPA than placebo, whereas learning rates did not differ between placebo and L-DOPA for older adults who won less on L-DOPA than placebo (‘win less on L-DOPA’, n = 17). *p<0.05 two-tailed. Error bars are ±1 SEM.
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Figure 2: Reinforcement learning model and behavioura: For young and older adults, the predicted choices from the learning model (red) closely matched subjects’ observed choices (blue). The red lines show the same time-varying probabilities, but evaluated on choices sampled from the model (see methods). Plots are shown for the two different sets of probability distributions used on the two test days.b: Older adults (n = 32) had a higher learning rate under L-DOPA compared with placebo and did not differ from young adults (n = 22). *p<0.05 two-tailed. Error bars are ±1 SEM.c: Older adults who won more on L-DOPA than placebo (‘win more on L-DOPA’, n = 15) had a significantly higher learning rate under L-DOPA than placebo, whereas learning rates did not differ between placebo and L-DOPA for older adults who won less on L-DOPA than placebo (‘win less on L-DOPA’, n = 17). *p<0.05 two-tailed. Error bars are ±1 SEM.
Mentions: We analysed trial-by-trial choice behaviour using a standard reinforcement learning model with a fixed β parameter (Figure 2a). Note that by using this methodological approach, the learning rate reflects a summary measure of reinforcement learning strength (see Methods). A model with a single fixed β = 1.27 across drug and placebo conditions, one single learning rate and one choice perseveration parameter provided the best model fit of older participants’ choices among the range of models that we compared, indexed by the lowest BIC values (Supplementary Table 2). When calculating the BIC, the log evidence was penalized using the number of data points associated with each parameter.

Bottom Line: Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons.The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults.Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cognitive Neuroscience, University College London, London, UK. rumana.neuro@gmail.com

ABSTRACT
Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. Using functional magnetic resonance imaging in humans, we found that healthy older adults had an abnormal signature of expected value, resulting in an incomplete reward prediction error (RPE) signal in the nucleus accumbens, a brain region that receives rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum, measured by diffusion tensor imaging, was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to the level of young adults. This drug effect was linked to restoration of a canonical neural RPE. Our results identify a neurochemical signature underlying abnormal reward processing in older adults and indicate that this can be modulated by L-DOPA.

Show MeSH
Related in: MedlinePlus