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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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Two armed bandit task design and performance in young and older adultsa: On each trial, participants selected one of two fractal images which was then highlighted in a red frame. This was followed by an outcome where a green upward arrow indicated a win of 10 pence and a yellow horizontal bar indicated the absence of a win. If they did not choose a stimulus, the written message “you did not choose a picture” was displayed. The same pair of images was used throughout the task, although their position on the screen (left or right) varied. The task consisted of 220 trials separated into two sessions with a short break in between. Participants’ earnings were displayed at the end of the task and given to them at the end of the test day. The probability of obtaining a reward associated with each image varied on a trial-by-trial basis according to a Gaussian random walk. Two different sets of probability distributions (Set A and Set B) were used on the two testing days, counterbalanced across the order of L-DOPA/placebo administration.b: Older adults (n = 32) in the placebo condition won less money than young adults (n = 22). When the same older adults (n = 32) received L-DOPA, performance was similar to young adults. *p<0.05. Error bars indicate ±1SEM.
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Figure 1: Two armed bandit task design and performance in young and older adultsa: On each trial, participants selected one of two fractal images which was then highlighted in a red frame. This was followed by an outcome where a green upward arrow indicated a win of 10 pence and a yellow horizontal bar indicated the absence of a win. If they did not choose a stimulus, the written message “you did not choose a picture” was displayed. The same pair of images was used throughout the task, although their position on the screen (left or right) varied. The task consisted of 220 trials separated into two sessions with a short break in between. Participants’ earnings were displayed at the end of the task and given to them at the end of the test day. The probability of obtaining a reward associated with each image varied on a trial-by-trial basis according to a Gaussian random walk. Two different sets of probability distributions (Set A and Set B) were used on the two testing days, counterbalanced across the order of L-DOPA/placebo administration.b: Older adults (n = 32) in the placebo condition won less money than young adults (n = 22). When the same older adults (n = 32) received L-DOPA, performance was similar to young adults. *p<0.05. Error bars indicate ±1SEM.

Mentions: We studied the effect of probabilistic rewarding outcomes on the separate reward and prediction components of a prediction error signal 19 in healthy older adults. To that end, we employed a simple probabilistic instrumental conditioning problem - the two armed bandit choice task (Figure 1a). Older adults underwent DTI and fMRI in combination with a pharmacological manipulation using the dopamine precursor levodopa (L-DOPA), using a within-subject double-blind placebo-controlled study. We collected behavioural data in a group of young adults to contextualise the effects of age on performance. We did not administer L-DOPA to these young controls, implying that the effects of L-DOPA could not be compared across age-groups. By exploiting a reinforcement learning model we could determine which component of the prediction error (the actual and/or expected reward representation) was impaired in older age. DTI enabled us to examine nigro-striatal structural connectivity strength, based on a hypothesis that individual differences in this structural measure would predict inter-individual differences in baseline functional reward prediction error signalling. A crucial observation here is the fact that L-DOPA administration has been associated with greater prediction errors in young adults 10 and higher learning rates in patients with Parkinson’s disease 11. We therefore predicted that L-DOPA would increase the learning rate evident in behaviour as well as boost the representation of a reward prediction error in the nucleus accumbens of healthy older adults, specifically by increasing the component associated with the expected value.


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)

Two armed bandit task design and performance in young and older adultsa: On each trial, participants selected one of two fractal images which was then highlighted in a red frame. This was followed by an outcome where a green upward arrow indicated a win of 10 pence and a yellow horizontal bar indicated the absence of a win. If they did not choose a stimulus, the written message “you did not choose a picture” was displayed. The same pair of images was used throughout the task, although their position on the screen (left or right) varied. The task consisted of 220 trials separated into two sessions with a short break in between. Participants’ earnings were displayed at the end of the task and given to them at the end of the test day. The probability of obtaining a reward associated with each image varied on a trial-by-trial basis according to a Gaussian random walk. Two different sets of probability distributions (Set A and Set B) were used on the two testing days, counterbalanced across the order of L-DOPA/placebo administration.b: Older adults (n = 32) in the placebo condition won less money than young adults (n = 22). When the same older adults (n = 32) received L-DOPA, performance was similar to young adults. *p<0.05. Error bars indicate ±1SEM.
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Related In: Results  -  Collection

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Figure 1: Two armed bandit task design and performance in young and older adultsa: On each trial, participants selected one of two fractal images which was then highlighted in a red frame. This was followed by an outcome where a green upward arrow indicated a win of 10 pence and a yellow horizontal bar indicated the absence of a win. If they did not choose a stimulus, the written message “you did not choose a picture” was displayed. The same pair of images was used throughout the task, although their position on the screen (left or right) varied. The task consisted of 220 trials separated into two sessions with a short break in between. Participants’ earnings were displayed at the end of the task and given to them at the end of the test day. The probability of obtaining a reward associated with each image varied on a trial-by-trial basis according to a Gaussian random walk. Two different sets of probability distributions (Set A and Set B) were used on the two testing days, counterbalanced across the order of L-DOPA/placebo administration.b: Older adults (n = 32) in the placebo condition won less money than young adults (n = 22). When the same older adults (n = 32) received L-DOPA, performance was similar to young adults. *p<0.05. Error bars indicate ±1SEM.
Mentions: We studied the effect of probabilistic rewarding outcomes on the separate reward and prediction components of a prediction error signal 19 in healthy older adults. To that end, we employed a simple probabilistic instrumental conditioning problem - the two armed bandit choice task (Figure 1a). Older adults underwent DTI and fMRI in combination with a pharmacological manipulation using the dopamine precursor levodopa (L-DOPA), using a within-subject double-blind placebo-controlled study. We collected behavioural data in a group of young adults to contextualise the effects of age on performance. We did not administer L-DOPA to these young controls, implying that the effects of L-DOPA could not be compared across age-groups. By exploiting a reinforcement learning model we could determine which component of the prediction error (the actual and/or expected reward representation) was impaired in older age. DTI enabled us to examine nigro-striatal structural connectivity strength, based on a hypothesis that individual differences in this structural measure would predict inter-individual differences in baseline functional reward prediction error signalling. A crucial observation here is the fact that L-DOPA administration has been associated with greater prediction errors in young adults 10 and higher learning rates in patients with Parkinson’s disease 11. We therefore predicted that L-DOPA would increase the learning rate evident in behaviour as well as boost the representation of a reward prediction error in the nucleus accumbens of healthy older adults, specifically by increasing the component associated with the expected value.

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