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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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Reward prediction in the nucleus accumbens in 32 older adultsa: A region in the right nucleus accumbens showed greater BOLD activity for reward (R) than for expected value (Q) at the time of outcome (‘putative’ reward prediction error). However, the lack of a negative effect of Q under placebo meant this prediction error signal was incomplete (*one sample t-test p<0.05 one-tailed). L-DOPA increased the negative effect of Q (paired t-test, +p < 0.05 two-tailed) resulting in a ‘canonical’ prediction error signal (both a positive effect of R and negative effect of Q). Bars ±1 SEM.b: Participants who ‘win more on L-DOPA’ (n = 15) only demonstrated a negative effect of Q under L-DOPA and not placebo (+paired t-test p < 0.05 two-tailed). R and Q parameter estimates did not differ between L-DOPA and placebo for participants who ‘win less on L-DOPA’, n = 17. Bars ±1 SEM.c: Time course plots of the nucleus accumbens BOLD response to reward and expected value. White box corresponds with BOLD responses elicited at the time participants’ made a choice; grey box corresponds with BOLD responses elicited when the outcomes were revealed. Under placebo the only reliable signal observed was a reward response. Under L-DOPA, a canonical reward prediction error was observed, involving a positive expectation of value at the time of the choice together with a positive reward response and a negative expectation of value at the time of the outcome. Reward anticipation (positive effect at the time of the choice) was only observed on L-DOPA. Solid lines are group means of the effect sizes, shaded areas represent ±1 SEM.
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Figure 3: Reward prediction in the nucleus accumbens in 32 older adultsa: A region in the right nucleus accumbens showed greater BOLD activity for reward (R) than for expected value (Q) at the time of outcome (‘putative’ reward prediction error). However, the lack of a negative effect of Q under placebo meant this prediction error signal was incomplete (*one sample t-test p<0.05 one-tailed). L-DOPA increased the negative effect of Q (paired t-test, +p < 0.05 two-tailed) resulting in a ‘canonical’ prediction error signal (both a positive effect of R and negative effect of Q). Bars ±1 SEM.b: Participants who ‘win more on L-DOPA’ (n = 15) only demonstrated a negative effect of Q under L-DOPA and not placebo (+paired t-test p < 0.05 two-tailed). R and Q parameter estimates did not differ between L-DOPA and placebo for participants who ‘win less on L-DOPA’, n = 17. Bars ±1 SEM.c: Time course plots of the nucleus accumbens BOLD response to reward and expected value. White box corresponds with BOLD responses elicited at the time participants’ made a choice; grey box corresponds with BOLD responses elicited when the outcomes were revealed. Under placebo the only reliable signal observed was a reward response. Under L-DOPA, a canonical reward prediction error was observed, involving a positive expectation of value at the time of the choice together with a positive reward response and a negative expectation of value at the time of the outcome. Reward anticipation (positive effect at the time of the choice) was only observed on L-DOPA. Solid lines are group means of the effect sizes, shaded areas represent ±1 SEM.

Mentions: We focussed our imaging analysis on within-subject comparisons of reward predictions errors in the nucleus accumbens (n = 32 older adults). Using a functional ROI approach (Supplementary Fig 2) we first defined voxels in the nucleus accumbens that signalled a ‘putative’ prediction error, namely voxels where there was an enhanced response at the time of outcome to actual rewards that was greater than that to expected rewards (R(t) > Qa(t)(t), see methods). Using this approach we identified a cluster in the right nucleus accumbens [peak voxel MNI co-ordinates x,y,z = 15, 11, −8; peak Z = 4.45, p<0.001 uncorrected; 34 voxels] (Figure 3a). Note this is a liberal definition of reward prediction errors, as voxels showing a significant effect with this contrast may not satisfy all the criteria to be considered for a ‘canonical’ reward prediction error, namely both a positive effect of reward and a negative effect of expected value2119. We adopted this approach to test the hypothesis that canonical reward prediction errors are not fully represented in older age and critically, to test for the orthogonal effects of L-DOPA on the separate reward and expected value components of the prediction error signal.


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)

Reward prediction in the nucleus accumbens in 32 older adultsa: A region in the right nucleus accumbens showed greater BOLD activity for reward (R) than for expected value (Q) at the time of outcome (‘putative’ reward prediction error). However, the lack of a negative effect of Q under placebo meant this prediction error signal was incomplete (*one sample t-test p<0.05 one-tailed). L-DOPA increased the negative effect of Q (paired t-test, +p < 0.05 two-tailed) resulting in a ‘canonical’ prediction error signal (both a positive effect of R and negative effect of Q). Bars ±1 SEM.b: Participants who ‘win more on L-DOPA’ (n = 15) only demonstrated a negative effect of Q under L-DOPA and not placebo (+paired t-test p < 0.05 two-tailed). R and Q parameter estimates did not differ between L-DOPA and placebo for participants who ‘win less on L-DOPA’, n = 17. Bars ±1 SEM.c: Time course plots of the nucleus accumbens BOLD response to reward and expected value. White box corresponds with BOLD responses elicited at the time participants’ made a choice; grey box corresponds with BOLD responses elicited when the outcomes were revealed. Under placebo the only reliable signal observed was a reward response. Under L-DOPA, a canonical reward prediction error was observed, involving a positive expectation of value at the time of the choice together with a positive reward response and a negative expectation of value at the time of the outcome. Reward anticipation (positive effect at the time of the choice) was only observed on L-DOPA. Solid lines are group means of the effect sizes, shaded areas represent ±1 SEM.
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Related In: Results  -  Collection

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Figure 3: Reward prediction in the nucleus accumbens in 32 older adultsa: A region in the right nucleus accumbens showed greater BOLD activity for reward (R) than for expected value (Q) at the time of outcome (‘putative’ reward prediction error). However, the lack of a negative effect of Q under placebo meant this prediction error signal was incomplete (*one sample t-test p<0.05 one-tailed). L-DOPA increased the negative effect of Q (paired t-test, +p < 0.05 two-tailed) resulting in a ‘canonical’ prediction error signal (both a positive effect of R and negative effect of Q). Bars ±1 SEM.b: Participants who ‘win more on L-DOPA’ (n = 15) only demonstrated a negative effect of Q under L-DOPA and not placebo (+paired t-test p < 0.05 two-tailed). R and Q parameter estimates did not differ between L-DOPA and placebo for participants who ‘win less on L-DOPA’, n = 17. Bars ±1 SEM.c: Time course plots of the nucleus accumbens BOLD response to reward and expected value. White box corresponds with BOLD responses elicited at the time participants’ made a choice; grey box corresponds with BOLD responses elicited when the outcomes were revealed. Under placebo the only reliable signal observed was a reward response. Under L-DOPA, a canonical reward prediction error was observed, involving a positive expectation of value at the time of the choice together with a positive reward response and a negative expectation of value at the time of the outcome. Reward anticipation (positive effect at the time of the choice) was only observed on L-DOPA. Solid lines are group means of the effect sizes, shaded areas represent ±1 SEM.
Mentions: We focussed our imaging analysis on within-subject comparisons of reward predictions errors in the nucleus accumbens (n = 32 older adults). Using a functional ROI approach (Supplementary Fig 2) we first defined voxels in the nucleus accumbens that signalled a ‘putative’ prediction error, namely voxels where there was an enhanced response at the time of outcome to actual rewards that was greater than that to expected rewards (R(t) > Qa(t)(t), see methods). Using this approach we identified a cluster in the right nucleus accumbens [peak voxel MNI co-ordinates x,y,z = 15, 11, −8; peak Z = 4.45, p<0.001 uncorrected; 34 voxels] (Figure 3a). Note this is a liberal definition of reward prediction errors, as voxels showing a significant effect with this contrast may not satisfy all the criteria to be considered for a ‘canonical’ reward prediction error, namely both a positive effect of reward and a negative effect of expected value2119. We adopted this approach to test the hypothesis that canonical reward prediction errors are not fully represented in older age and critically, to test for the orthogonal effects of L-DOPA on the separate reward and expected value components of the prediction error signal.

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