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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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Nigro-striatal tract connectivity strength and functional prediction errorsUnder placebo, individuals with higher white matter nigro-striatal tract connectivity strength (determined using DTI) had a more negative effect of expected value whereas there was no correlation with functional parameters estimates of reward. Each dot on the plots represents one subject (n = 30; note two participants are overlapping on the plot on the left), the solid line is the regression slope, dashed lines represent 95% confidence intervals.
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Figure 4: Nigro-striatal tract connectivity strength and functional prediction errorsUnder placebo, individuals with higher white matter nigro-striatal tract connectivity strength (determined using DTI) had a more negative effect of expected value whereas there was no correlation with functional parameters estimates of reward. Each dot on the plots represents one subject (n = 30; note two participants are overlapping on the plot on the left), the solid line is the regression slope, dashed lines represent 95% confidence intervals.

Mentions: Our analysis identified substantial inter-individual variability amongst older adults for both reward and expected value representations in the nucleus accumbens at baseline (i.e. under placebo) (Supplementary Fig 5), whereby the latter was associated with task performance. We hypothesised that this might be associated with the known variability in the age-related decline of dopamine neurons from the SN/VTA, which may, in principle, be indexed through anatomical nigro-striatal connectivity. Using DTI and probabilistic tractography (n = 30 older adults) we defined a measure of connection strength between the right SN/VTA and right striatum (see Methods & Supplementary Fig 6). Nigro-striatal tract connectivity strength measured with DTI correlated with the fMRI parameter estimate under placebo associated with expected value (Qa(t)(t)) (Spearman’s rho = −.46, p = .010) but not with that associated with reward (R(t)) (Spearman’s rho = .12, p = .54) (Figure 4). These correlations were significantly different from each other suggesting that individual functional activation differences of the representation of expected value but not reward were linked to anatomical connectivity strength between the SN/VTA and striatum (Fishers r-to-z transformation, z = −2.32, p = .002). This relationship between greater tract connectivity strength and more negative expected value parameter estimates remained significant after controlling for age, gender, total intracranial volume, size of the seed region from which tractography was performed and global white matter integrity indexed by fractional anisotropy (FA) (partial Spearman’s rho = −0.44, p = .027). There was no difference in this correlation between subgroups of older adults (‘win more on L-DOPA’ group, n = 14: Rho = −0.54, p = .047; ‘win less on L-DOPA’ group, n = 16: Rho = −0.37, p = .154; Fisher’s r-to-z transformation comparing both groups, z = 0.53, p = .596; Supplementary Fig 7). Neither FA values of SN/VTA nor nucleus accumbens functional ROI correlated with expected value (Pearson’s r = .26 and r = .17, p = .16 and p = .38 respectively), suggesting that this correlation was related to circuit strength rather than local structural integrity as determined by FA.


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)

Nigro-striatal tract connectivity strength and functional prediction errorsUnder placebo, individuals with higher white matter nigro-striatal tract connectivity strength (determined using DTI) had a more negative effect of expected value whereas there was no correlation with functional parameters estimates of reward. Each dot on the plots represents one subject (n = 30; note two participants are overlapping on the plot on the left), the solid line is the regression slope, dashed lines represent 95% confidence intervals.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672991&req=5

Figure 4: Nigro-striatal tract connectivity strength and functional prediction errorsUnder placebo, individuals with higher white matter nigro-striatal tract connectivity strength (determined using DTI) had a more negative effect of expected value whereas there was no correlation with functional parameters estimates of reward. Each dot on the plots represents one subject (n = 30; note two participants are overlapping on the plot on the left), the solid line is the regression slope, dashed lines represent 95% confidence intervals.
Mentions: Our analysis identified substantial inter-individual variability amongst older adults for both reward and expected value representations in the nucleus accumbens at baseline (i.e. under placebo) (Supplementary Fig 5), whereby the latter was associated with task performance. We hypothesised that this might be associated with the known variability in the age-related decline of dopamine neurons from the SN/VTA, which may, in principle, be indexed through anatomical nigro-striatal connectivity. Using DTI and probabilistic tractography (n = 30 older adults) we defined a measure of connection strength between the right SN/VTA and right striatum (see Methods & Supplementary Fig 6). Nigro-striatal tract connectivity strength measured with DTI correlated with the fMRI parameter estimate under placebo associated with expected value (Qa(t)(t)) (Spearman’s rho = −.46, p = .010) but not with that associated with reward (R(t)) (Spearman’s rho = .12, p = .54) (Figure 4). These correlations were significantly different from each other suggesting that individual functional activation differences of the representation of expected value but not reward were linked to anatomical connectivity strength between the SN/VTA and striatum (Fishers r-to-z transformation, z = −2.32, p = .002). This relationship between greater tract connectivity strength and more negative expected value parameter estimates remained significant after controlling for age, gender, total intracranial volume, size of the seed region from which tractography was performed and global white matter integrity indexed by fractional anisotropy (FA) (partial Spearman’s rho = −0.44, p = .027). There was no difference in this correlation between subgroups of older adults (‘win more on L-DOPA’ group, n = 14: Rho = −0.54, p = .047; ‘win less on L-DOPA’ group, n = 16: Rho = −0.37, p = .154; Fisher’s r-to-z transformation comparing both groups, z = 0.53, p = .596; Supplementary Fig 7). Neither FA values of SN/VTA nor nucleus accumbens functional ROI correlated with expected value (Pearson’s r = .26 and r = .17, p = .16 and p = .38 respectively), suggesting that this correlation was related to circuit strength rather than local structural integrity as determined by FA.

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