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Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson ’ s disease

View Article: PubMed Central - PubMed

ABSTRACT

Apathy is extremely common in neurodegenerative disorders such as Parkinson’s disease. Muhammed et al. report that lack of sensitivity to rewards may underlie apathy, with dopamine playing a modulatory role. The study provides a basis for objective clinical markers of motivation and treatment efficacy in neurodegenerative conditions.

No MeSH data available.


Related in: MedlinePlus

Pupillary responses in control participants. (A) Mean pupillary trace in young control participants after onset of reward cue at time 0 ms to end of trial. Pupil dilation was measured as proportional change from baseline prior to stimuli onset. Greater proportional change was observed for larger rewards compared to 0p reward. A significant difference between the 50p maximal reward (dark purple) and 0p reward level (light purple) was present from ∼630 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. Shaded areas represent standard errors of the mean (SEM). (B) Mean pupillary trace in elderly control participants after onset of reward cue. A significant difference between 50p maximal reward (black) and 0p reward (grey) was present from ∼1200 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Young controls had significantly larger baseline pupil size compared to elderly controls. (D) Proportional pupillary change as a function of reward level in young compared to elderly controls, taken as mean pupil dilation between 1400–2400 ms. Plots have been normalized to the 0p baseline to demonstrate the reward sensitivity slopes between young (purple) and elderly control participants (grey). Although both groups demonstrated greater pupillary dilation with increasing reward magnitude, there was reduced pupil reward sensitivity in elderly compared to young participants despite elderly controls having a smaller baseline pupil size and therefore more capacity to dilate for rewards.
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aww188-F2: Pupillary responses in control participants. (A) Mean pupillary trace in young control participants after onset of reward cue at time 0 ms to end of trial. Pupil dilation was measured as proportional change from baseline prior to stimuli onset. Greater proportional change was observed for larger rewards compared to 0p reward. A significant difference between the 50p maximal reward (dark purple) and 0p reward level (light purple) was present from ∼630 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. Shaded areas represent standard errors of the mean (SEM). (B) Mean pupillary trace in elderly control participants after onset of reward cue. A significant difference between 50p maximal reward (black) and 0p reward (grey) was present from ∼1200 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Young controls had significantly larger baseline pupil size compared to elderly controls. (D) Proportional pupillary change as a function of reward level in young compared to elderly controls, taken as mean pupil dilation between 1400–2400 ms. Plots have been normalized to the 0p baseline to demonstrate the reward sensitivity slopes between young (purple) and elderly control participants (grey). Although both groups demonstrated greater pupillary dilation with increasing reward magnitude, there was reduced pupil reward sensitivity in elderly compared to young participants despite elderly controls having a smaller baseline pupil size and therefore more capacity to dilate for rewards.

Mentions: In young and elderly controls, pupillary dilation was significantly increased by the magnitude of monetary reward on offer (Fig. 2A and B). As mentioned previously, reward sensitivity was defined as the difference in pupil response between the maximal 50p reward on offer and the 0p reward. Repeated measures ANOVA in the young controls over the time epoch of interest demonstrated a significant main effect of reward [F(1.5,28.2) = 20.2, P < 0.001] and post hoc comparisons between rewards (0p versus 10p, 10p versus 50p and 0p versus 50p) revealed significant differences in pupillary response between each level (P < 0.01). In elderly controls there was also a main effect of reward, [F(1.7,49.6) = 9.0, P < 0.001]. However, the extent of reward sensitivity was not as great, as conveyed by the shallower slope of the pupil size between 0p and 50p against reward on offer (Fig. 2D). In the elderly, post hoc comparisons showed a change in pupillary size between each reward at the P < 0.01 significance level, except between 0p and 10p where no significant difference was found. The reduction in reward sensitivity with age was reiterated when comparing directly between young and elderly controls. Here, there was no significant overall main effect of group demonstrated [F(1,49) = 1.1, P = 0.3]. However, a significant main effect of reward was still evident [F(1.6,78.6) = 30.8, P < 0.001] and crucially there was also a significant reward by group interaction, so the extent of pupillary response to reward for increasing reward magnitudes was reduced dependent on increasing age group, F(1.6,49) = 4.8, P < 0.02. These findings were evident despite young controls having significantly larger mean baseline pupil size compared to elderly controls and therefore less capacity to dilate for reward (Fig. 2C). Although elderly participants had on average smaller pupils compared to young people, and therefore more scope for proportional change, their pupillary response did not modulate with reward to the same degree, i.e. they had less change in pupil size between the 0p and 50p conditions.Figure 2


Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson ’ s disease
Pupillary responses in control participants. (A) Mean pupillary trace in young control participants after onset of reward cue at time 0 ms to end of trial. Pupil dilation was measured as proportional change from baseline prior to stimuli onset. Greater proportional change was observed for larger rewards compared to 0p reward. A significant difference between the 50p maximal reward (dark purple) and 0p reward level (light purple) was present from ∼630 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. Shaded areas represent standard errors of the mean (SEM). (B) Mean pupillary trace in elderly control participants after onset of reward cue. A significant difference between 50p maximal reward (black) and 0p reward (grey) was present from ∼1200 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Young controls had significantly larger baseline pupil size compared to elderly controls. (D) Proportional pupillary change as a function of reward level in young compared to elderly controls, taken as mean pupil dilation between 1400–2400 ms. Plots have been normalized to the 0p baseline to demonstrate the reward sensitivity slopes between young (purple) and elderly control participants (grey). Although both groups demonstrated greater pupillary dilation with increasing reward magnitude, there was reduced pupil reward sensitivity in elderly compared to young participants despite elderly controls having a smaller baseline pupil size and therefore more capacity to dilate for rewards.
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aww188-F2: Pupillary responses in control participants. (A) Mean pupillary trace in young control participants after onset of reward cue at time 0 ms to end of trial. Pupil dilation was measured as proportional change from baseline prior to stimuli onset. Greater proportional change was observed for larger rewards compared to 0p reward. A significant difference between the 50p maximal reward (dark purple) and 0p reward level (light purple) was present from ∼630 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. Shaded areas represent standard errors of the mean (SEM). (B) Mean pupillary trace in elderly control participants after onset of reward cue. A significant difference between 50p maximal reward (black) and 0p reward (grey) was present from ∼1200 ms to the end of the trial (P < 0.05), denoted by grey bar at bottom of plot. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Young controls had significantly larger baseline pupil size compared to elderly controls. (D) Proportional pupillary change as a function of reward level in young compared to elderly controls, taken as mean pupil dilation between 1400–2400 ms. Plots have been normalized to the 0p baseline to demonstrate the reward sensitivity slopes between young (purple) and elderly control participants (grey). Although both groups demonstrated greater pupillary dilation with increasing reward magnitude, there was reduced pupil reward sensitivity in elderly compared to young participants despite elderly controls having a smaller baseline pupil size and therefore more capacity to dilate for rewards.
Mentions: In young and elderly controls, pupillary dilation was significantly increased by the magnitude of monetary reward on offer (Fig. 2A and B). As mentioned previously, reward sensitivity was defined as the difference in pupil response between the maximal 50p reward on offer and the 0p reward. Repeated measures ANOVA in the young controls over the time epoch of interest demonstrated a significant main effect of reward [F(1.5,28.2) = 20.2, P < 0.001] and post hoc comparisons between rewards (0p versus 10p, 10p versus 50p and 0p versus 50p) revealed significant differences in pupillary response between each level (P < 0.01). In elderly controls there was also a main effect of reward, [F(1.7,49.6) = 9.0, P < 0.001]. However, the extent of reward sensitivity was not as great, as conveyed by the shallower slope of the pupil size between 0p and 50p against reward on offer (Fig. 2D). In the elderly, post hoc comparisons showed a change in pupillary size between each reward at the P < 0.01 significance level, except between 0p and 10p where no significant difference was found. The reduction in reward sensitivity with age was reiterated when comparing directly between young and elderly controls. Here, there was no significant overall main effect of group demonstrated [F(1,49) = 1.1, P = 0.3]. However, a significant main effect of reward was still evident [F(1.6,78.6) = 30.8, P < 0.001] and crucially there was also a significant reward by group interaction, so the extent of pupillary response to reward for increasing reward magnitudes was reduced dependent on increasing age group, F(1.6,49) = 4.8, P < 0.02. These findings were evident despite young controls having significantly larger mean baseline pupil size compared to elderly controls and therefore less capacity to dilate for reward (Fig. 2C). Although elderly participants had on average smaller pupils compared to young people, and therefore more scope for proportional change, their pupillary response did not modulate with reward to the same degree, i.e. they had less change in pupil size between the 0p and 50p conditions.Figure 2

View Article: PubMed Central - PubMed

ABSTRACT

Apathy is extremely common in neurodegenerative disorders such as Parkinson&rsquo;s disease. Muhammed et al. report that lack of sensitivity to rewards may underlie apathy, with dopamine playing a modulatory role. The study provides a basis for objective clinical markers of motivation and treatment efficacy in neurodegenerative conditions.

No MeSH data available.


Related in: MedlinePlus