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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 patients. (A) Mean pupillary trace in Parkinson’s disease patients ON dopaminergic medication. Greater proportional change was observed for the larger reward, with a significant difference between 50p maximal reward (dark blue) and 0p reward level (light blue) present from ∼1100 ms (P < 0.05), denoted by grey bar at bottom of plot. (B) Mean pupillary trace in Parkinson’s disease OFF dopaminergic medication after onset of reward cue. A significant difference between the 50p maximal reward (dark red) and 0p reward (light red) was observed but only from ∼2100 ms onwards (P < 0.05), denoted by grey bar at bottom of plot. This differential effect of reward was significantly delayed in onset compared to when ON dopaminergic medication. Moreover, the difference in response to the two reward levels was less in the OFF drug state. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Parkinson’s disease ON had significantly larger baseline pupil size compared to Parkinson’s disease OFF. (D) Proportional pupillary change as a function of reward level in Parkinson’s disease ON (blue) compared to Parkinson’s disease OFF (red) dopaminergic medication, taken as the mean pupil dilation between 1400–2400 ms. Changes have been normalized to the 0p baseline to demonstrate the relationship between reward sensitivity slopes. There was a reduced reward sensitivity in the OFF drug state compared to ON, despite increased scope for dilation when OFF due to smaller baseline pupil sizes.
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aww188-F3: Pupillary responses in patients. (A) Mean pupillary trace in Parkinson’s disease patients ON dopaminergic medication. Greater proportional change was observed for the larger reward, with a significant difference between 50p maximal reward (dark blue) and 0p reward level (light blue) present from ∼1100 ms (P < 0.05), denoted by grey bar at bottom of plot. (B) Mean pupillary trace in Parkinson’s disease OFF dopaminergic medication after onset of reward cue. A significant difference between the 50p maximal reward (dark red) and 0p reward (light red) was observed but only from ∼2100 ms onwards (P < 0.05), denoted by grey bar at bottom of plot. This differential effect of reward was significantly delayed in onset compared to when ON dopaminergic medication. Moreover, the difference in response to the two reward levels was less in the OFF drug state. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Parkinson’s disease ON had significantly larger baseline pupil size compared to Parkinson’s disease OFF. (D) Proportional pupillary change as a function of reward level in Parkinson’s disease ON (blue) compared to Parkinson’s disease OFF (red) dopaminergic medication, taken as the mean pupil dilation between 1400–2400 ms. Changes have been normalized to the 0p baseline to demonstrate the relationship between reward sensitivity slopes. There was a reduced reward sensitivity in the OFF drug state compared to ON, despite increased scope for dilation when OFF due to smaller baseline pupil sizes.

Mentions: Similar to controls, there was a main effect of reward on pupil size in the Parkinson’s disease group, with larger rewards on offer eliciting greater pupillary dilation over time (Fig. 3A and B). A main effect of drug state was also present, revealing Parkinson’s disease patients ON dopamine had greater pupillary response to rewards compared to when OFF [Fig. 3D; main effect of drug state F(1,28) = 17.6, P < 0.001; main effect of reward F(1.4,39.5) = 15.0, P < 0.0001]. There was also a significant interaction between drug state and reward, with reduced reward sensitivity when OFF dopaminergic medication as indicated by a shallower sensitivity slope, [F(1.9,53.8) = 5.7, P < 0.01]. Post hoc pairwise comparisons emphasised this further by revealing significantly larger pupillary changes for increasing reward levels when ON dopamine (0p versus 10p, P < 0.01; 10p versus 50p, P < 0.001; 10p versus 50p, P < 0.0001). However, this was blunted in the OFF state, with significant differences only between 0p versus 50p (P < 0.01) and 10p versus 50p (P < 0.01) and not between 0p versus 10p.Figure 3


Reward sensitivity deficits modulated by dopamine are associated with apathy in Parkinson ’ s disease
Pupillary responses in patients. (A) Mean pupillary trace in Parkinson’s disease patients ON dopaminergic medication. Greater proportional change was observed for the larger reward, with a significant difference between 50p maximal reward (dark blue) and 0p reward level (light blue) present from ∼1100 ms (P < 0.05), denoted by grey bar at bottom of plot. (B) Mean pupillary trace in Parkinson’s disease OFF dopaminergic medication after onset of reward cue. A significant difference between the 50p maximal reward (dark red) and 0p reward (light red) was observed but only from ∼2100 ms onwards (P < 0.05), denoted by grey bar at bottom of plot. This differential effect of reward was significantly delayed in onset compared to when ON dopaminergic medication. Moreover, the difference in response to the two reward levels was less in the OFF drug state. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Parkinson’s disease ON had significantly larger baseline pupil size compared to Parkinson’s disease OFF. (D) Proportional pupillary change as a function of reward level in Parkinson’s disease ON (blue) compared to Parkinson’s disease OFF (red) dopaminergic medication, taken as the mean pupil dilation between 1400–2400 ms. Changes have been normalized to the 0p baseline to demonstrate the relationship between reward sensitivity slopes. There was a reduced reward sensitivity in the OFF drug state compared to ON, despite increased scope for dilation when OFF due to smaller baseline pupil sizes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5035817&req=5

aww188-F3: Pupillary responses in patients. (A) Mean pupillary trace in Parkinson’s disease patients ON dopaminergic medication. Greater proportional change was observed for the larger reward, with a significant difference between 50p maximal reward (dark blue) and 0p reward level (light blue) present from ∼1100 ms (P < 0.05), denoted by grey bar at bottom of plot. (B) Mean pupillary trace in Parkinson’s disease OFF dopaminergic medication after onset of reward cue. A significant difference between the 50p maximal reward (dark red) and 0p reward (light red) was observed but only from ∼2100 ms onwards (P < 0.05), denoted by grey bar at bottom of plot. This differential effect of reward was significantly delayed in onset compared to when ON dopaminergic medication. Moreover, the difference in response to the two reward levels was less in the OFF drug state. (C) Mean pupil baseline size as taken at the start of each trial and measured using Eyelink arbitrary units (A.U). Parkinson’s disease ON had significantly larger baseline pupil size compared to Parkinson’s disease OFF. (D) Proportional pupillary change as a function of reward level in Parkinson’s disease ON (blue) compared to Parkinson’s disease OFF (red) dopaminergic medication, taken as the mean pupil dilation between 1400–2400 ms. Changes have been normalized to the 0p baseline to demonstrate the relationship between reward sensitivity slopes. There was a reduced reward sensitivity in the OFF drug state compared to ON, despite increased scope for dilation when OFF due to smaller baseline pupil sizes.
Mentions: Similar to controls, there was a main effect of reward on pupil size in the Parkinson’s disease group, with larger rewards on offer eliciting greater pupillary dilation over time (Fig. 3A and B). A main effect of drug state was also present, revealing Parkinson’s disease patients ON dopamine had greater pupillary response to rewards compared to when OFF [Fig. 3D; main effect of drug state F(1,28) = 17.6, P < 0.001; main effect of reward F(1.4,39.5) = 15.0, P < 0.0001]. There was also a significant interaction between drug state and reward, with reduced reward sensitivity when OFF dopaminergic medication as indicated by a shallower sensitivity slope, [F(1.9,53.8) = 5.7, P < 0.01]. Post hoc pairwise comparisons emphasised this further by revealing significantly larger pupillary changes for increasing reward levels when ON dopamine (0p versus 10p, P < 0.01; 10p versus 50p, P < 0.001; 10p versus 50p, P < 0.0001). However, this was blunted in the OFF state, with significant differences only between 0p versus 50p (P < 0.01) and 10p versus 50p (P < 0.01) and not between 0p versus 10p.Figure 3

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