Sensory attenuation in Parkinson's disease is related to disease severity and dopamine dose

Abstract

Abnormal initiation and control of voluntary movements are among the principal manifestations of Parkinson's disease (PD). However, the processes underlying these abnormalities and their potential remediation by dopamine treatment remain poorly understood. Normally, movements depend on the integration of sensory information with the predicted consequences of action. This integration leads to a suppression in the intensity of predicted sensations, reflected in a 'sensory attenuation'. We examined this integration process and its relation to dopamine in PD, by measuring sensory attenuation. Patients with idiopathic PD (n = 18) and population-derived controls (n = 175) matched a set of target forces applied to their left index finger by a torque motor. To match the force, participants either pressed with their right index finger ('Direct' condition) or moved a knob that controlled a motor through a linear potentiometer ('Slider' condition). We found that despite changes in sensitivity to different forces, overall sensory attenuation did not differ between medicated PD patients and controls. Importantly, the degree of attenuation was negatively related to PD motor severity but positively related to individual patient dopamine dose, as measured by levodopa dose equivalent. The results suggest that dopamine could regulate the integration of sensorimotor prediction with sensory information to facilitate the control of voluntary movements.

Figure 1

Force matching task illustration. Illustration of the force matching task. In each trial, a torque motor pseudorandomly applied one of four force levels (target force) through a lever to the participants’ left index finger. Participants were asked to match the force they had just sensed (matched force) either by pressing the lever with their right index finger (‘Direct’ condition); or by sliding a linear potentiometer which controlled the torque motor (‘Slider’ condition).

Figure 2

Differences in sensorimotor attenuation between PD patients and controls. (A) Standard boxplots showing the distribution of mean force overcompensation values across all patients and controls in the Direct (shades of blue) and Slider (shades of red) conditions. Positive value indicates sensory attenuation. (B) Mean regression plots of matched versus target force in the Direct and Slider conditions for both groups. Colour scheme is the same as in (A). Dashed line indicates the line of equality. Error bars indicate ± 2 standard error of group mean. Control data points and error bars are offset by 2 pixels for illustration.

Figure 3

Association between dopamine and patient attenuation. (A) Illustration of the standardised beta estimates of all independent variable coefficients included in the multiple regression model (R²_adj = 0.40), predicting Direct intercept. Clinical variables of interest were disease severity, which had a negative effect on attenuation, and levodopa doses, which had a positive effect on attenuation. Error bars indicate ± 1 standard error of group mean. LDE = Levodopa dose equivalent. Significance level indicated by *P  <  0.05; **P  <  0.01; ns = non-significant. (B) Illustration of the relationship between Direct force overcompensation and levodopa dose equivalent, before entered into the regression model.