Characteristics of the sequence effect in Parkinson's disease

Abstract

The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer-based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo-controlled, four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.

FIG. 1

An example of the order of the four interventions: levodopa and rTMS, levodopa and sham, placebo and rTMS, placebo and sham. The orders of the four interventions were randomly assigned.

FIG. 2

Sequence effect (SE) in 11 patients pre-intervention over four interventions. Circles indicate time to move the first four pegs (1st–4th) (open circles) and time to move the last four pegs (5th–8th) (closed circles) (individual data as circles, group averages as bars). Increased mean value in closed circles indicates a SE (progressive slowing during peg movements) and decreased mean value indicates the opposite (speeding up during peg movements). The SE was significant in peg movements with the right hand, but did not reach a level of significance with the left hand (right hand, p=0.04; left hand, p=0.28; paired t-test).

FIG. 3

(%) Relative change of general slowness in the right hand of PD patients. General slowness is defined as total time for eight peg movements. The y-axis shows the value (mean±SEM) of (%) relative change for the general slowness between pre- and post-intervention in 11 patients. A positive value indicates increased total time after intervention; a negative value indicates decreased total time after intervention. There was a significant improvement of (%) relative change in peg movements between rTMS and sham stimulation in the placebo condition (*p<0.05).

FIG. 4

(%) Relative change of sequence effect (SE) in the right hand of PD patients. The y-axis shows (mean±SEM value of the (%) relative change in the SE between pre- and post-intervention in 11 patients. A positive value indicates that the intervention did not reverse the SE; A negative value indicates improvement of the SE after intervention. There was no significant difference among the four interventions (p>0.1).