Cognitive slowing in Parkinson's disease: a behavioral evaluation independent of motor slowing

Abstract

Parkinson's disease (PD) is attributable primarily to depletion of dopamine in the basal ganglia, but the full effects of this depletion are unknown. It is well known that PD involves motor slowing, and although it is not easy to distinguish between the motor and cognitive components of behavior, clinical observations suggest that cognitive processing may also be compromised. However, it remains unclear whether such cognitive involvement exists, and if so, to what extent. Previous studies of cognitive slowing in PD have yielded conflicting results. This may be attributable to variations in experimental procedures, because most of the experiments used reaction-time tasks, which are inevitably confounded by motor components. In the present study, we evaluated the speed of cognitive processing in patients with PD without bradykinesia as a variable. We developed a mental-operation task that required serial updating of mental representations in response to a series of visual stimuli. By changing the speed of visual presentation and evaluating performance accuracy, the speed of cognitive processing was assessed independently of motor slowing. Cognitive impairment in PD became evident when higher speeds of cognitive processing (verbal more so than spatial) were required. In addition, cognitive slowing and motor slowing were significantly correlated. The results of the present study suggest that slowing in PD is not restricted to the motor domain but can be generally observed in other domains of behavior, including cognitive mental operations.

Fig. 1.

Experimental paradigms. A, MO-s.B, MO-v. The top row illustrates the visual stimuli used in each version of the task, and the bottom row illustrates the expected mental representations in the subjects. For both tasks, a trial started with the presentation of a prime stimulus (PS), followed by the presentation of seven instruction stimuli (IS). Subjects serially manipulated mental representations according to the instruction stimulus. C, Schematic representations of the experimental procedure. The frequency of presentation of the instructional stimuli was constant within a trial but varied across trials. Eight different stimulus frequencies (0.4–1.8 Hz in 0.2 Hz steps) were used for each task. Each task was broken into one practice block (open circles) and five experimental blocks (filled circles). The stimulus frequency was serially increased in the first half of the block and then serially decreased in the second half.

Fig. 2.

The number of correct answers for the MO-s (A) and MO-v (B) in patients with PD and controls. The number of correct answers for both groups decreased as the stimulus frequency increased. At stimulus frequencies of ≥1.4 Hz, their performance approached chance (gray horizontal line) or even below.C, Difference in the number of correct answers between patients with PD and controls at each stimulus frequency for each task. The performance deficit in patients with PD was most prominent at 1.0 Hz in both MO-s and MO-v. Moreover, the deficit in patients with PD was greater in MO-v compared with MO-s. *p < 0.05;^#p < 0.01;^##p < 0.001.

Fig. 3.

Difference between the number of correct answers for MO-s and MO-v at each stimulus frequency for each group. At 0.4 Hz, the number of correct answers was the same for both tasks and for both groups. At greater speeds, the PD group exhibited a greater deficit in MO-v than MO-s. This divergence in performance level was not observed for controls. The performance at ≥1.4 Hz was difficult to evaluate because the number of correct answers was near the chance level, especially for the PD group for MO-v. The horizontal dotted line indicates equal performance level of MO-v and MO-s.

Fig. 4.

Correlation between the bradykinesia subscale and the bradyphrenia score for MO-s and MO-v. Correlational analysis of motor impairment and cognitive slowing in PD demonstrates a significant relationship between bradykinesia and bradyphrenia in MO-s (r = 0.42; p < 0.05) and MO-v (r = 0.43; p < 0.05).