Maladaptive avoidance patterns in Parkinson's disease are exacerbated by symptoms of depression

Abstract

Parkinson's disease (PD) is a chronic, progressive neurodegenerative disorder, characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. Given that dopamine is critically involved in learning and other cognitive processes, such as working memory, dopamine loss in PD has been linked both to learning abnormalities and to cognitive dysfunction more generally in the disease. It is unclear, however, whether avoidance behavior is impacted in PD. This is significant, as this type of instrumental behavior plays an important role in both decision-making and emotional (dys) function. Consequently, the aim of the present study was to examine avoidance learning and operant extinction in PD using a computer-based task. On this task, participants control a spaceship and attempt to shoot an enemy spaceship to gain points. They also learn to hide in safe areas to protect from (i.e., avoid) aversive events (on-screen explosions and point loss). The results showed that patients with PD (N = 25) acquired an avoidance response during aversive periods to the same extent as healthy age-matched controls (N = 19); however, patients demonstrated greater hiding during safe periods not associated with aversive events, which could represent maladaptive generalization of the avoidance response. Furthermore, this impairment was more pronounced during the extinction phase, and in patients who reported higher levels of depression. These results demonstrate for the first time that PD is associated with maladaptive avoidance patterns, which could possibly contribute to the emergence of depression in the disease.

Keywords: Avoidance; Computer-based task; Depression; Extinction; Generalization; Parkinson’s disease.

Figure 1.

Schematic of within-trial timeline of the escape-avoidance task. (A) In the acquisition phase, 12 trials consisted of a 10-sec warning period, a 10-sec punishment period and a 20-sec inter-trial interval (ITI). (B) In the extinction phase, 12 trials consisted of a 10-sec warning period and a 30-sec ITI.

Figure 2.

Schematic of the computer-based avoidance task. (A) A target enemy spaceship appears in one of six locations in the upper half of the screen approximately every second. (B) To earn points, the participants must position themselves below the target, allowing them to shoot the target. (C) A large mothership appears on the screen every 40 sec, signaling the 10-sec warning period. (D) During the acquisition phase, the warning period is followed by the appearance of ‘blue lasers’, which fire on screen for 10 sec (punishment period). Every time the participant’s spaceship is hit, it results in a 5-point loss, with a maximum of 50 points lost. (E) ‘Safe areas’ are located at the bottom right and left of the screen. Moving into one of these areas is defined as ‘hiding’. (F) When the participant’s spaceship is located in a ‘safe area’, points cannot be lost, nor can they be gained.

Figure 3.

Average trial-by-trial hiding scores during the warning, punishment, and ITI periods of each trial in controls and patients. Note that the lasers were not presented during extinction; the “punishment period” during extinction phase in the figure above corresponds to the 10 sec that followed the warning period and is identical to the 20-sec ITI period. Data are expressed as mean ± standard error of the mean.

Figure 4.

Average hiding scores during the extended 30-sec ITI period during extinction (comprising the 10-sec punishment period and the 20-sec ITI period) plotted as a function of BDI scores and group.

Figure 5.

Relative importance metrics for each predictor obtained from a relative importance regression model on the 30-sec extinction ITI hiding scores.