Impairment of context-adapted movement selection in a primate model of presymptomatic Parkinson's disease.
The MPTP model allows the presymptomatic stage of parkinsonism to be studied in primates and hence specific behavioural manifestations of moderate nigrostriatal denervation to be identified. On the basis of the physiological literature, we hypothesized that depletion of striatal dopamine could impair the selection of context-relevant habits. To examine this hypothesis, we trained three African green monkeys to perform a simple reach-and-grasp task, including three contexts differing only in terms of the presence and position of transparent obstacles. At the end of training, the analysis of reaching trajectories showed that intact monkeys had built a repertoire of movements, from which they could select the appropriate one depending on the context. In the course of MPTP intoxication (0.3-0.4 mg/kg every 4-5 days) and before parkinsonian motor symptoms appeared, the reaction time (RT), movement time (MT) and variability of reaching trajectories increased in all monkeys. Frequently, the initial direction was not adapted to the context, and consequently the movement was either corrected online or restarted under visual assistance. These non-adapted trajectories appeared to be the main reason for the increase in both RT (because of difficulty in selecting) and MT (because of the need to make corrections). These observations indicate that moderate MPTP-induced dopamine depletion results in a deficit in the selection of context-adapted movement, which is compensated by corrections using either proprioceptive or visual feedback. Similar behavioural disorders might therefore occur in the presymptomatic stage of human Parkinson's disease.
Pessiglione
Mathias
M
Neurologie et Thérapeutique expérimentale, INSERM U289, Hôpital de la Salpêtrière, Paris, France.
Guehl
Dominique
D
Agid
Yves
Y
Hirsch
Etienne C
EC
Féger
Jean
J
Tremblay
Léon
L
D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology; D002522:Chlorocebus aethiops; D002755:Choice Behavior; D004195:Disease Models, Animal; D018450:Disease Progression; D005133:Eye Movements; D030141:Feedback, Psychological; D006225:Hand / Q000503:physiopathology; D007858:Learning; D020267:MPTP Poisoning / Q000503:physiopathology* / Q000523:psychology*; D008297:Male; D009068:Movement; D011597:Psychomotor Performance; D011930:Reaction Time