Movement-related activity in the internal globus pallidus of the parkinsonian macaque

Abstract

ABSTRACTAlthough the basal ganglia (BG) plays a central role in the motor symptoms of Parkinson’s disease, few studies have investigated the influence of parkinsonism on movement-related activity in the BG. Here, we studied the perimovement activity of neurons in globus pallidus internus (GPi) of non-human primates before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Neuronal responses were equally common in the parkinsonian brain as seen prior to MPTP and the distribution of different response types was largely unchanged. The slowing of behavioral reaction times and movement durations following the induction of parkinsonism was accompanied by a prolongation of the time interval between neuronal response onset and movement initiation. Neuronal responses were also reduced in magnitude and prolonged in duration after the induction of parkinsonism. Importantly, those two effects were more pronounced among decrease-type responses, and they persisted after controlling for MPTP-induced changes in the trial-by-trial timing of neuronal responses. Following MPTP The timing of neuronal responses also became uncoupled from the time of movement onset and more variable from trial-to-trial. Overall, the effects of MPTP on temporal features of neural responses correlated most consistently with the severity of parkinsonian motor impairments whereas the changes in response magnitude and duration were either anticorrelated with symptom severity or inconsistent. These findings point to a potential previously underappreciated role for abnormalities in the timing of GPi task-related activity in the generation of parkinsonian motor signs.New & NoteworthyPerimovement responses were present in the parkinsonian GPi at roughly the same overall abundance as seen in the neurologically normal state. Nonetheless, parkinsonism was associated with three abnormalities in perimovement activity: 1) Timings of GPi response became uncoupled from movement onset both with respect to both mean latency and trial-to-trial timing variability. 2) Response magnitudes were attenuated. 3) Response durations were prolonged. The effects on both response magnitude and duration were accentuated in decrease-type responses.