Attention and executive function deficits in chronic low-dose MPTP-treated non-human primates

Parkinson's disease (PD) is a complex disorder consisting of motor deficits coupled with dysfunction in cognitive domains that are dependent upon the integrity of the frontal lobes and/or the fronto-striatal axis. Although it is increasingly acknowledged that PD patients have attentional and executive function deficits, it has been difficult to model these in nonhuman primates because of the nature of the cognitive tasks that have been used previously. The present studies were conducted to further define the nature of the cognitive impairment in a nonhuman primate model of early parkinsonism consequent to chronic low dose MPTP exposure and to further validate this model in monkeys trained to perform a battery of attentional and executive function tasks. Following chronic low dose MPTP exposure, monkeys developed deficits in maintenance of a response set as well problems in shifting attentional sets, suggesting decreased mental flexibility. On other tasks inattentiveness, an impaired ability to sustain spatial attention or to focus attention, a deficit in motor readiness and planning, and impaired time estimation were also observed. These results provide direct evidence of attention and executive function deficits in a nonhuman primate model of early parkinsonism. Based on these findings, we suggest that in addition to being useful for studying the cognitive deficits related to early PD and for developing new therapeutics for these problems, this model and these testing procedures may also provide a useful large animal model for studying attention deficit disorder and for developing new therapeutics for that condition as well.