Exploring Magnetic and Electrical Brain Stimulation in Parkinsonian Dyskinetic Monkeys.

Background: Parkinson's disease (PD) chronic L-Dopa treatment often triggers motor complications, such as L-Dopa-induced dyskinesias (LID). LID are reported to be associated with abnormal glutamatergic activity between the striatum and primary motor cortex (M1), resulting in M1 hyperactivation. Beneficial noninvasive brain stimulation (NIBS) paradigms were reported to normalize glutamatergic activity. The objective of the present study was thus to set up a NIBS paradigm in parkinsonian monkeys to investigate motor behavior under basal conditions and with L-Dopa treatment-inducing dyskinesias.

Methods: Motor behavior was investigated in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dyskinetic female Macaca fascicularis monkey models of PD, allowing us to monitor the administration of NIBS and drugs. NIBS used were inhibitory protocols, that is, cathodal transcranial direct current stimulation (c-tDCS) and continuous theta-burst stimulation (cTBS). A procedure of three weeks was developed to progressively acclimate animals to the experimental conditions, equipment and noise of c-tDCS and cTBS before stimulating them with either vehicle or L-Dopa.

Results: One session of c-tDCS with L-Dopa yielded no effect, whereas five sessions briefly reduced LID but decreased the duration of L-Dopa anti-PD effects. cTBS alone improved (decreased) parkinsonian scores as compared to sham stimulation or vehicle alone. Two sessions of cTBS with L-Dopa decreased LID without affecting L-Dopa anti-PD effects.

Conclusion: This is the first study testing c-tDCS and cTBS on the motor behavior of MPTP dyskinetic monkeys. As compared to medicated patients, MPTP monkeys offer the opportunity to evaluate NIBS after-effects in drug-free and LID conditions, which are critical in the search for new PD treatment.