Article
Functionnal recovery in a primate model of Parkinson’s disease following cortical stimulation
Search Medline for
Authors
Published: | May 4, 2005 |
---|
Outline
Text
Objective
A concept in movement disorders has emerged postulating that the cortex may be implicated in the genesis of motor symptoms. Further experimental and clinical studies in Parkinson’s disease showed that motor cortex may also pattern abnormal rhythmic activity in the basal ganglia that underlies the observed motor symptoms. Here, we describe the use of electrical interference of motor cortex in a primate model of Parkinson’s disease.
Methods
A Resume® electrode was placed flat over the dura mater along the left precentral gyrus in seven adult Papio papio baboons (2 controls, 5 MPTP-treated). The flow chart of the full experiment implicated a series of behavioral and functional imaging analyses with Positron Emission Tomography (PET), before any MPTP administration and during a 52 week-long systemic MPTP intoxication paradigm associated with electrophysiological recordings in the STN and GPi performed in the final stage of the experiments. Two animals were kept unlesioned and served as controls for electrophysiology and histology.
Results
Using high frequency trains of pulses, motor cortex stimulation significantly reduces akinesia and bradykinesia in MPTP baboons. This behavioral benefit was associated with an increase metabolic activity and cerebral blood flow in the supplementary motor area, normalization of mean firing rate in internal globus pallidus (GPi) and subthalamic nucleus (STN) and reduction of synchronized oscillatory neuronal activities in the STN and GPi using unitary neuronal recordings.
Conclusions
All these functional effects were similar to that reported for deep brain stimulation in STN or GPi, using intraparenchymal electrodes. Most importantly, the present series of experiments were conducted as a preclinical study assessing the behavioral benefit in a chronic MPTP primate model in which dopamine depletion was progressive and regularly documented using 18-F-dopa Pet-scan. The data also suggest that motor cortex stimulation was more effective in severely disabled animals implying therapeutic potential for advanced parkinsonian patients. Moreover, the major advantage of such a surgical approach is the simplicity and safety of the procedure entailing an epidural electrode that can be introduced without a deep brain stereotaxic surgery.