Etude de la dynamique des interactions dans la boucle cortex/basal ganglia/cortex : étude par IRMf chez le singe – DyProBaG
Basal Ganglia disorganization induced by Parkinson’s disease
Functional MRI imaging of basal ganglia associated with cortical activation in different clinical parkinsonian situations
issues and objectives
Parkinson's disease is a neurodegenerative disease that affects the central nervous system. If neuronal death affects only a small population of neurons (0.5%) in the brain, the entire neuronal organization is disturbed. In order to consider new therapeutic approaches, it is of prime importance to accurately quantifying this disruption of neural networks supporting voluntary movement.<br />1 ) to highlight this disorganization, a longitudinal study must be carried on : We need to study the evolution of the organization of networks in the same animals from the normal situation, then in parkinsonian animals and in animals treated with the conventional treatment (L- DOPA) and in dyskinetic animals.<br />2) the only animal capable of mimicking the clinical signs of Parkinson's disease model is the non-human primate.<br />3) the only experimental approach able to observe neural networks and to be longitudinal is the functional MRI.<br />The goal of this work was to better understand the pathophysiology of Parkinson's disease in order to consider new therapeutic approaches.<br />
First, we demonstrated that we could obtain functional images on an anesthetized non-human primate with a 3T MRI. The monkey is under gas anesthesia at very low concentration (1.5 %) and forced ventilation to be constantly on the verge of awakening and reduce movement artifacts. The first results were obtained thanks to the visual cortex activates light stimulation. We then have implanted stimulation electrodes at different cortical sensorimotor areas in order to activate basal ganglia loops (BG).
The most difficult point was to determine an intensity of stimulation able to generate an activation of the studied basal ganglia loops in the MRI magnet.
The solution found was to place an electrode at the primary motor cortex (in relation to the periphery ) and to increase the intensity until the appearance of a motor response, through the pyramidal tract , while checking that the signal was not distorted.
The realization of the model of Parkinson's disease with selective neurotoxic DA neurons, the MPTP, allowed us to quantify the neural networks of the basal ganglia in situations: normal animal, parkinsonian animal, parkinsonian animal treated with L- DOPA, dyskinetic parkinsonian animal.
fMRI is the traditional technique to quantify cerebral cognitive activity. Therefore, data on an awake human or animal is collected!
The first major result of this work is that we can obtain functional images from anesthetized animals. The idea is to activate neural circuits from electrical stimulation!
The second important result is the identification of differences in activations within the basal ganglia after stimulation of the primary motor cortex (MI) and the supplementary motor cortex (SMA).
Finally, longitudinal study shows that BG activation following MI stimulation was significantly disrupted by clinical situations whereas BG activation following stimulation of SMA stays stable in all clinical situations.
This basic research project has been led by Dr. Christian GROSS . It also associates Dr. Palma PRO (CYCERON, Caen). It was conducted between 1 March 2009 and 31 December 2013. The project has received support from ANR € 500,000 for a total cost of around € 1.27 million.
The project was very complicated to carry out due to the animal model, but also because of the difficulty in performing fMRI in anesthetized monkeys with electrical stimulation within the magnet. We have taken several years of delay. Nevertheless, we published evidence of the ability to work on anesthetized animals. Insofar as we are fortunate that the post doc in charge of this study was recruited in the structure where this study took place, we are publishing the remaining papers. These results provide a new understanding of the evolution of the organization of control loops of voluntary movement in Parkinson's disease.
Project coordination
Christian GROSS (Université)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
Partner
Help of the ANR 500,000 euros
Beginning and duration of the scientific project:
- 48 Months
