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Exploration of the mechanisms underlying subtalemic deep brain stimulation for Parkinson's disease by a computer model and an analysis of the electrophysiological response of the brain to stimulation

English title Exploration of the mechanisms underlying subtalemic deep brain stimulation for Parkinson's disease by a computer model and an analysis of the electrophysiological response of the brain to stimulation
Applicant Pollo Claudio
Number 108318
Funding scheme Project funding (Div. I-III)
Research institution Service de Neurochirurgie CHUV
Institution of higher education University of Lausanne - LA
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2005 - 31.10.2010
Approved amount 227'000.00
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All Disciplines (2)

Neurophysiology and Brain Research
Information Technology

Keywords (6)

subthalamic nucleus; deep brain stimulation; Parkinson's disease; electrical field; finite-element method; diffusion tensor imaging

Lay Summary (English)

Lay summary
The subthalamic nucleus (STN) high-frequency deep brain stimulation (DBS)has widely shown to significantly improve the motor symptoms of Parkinson’s disease. However, such improvements emerge despite a lack ofunderstanding of either the precise role of STN in human motor control orthe mechanism(s) of action of DBS.

The actual electrical field distribution from the DBS electrode within thebrain volume-conductor, or the site and volume of tissue influenced by thestimulation are not precisely known under the conditions used for the STNDBS. The models based on finite element method (FEM) are limited either bythe lack of precise information about the anisotropic properties of neuralmedium, or they don’t take into account the fundamental dielectricproperties of living tissues (quasistatic approach). The recentdevelopment of diffusion tensor magnetic resonance imaging (DT-MRI) hasprovided access to a non-invasive mapping of the brain conductivity at avoxel level. Recent studies have been focused on the use of DT-MRI inFEM-based models. However, they were implemented for limited areas of thebrain conductor-volume. The relevance of such restrictions may bequestioned with respect to the accuracy of the boundary conditions.Moreover, they may be of limited use for the exploration of brain responseto DBS at coarser levels such as cortico-subcortical networks.
Non-invasive investigation of DBS influences at a level of brain networksrequires methods that allow to record neuronal activity on a brain scalein real time. Electroencephalography (EEG) and evoked potentials (EP) inprinciple provide this possibility through the solution of the so-calledinverse problem. EEG source imaging has found important applications inclinical neuroscience for the consideration of temporal and spatialdimensions of brain network activity simultaneously.

In order to explore the mechanisms underlying STN DBS at a level of brainnetworks, the aims of the present project are (1) to develop an accurate3-dimensional computer model of the brain electrical propagation from alocalisable source, based on FEM and including a model of anisotropymeasured DT-MRI and dielectric properties of brain tissue (time- andfrequency-domain FEM), and (2) to perform an electrophysiological study ofthe brain response to DBS based on distributed inverse solutions to eachtime point of the scalp EEG and computed spatio-temporal signalanalysis.

This project involves a close collaboration between centers of expertisein the fields of electromagnetism, signal and image processing, brainmapping and treatment of movement disorders. It will improve ourunderstanding on the identification of the mechanisms and neural networksinvolved in STN DBS. It should provide a more accurate determination ofthe best target(s), the best active contact and the best stimulationparameters depending on the contact position, which has a majortherapeutic impact on parkinsonian patients. Moreover, the model can beextended to other brain functional targets that have recently been shownto improve movement, psychiatric, epileptic and pain disorders.
Direct link to Lay Summary Last update: 21.02.2013

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