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Modelling local field potentials in the subthalamic nucleus

Kleinsman, E.J.E. (2013) Modelling local field potentials in the subthalamic nucleus.

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Abstract:Due to the increasing number of elderly people in the western world the amount of patients that suffer from Parkinson’s disease is growing. This brain disorder causes a range of symptoms that seriously affect the quality of life for the patient. The cause of these symptoms is determined to be a pathological decrease of dopamine in the brains, which negatively affects the functioning of the basal ganglia (BG). This is a collection of nuclei in the brain that plays an important role in the control of the motoric system. The surgical ablation of one of these nuclei, the subthalamic nucleus (STN), has been a discovered to be an effective treatment for Parkinson's disease. In more recent history, this procedure has been replaced by electrically stimulating the STN, through a process known as deep brain stimulation (DBS) using an electrode that is implanted in the STN. Applying continuous highfrequency stimulation using this electrode has been found to have the same effect on Parkinsonian symptoms as the permanent destruction of the STN. In addition to stimulation of the nucleus, this implanted electrode can also be used for the measurement of electrical activity in the STN in the form of local field potentials (LFPs). An LFP is the electric field that results from synchronous synaptic activity acting on neurons in a relatively large area around the measuring electrode. This synaptic input causes a local electrical current to flow through the cell membrane of the neuron. The current can be seen as a source with a particular polarity (depending on the type of synapse which determines the direction of the transmembrane current). An opposing current will flow through the rest of the membrane of the affected neuron (some parts of the cell conduct more current than others) to compensate for the current that is entering the cell at the site of the active synapse. This current is the so-called return current and constitutes a second, spatially more distributed source of opposite polarity. Through different pathways that lead from other brain regions towards and through the BG the STN primarily receives input signals from the motor cortex (MC) and the globus pallidus externus (GPe). The input coming from the MC is excitatory while the projections from the GPe have an inhibitory effect on the STN. Previous research has shown that these two synaptic inputs project to different areas within the STN. Although there have been many studies into the general origin of LFPs and the functionality of the STN, the influence that different forms of mutual organizations of neurons and the type of synaptic inputs that these neurons receive have on the LFP that is generated in the STN is still largely unknown. This study investigates the influence that these factors have on the measurable LFP by means of computer simulations. For these simulations, a computational model of a typical STN neuron was used. With this, the influence of groups of neurons that have different orientations relative to each other and to the measuring electrodes has been investigated. Simulated neurons were given various orientations and different positions in a three-dimensional array of electrodes and were provided with synaptic input. This synaptic input modelled projections from one of the main origins (MC or GPe) and was varied in amplitude throughout series of simulations. For each unique set of these parameters, the simulation resulted in a specific organization of the different current sources within the electrode array. The array was then used to measure the LFP that was generated by this constellation of sources, enabling the investigation of the effects of varying both neuronal orientations and the influence of different types of input. The influence of the various factors has been assessed by examining the differences in the LFPs that are measured in both a single measuring electrode, as well as the effect they have on the LFPs’ spatial distribution over the entire array. As these simulations were performed with known parameters, comparing their results to corresponding in vivo measurements from earlier research enabled us to hypothesize on the organization of neurons in the STN around the projection areas from the MC and the GPe. The measurements and some of the simulations both clearly showed the sources that resulted from the different projection synapses, while the sources that were caused by the return currents had a much lower amplitude and had a relatively wide distribution over the area around the MC or GPe projection. Based on these observations and the parameters that constituted the simulations that best approximated the in vivo measurements, we believe that the neurons that receive input from the various projections do not have a particular parallel organization, but rather are individually orientated towards the projection area. This causes a concentrated source of synaptic activity, while the sources of the return current are much more distributed and therefore form a much less powerful source.
Item Type:Essay (Master)
Faculty:EEMCS: Electrical Engineering, Mathematics and Computer Science
Subject:53 electrotechnology
Programme:Electrical Engineering MSc (60353)
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