MIRA University of Twente
Applied Analysis


Current BSc & MSc project:

  • Normen Oude Booiink (MSc)
  • Nick Luiken (MSc)
  • Yoeri Boink (MSc)

Finished MSc projects

This list   (under construction, by no means complete) is meant to give you an impression about what could be achieved during your final project period, and how a thesis in our area could look like.

Vacant Msc projects

Two projects on "Electrical Activity Mapping of the Subthalamic Nucleus: improvement of DBS protocols in Parkinson's Disease Deep brain stimulation (DBS) for Parkinson's Disease is an effective treatment for many patients for whom medication is no longer sufficient. It consists of placing an electrode with a stereotactic procedure in the subthalamic nucleus (STN), a brain structure in the basal ganglia involved in motor control. Next, continuous high frequency current stimulation diminishes symptoms. The stimulation amplitude must be high enough to achieve a therapeutic effect but cannot be too high as that will cause unwanted side effects. Then the stimulation also affects other brain nuclei and fiber bundles leading to muscle contractions, sensory deficits but also mood changes.

Side effects may be diminished using directional steering of the applied electrical field. The aim is to target only the desired part of the STN and not on the surrounding nerve fibers. This claim has been proven in a recent study [1] where stimulation with steering induced side effects at higher stimulation amplitudes. During that study also local field potentials (LFP) were recorded [2]. The lead, i.e. electrode, has a new design with 32 contact points in a checkerboard pattern. The current electrode only has 4 simple circular contact points, and typically only two of them lie within the desired subregion of the STN. Hence these new high resolution LFP data enable two new explorative studies.

Project 1.:

Source reconstruction to optimize steering

The STN is the preferred target for DBS, but its size is small comparable to a peanut. Despite careful planning the electrode might be placed suboptimally within the STN. As a result, the stimulation amplitude required for a therapeutic effect may be out of reach as the electrical field could activate neural tissue outside the STN or the wrong, non-sensomotoric part of the STN [3]. In this case, the use of steering is very attractive as it enables a much more specific modulation of STN electrical activity.

It is not so clear, however, which directional mode would be optimal for stimulation. A manual optimization of the 32 contact points is clearly unfeasible. LFP measurements through the same contact points as with which stimulation is performed, could reveal which part of the STN displays pathological beta activity. This requires inverse modelling where the source should be required to lie within the STN. In addition, multiple sources may be found. The results of this project will allow to optimize which electrodes to use for stimulation. In this way the LFP recordings can be used as an automatic feedback for the stimulation parameters and no extensive clinical testing to optimize the stimulation parameters is necessary.


Project 2.:

Analysis of phase-amplitude coupling in the STN for coordinated-reset stimulation

Coordinated reset (CR) has been proposed as a more efficient stimulation protocol for deep brain stimulation [4] as opposed to continuous stimulation, which is being used conventionally [5]. This novel stimulation protocol consists of stimulation with a cycling pattern of brief high-frequency pulse trains at multiple electrode contacts. This type of stimulation is done to consecutively reset the phases of the different stimulated neuronal subpopulations. This is hypothesized to divide the neuronal population into phase-shifted subpopulations, causing an unlearning of both pathological neuronal synchrony and pathological synaptic connectivity. This means that once the connectivity has been changed, in contrast to the conventional stimulation, the high frequency stimulation temporarily can be turned off. If the mean frequency of stimulation, pulse amplitude can be reduced with CR stimulation, less energy is needed, and batteries can be replaced or recharged after longer intervals. Moreover, smaller stimulators can be developed. Most importantly, a reduced stimulation current could result in less side effects. Such improvements can result in a further improved quality of life for patients undergoing DBS. Hypothetically the CR protocol by plastic changes would affect the pathological neural circuits and reset them in a persistent way.

To apply CR stimulation optimally the new LFP data will allow to investigate the synchronization within the STN in a much higher spatial and temporal resolution. In particular it could reveal whether the synchronization in the STN is homogeneous, or that there are substructures with a particular phase difference in their activity. This can be revealed through a Phase-Amplitude Coupling (PAC) analysis [6]. This kind of analysis may reveal substructures within the STN and thismay aid in the design of CR-protocols. Also our understanding of the spatial distribution of neural activity at particular frequencies in STN will be increased.


  1. Directional steering: A novel approach to deep brain stimulation.
    Contarino, M.F., Bour, L.J., Verhagen, R., Lourens, M.A.J., de Bie, R.M.A., van den Munckhof, P. and P.R. Schuurman, Neurology (2014) vol. 83(13): 1163-1169
  2. Directional Recording of Subthalamic Spectral Power Densities in Parkinson's Disease and the Effect of Steering Deep Brain Stimulation.
    Bour, L.J., Lourens, M.A.J., Verhagen, R., de Bie, R.M., van den Munckhof, P., Schuurman, P.R. and Contarino, M.F., Brain Stimulation (2015) vol. 8(4):730-741.
  3. Functional neuronal activity and connectivity within the subthalamic nucleus in Parkinson's disease.
    Lourens, M.A.J., Meijer, H.G.E., Contarino, M.F., van den Munckhof, P., Schuurman, P.R., van Gils, S.A. and Bour, L.J., Clin Neurophysiol (2013) vol. 124(5):967-981
  4. Coordinated reset stimulation in a large-scale model of the STN-GPe circuit.
    Ebert, M., Hauptmann, C. and Tass, P.A., Front Comput Neurosci (2014) 8:154
  5. Long-term electrical inhibition of deep brain targets in movement disorders.
    Benabid A.L., Benazzouz, A., Hoffmann, D., Limousin, P., Krack, P. and Pollak, P., Mov Disord (1998) Vol. 13 Suppl 3: 119-125
  6. Subthalamic nucleus phase-amplitude coupling correlates with motor impairment in Parkinson's disease,
    van Wijk, B.C., Beudel, M., Jha, A., Oswal, A., Foltynie, T., Hariz, M.I., Limousin, P., Zrinzo, L., Aziz, T.Z., Green, A.L., Brown, P. and Litvak, V., Clin Neurophysiol (2016) vol. 127(4): 2010-2019

When interested please contact:  Dr. H.G.E. Meijer