Local field potentials in Parkinson’s disease patients

Local field potentials in Parkinson’s disease patients.

Background and problem statement

High frequency stimulation of the subthalamic nucleus (STN) is a relatively novel treatment method for advanced Parkinson’s disease. Though deep brain stimulation (DBS) has proven its ability to suppress Parkinson’s disease symptoms, the exact underlying mechanisms of STN-DBS are still unknown. Nowadays, effective stimulation parameters are empirically found by testing each of the four possible contacts on the implanted electrode. Once the stimulation parameters are selected, they can only be modified in the neural-modulation clinic, a few times a year.

deep-brain-stimulation

A new generation of stimulation electrodes is developed by Sapiens, a high-tech Dutch company, consisting of 64 instead of four contacts. The new electrode design makes it possible to not only stimulate, but also measure brain activity in the form of local field potentials (LFPs) during stimulation. Therefore, in the future a feedback controlled stimulation protocol can be developed based on the clinical symptoms of the patient using the measured LFPs as a state variable.

For the past two years the departments of clinical neurophysiology and neurosurgery at the Academic Medical Center (AMC) in Amsterdam have been working together to study LFPs measured intraoperatively in order to get a better understanding of the relation between LFPs in the STN and the clinical conditions of the Parkinson patient. To improve this understanding, the AMC and the University of Twente work together to combine modeling studies with the analysis of clinical data. Modeling should help to understand what creates the pathological oscillations in STN LFPs that have been found in Parkinson patients and how high frequency stimulation modifies the LFPs.

Assignment

The master assignment consists of two parts:

Part 1: (modeling)

Recent modeling studies have shown that LFPs in the cortex are related to synchronized subthreshold activity in nearby neuronal populations. However, the cortex consists of a nicely aligned structure of cortical cells, while the STN cells probably have a less structured organization. Therefore the influence of neuronal structures and organizations on the LFP output needs to be studied.

Part 2: (data analysis)

In the coming months, the new Sapiens electrode will be used to measure LFPs in the human STN, first intraoperatively. By comparing these measured LFPs with the outcome of the modeling study, a statement can be made on the neuronal structure within (the sensorimotor part of) the STN.

Components

· Perform a literature study on LFPs, the STN and its neuronal structure and neuronal network models.

· Investigate the use of Neuron (http://www.neuron.yale.edu/) and LFPy (http://compneuro.umb.no/LFPy/) as a simulation environment.

· Develop computational models of simple neural network with different structures.

· Relate LFP recordings to the different network structures.

· Discuss the results

· Report writing and final presentation

Educational program

MSc

EL/BMT

Research theme

From Neural Circuit Behavior to Human Sensory-Motor Function

Principal Investigator track

Ciska Heida (UT):

Central motor control

Supervision and info

Kees van Dijk (UT)