New technique can precisely locate subthalamic nucleus in Parkinson's patients

Deep brain stimulation stops limb tremors in Parkinson's patients. But positioning the stimulation electrode in the brain must be done very precisely to avoid undesired side-effects. To make this possible, researcher Ellen Brunenberg of Eindhoven University of Technology (TU/e) has developed a method for precise, external localization of the right part of the brain: the motor area of the subthalamic nucleus. She has found an ingenious way to localize this 'magic area': by using MRI to visualize the pathways in the brain that lead to it. "If you take away the towns and cities on a map, you can still see where they are located from the pattern of the roads", says Brunenberg, who will gain her PhD on Thursday 8 September for her thesis entitled 'Hitting the right target'.

Deep brain stimulation has been used since the 1980s on patients with a severe form of Parkinson's disease. Symptoms of this incurable brain disease include the well-known tremors of arms and legs. In deep brain stimulation, an electrode is introduced into the subthalamic nucleus of the patient's brain, an area the size of a cashew nut. The pulses from the electrode cause the tremors to virtually disappear. But there are often side-effects, ranging from memory loss and behavioral abnormalities through to depression and extreme susceptibility to addiction. This is because the pulses stimulate not only the motor area of the subthalamic nucleus, but also the areas associated with emotions and thought. It is therefore important to position the electrode precisely: not just in the subthalamic nucleus itself, but also in the right part of it. But how can physicians see exactly where this tiny area is located in a patient's brain?

Roads

Brunenberg and her colleagues have developed a technique that for the first time allows non invasive imaging of the different areas in the subthalamic nucleus. They do this using advanced MRI technology. "It's difficult to image the nucleus directly with MRI, because it is too much like the surrounding brain tissue. But as my supervisor professor Bart ter Haar Romeny says: if you take away the towns and cities on a map, you can still see where they should be located from the pattern of the roads."

Motor area

By using a few complicated techniques, Brunenberg can see the 'roads' in the brain. "MRI allows you to make an image of the structures along which water molecules move through the brain. And that in turn shows the paths of the transport fibers through the various areas: the 'roads' on the map of the brain, which lead to the subthalamic 'city center'. From the links between the subthalamic nucleus and motor areas elsewhere in the brain, you can see which part of the nucleus is the motor area", Brunenberg explains.

Brain surgeons

This research is an important step towards more effective treatment of Parkinson's patients. The new technique should in the near future make it possible to tell brain surgeons before an operation exactly where to introduce the electrode for an optimal result with the minimum possible side effects. But before that can be done, research first has to be carried out with Parkinson's patients. "Up to now we've worked with healthy volunteers. But one of the problems with Parkinson's patients is that it's more difficult for them to lie still." It's also not yet certain whether the brain of someone with Parkinson's looks the same on an MRI scan. Other researchers at TU/e now plan to continue the research.