Selective stimulation of the subthalamic nucleus

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates motor symptoms in Parkinson’s disease (PD) patients. However, some patients suffer from cognitive and emotional changes. We hypothesize that by identifying the motor part of the STN, the stimulation field can be positioned such that current spread to the cognitive and limbic territories is prevented therewith reducing side effects. In this thesis, methods to identify the motor part of the STN during DBS surgery were assessed in order to reduce stimulation-induced behavioral side effects and to optimize the therapeutic benefit. First, the use of motor cortex stimulation (MCS) to locate the STN motor area was investigated. We found that MCS evokes responses in the unit activity specifically within certain areas of the STN. The spatial resolution of responses measured in the LFP to MCS was not high enough to identify the STN motor region. To improve MCS, we developed a model with a 3D representation of several axonal populations. The model predicted that a cortically evoked STN response can best be achieved using anodal rather than cathodal and bipolar stimulation. To interpret the subthalamic response to MSC, we assessed the inverse current source density method in anaesthetized rat, which resulted in clear and well discriminable sources and sinks of the neuronal input activity in the STN. Second, we evaluated the spatial distribution of spontaneous oscillations in the beta and gamma local field potentials (LFPs) in the STN’s of 25 PD patients undergoing DBS surgery. The results indicated that LFP gamma oscillations may provide a useful tool for locating the borders of the STN, and LFP beta oscillations could be used to locate the dorsolateral sensorimotor area within the STN. Finally, to determine the therapeutic benefit of DBS, an advanced ambulant method to quantify motor improvement was developed. We present a novel ambulatory monitoring system that provides a complete motor assessment by simultaneously analyzing current motor activity of the patient (e.g. sitting, walking) and the severity of many aspects related to tremor, bradykinesia, and hypokinesia.