MEG in Parkinson¡¯s disease patients with DBS

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective surgical intervention for motor symptoms in Parkinson’s disease (PD), but it can induce negative cognitive and psychiatric side effects in up to 25% of patients. Usually the electrodes targeted at the STN are implanted bilaterally. Each electrode may have four or eight contact points. Clinical improvement and side effects differ per stimulated contact point, but the cause of these effects is only partly understood. At present, it may take months to identify the optimal DBS settings via trial and error. Stimulation of white matter tracts surrounding the STN is considered important for the clinical effects of DBS. The relationship between contact points and white matter tracts, hence the stimulation sites, can be approximated using diffusion tensor imaging (DTI). Magnetoencephalography (MEG, a recording of magnetic fields related to brain activity) can be used to characterize stimulation site dependent functional networks that can be associated with the occurrence of (side) effects. The combination of contact point-specific functional and structural brain network characteristics can help to identify stimulation sites prone to induce side effects. This could improve clinical outcome by aiding DBS electrode placement and contact point selection.

Objectives are: a) Identification of stimulation site-specific functional and structural brain network characteristics in patients with PD and STN-DBS.

b) Relating subject-specific stimulation sites and functional network changes to measures of cognitive and psychiatric side effects.

Study design: This explorative study is an observational, cross-sectional study using MEG to characterize stimulation site-specific functional brain network characteristics. The functional networks will be obtained by alternatingly stimulating individual stimulation sites. This will be combined with clinical data from the Academic Medical Center (AMC) Amsterdam, where patients have undergone STN DBS. In the context of standard clinical care, pre- and post-DBS neuroimaging and evaluation of cognitive side effects will be conducted. Pre-DBS assessment of psychiatric symptoms takes place in the context of standard clinical care as well, whereas post-DBS information on psychiatric side effects will be obtained using questionnaires in anticipation of- and during the study visit for MEG recordings at VUmc.

DBS-related cognitive decline and psychiatric side-effects in Parkinson's disease (PD) patients can be studied from a functional- and structural network point of view. We will characterize functional and structural brain networks in PD patients treated with DBS and correlate this with DBS-related non-motor side effects. We expect that the knowledge obtained in this study can improve electrode positioning and contact point selection.

One study visit in which MEG-measurements and questionnaires on psychiatric symptoms take place.

In each subject, eleven MEG recordings of 5 minutes duration will be completed in a single session. The first MEG recording will be performed in the optimal DBS settings of the participant. After this, nine MEG recordings will take place using different DBS settings in a randomized order: during eight recordings in turn unilateral stimulation of each of the individual contact points takes place and one recording will be performed in the DBS-OFF state.