Grants & Funding > Parkinson`s Disease Foundation Research Grants 2013


Parkinson's Disease Foundation is using its 2013 distribution to fund:

Identifying Connectivity Changes with Deep Brain Stimulation in Parkinson’s Disease


PROJECT TITLE:  Identifying Connectivity Changes with Deep Brain Stimulation in Parkinson’s Disease

Investigators/Authors:  Matthias L. Schroeter, M.D., M.A., Ph.D.; Karsten Mueller, Ph.D., Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Sachsen, Germany

Objective: We plan to investigate how neural networks change with DBS and compare these changes with those caused by Parkinson’s medications.
Background:  In recent years, deep brain stimulation (DBS) has been established as a successful surgical method for treating some people with Parkinson’s disease. DBS provides a small electric current to structures of the brain in order to block motor symptoms of PD. The technique involves the surgical insertion of tiny electrodes deep into the basal ganglia region of the brain and the implantation of an impulse generator (similar to a pacemaker) under the person’s collarbone to provide an electrical impulse to their brain. However, it is still unknown how DBS improves motor symptoms. One idea is that the treatment may alter connections among circuits of neurons, or neural networks, in the brain.

Methods/Design:  We will use a brain scan called functional magnetic resonance imaging (fMRI) to study resting state brain activity before and after taking PD medications, and with and without DBS.

Relevance to Diagnosis/Treatment of Parkinson’s disease:   By examining a person’s brain images before treatment, we may be able to predict their response to the treatment. In this way, we could identify people who would benefit from DBS before they undergo surgery. We expect this research project to advance our knowledge of PD and our understanding of therapeutic approaches.

September 2014 Project Update:

Our innovative, interdisciplinary and transnational research project has a very high potential to significantly advance knowledge of Parkinson’s disease. First year results of the project are contributing to the understanding of well-established and new therapeutic approaches for PD. The importance of our findings is underlined by seven papers, nine abstracts and four awards, which we have published or received since the beginning of our Parkinson’s Disease Foundation IRGP-project.

We have been using resting-state and functional MRI to investigate the PD brain.  These are state of the art imaging approaches to detect connectivity changes and brain activity. A current way to view neurodegenerative disease is to think of these diseases as “nexopathies” or neural connection diseases where deleterious changes in brain connectivity are the byproduct of specific disease processes. As a result, we can use MRI to examine these changes in brain connections.

In the first year of the project, we built on our prior work and we now have identified the typical neural networks involved in PD.  This provides an independent imaging template to facilitate our functional MRI studies in PD patients during motor paradigms (Holiga et al. 2013).  We have also investigated connectivity changes just after DBS (so called micro lesion effect; Holiga et al. submitted) and in DBS compared with the classical dopaminergic treatment (Mueller et al. in preparation). These results add crucial knowledge to our two earlier pilot studies investigating connectivity changes in PD as elicited by treatment. The first study (Mueller et al. 2013) investigated stimulation effects due to DBS, whereas the second examined the impact of dopaminergic medication in PD with a similar approach (Jech et al. 2013). We found higher connectivity was associated with lower scores on the Unified Parkinson’s Disease Rating Scale (UPDRS), indicating clinical effects of connectivity changes.

Our first year’s results complete the understanding of PD in the framework of “nexopathies”. Data prove the usefulness of the chosen statistical approach and identify, as a ‘missing link’ between DBS/dopaminergic treatment and clinical symptom improvements, most important hubs optimized by DBS and demonstrate its effects on long ranging motor circuits in PD.

September 2015 Project Update:

We have investigated the so called microlesion effect due to deep brain stimulation in PD - that is the improvement of clinical (motor) symptoms after implantation of the DBS electrodes but without stimulation. Penetration of electrodes in target regions led to higher EC/connectivity in the brainstem in close relation to clinical improvement. In the interim between our last report and this current one we significantly revised our paper summarizing our work and have now integrated the effects of deep brain stimulation per se (on vs. off), leading to connectivity changes in premotor areas. The paper is very important as it separates short and long term effects of deep brain stimulation.

Š. Holiga, K. Mueller, H.E. Möller, D. Urgošík, E. Růžička, M.L. Schroeter, R. Jech. Resting-state functional magnetic resonance imaging of the subthalamic microlesion and stimulation effects in Parkinson’s disease: Indications of a principal role of the brainstem. NeuroImage: Clinical. Available online 21 August 2015.

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