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Funded Studies

Role of the Posterior Parietal Cortex and Pedunculopontine Nucleus in the Pathophysiology of Freezing of Gait: An MRI and TMS Study

Objective/Rationale:
Although disturbances in the posterior parietal cortex (PPC) and pedunculopontine nucleus (PPN) are thought to be involved in the development of freezing of gait (FOG) in PD patients, their respective roles remain poorly understood. Here, we will use brain magnetic resonance imaging (MRI) to investigate how these key brain regions interact with other areas when they are engaged in the control of gait in PD. We will test if repetitive transcranial magnetic stimulation (rTMS) of one node of the identified network can alleviate FOG.
Project Description:
We will study 30 PD patients with different levels of FOG assessed by a new scale we are currently validating in our laboratory (Unified Freezing of Gait Rating Scale, UFOGS) and 30 normal volunteers (NV) matched for age, gender and cognition. We will first use BOLD fMRI to study brain activity changes during mental imagery of gait. Diffusion tensor imaging (DTI) data will be used to examine anatomical connectivity of several brain areas presumably involved in the control of gait in NV and PD patients, based on the results of the BOLD fMRI experiment (e.g. PPC and PPN). In some selected PD patients who combine FOG and anatomical/functional disturbances in the PPC, we will test the immediate and long term therapeutic effects of rTMS on gait performance.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The UFOGS is designed to become a practical clinimetric tool to quantify FOG in PD patients. On the basis of the hypothesized dysfunction of the PPC and other connected areas, rTMS of one node of this network might be a new therapeutic approach in addition to current physical rehabilitation techniques in PD patients suffering from FOG.
Anticipated Outcome:
We anticipate that the UFOGS is a sensitive and accurate clinical tool to easily diagnose FOG and assess its progression over time. The results of this research study should also help to better understand the brain mechanisms underlying FOG. We also expect that rTMS will be a useful treatment of FOG in PD patients.

Progress Report

Functional and anatomical data using MRI were obtained in patients with Parkinson’s disease with different levels of freezing of gait assessed with our home-made freezing of gait rating scale and in a population of healthy controls matched for age and gender. Preliminary data show a wide pattern of disturbances in cortical regions and brainstem among patient with Parkinson’s disease as compared with healthy controls. Altered brain regions in patients with freezing of gait are potential targets for stimulation or inhibition using repetitive transcranial magnetic stimulation. A study evaluating the effect of this technique on gait capacities is currently on-going.

Presentations & Publications
- Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of motor imagery of gait in Parkinson’s disease. Poster presentation at the Belgian Brain Congress 2010, Brussels (Belgium), September 17-18, 2010
- Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of brisk and comfortable walking in the elderly. Poster presentation at the Belgian Brain Congress 2010, Brussels (Belgium), September 17-18, 2010
- Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of mental imagery of gait in Parkinson’s disease. Poster presentation at the 7th International Congress on Mental Dysfunction & Other Non-Motor Features in Parkinson’s Disease & related Disorders, Barcelona (Spain), December 9-12, 2010

Final Outcome

The results of our brain MRI data analyses showed that PD-related gait disturbances is associated with widespread cortico-subcortical (including the posterior parietal cortex and the pedunculopontine nucleus) functional and anatomic abnormalities. Our results provide evidence that PD patients with more severe episodic gait disturbances such as freezing of gait have impaired activation of a fronto-cingulo-parietal network and that the PD-related inability to increase gait speed is associated with abnormal activity and connectivity of the posterior parietal cortex. These observations are currently verified using repetitive transcranial magnetic stimulation applied on the posterior parietal cortex in PD patients with severe gait disturbances. The aim of this approach is to provide a therapeutic procedure to alleviate PD-related gait disturbances such as freezing of gait by refocusing the activity within the posterior parietal cortex.

Presentations & Publications

-          Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of motor imagery of gait in Parkinson’s disease. Poster presentation at the Belgian Brain Congress 2010, Brussels (Belgium), September 17-18, 2010

-          Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of brisk and comfortable walking in the elderly. Poster presentation at the Belgian Brain Congress 2010, Brussels (Belgium), September 17-18, 2010

-          Crémers J, Stamatakis J, D’Ostilio K, Garraux G. fMRI study of mental imagery of gait in Parkinson’s disease. Poster presentation at the 7th International Congress on Mental Dysfunction & Other Non-Motor Features in Parkinson’s Disease & related Disorders, Barcelona (Spain), December 9-12, 2010

-          Construction and validation of the Dynamic Parkinson Gait Scale (DYPAGS). In revision in Parkinsonism and Related Disorders.

-          Crémers J, D’Ostilio K, Stamatakis J, Delvaux V, Garraux G. Scattered brain activity and gait control in Parkinson’’s disease. In revision in Movement Disorders.

-          Crémers J, Stamatakis J, D’Ostilio K, Garraux G Neural correlates of Gait Hypokinesia in Parkinson’s Disease. Submitted in Journal of Neuroscience.


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