Uncovering an Electrical Biomarker for Freezing of Gait in Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      The purpose of this study is to investigate brain signals related to freezing of gait (FoG),
      a symptom of Parkinson's Disease, that can lead to dangerous falls. The investigators
      hypothesize that uncovering these signals can lead to better deep brain stimulation
      interventions.
    

Detailed description: 
      Freezing of gait (FoG) is a devastating symptom of Parkinson's disease (PD) that affects more
      than half of the patient population. Defined as an intermittent failure to initiate or
      maintain effective stepping, FoG is a common cause of falls and injuries in PD. There is an
      unmet but pressing need to develop novel therapeutic strategies to treat disabling drug- and
      deep brain stimulation (DBS)-resistant FoG in PD. The objective of this research study is to
      uncover an electrical biomarker for FoG from human electroencephalography (EEG) to better
      understand the neurophysiological underpinnings of the symptom and to inform the development
      of clinical interventions for FoG. The central hypothesis is that EEG activity over the motor
      cortex will exhibit significant changes leading up to and during FoG episodes. This biomarker
      can then facilitate the detection of FoG events directly from scalp recordings. The rationale
      for the proposed research is that non-invasive detection of FoG episodes can be used to guide
      responsive DBS strategies to resolve the episode and prevent potential injuries. Furthermore,
      it is hypothesize that this biomarker will modulate when therapeutic DBS settings for FoG are
      turned on. Given the vast number of DBS parameter combinations that need to be tested and
      chronically verified, such a biomarker can significantly shorten clinical programming and
      prevent side effects of non-optimal stimulation settings. This study will review changes in
      scalp recorded EEG and gait parameters during natural FoG episodes while participants are
      ambulatory in an advanced gait laboratory setting using a wireless EEG amplifier with active
      electrodes. The modulation of the uncovered biomarker during clinical programming of DBS
      settings in participants with bilateral DBS implants in the globus pallidus internus (GPi)
      and pedunculopontine nucleus (PPN). This project is innovative as the dataset acquired will
      be the first of its kind in PD patients with FoG, and will open a new direction of
      multidisciplinary investigation that can potentially uncover the cortical mechanisms of FoG
      in humans and which in turn could lead to novel and effective therapies for those suffering
      from PD. This contribution will be significant because it will provide a critical and unmet
      therapeutic option for FoG and decrease morbidity and mortality associated with FoG related
      falls.

      In summary, the following goals will be accomplished:

        -  Recruit subjects who have undergone DBS implantation for the treatment of PD and who
           have clinically verified FoG.

        -  Collect EEG data during ambulatory tasks that often induce FoG episodes and uncover
           biomarkers of FoG.

        -  Develop a closed-loop paradigm for acute testing when FoG events are detected from EEG
           data.

        -  Use the EEG biomarkers to guide DBS parameter selection for treatment of FoG.
    

Intervention name(s): Deep brain stimulation; Electroencephalography
Intervention type(s): Device; Other
Intervention description(s): The programming of DBS settings in all participants with bilateral DBS implants in the globus pallidus internus (GPi) and pedunculopontine nucleus (PPN) will be performed.; An electroencephalography (EEG) will be performed on all participants to better understand the neurophysiological underpinnings of the symptom.
Other intervention name(s): DBS; EEG
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Device Feasibility
Keywords: Parkinson's Disease with Freezing of Gait Symptoms