Objective: Medically refractory FoG presents an unmet and pressing need to develop novel therapeutic strategies. We seek to describe the electrophysiology of the pedunculopontine nucleus (PPN), a brain stem structure found to excite spinal central pattern generators and the globus pallidus interna (GPi), in human walking. We will identify the underlying neural mechanisms and pathogenesis of FoG for real-time detection of FoG episodes. A real-time, onboard detector will be designed using the extracted features, stimulation will be delivered in response to positive detection, and the delivered therapy effectiveness will be assessed via clinical scoring standards.

Background: Freezing of gait (FoG) is a poorly understood and an often intractable symptom of Parkinson’s Disease (PD) affecting patients regardless of disease progression or medical therapy. Dopamine therapies or deep brain stimulation (DBS), often do not provide adequate management of FoG.

Methods: All participants must meet the inclusion criterion, including minimum scores on FoG-Q and a minimum of 5 freezing episodes incited by FoG provocation tasks. A total of five participants will receive bilateral GPI and PPN DBS electrode implantation with two Activa PC+S Neurostimulation system, (Medtronic, Minneapolis, MN. These novel devices are capable of capturing data while simultaneous delivering stimulation to the depth electrodes. Concurrently, data will be collected from multiple EMG+acceleration sensors (Delsys, Inc., Natick, MA), a 10-camera motion capture system (Vicon Peak, Oxford, UK), and ground reaction forces (Bertec, Newton, MA) over two-day monthly visits over a a span of a year.

Results: We have observed a correlation between medication state and task intensity and the mu-low beta activity in GPi. Similarly, low frequency activity (<10Hz) in the PPN changes with medication and is positively correlated with the intensity of the task. Clinical labels of FoG have also been identified to correlate to FoG episodes and the low frequency activity. A neurologist’s time-aligned labeling of onset and cessation of FoG episodes during a continuous walking task was compared to the onboard threshold detector.

Conclusions: Our initial results are promising and consistent across 4 subjects. The fifth patient was levadopa non-responsive, and may explain why similar patterns were not observed.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/towards-responsive-deep-brain-stimulation-for-medically-refractory-freezing-of-gait-in-parkinsons-disease/