CoEN5020 Advancing adaptive deep brain stimulation for gait disturbances and freezing of gait in Parkinson's disease

Freezing of Gait (FoG) is characterized by sudden motor blocks during walking, and can occur with a wide variety of triggers such as extra cognitive load or during turning. This is a devastating symptom of Parkinson's disease (PD) effecting more than half of all patients. Associated with an increased risk of falls, fall-related injuries and mortality, it poses a major burden to patients and their families. Despite its significant health and socioeconomic impacts, FoG still represents a major therapeutic challenge in PD, as it is often unresponsive to dopaminergic medication or conventional continuous deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi). In
this proposal, we aim to better understand the neural basis of FoG in PD with the aim to predict the likely occurrence of these transient FoG episodes, and to evaluate the effectiveness a novel biomimetic pattern of STN stimulation as a treatment promoting resistance to FoG. This would pave the way for early detection of episodic gait disturbances such as the onset of FoG that could be used to control switching between DBS stimulation patterns that are most appropriate for minimizing risk of falling at a given moment in time.

Episodic gait disturbances such as Freezing of Gait (FoG) are difficult to treat because they have a complex pathophysiology involving an interplay between motor and cognitive functions that remains poorly understood. A major roadblock to progress is that conventional treatments including continuous high-frequency STN-DBS treat gait disturbances as a relatively steady-state problem, with treatments being applied chronically with fixed stimulation parameters over long timescales. Such an approach is poorly adapted to the actual complexity of gait disturbances, which are multifactorial, episodic, and highly context or state-dependent over short timescales. We hypothesize that automatically modifying DBS parameters to match state-dependent locomotor demands could be a promising strategy for treating gait disturbances. We posit that a novel STN stimulation regime that promotes physiological, alternating patterns of activity within the STN will serve to reinforce the automaticity of gait, and protect against gait disturbances. We also propose that early detection of FoG will allow a shift to another stimulation regime that specifically terminates FoG. By potentially triggering two distinct stimulation regimes, one during gait to support a more physiological pattern and another at the onset of FoG, we can afford to utilise stimulation parameters that might not be optimal outside of gait.