Subthalamic Nucleus Deep Brain Stimulation Alleviates the Sequence Effect and Freezing of Gait in Parkinson's Disease

The sequence effect in gait (progressive shortening of strides) contributes to freezing of gait (FOG), a debilitating feature of Parkinson's Disease (PD). The sequence effect is refractory to dopaminergic medication or attentional strategies, with alleviation observed only from external cueing. While subthalamic nucleus (STN) deep brain stimulation (DBS) is a standard treatment for PD, its efficacy for gait impairment and FOG remains debated. To characterize the sequence effect in spatial-temporal gait parameters in PD and investigate the effect of STN-DBS. Eighteen individuals with PD with bilateral STN-DBS and fourteen age-matched healthy controls performed a harnessed stepping-in-place task, which we previously validated to elicit FOG. PD participants were assessed OFF and ON DBS in the off-medication state. Spatial-temporal gait parameters were obtained from inertial measurement units placed on both shanks, and the sequence effect was modeled with an exponential decay function for each gait parameter over time. The sequence effect was evident in shank swing angular velocity and range among PD participants, which was absent in healthy controls. The degree of sequence effect was significantly correlated with the time spent freezing during off therapy ( p < 0.001). STN-DBS significantly alleviated the sequence effect ( p = 0.002) and reduced the time spent freezing ( p = 0.01). The stepping-in-place task elicited the sequence effect in both velocity and spatial aspects of gait in individuals with PD. The sequence effect contributed to FOG severity. STN-DBS was effective in alleviating the sequence effect, thereby improving FOG in PD.