Auditory cues modulate the short timescale dynamics of STN activity during stepping in Parkinson's disease

Background: Gait impairment has a major impact on quality of life in patients with Parkinson's disease (PD). It is believed that basal ganglia oscillatory activity at beta frequencies (15-30 Hz) may contribute to gait impairment, but the precise dynamics of this oscillatory activity during gait remain unclear. Additionally, auditory cues are known to lead to improvements in gait kinematics in PD. If the neurophysiological mechanisms of this cueing effect were better understood they could be leveraged to treat gait impairments using adaptive Deep Brain Stimulation (aDBS) technologies. Objective: We aimed to characterize the dynamics of subthalamic nucleus (STN) oscillatory activity during stepping movements in PD and to establish the neurophysiological mechanisms by which auditory cues modulate gait. Methods: We studied STN local field potentials (LFPs) in eight PD patients while they performed stepping movements. Hidden Markov Models (HMMs) were used to discover transient states of spectral activity that occurred during stepping with and without auditory cues. Results: The occurrence of low and high beta bursts was suppressed during and after auditory cues. This manifested as a decrease in their fractional occupancy and state lifetimes. Interestingly, alpha transients showed the opposite effect, with fractional occupancy and state lifetimes increasing during and after auditory cues. Conclusions: We show that STN oscillatory activity in the alpha and beta frequency bands are differentially modulated by gait-promoting oscillatory cues. These findings suggest that the enhancement of alpha rhythms may be an approach for ameliorating gait impairments in PD.