Anticipatory postural adjustments are modulated by substantia nigra stimulation in people with Parkinson's disease and freezing of gait.

BACKGROUND: A precise understanding of the neuronal circuits involved in the control of anticipatory postural adjustments (APAs) for gait initiation is missing. Neurostimulation in Parkinson's disease (PD) provides a method of modulating APAs to gain insight into the underlying circuitry. OBJECTIVE: Our objective was to investigate if APA kinematics for step initiation could be modulated by high frequency stimulation of the subthalamic nucleus (STN) or substantia nigra pars reticulata (SNr) in people with PD and freezing of gait (FoG). METHODS: We studied 14 people with PD and FoG using neurostimulation of the STN and SNr areas after overnight withdrawal of dopaminergic medication on the instrumented stand and walk test. We tested patients in the following randomized conditions: 'off stimulation', 'STN' stimulation (only), and 'SNr' stimulation (only). Patients were blinded to the stimulation condition. The APAs were recorded with inertial sensors and processed offline. Moreover, we assessed clinical scores with respect to motor symptoms, non-motor symptoms, executive function, and FoG. RESULTS: SNr but not STN stimulation modulated the anterio-posterior size of APA. The SNr modulation of APA was associated with the stimulation effect on FoG (trend; r = 0.580, P = 0.102). The APA modulation was not correlated with any other cognitive or clinical measures. CONCLUSION: Neuromodulation of the SNr but not of the STN modulated APAs in PD patients with FoG. The different effects of STN or SNr on the kinematic parameters of APA support the concept of segregate targets in order to address diverse kinematic components of PD gait.

Effects of Subthalamic and Nigral Stimulation on Gait Kinematics in Parkinson's Disease.

Conventional subthalamic deep brain stimulation for Parkinson's disease (PD) presumably modulates the spatial component of gait. However, temporal dysregulation of gait is one of the factors that is tightly associated with freezing of gait (FOG). Temporal locomotor integration may be modulated differentially at distinct levels of the basal ganglia. Owing to its specific descending brainstem projections, stimulation of the substantia nigra pars reticulata (SNr) area might modulate spatial and temporal parameters of gait differentially compared to standard subthalamic nucleus (STN) stimulation. Here, we aimed to characterize the differential effect of STN or SNr stimulation on kinematic gait parameters. We analyzed biomechanical parameters during unconstrained over ground walking in 12 PD patients with subthalamic deep brain stimulation and FOG. Patients performed walking in three therapeutic conditions: (i) Off stimulation, (ii) STN stimulation (alone), and (iii) SNr stimulation (alone). SNr stimulation was achieved by stimulating the most caudal contact of the electrode. We recorded gait using three sensors (each containing a tri-axial accelerometer, gyroscope, and magnetometer) attached on both left and right ankle, and to the lumbar spine. STN stimulation improved both the spatial features (stride length, stride length variability) and the temporal parameters of gait. SNr stimulation improved temporal parameters of gait (swing time asymmetry). Correlation analysis suggested that patients with more medial localization of the SNr contact associated with a stronger regularization of gait. These results suggest that SNr stimulation might support temporal regularization of gait integration.