TY - JOUR
T1 - Anticipatory postural adjustments are modulated by substantia nigra stimulation in people with Parkinson's disease and freezing of gait
AU - Heilbronn, Melanie
AU - Scholten, Marlieke
AU - Schlenstedt, Christian
AU - Mancini, Martina
AU - Schöllmann, Anna
AU - Cebi, Idil
AU - Pötter-Nerger, Monika
AU - Gharabaghi, Alireza
AU - Weiss, Daniel
N1 - Funding Information:
Remarkably, APAs are smaller in PD patients with FoG compared to patients without FoG [9,33]. Interestingly, within the group of PD patients with FoG, APAs were larger in gait initiation trials with observed start hesitation as opposed to trials without FoG [9]. To this end, it was argued that PD freezers might encounter problems to control for larger APA size when coordinating the temporal sequence of postural adjustment, effective gait initiation and consecutive, rhythmic stepping behavior. To this end, it is speculated that smaller APAs might be easier to control and reflect compensatory adjustment in order to attenuate the susceptibility of PD gait freezers to gait initiation failure [9]. This assumption seems to receive support from our findings, given a positive (albeit non-significant) correlation between the reduction in anterio-posterior size of APA and reduction in FoG severity with SNr stimulation. However, this finding needs reevaluation in future larger studies. In addition, future neuromodulation studies should further assess the relationship between APAs and gait improvement (as was postulated for STN stimulation), or conversely, unintended worsening in gait function [24,25].We would like to thank Dr. Patty Carlson-Kuhta (Balance Disorders Laboratory, Oregon Health & Science University, Portland, OR, United States) for proofreading and language editing of this manuscript. Daniel Weiss received research support from the German Research Council (DFG; WE5375/1-1; WE5375/1-3) and the Michael J Fox Foundation.
Funding Information:
Daniel Weiss received research support from the German Research Council ( DFG ; WE5375/1-1 ; WE5375/1-3 ) and the Michael J Fox Foundation.
Funding Information:
There is no conflict of interest specific to this work. Daniel Weiss (DW) and Alireza Gharabaghi (AG) receive research support, travel grants, and speaker's honoraria from Medtronic, Abbott, and Boston Scientific. DW is supported by research grants from the German Research Council (DFG; WE5375/1–3) and the Michael J Fox Foundation. AG is supported by research grants from the German Federal Ministry of Education and Research [BMBF 13GW0119B, IMONAS; 13GW0214B, INSPIRATION; 13GW0270B, INAUDITAS].
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/9
Y1 - 2019/9
N2 - 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.
AB - 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.
KW - Anticipatory postural adjustment
KW - Deep brain stimulation
KW - First step
KW - Freezing
KW - Gait
KW - Parkinson's disease
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U2 - 10.1016/j.parkreldis.2019.06.023
DO - 10.1016/j.parkreldis.2019.06.023
M3 - Article
C2 - 31272926
AN - SCOPUS:85068088604
SN - 1353-8020
VL - 66
SP - 34
EP - 39
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -