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@ARTICLE{Kabaoglu:285741,
author = {Kabaoglu, Burce and Garulli, Elisa L and De Sa, Rafael and
Vogt, Arend and Behrsing, Ruben and Skrobot, Matej and
Paulat, Raik and Pollak, Patrick and Guldin, Lynn S and
Gerster, Moritz and Neumann, Wolf-Julian and Endres,
Matthias and Harms, Christoph and Wenger, Nikolaus},
title = {{S}hift in motor-state equilibrium explains gait therapy
effects of apomorphine in experimental {P}arkinsonism.},
journal = {Experimental neurology},
volume = {401},
issn = {0014-4886},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {DZNE-2026-00298},
pages = {115704},
year = {2026},
abstract = {Gait impairments remain a major therapeutic challenge in
Parkinson's disease (PD). Apomorphine is gaining renewed
clinical attention with the expanding use of pump infusion
systems. Yet the specific role of apomorphine on the neural
regulation of gait has remained poorly characterized,
limiting its targeted use for symptom-specific therapy in
PD. Here, we examined the neurobehavioral effects of
apomorphine on runway locomotion in the unilateral
6-hydroxydopamine (6-OHDA) rat model. Therapeutic drug doses
significantly increased total walking distance, related to
reduced akinesia and prolonged gait episodes. Conversely, 3D
kinematic analysis revealed reduced limb velocities under
medication. At the neural level, therapy doses selectively
enhanced cortical high-gamma rhythms without substantially
altering beta or low-gamma activity. Instead, beta and
low-gamma oscillations were consistently suppressed during
motor activity in both medication ON and OFF conditions.
Neurobehavioral correlations showed that transitions into
gait were facilitated by reductions in beta and low-gamma
activity, whereas transitions to akinesia were primarily
suppressed when high-gamma activity was elevated. Our
findings highlight that cortical oscillations can serve as
state specific biomarkers for gait impairments in PD. We
further propose that the complex therapy effects of
apomorphine are best explained by a shift in motor-state
equilibrium that is defined by the transitions of akinesia,
stationary movements and gait. Together, these insights
establish a mechanistic framework to guide the development
of targeted gait therapies in PD.},
keywords = {Gait therapy (Other) / Motor control (Other) / Neural
oscillations (Other) / Parkinson's disease (Other)},
cin = {AG Endres},
ddc = {610},
cid = {I:(DE-2719)1811005},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41765318},
doi = {10.1016/j.expneurol.2026.115704},
url = {https://pub.dzne.de/record/285741},
}