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024 7 _ |a 10.1016/j.expneurol.2026.115704
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024 7 _ |a 1090-2430
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037 _ _ |a DZNE-2026-00298
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Kabaoglu, Burce
|b 0
245 _ _ |a Shift in motor-state equilibrium explains gait therapy effects of apomorphine in experimental Parkinsonism.
260 _ _ |a Amsterdam [u.a.]
|c 2026
|b Elsevier
336 7 _ |a article
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520 _ _ |a 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.
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650 _ 7 |a Gait therapy
|2 Other
650 _ 7 |a Motor control
|2 Other
650 _ 7 |a Neural oscillations
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650 _ 7 |a Parkinson's disease
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700 1 _ |a Garulli, Elisa L
|b 1
700 1 _ |a De Sa, Rafael
|b 2
700 1 _ |a Vogt, Arend
|b 3
700 1 _ |a Behrsing, Ruben
|b 4
700 1 _ |a Skrobot, Matej
|b 5
700 1 _ |a Paulat, Raik
|b 6
700 1 _ |a Pollak, Patrick
|b 7
700 1 _ |a Guldin, Lynn S
|b 8
700 1 _ |a Gerster, Moritz
|b 9
700 1 _ |a Neumann, Wolf-Julian
|b 10
700 1 _ |a Endres, Matthias
|0 P:(DE-2719)2811033
|b 11
|u dzne
700 1 _ |a Harms, Christoph
|b 12
700 1 _ |a Wenger, Nikolaus
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773 _ _ |a 10.1016/j.expneurol.2026.115704
|g Vol. 401, p. 115704 -
|0 PERI:(DE-600)1466932-8
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|t Experimental neurology
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856 4 _ |u https://pub.dzne.de/record/285741/files/DZNE-2026-00298.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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