TY  - JOUR
AU  - Kabaoglu, Burce
AU  - Garulli, Elisa L
AU  - De Sa, Rafael
AU  - Vogt, Arend
AU  - Behrsing, Ruben
AU  - Skrobot, Matej
AU  - Paulat, Raik
AU  - Pollak, Patrick
AU  - Guldin, Lynn S
AU  - Gerster, Moritz
AU  - Neumann, Wolf-Julian
AU  - Endres, Matthias
AU  - Harms, Christoph
AU  - Wenger, Nikolaus
TI  - Shift in motor-state equilibrium explains gait therapy effects of apomorphine in experimental Parkinsonism.
JO  - Experimental neurology
VL  - 401
SN  - 0014-4886
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - DZNE-2026-00298
SP  - 115704
PY  - 2026
AB  - 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.
KW  - Gait therapy (Other)
KW  - Motor control (Other)
KW  - Neural oscillations (Other)
KW  - Parkinson's disease (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41765318
DO  - DOI:10.1016/j.expneurol.2026.115704
UR  - https://pub.dzne.de/record/285741
ER  -