Levodopa induced dyskinesia severity is linked to distinct microstructural alterations in nigrostriatal and brainwide neural circuits
- 1University of Wisconsin-Madison
Abstract
Dopaminergic replacement therapy via L-DOPA is the major medical therapy for Parkinsons Disease. Long-term L-DOPA administration is known to cause dyskinetic movements, L-DOPA Induced Dyskinesia (LID). It remains unclear if the LID related, maladaptive changes in brain structure/function are localized to neural circuits within the nigrostriatal DA system or have brainwide impact. We employed multi-shell diffusion magnetic resonance imaging and correlational tractography to investigate structural brain networks associated with daily administration of L-DOPA and the development of LID in the unilateral 6-hydroxydopamine rat model. 53% of rats receiving L-DOPA therapy developed severe LID. Tractography found brainwide statistical maps positively and negatively associated with LID severity highlighted by bilateral neural circuits contained in the lesioned nigrostriatal system as well as others including the cerebellum and prefrontal cortex. These results suggest that systemic dysfuntion in brainwide neural circuits forms the mechanistic basis the maladaptive changes underlying LID.
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BibTeX
@misc{moshchin2026levodopa,
title = {{Levodopa induced dyskinesia severity is linked to distinct microstructural alterations in nigrostriatal and brainwide neural circuits}},
author = {M. Moshchin and S. Osting and E. Yakel and R. J. Schultz and K. P. Cheng and J. E. Davis and C. P. Luu and J. K. Trevathan and W. B. Lake and S. A. Hurley and E. K. Purcell and C. Bishop and K. Ludwig and A. J. Suminski},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763167},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763167v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Levodopa induced dyskinesia severity is linked to distinct microstructural alterations in nigrostriatal and brainwide neural circuits
AU - M. Moshchin
AU - S. Osting
AU - E. Yakel
AU - R. J. Schultz
AU - K. P. Cheng
AU - J. E. Davis
AU - C. P. Luu
AU - J. K. Trevathan
AU - W. B. Lake
AU - S. A. Hurley
AU - E. K. Purcell
AU - C. Bishop
AU - K. Ludwig
AU - A. J. Suminski
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763167
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763167v1
AB - Dopaminergic replacement therapy via L-DOPA is the major medical therapy for Parkinsons Disease. Long-term L-DOPA administration is known to cause dyskinetic movements, L-DOPA Induced Dyskinesia (LID). It remains unclear if the LID related, maladaptive changes in brain structure/function are localized to neural circuits within the nigrostriatal DA system or have brainwide impact. We employed multi-shell diffusion magnetic resonance imaging and correlational tractography to investigate structural brain networks associated with daily administration of L-DOPA and the development of LID in the unilateral 6-hydroxydopamine rat model. 53% of rats receiving L-DOPA therapy developed severe LID. Tractography found brainwide statistical maps positively and negatively associated with LID severity highlighted by bilateral neural circuits contained in the lesioned nigrostriatal system as well as others including the cerebellum and prefrontal cortex. These results suggest that systemic dysfuntion in brainwide neural circuits forms the mechanistic basis the maladaptive changes underlying LID.
ER -