Ketamine Restores Movement Control in Parkinson’s Patients
Ketamine may counter levodopa-induced dyskinesia in Parkinson’s by restoring motor cortex control.
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University of Arizona researchers have advanced understanding of a common complication in Parkinson’s disease treatment: involuntary movements known as levodopa-induced dyskinesia. Published in Brain, the study reveals how long-term treatment with levodopa alters brain function and explores how ketamine may offer therapeutic benefits.
Levodopa-induced dyskinesia
A side effect of long-term levodopa treatment for Parkinson's disease, characterized by involuntary, often uncontrollable, movements.The origins of levodopa-induced dyskinesia
Parkinson’s disease occurs when dopamine levels in the brain decline, impairing movement. Levodopa, a key treatment, restores dopamine but can lead to dyskinesia over time. The research team recorded activity from neurons in the motor cortex, the brain region controlling movement, to better understand this phenomenon.
Motor cortex
A region of the brain responsible for planning, controlling, and executing voluntary movements.Contrary to the prevailing belief that the motor cortex directly causes dyskinesia, the study found it becomes functionally disconnected during these episodes. This suggests dyskinesia arises from downstream neural circuits acting independently of the motor cortex.
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Subscribe for FREE"It's like an orchestra where the conductor goes on vacation. Without the motor cortex properly coordinating movement, downstream neural circuits are left to spontaneously generate these problematic movements on their own."
Dr. Stephen Cowen
Exploring ketamine’s therapeutic role
The study also investigated ketamine, an anesthetic, as a potential treatment for dyskinesia. The researchers found that ketamine disrupts abnormal electrical patterns in the brain and promotes neuroplasticity – the ability of neurons to form new connections. These changes may help the motor cortex regain control over movement.
Neuroplasticity
The brain's ability to reorganize by forming new neural connections in response to learning, injury, or environmental changes.A single dose of ketamine provided benefits lasting weeks to months in initial trials, raising the possibility of developing more targeted therapies. Adjusting ketamine doses to maintain therapeutic effects while minimizing side effects is an area of ongoing research.
Clinical trials and implications
The findings coincide with an ongoing Phase 2 clinical trial at the University of Arizona, testing low-dose ketamine infusions for dyskinesia in Parkinson’s patients. Preliminary results indicate promising outcomes, offering hope for improving quality of life for those affected.
By uncovering the disconnect in motor cortex activity and demonstrating ketamine’s effects, this research provides a foundation for rethinking dyskinesia treatments. Future studies may refine these approaches to better address the needs of Parkinson’s patients.
Reference: Vishwanath A, Bartlett MJ, Falk T, Cowen SL. Decoupling of motor cortex to movement in Parkinson’s dyskinesia rescued by sub-anaesthetic ketamine. Brain. 2024:awae386. doi: 10.1093/brain/awae386
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