Tucson Standard

University of Arizona researchers have published a study offering new insights into the complications faced by Parkinson's disease patients, specifically focusing on uncontrollable movements that arise after years of treatment. Parkinson's disease, a neurological disorder affecting movement, is treated with levodopa to compensate for dwindling dopamine levels in the brain. However, long-term use of levodopa can lead to involuntary movements known as levodopa-induced dyskinesia.

The study, featured in the journal Brain, examines the nature of these dyskinetic movements and explores how ketamine, an anesthetic, might help address this condition. Abhilasha Vishwanath, the study's lead author and a postdoctoral research associate at the University of Arizona Department of Psychology, explained that over time, the brain adapts to levodopa treatment. This adaptation leads to dyskinesia because "the motor cortex – the brain region responsible for controlling movement – becomes essentially 'disconnected' during dyskinetic episodes."

The research team recorded activity from thousands of neurons in the motor cortex and found little correlation between their firing patterns and dyskinetic movements. This suggests an indirect generation of these movements rather than direct causation. Stephen Cowen, senior author and associate professor in the Department of Psychology, likened it to "an orchestra where the conductor goes on vacation," indicating that without proper coordination from the motor cortex, other neural circuits generate problematic movements independently.

In addition to understanding dyskinesia's mechanism, the study highlights ketamine's therapeutic potential. Ketamine disrupts abnormal electrical patterns in the brain during dyskinesia and promotes neuroplasticity—changes in connectivity and activity among brain cells—that could help regain control over movement. According to Vishwanath, beneficial effects from a single dose can last months.

These findings are particularly relevant given an ongoing Phase 2 clinical trial at the University of Arizona testing low doses of ketamine infusions for treating dyskinesia in Parkinson's patients. Early results appear promising with some patients experiencing prolonged benefits after treatment.

Cowen noted that adjusting ketamine doses could maintain therapeutic benefits while minimizing side effects. The study opens avenues for new therapeutic approaches based on its findings about motor cortex involvement in dyskinesia. "By understanding the basic neurobiology underlying how ketamine helps these dyskinetic individuals," Cowen said, "we might be able to better treat levodopa-induced dyskinesia in the future."

Funding for this research was provided by National Institute of Neurological Disorders and Stroke (grants R56 NS109608 and R01 NS122805) and Arizona Biomedical Research Commission (grant ADHS18-198846).