Meet the Researcher Shining a Light on Parkinson’s Treatment-Induced Impulsivity

Dopamine replacement therapies, such as dopamine agonists and the commonly used drug levodopa, can alleviate some of the more debilitating movement symptoms of Parkinson’s disease (PD), restoring precious autonomy and quality of life to those that need it. However, these therapies are not without side effects, one of which is the potential to develop an impulse control disorder. 

Up to 40% of people who take dopamine-replacing drugs for their PD experience impulse control disorders (ICDs). ICDs can present themselves in many ways, including gambling addictions or excessive eating.  

Xiaowen Zhuang, PhD, and recipient of a Parkinson’s Foundation Launch Award, wants to better understand the neuroscience behind this medication-induced impulsivity so that we can improve future treatments to avoid this side effect altogether. 

Dr. Zhuang will study ICD using mice, measuring what is known as delay discounting behavior, which is how much a subject is willing to ignore an immediate smaller award (like treats) and wait for a larger award instead. She uses tools called operant boxes that allow her to train mice on this “small award now vs. larger reward later” scenario and collect data on how their impulsivity changes in different conditions. 

Once the mice are trained, Dr. Zhuang will then utilize a cutting-edge scientific method called optogenetics to turn on or off certain decision-associated neurons in the brain and observe how that affects the mice’s impulsivity. From these experiments, she hopes to home in on the specific parts of the brain connected to ICD and discover how exactly they are affected by PD medications. This knowledge could then guide the development of future treatments where such impulsivity symptoms are no longer a concern. 

Dr. Zhuang’s interest in this topic began once she joined the lab of Alexandra Nelson, MD, PhD, at the University of California, San Francisco, CA, in 2020. 

“Discussions with my mentor, Dr. Nelson, deepened my understanding of the severe complications experienced by Parkinson's disease patients, among which impulse control disorder is a salient one,” Dr. Zhuang said. “These severe consequences intensified my desire to learn new skill sets to dissect the circuit mechanisms.” 

Shortly after joining, the COVID-19 pandemic forced all researchers away from labs and into their homes. But this didn’t stop Dr. Zhuang’s scientific enthusiasm.  

“While she had little coding experience or familiarity with operant behavior prior to joining my lab, with only modest guidance and the loan of a power drill and soldering iron, she built custom operant boxes at home, wrote code to run them, and developed a plan for progressive training and testing with a delay discounting task,” said Dr. Nelson. “She tested her boxes over Zoom, using a fuzzy mouse toy to trigger nose pokes.” 

Back in the lab and ready to begin her Foundation-supported research, Dr. Zhuang is excited about how her research may improve the lives of those relying on PD medicine.  

“Despite its prevalence, our understanding of ICD’s cause is limited, and effective treatments or interventions are yet to be discovered,” she said. “My research could pave the way for new treatments for Parkinson's disease that help manage symptoms more effectively without leading to these impulse control issues.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers.