My PD Story

Illuminating the Neurobiology Behind Impulsivity Associated with Parkinson’s Medication  

Studies estimate that at up to 40% of people taking dopamine-related drugs to treat Parkinson’s disease (PD) symptoms develop an impulse control disorder (ICD) as a side effect of the medication. While this phenomenon is likely related to dopamine’s role in reward-seeking decision-making in the brain, the specific biological patterns involved are still not fully understood.  

Xiaowen Zhuang, PhD, recipient of a Parkinson’s Foundation Launch Award and previous Postdoctoral Fellow, will be utilizing her new mouse model of ICD, along with complex brain analysis and manipulation technology, to shed light on the neurobiology of the condition. She hopes this research can inspire future PD treatments that avoid the side effect altogether. 

In humans, ICD can present in many ways such as binge eating, impulse shopping or excessive gambling. To study impulsivity in lab animals, researchers often measure what is known as delay discounting behavior, reflecting the subject’s ability to weigh reward value against the time required to receive it. High impulsivity results in high delay discounting, favoring a smaller immediate reward to a larger delayed reward.  

Under the mentorship of Dr. Alexandra Nelson at the University of California, San Francisco, CA, a Parkinson’s Foundation Center of Excellence, Dr. Zhuang will use a delay discounting experiment for mice which measures how long they are willing to wait for a larger reward of food, or conversely how impulsive they act in taking a smaller reward right away.  

Previously, she used this test on healthy mice and mice with PD-like neurodegeneration taking dopamine medication. The major finding was that the latter group showed increased impulsive behavior, taking the smaller immediate rewards significantly more often than the healthy mice. 

Building upon these preliminary experiments, Dr. Zhuang will next utilize optogenetics (a biological technique that uses light to turn specific neurons on and off on demand) to test if specific neurons in the striatum region of the brain are responsible for ICD behavior.  

She expects that activating certain neurons and inhibiting others during the tasks will make the mice more impulsive, confirming the neurons’ relevance to the condition.  Dr. Zhuang will also use her optogenetic tools to determine if altering the neurons’ synaptic plasticity — their adaptive increase or decrease in ability to receive signals — can contribute to impulsive behavior as well. 

These in-depth experiments will greatly add to our understanding of how brain changes during PD treatment may cause ICD, providing valuable insight into how future medicines might prevent or remedy such side effects.  

Discussing what this support means to her research and professional development, Dr. Zhuang said, “This award will lead me to be able to ask questions in the field of cognitive deficits of PD with a focus on impulsivity using a multi-disciplinary approach. The findings gained from this research will not only provide greater insight into the synaptic mechanisms of ICD, but also inform the use of dopamine replacement therapy with a goal of preventing or ameliorating impulse control disorders.” 

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