New study points to promising ultrasound treatment for Parkinson’s tremor

Parkinson’s disease affects nearly 12 million people worldwide—a number expected to more than double by 2050. Among its most disruptive symptoms is tremor, which can interfere with daily activities, social life, and well-being.

Currently, there is no cure for Parkinson’s. Medications for treatment, such as levodopa, work well to reduce stiffness and slowness of movement, but reduce tremor inconsistently. More invasive options, such as deep brain stimulation or high-intensity focused ultrasound in specific brain regions can be effective, but involve surgical risks or result in permanent lesions.

A new study recently published in the journal Brain Stimulation by Dr. Martin McKeown’s lab explores a promising target using a non-invasive alternative: low-intensity transcranial ultrasound stimulation.

“Our goal was to find out whether we could safely reduce tremor by targeting key regions in the brain’s tremor network,” says Dr. Varsha Sreenivasan, co-lead author and postdoctoral fellow in the McKeown lab.

Two targets, two different effects

With transcranial ultrasound stimulation (TUS), which uses low-intensity sound waves to modulate brain activity, Dr. McKeown’s team compared two main target areas: the ventral intermediate nucleus (VIM) of the thalamus and a less-studied region called the zona incerta (ZI) to determine which might better reduce Parkinsonian tremor.

“This is the first study to directly compare these two targets using ultrasound stimulation in Parkinson’s patients,” says Maggie Vuong, co-lead author and Biomedical Technologist in the McKeown lab. “So we wanted to see not just whether tremor improved, but also how the brain’s networks changed.”

In this study, the research team measured postural tremor (tremor when holding a position) and rest tremor (tremor when muscles are relaxed), along with resting-state brain activity using functional MRI.

They found that stimulating the VIM improved postural tremor but did not significantly improve rest tremor, which is more characteristic of Parkinson’s disease. In contrast, stimulation of the ZI showed broader benefits.

“We found that targeting the zona incerta improved both postural and rest tremor,” explains Dr. McKeown, Professor and Head of the Division of Neurology in UBC’s Department of Medicine. “This may be because Parkinsonian tremor involves a distributed network. The ZI is a promising treatment target because it connects to key areas involved in tremor, including the basal ganglia, cerebellum and primary motor cortex.”

Looking inside the tremor network

Beyond measuring tremor severity, the researchers used brain imaging to examine changes in network activity. While overall connectivity changes were subtle, individual shifts in ZI brain activity strongly predicted who experienced tremor improvement.

“Changes in ZI network connectivity were closely tied to symptom relief,” notes Dr. Sreenivasan. “That suggests we may be able to use these brain features as biomarkers to predict who will benefit most from this treatment.”

A safer, reversible option

Unlike surgical approaches or permanent lesioning procedures, TUS is non-invasive and reversible. While a safer alternative, it is currently unclear if this new technology results in improvements of sufficient duration to be a practical therapy or if it should be used to safely explore new targets for more permanent procedures.

“The transient nature of ultrasound stimulation is a major advantage,” says Maggie. “It allows us to explore new targets like the ZI safely.” No adverse effects were reported in this study.

Although the study involved a small group of participants, it is the first to directly compare these two ultrasound targets in Parkinson’s disease. The findings suggest that while VIM may remain a strong option for postural tremor, the ZI could be a more effective target when both rest and postural tremor are present.

Looking ahead

Dr. McKeown and his team emphasize that larger studies are needed to confirm the results and refine stimulation protocols. Future work may also explore whether brain connectivity changes can guide personalized treatment decisions.

The study also observed possible “network priming” effects, meaning that stimulating one target first may influence how the brain responds to stimulation at another target later. It raises new questions about how ultrasound might reshape brain circuits over time.

“Our findings support continued investigation into the zona incerta as a target for treating Parkinson’s tremor,” says Dr. McKeown. “As we improve our ability to modulate specific brain networks, we hope to move closer to more precise and individualized therapies for Parkinson’s disease.”

For millions living with Parkinsonian tremor, that precision could make a meaningful difference in quality of life.