A landmark 15-year study reveals that the two main types of tremor in Parkinson’s disease are not the same, responding differently to treatment and following separate paths over time. This challenges long-held beliefs and paves the way for more targeted therapies.
When we think of Parkinson’s disease (PD), the image that often comes to mind is a tremor—an involuntary shaking that affects about 75% of patients. For many, this is one of the most distressing symptoms of the condition. But not all tremors are created equal. The classic Parkinson’s tremor is a "resting tremor," which occurs when the muscles are relaxed, like when a hand is resting on a lap. However, many patients also experience an "action tremor," which emerges during voluntary movements like writing or holding a cup.
For years, the scientific community has debated whether these two types of tremor are simply different expressions of the same underlying problem or if they are two distinct disorders that happen to coexist. Are they two sides of the same coin? A groundbreaking new study, following patients for up to 15 years, provides the clearest answer yet: they are different. This discovery could fundamentally change how we understand and treat tremor in Parkinson’s disease.
A Deep Dive into the Brain’s Wiring
To untangle the relationship between resting and action tremors, researchers conducted a long-term observational study involving 301 patients with Parkinson’s disease. What made this study unique was its long-term perspective and its use of deep brain stimulation (DBS) as a powerful investigative tool. DBS involves implanting electrodes in a specific brain region—in this case, the subthalamic nucleus (STN)—to deliver electrical impulses that help manage motor symptoms.
By observing how each tremor type responded to both standard medication (L-Dopa) and DBS over a span of up to 15 years, the scientists could probe the distinct neural circuits involved. They meticulously tracked tremor severity before and after surgery, under various treatment conditions, providing an unprecedented look at their long-term behavior.
A Tale of Two Responses to Treatment
The first major clue that these tremors were different came from how they responded to therapy. The study found that both L-Dopa and STN-DBS were effective at reducing both types of tremor. However, the degree of improvement was strikingly different.
Resting tremor showed a dramatic and highly favorable response to all treatments. Dopaminergic therapy (L-Dopa) reduced resting tremor by a staggering 95.7%. In contrast, action tremor improved by a more modest, though still significant, 82.3%.
When looking at DBS, the pattern held. STN-DBS alone was significantly more effective at controlling resting tremor than action tremor. These results strongly suggest that the two tremors rely on different brain pathways, which are not equally sensitive to the same treatments. Resting tremor appears to be deeply connected to the dopamine-dependent circuits in the basal ganglia that DBS and L-Dopa directly target, while action tremor seems to have a different origin story.
Diverging Paths Over a Decade
Perhaps the most compelling evidence came from the long-term follow-up. If the two tremors were part of the same process, you would expect them to progress in a similar fashion over time. That’s not what the researchers found.
One year after DBS surgery, both tremors showed similar levels of improvement. But as the years went on, their paths diverged. At the 10- and 15-year follow-ups, the severity of resting tremor remained stable and well-controlled. In contrast, action tremor showed a mild but significant worsening over the long term, especially in patients who had a tremor-dominant form of Parkinson’s.
This long-term divergence is a powerful argument against the idea of a single tremor entity. The sustained control of resting tremor suggests that DBS effectively modulates its underlying network for years. The gradual worsening of action tremor, however, indicates that its source network is either less affected by STN-DBS or that the disease’s progression in that separate network continues despite the treatment.
Unpacking the Brain’s Circuitry
So, what does this mean for the wiring in the brain? The study’s findings support a model where resting and action tremors arise from distinct, though interconnected, neural oscillators.
- Resting Tremor: This tremor is thought to originate primarily within the basal ganglia, a group of structures deep in the brain that are heavily reliant on the neurotransmitter dopamine. The profound loss of dopamine in Parkinson’s disrupts this circuit, leading to the classic 4-6 Hz resting tremor. This explains why it responds so well to dopamine-replacing drugs like L-Dopa and to DBS targeting the STN, a key node in the basal ganglia network.
- Action Tremor: The evidence points to the cerebello-thalamo-cortical circuit as the main driver of action tremor. This network, which involves the cerebellum (critical for coordinating movement), is less dependent on dopamine. While it’s affected in Parkinson’s, its dysfunction isn’t as easily corrected by L-Dopa or STN-DBS. This aligns with the study’s findings of a less robust treatment response and long-term worsening.
The researchers also found that while the two tremors were moderately correlated when patients were off their medication, this link weakened significantly once treatments were active. This further supports the idea of two separate systems that are only partially linked, with therapies selectively acting on one more than the other.
The Future of Tremor Treatment
By demonstrating that resting and action tremors are distinct phenomena with different underlying mechanisms and long-term trajectories, this study opens the door for more personalized and targeted therapeutic strategies. Treating all tremors as a single symptom is no longer sufficient.
Future research can now focus on developing therapies aimed specifically at the cerebellar networks responsible for action tremor, which remains more difficult to manage. This could involve refining DBS targets, exploring different stimulation patterns, or developing new pharmacological agents that act on non-dopaminergic pathways.
For the millions living with Parkinson’s disease, this deeper understanding is more than just an academic exercise. It represents a critical step toward developing more effective treatments that can better address the full spectrum of their symptoms and improve their quality of life.
Reference
Zampogna, A., Suppa, A., Patera, M., Cavallieri, F., Bove, F., Fraix, V., Castrioto, A., Schmitt, E., Pelissier, P., Chabardes, S., Meoni, S., & Moro, E. (2025). Resting and action tremor in Parkinson’s disease: pathophysiological insights from long-term STN-DBS. npj Parkinson’s Disease, 11(1), 284. https://doi.org/10.1038/s41531-025-01130-9
