While Parkinson’s disease is often regarded as a singular condition, it manifests in varied ways among the over 1.1 million individuals in the U.S. Researchers at Carnegie Mellon University, led by Aryn Gittis, have uncovered that the hallmark symptoms — tremor and slowed movement — stem from disruptions in distinct motor circuits in the brain. This discovery may shed light on why treatments don’t uniformly benefit all patients.
A Central Movement Hub
The research examined the motor thalamus, a crucial brain region that facilitates communication for movement by connecting the basal ganglia and the cerebellum. “The thalamus is kind of where everything comes together,” explained Gittis.
Using two different mouse models, the team compared brain activity associated with varying symptoms. One model simulated dopamine loss, which is linked to slowed movement, while the other, new to the research team, produced tremor.
This discovery was pivotal, said Shruti Nanivadekar, the study’s first author and a recent graduate from the Neuroscience Institute’s Ph.D. in Systems Neuroscience Program and the Medical Scientist Training Program at the University of Pittsburgh.
“This study shows that different Parkinson’s symptoms may emerge from different brain circuits,” Nanivadekar noted. “That’s important because it suggests treatments may need to target those circuits differently.”
Distinct Symptoms, Distinct Signals
When analyzing neural activity in the thalamus, researchers observed distinct differences between the models. Mice with slowed movement exhibited widespread abnormal activity, indicating broad motor circuit disruption. In contrast, mice with tremor showed more localized dysfunction, particularly in regions associated with the cerebellum.
“The patterns of activity look different depending on the symptom,” Gittis stated. “You can tell from the neural signals whether an animal has tremor or slow movement.”
The cerebellum, known for receiving sensory inputs, acts as a real-time motor control predictor. Malfunction in this system can lead to a feedback loop causing tremors, supporting the cerebellum’s significant role in these symptoms.
Understanding Treatment Variability
The study may clarify why standard Parkinson’s treatments are more effective for certain symptoms. Most therapies target dopamine, impacting the basal ganglia and often ameliorating bradykinesia but less consistently improving tremors.
“Dopamine therapies work really well for slow movement, but they’re hit or miss for tremor,” Gittis remarked. “That suggests they’re not affecting the right circuit for that symptom.”
Advancing Tremor Research
This research introduces a novel tool for studying tremors, a symptom often overlooked in animal models focused on dopamine loss. “This gives us a way to actually study the circuits underlying tremor,” Gittis said.
Nanivadekar agreed, noting, “For patients with tremor-dominant or bradykinesia-dominant Parkinson’s disease, we can now begin to understand the distinct neural patterns underlying those symptoms. That could eventually help guide more targeted therapies or refine interventions like deep brain stimulation.”
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