Parkinson’s Symptoms Trace to Distinct Brain Circuits
şÚÁĎÉçÇř research shows tremor and slowed movement arise from separate neural pathways, opening new directions for targeted research and more personalized treatments
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Parkinson's disease is often treated as a single disorder. But for theĚý living with it in the United States, the disease can look different from one person to the next. Research from şÚÁĎÉçÇř’sĚýAryn Gittis(opens in new window) and colleagues suggests the most recognizable symptoms — tremor and slowed movement — result fromĚý of the brain, an insight that could help explain why current treatments don’t work equally for all patients.
A better map of brain circuits behind specific symptoms could point researchers toward therapies that are more precisely matched to how Parkinson’s affects an individual person.
A movement hub in the brain
The research team focused on the motor thalamus, a region of the brain that acts as a communication hub for movement. It relays signals between different parts of the brain that control major motor systems, including the basal ganglia — long associated with Parkinson’s disease and an area of research for the Gittis lab — and the cerebellum, which helps fine-tune movement.
“The thalamus is kind of where everything comes together,” Gittis said. “It links these major systems that control how we move.”
Using two different mouse models, the researchers were able to compare brain activity linked to distinct symptoms. One model, commonly used in Parkinson’s research, mimics the dopamine loss Parkinson’s patients experience that slows movement. The other — new to Gittis’ team — produces tremor, something most animal models do not.
That difference proved to be important, and opened up new lines of research, said Shruti Nanivadekar, the paper’s first author and a recent graduate from theĚýNeuroscience Institute(opens in new window)’s Ph.D. in Systems Neuroscience(opens in new window) Program and theĚýat the University of Pittsburgh.Ěý
“This study shows that different Parkinson’s symptoms may emerge from different brain circuits,” Nanivadekar said. “That’s important because it suggests treatments may need to target those circuits differently.”
Different symptoms, different signals
When the researchers recorded neural activity in the thalamus, they found clear differences between the two models.
In mice with slowed movement, known as bradykinesia, abnormal activity was widespread across the thalamus, reflecting broad disruption in motor circuits. But in mice with tremor, dysfunction was more localized, concentrated in regions connected to the cerebellum.
“The patterns of activity look different depending on the symptom,” Gittis said. “You can tell from the neural signals whether an animal has tremor or slow movement.”
The researchers described the cerebellum, which receives sensory information, as a predictor for real-time motor control. When that system goes awry, it can create a loop of overcorrection that may produce tremor. The findings add to growing evidence that the cerebellum plays an important role in tremor, Gittis said.
“If the system is constantly trying to fix a movement, it can get stuck in that back-and-forth,” she explained.
Why Parkinson’s treatments don’t work the same for everyone
The study may also help explain a longstanding clinical puzzle: why common treatments improve some symptoms more than others.
Most medications for Parkinson’s disease target dopamine, a chemical that affects the basal ganglia. These treatments are often effective for bradykinesia but less reliable for tremor.
“Dopamine therapies work really well for slow movement, but they’re hit or miss for tremor,” Gittis said. “That suggests they’re not affecting the right circuit for that symptom.”
A new tool for studying tremor
The research introduces a valuable new tool for studying tremor. Because many Parkinson’s animal models focus on dopamine loss and slowed movement, tremor has been harder to examine in the lab.Ěý
“This gives us a way to actually study the circuits underlying tremor,” Gittis said. “That’s something we haven’t really been able to do before.”
Nanivadekar agreed.Ěý
“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,” she said.Ěý
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