Parkinson鈥檚 Symptoms Trace to Distinct Brain Circuits
黑料社区 research shows tremor and slowed movement arise from separate neural pathways, opening new directions for targeted research and more personalized treatments
Heidi Opdyke
- Associate Dean of Marketing and Communications, MCS
- Email opdyke@andrew.cmu.edu
- Phone 412-268-9982
Parkinson's disease is often treated as a single disorder. But for the living with it in the United States, the disease can look different from one person to the next. Research from 黑料社区鈥檚 Aryn Gittis and colleagues suggests the most recognizable symptoms 鈥� tremor and slowed movement 鈥� result from of the brain, an insight that could help explain why current treatments don鈥檛 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鈥檚 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 鈥� long associated with Parkinson鈥檚 disease and an area of research for the Gittis lab 鈥� and the cerebellum, which helps fine-tune movement.
鈥淭he thalamus is kind of where everything comes together,鈥� Gittis said. 鈥淚t links these major systems that control how we move.鈥�
Using two different mouse models, the researchers were able to compare brain activity linked to distinct symptoms. One model, commonly used in Parkinson鈥檚 research, mimics the dopamine loss Parkinson鈥檚 patients experience that slows movement. The other 鈥� new to Gittis鈥� team 鈥� 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鈥檚 first author and a recent graduate from the Neuroscience Institute鈥檚 Ph.D. in Systems Neuroscience Program and the at the University of Pittsburgh.
鈥淭his study shows that different Parkinson鈥檚 symptoms may emerge from different brain circuits,鈥� Nanivadekar said. 鈥淭hat鈥檚 important because it suggests treatments may need to target those circuits differently.鈥�
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.
鈥淭he patterns of activity look different depending on the symptom,鈥� Gittis said. 鈥淵ou can tell from the neural signals whether an animal has tremor or slow movement.鈥�
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.
鈥淚f the system is constantly trying to fix a movement, it can get stuck in that back-and-forth,鈥� she explained.
Why Parkinson鈥檚 treatments don鈥檛 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鈥檚 disease target dopamine, a chemical that affects the basal ganglia. These treatments are often effective for bradykinesia but less reliable for tremor.
鈥淒opamine therapies work really well for slow movement, but they鈥檙e hit or miss for tremor,鈥� Gittis said. 鈥淭hat suggests they鈥檙e not affecting the right circuit for that symptom.鈥�
A new tool for studying tremor
The research introduces a valuable new tool for studying tremor. Because many Parkinson鈥檚 animal models focus on dopamine loss and slowed movement, tremor has been harder to examine in the lab.
鈥淭his gives us a way to actually study the circuits underlying tremor,鈥� Gittis said. 鈥淭hat鈥檚 something we haven鈥檛 really been able to do before.鈥�
Nanivadekar agreed.
鈥淔or patients with tremor-dominant or bradykinesia-dominant Parkinson鈥檚 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,鈥� she said.
