Brain ‘short circuit’ behind Parkinson’s motor issues: Study
Dysfunctional nerve cells create bottlenecks that disrupt signals to spine
- Parkinson's motor issues stem from dysfunctional PT5B neurons in the brain.
- This dysfunction causes exaggerated beta brain waves, disrupting movement signals.
- Targeting PT5B neurons could lead to new therapies for motor symptoms.
Dysfunctional nerve cells in the brain’s motor command center may be driving the rigid brain wave patterns associated with Parkinson’s disease, a new supercomputer simulation reveals.
The study suggests that specific neurons, known as PT5B, significantly alter brain wave frequency during movement. These neurons are responsible for sending signals from the motor cortex down to the spinal cord to control voluntary movement. In the Parkinson’s simulation, their activity became irregular, contributing to the motor deficits characteristic of the disease.
“Knowing that PT5B neurons are both impacted by the disease and essential for movement gives us a specific cellular target,” Donald W. Doherty, PhD, a research scientist at State University of New York Downstate Medical Center, said in a UC San Diego news story. “That could lead to therapies that treat the root cause of motor symptoms rather than just managing them.”
The study, “Enhanced beta power emerges from simulated parkinsonian primary motor cortex,” was published in npj Parkinson’s disease.
The ripple effect of neuron loss
Parkinson’s disease is caused by the progressive dysfunction and death of dopaminergic neurons, the nerve cells responsible for producing dopamine, a key signaling molecule involved in motor control, resulting in the disease’s motor symptoms.
Studies suggest that the loss of these neurons triggers additional changes in other brain regions involved in motor control, such as changes in the activity of PT5B neurons in the primary motor cortex and the emergence of a type of brain waves called beta oscillations. These are rhythmic brain waves, similar to steady pulses, that help coordinate thinking, movement, and attention. However, in Parkinson’s, they become exaggerated and overly synchronized, actively suppressing the ability to initiate or execute new movements.
In the study, researchers from the Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network used the Expanse supercomputer, provided by the U.S. National Science Foundation’s ACCESS program at UC San Diego, to predict how changes in PT5B neuronal activity affect beta oscillations in the motor cortex. Specifically, they utilized NEURO/NetPyNE, a software framework designed to build, simulate, and analyze detailed models of brain circuits, to implement computer simulations of PT5B neurons based on data from a mouse model of Parkinson’s.
“To create a faithful model of Parkinson’s disease in the brain, we started with data from rodent models and fed it into sophisticated simulations powered by Expanse,” said Doherty, who is also a researcher with ASAP.
The simulation provided a high-definition view of how the motor cortex organizes its electrical signals, comparing the brain at both resting and active movement conditions in healthy control mice and in the Parkinson’s model. In the resting state, activity was dominated by steady, slower beta waves, in which the key PT5B neurons fired in a carefully coordinated pattern alongside other local cells.
In contrast, when the brain shifted to the movement state, the system underwent a rapid reorganization: the PT5B neurons increased their firing rate and changed their pattern. Simultaneously, many local coordinating neurons effectively shut down their activity, and the entire neuronal network replaced the slow beta rhythms with very fast gamma oscillations, which signal intense, active processing to execute motor commands.
A short circuit in the cortex
The simulation revealed a significant electrical “short circuit” in the motor cortex of the Parkinson’s model compared with the healthy brain. In the Parkinson’s model, when the brain was at rest, the disease-associated beta waves were found to be slower and marked by continuous, high-power rhythmic bursts. Importantly, PT5B neurons became dysfunctional: while their overall firing rate was higher, their signaling became less flexible and repetitive.
These firing patterns persisted even when the brain shifted to the movement state, demonstrating that the motor cortex is less adaptable and overly synchronous in the Parkinson’s model, contributing to motor symptoms.
“These simulations revealed how reduced activity in PT5B neurons — located in the primary motor cortex — disrupts communication across the entire brain network.” Doherty said. “What’s remarkable is that when these neurons stop working properly, they create a bottleneck that affects the whole motor system.”
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