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Computational Model Addresses How DBS Works in Patients With Parkinson Disease
A deep physiology-based computation model developed by scientists at Boston University and the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology may explain how deep brain stimulation (DBS) eases motor symptoms in patients with Parkinson disease. The authors published their detailed explanation in the Proceedings of the National Academy of Sciences.
In people with Parkinson disease, a deficit of the neuromodulator dopamine is linked with abnormally high beta-frequency rhythms, the team explained. High-frequency electrical stimulation to the subthalamic nucleus (STN) via DBS appears to suppress beta rhythms, restore balance with other rhythm frequencies, and subsequently improve movement control.
The new model suggests DBS interrupts the cycle of runaway beta in a circuit loop between the STN and the striatum. Under healthy conditions with adequate dopamine, fast-spiking interneurons (FSIs) in the striatum are able to produce gamma-frequency rhythms that regulate beta activity of medium spiny neurons (MSNs). But without dopamine, FSIs are unable to limit MSN activity, and beta dominates the circuit loop.
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“The FSI gamma is important to keep the MSN beta in check,” said lead study author Elie M. Adam, PhD, a postdoctoral fellow at the Picower Institute. “When dopamine levels go down, the MSNs can produce more beta and the FSIs lose their ability to produce gamma to quench that beta, so the beta goes wild. The FSIs are then bombarded with beta activity and become conduits for beta themselves, leading to its amplification.”
High-frequency DBS to the STN replaces overwhelming beta input received by FSIs and restores their excitability, according to the model. The interneurons are then able to resume producing gamma oscillations that suppress the beta activity of the MSNs.
“DBS stops the beta from propagating towards FSIs so that it is no longer amplified,” said Dr Adam, “and then, by additionally exciting FSIs, restores the ability of FSIs to produce strong gamma oscillations that will in turn inhibit beta at its source.”
In patients with Parkinson disease, FSIs lose regulatory flexibility from a lack of dopamine and dominant beta. However, with beta dominance disrupted, FSIs can be modulated by input from the cortex even with dopamine still absent, enabling a harmonious expression of beta, gamma, and theta rhythms, according to the model.
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