The new model provides a deep physiology-based explanation of how deep brain stimulation works.

People with Parkinson’s disease and their physicians face many unknown questions, including answers on how deep brain stimulation (DBS) alleviates some of the motor symptoms experienced by patients. In a new study, scientists at the University of Boston and the Picower Institute for Learning and Memory at MIT present a detailed model that explains the dynamics of the underlying circuit, explaining that treatment can be further improved if confirmed ly. Provide.

What is known about Parkinson’s disease is that deficiency of the neuromodulator dopamine is associated with abnormally high beta-frequency rhythms (brain waves at frequencies of about 20 Hz). DBS, which includes the delivery of radiofrequency electrical stimuli to a region called the subthalamic nucleus (STN), clearly suppresses these elevated beta rhythms, providing a healthier balance with other rhythm frequencies and better motor control. I will recover.

Computational model based on the new biophysics described in Minutes of the National Academy of Sciences We believe that the beneficial effects of DBS stem from how the circuit loop between the STN and the region called the striatum breaks the vicious circle that promotes runaway beta. In 2011, research co-author Michelle McCarthy, assistant professor of mathematics and statistics at BU, used a mathematical model to show excess between cells present in the striatum, called the medium, in the absence of dopamine. Thorny neurons (MSN) have shown that excitement can lead to runaway beta in the striatum.

The model, led by Erie Adam, a postdoc at the Picower Institute, is based on McCarthy’s discovery. Joining Adam and McCarthy are co-author Emery N. Brown, Professor Edward Hood Taprin of MIT’s Biomedical Engineering and Computational Neuroscience, and Nancy Kopell and William Fairfield Warren. Famous Professor of Mathematics and Statistics at Boston University. Quartet studies show that striatal cells called fast spike-mediated neurons (FSIs) generate gamma frequency rhythms (30-100 Hz) that regulate MSN beta activity under healthy conditions containing appropriate dopamine. It shows that you can do it. But without dopamine, FSI cannot limit MSN activity, and beta will dominate the entire circuit loop that connects STN to FSI, MSN, and other regions, and then back to STN.

FSI gamma is important for suppressing MSN beta. 0 When dopamine levels drop, the beta becomes wild because the MSN can generate more beta and the FSI loses the ability to generate gamma and quench that beta. The FSI is then attacked by beta activity, becoming a conduit for the beta itself, leading to its amplification. “

Ellie Adam, Postdoctoral Fellow at Picower Institute

When DBS high-frequency stimulation is applied to STN, the model shows that it replaces the overwhelming beta input received by FSI and restores excitability. Once reactivated and released from these beta constraints, interneurons resume production of gamma oscillations (about half the DBS stimulation frequency, usually 135 Hz) and suppress the beta activity of MSNs. The loop back to STN and then back to FSI is no longer dominated by that frequency because the MSN no longer produces too many betas.

“DBS stops the beta from propagating toward the FSI and prevents it from being amplified. Then, by further exciting the FSI, the FSI regains its ability to generate strong gamma oscillations, resulting in beta. Is suppressed at its source, “says Adam.

The model reveals another important wrinkle. Under normal circumstances, different levels of dopamine help form the gamma produced by FSI. However, FSI also receives input from the cerebral cortex. In Parkinson’s disease, where dopamine is absent and beta dominates, FSI loses regulatory flexibility, but in DBS, when beta dominance collapses, FSI is from the cortex, even if dopamine is not yet present. It can be modulated by the input. This suppresses the gamma provided to MSN and enables a harmonious expression of beta, gamma and theta rhythms.

By providing a deep physiology-based explanation of how DBS works, this study may also provide clinicians with clues on how to make DBS work best for patients. Said the author. The important thing is to find the optimal gamma rhythm for the FSI. This may vary slightly from patient to patient. If that can be determined, adjusting the DBS stimulation frequency to boost its gamma output should give the best results.

However, before testing it, you need to ly validate the basic findings of your model. The author said that this model makes the necessary predictions to proceed with such tests.

The National Institutes of Health funded the research.