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Deep brain stimulation (DBS) is used to treat multiple neuropsychiatric disorders, including Parkinson's Disease (PD). Despite widespread clinical use, its therapeutic mechanisms are unknown. Here, we developed a mouse model of subthalamic nucleus (STN) DBS for PD, to permit investigation using cell type-specific tools available in mice. We found that electrical STN DBS relieved bradykinesia, as measured by movement velocity. In addition, our model recapitulated several hallmarks of human STN DBS, including rapid onset and offset, frequency dependence, dyskinesia at higher stimulation intensity, and associations between electrode location, therapeutic benefit, and side effects. We used this model to assess whether high frequency stimulation is necessary for effective STN DBS, or if low frequency stimulation can be effective when paired with compensatory adjustments in other parameters. We found that low frequency stimulation, paired with greater pulse width and amplitude, relieved bradykinesia. Moreover, a composite metric incorporating pulse width, amplitude, and frequency predicted therapeutic efficacy better than frequency alone. We found a similar relationship between this composite metric and movement speed in a retrospective analysis of human data, suggesting correlations observed in the mouse model may extend to human patients. Together, these data establish a mouse model for elucidating mechanisms of DBS.
This article was published in the following journal.
Name: The Journal of clinical investigation
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Stimulation of the brain, which is self-administered. The stimulation may result in negative or positive reinforcement.
Therapy for MOVEMENT DISORDERS, especially PARKINSON DISEASE, that applies electricity via stereotactic implantation of ELECTRODES in specific areas of the BRAIN such as the THALAMUS. The electrodes are attached to a neurostimulator placed subcutaneously.
A technique of brain electric stimulation therapy which uses constant, low current delivered via ELECTRODES placed on various locations on the scalp.
Measurable changes in activities in the CEREBRAL CORTEX upon a stimulation. A change in cortical excitability as measured by various techniques (e.g., TRANSCRANIAL MAGNETIC STIMULATION) is associated with brain disorders.
Stimulation at an intensity below that where a differentiated response can be elicited.
Parkinson's is a progressive neurological condition, affecting one person in every 500, 95% of which are over 40. It is caused by degeneration of more than 70% of the substantia nigra, which depletes the dopamine (the neurotransmitter involved in pro...