Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential Tremor

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Project Abstract Essential Tremor (ET) is a progressive disease that leads to significant disability and markedly diminished quality of life. Deep brain stimulation (DBS) in the ventralis intermedius (VIM) thalamus has been an effective treatment for ET control, but is associated with problematic side effects (e.g. dysarthia, imbalance) and may lose efficacy over time in people with severe ET. The ability to improve tremor control and reduce side effects with multifocal, current steering DBS techniques will be an important advance to the field. Furthermore, the ability to concurrently perform Deep Brain Recording (DBR) during DBS is of critical importance for characterizing both the pathologic neural circuitry of tremor and network mechanisms of DBS. We seek to restore optimal tremor control to subjects with refractory ET by replacing a failing single lead VIM thalamic DBS system with a dual lead (VIM + Ventralis Oralis (VOP)) thalamic DBS system in patients seeking revision surgery. The dual lead system will not only offer an effective rescue strategy for patients with severe tremor (open loop) and failure of standard VIM DBS, but the optional use of a DBR-capable system will also afford us an unprecedented opportunity to explore closed loop, on-demand, patient-specific tremor control. We propose to conduct this clinical feasibility study in 10 human subjects. Our specific aims are: Aim 1: Evaluate the efficacy and safety of dual lead thalamic DBS for treatment of severe essential tremor that has failed standard VIM DBS; Aim 2: Identify neurophysiologic markers of action tremor using a dual lead DBS/DBR system Aim 3: Develop neural decoding and control strategies for closed loop dual lead stimulation The proposal addresses what are arguably some of the most important limitations of currently available treatment for severe ET patients. We have assembled a highly experienced team of investigators and established an exclusive industrial partnership with Medtronic to fulfill the goals of this project. The proposed plan is driven by solid neuroscience and engineering principles that may have overarching impact on clinical applications of DBS technology for years to come.