PROJECT SUMMARY Essential tremor (ET) is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US (2.2% of the population). While the economic impact of ET is indeterminate, it is surely quite substantial. In one study, 25% of ET patients were forced to change jobs or take early retirement because of tremor. ET is directly linked to progressive functional impairment, social embarrassment, and even depression. The tremor associated with ET is typically slow (~5 Hz), involves the hands (and sometimes the head and voice), worsens with intentional movements, and is insidiously progressive over many years. Deep Brain Stimulation (DBS) has emerged as a highly effective treatment for intractable, debilitating ET. However, since the intention tremor of ET is typically intermittent, and commonly absent at rest, the currently available continuous DBS may be delivering unnecessary current to the brain that increases undesirable side effects such as slurred speech and walking difficulty, and hastens the depletion of device batteries, necessitating more frequent surgical procedures to replace spent pulse generators. The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of “closed-loop” DBS for intention tremor using novel DBS devices capable of continuously sensing brain activity and delivering therapeutic stimulation only when necessary to suppress tremor. We will measure and compare the power usage and the assessment of side-effects with adaptive (closed-loop) vs. continuous (open-loop) DBS. In Aim 1, we will identify the neural correlates of movement intention in local field potential (LFP) recordings from subdural electrode arrays implanted over the premotor hand cortex. In Aim 2, we will first determine the neural correlates of hand tremor from the primary motor hand cortex and in the ventral intermediate (Vim) nucleus LFPs. We will then use these markers to actuate therapeutic DBS when intention and/or tremor is detected, and terminate DBS when absence of tremor is detected. These aims will be achieved using first generation Medtronic Activa PC+S devices, which are capable stimulation and recording simultaneously. The proposed project is expected to provide proof-of-concept for the first chronic closed-loop DBS system for the treatment of a debilitating movement disorder in humans. We expect that this project will also lead the way for future closed-loop adaptive DBS systems designed for other movement disorders.

PROJECT NARRATIVE The proposed research is relevant to public health because the development of closed-loop, adaptive deep brain stimulation systems has the potential to provide significantly improved, patient-tailored treatment options for those suffering from debilitating movement disorders and other disorders of neural circuitry. Thus, the proposed early feasibility study is well aligned with the missions of the NIH NINDS, the BRAIN Initiative, and the Clinical Studies to Advance Next-Generation Invasive Devices for Recording and Modulation in the Human Central Nervous System (UH3) funding opportunity announcement.