PROJECT SUMMARY Here, our multidisciplinary group with expertise in movement disorders and motor physiology, proposes to study the effects of deep brain stimulation of the ventralis intermedius nucleus (VIM DBS) on balance and gait tasks of patients with Essential Tremor (ET). Although VIM DBS is effective in controlling upper limb tremor, it does not address balance and gait disturbances in ET. This is a significant problem because balance and gait disturbances occur in >40% of ET patients, who exhibit lower quality of life and increased risk for falls and mortality. The inability to mitigate balance and gait disturbances may be a consequence of the DBS targeting a location within the VIM that reduces hand tremor but not tremor relevant to balance and gait. Our preliminary data show that only when VIM DBS reduced midline tremor, balance and gait improved. These findings are based on measurements of midline tremor with sensitive accelerometers during balance and gait tasks. In contrast, current measures of midline tremor are based on qualitative clinical assessments and have never been performed during balance and gait tasks. Thus, current measures of midline tremor are not task-relevant and lack sensitivity. In this proposal, therefore, we will determine if midline tremor is a marker for balance and gait impairments using sensitive accelerometry and electromyography (EMG) of postural muscles and innovative analyses. We will test the central hypothesis that when thalamic neurostimulation reduces midline tremor amplitude, balance and gait improve and risk for falls decreases. In Aim 1, we propose to characterize the effects of neurostimulation on tremor at multiple body locations during static and dynamic balance tasks and during straight and obstacle overground walking tasks (task-relevant tremor). We will quantify tremor using sensitive accelerometers and EMG when ET patients perform balance and gait tasks with their DBS ON or OFF. We test the hypothesis that only the VIM DBS-induced reduction of midline tremor will relate to balance and gait improvements. In Aim 2, we examine the association between the change in risk for falls (pre/post DBS surgery) and the change in tremor quantified at various locations during balance and gait tasks (DBS ON/OFF). We will quantify the risk for falls before and after DBS surgery by using the Activities Specific Balance Confidence scale (ABC), a validated and sensitive scale for risk for falls. In addition, we will quantify performance during the Berg Balance Test (BBS) and Timed Up and Go Test (TUG) with DBS ON and OFF. We will test the hypothesis that a greater VIM DBS-induced reduction in midline tremor amplitude will relate to decreased risk for falls. If successful, the outcomes of this proposal are clinically impactful because they will advance the use of DBS for treating balance and gait disturbances in ET and in other disorders.