ADVANCING THALAMIC NEUROSTIMULATION FOR SUPPRESING ESSENTIAL VOICE TREMOR - PROJECT SUMMARY Essential voice tremor (EVT) affects over 40% of individuals with essential tremor (ET), one of the most common movement disorders. While ET is characterized primarily by upper limb tremor, EVT is a significant problem because it profoundly disturbs communication and quality of life. Unfortunately, EVT remains poorly treated and the few available treatments, such as propranolol and botulinum toxin injections, have limited efficacy. Deep brain stimulation (DBS) of the ventral intermedius nucleus (VIM) of the thalamus is the treatment of choice for severe upper limb tremor no longer responding to medication. There is evidence that patients undergoing successful DBS therapy for upper limb tremor, can also exhibit some suppression of voice tremor. However, the effectiveness of DBS remains unclear because the few available supportive studies used perceptual ratings or acoustic analysis with a limited number of subjects. EVT suppression with DBS is likely as few case studies show that the placement of a DBS lead in specific thalamic locations could affect both hand and head regions and consequently suppress EVT and upper limb tremor. To establish VIM DBS as a treatment for EVT, there is a critical need to determine the optimal thalamic location for neurostimulation that will mediate upper limb and voice tremor suppression. This requires precise quantification of voice tremor changes in a large and well- established cohort. Here, our multidisciplinary group, proposes to address the current knowledge gaps and determine how VIM DBS leads to effective EVT suppression. We propose to leverage our ability to recruit 140 ET patients undergoing thalamic DBS for upper limb tremor suppression. We expect that 56 of these patients will exhibit EVT and will be matched to ET patients that do not exhibit EVT (ETNVT).We will test the central hypothesis that neurostimulation applied onto specific thalamic neurocircuitry will suppress EVT and limb tremor. In Aim 1, we will use sensitive acoustic analyses to precisely quantify the effectiveness of DBS on EVT. We will test the hypothesis (H1) that bilateral thalamic DBS will significantly suppress voice tremor in patients with EVT, reducing voice tremor to the ETNVT level. In Aim 2, based on our strong preliminary data, we propose to examine the association between voice tremor and axial tremor/fall risk. We will test the hypothesis (H2) that DBS-induced voice tremor suppression will be associated with reduced axial tremor and reduced fall risk. In Aim 3, we will use cutting-edge neuroimaging techniques to determine the effect of the volume of tissue activated (VTA) locations and related neurocircuitry on EVT suppression. This proposition is based on our preliminary data that stimulation of the non-decussating dentato-rubral-thalamo-tract (nDRTT) associated with reduced EVT. We will test the hypotheses that neurostimulation of the nDRTT will suppress EVT (H3.a) and EVT suppression will be greater when the VTAs are located in medial thalamic areas that affect both the hand and head (H3b). The outcomes will be clinically impactful and improve current treatment of ET as they will identify thalamic targets that optimize EVT suppression and determine if this EVT suppression is a marker for reduced fall risk in ET.
