Deep brain stimulation (DBS) targeting the Vim thalamus (ventralis intermedius nucleus) is an FDA-approved neuromodulation therapy for treating postural and action tremor in individuals with essential tremor (ET). The success of this treatment, however, is highly dependent on the ability of clinicians to identify therapeutic stimulation settings through a laborious programming process. There is a strong and growing clinical need for new approaches to provide clinicians with more efficient guidance on how to titrate stimulation settings. This study will leverage subject-specific computational models that can predict neural activation of axonal pathways adjacent to the active electrode(s) and implicated in the therapeutic mechanisms of Vim-DBS to in turn guide clinicians with which stimulation settings are likely to be the most therapeutic on tremor.

Primary Endpoint/Event/Outcome:

Endpoint: Identify the neural pathways within the brain that are involved in the reduction of action and postural tremor using directional DBS leads and advanced computational optimization algorithms.

Event: Using anatomical segmentation of high-field 7-Tesla MRI and diffusion tensor imaging from 25 human ET subjects, the investigators will build prospective subject-specific, multi-compartment neuron models of the afferent and efferent projections from and to the sensorimotor thalamus. Using these models, the investigators will then apply a semi-automated algorithm that can efficiently identify stimulation settings that most selectively target one pathway over other adjacent pathways. Note that these stimulation settings will not exceed the FDA-approved safety limits that are already programmed into the implanted pulse generator. The optimization algorithm defined stimulation settings will then be tested in human ET subjects to compare the therapeutic efficacy and efficiency of DBS targeting the: interposed-receiving area of motor thalamus, dentate-receiving area of motor. Rendering of a 4-channel DBS lead implant in the VIM nucleus (ventralis intermedius nucleus) of thalamus for treating Essential Tremor.

thalamus, pre-lemniscal radiations (raprl) with medial and lateral divisions, and zona incerta, all of which have been implicated in the therapeutic mechanisms of DBS. This clinical evaluation will occur during routine clinical follow-up sessions in which the Essential Tremor Rating Assessment Scale (TETRAS) will serve as the primary form of qualification scoring of each setting tested.

Outcome: The investigators hypothesize that targeting the interposed-receiving region of motor thalamus and in particular the ascending cerebello-thalamic fibers to this region will result in the strongest and most energy-efficient suppression of action and postural tremor.

Inclusion Criteria:

• diagnosis of ET
• medication-refractory tremor
• VIM-DBS implant (unilateral or bilateral)
• 7T MRI pre-operative scan under Dr. Harel's IRB (institutional review board) protocol (#1210M22183)
• Post-operative CT scan

Exclusion Criteria:

• history of musculoskeletal disorders that affect movement of the limbs
• other significant neurological disorder
• prior history of stereotactic neurosurgery (other than VIM-DBS surgery)
• pregnancy

participants will be blinded to the timing of the experimental settings