Quantifying the pathways modulated by deep brain stimulation for essential tremor using computational modeling

Abstract

Deep brain stimulation (DBS) within or near the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with Essential Tremor (ET). For patients with DBS leads placed near the caudal border of Vim, however, there is an increased likelihood of inducing paresthesias through activation of the sensory ventral caudal (Vc) nucleus of thalamus. The aim of this computational modeling study was to provide a patient-specific modeling framework for comparing the current steering abilities of the clinical Medtronic 3389 DBS lead to a novel DBS lead with directionally-oriented electrodes (dDBS). We developed patient-specific computational neuron models from three ET patients implanted with a Medtronic 3389 DBS lead. Multi-compartment models of Vim / Vc thalamocortical neurons and cerebellothalamic / medial lemniscal axonal afferents were simulated in the context of patient-specific anatomies, lead placements, and programming parameters. Complete suppression of tremor was associated with stimulating the axonal output from an average of 62.4% of Vim afferents (n=10), and persistent paresthesias were associated with activation of 35.3% of Vc afferents (n=12). The dDBS models demonstrated superior targeting of cerebello-thalamo-cortical pathways, enabling one to selectively modulate Vim and avoid activation of Vc. For patients with leads positioned near the Vc nucleus of thalamus, dDBS may allow clinicians to more selectively modulate pathways within and near the thalamus in order to achieve better therapy without inducing side effects.