Optimising DBS in essential tremor: clinical and neurophysiological considerations for targeting and programming

Deep brain stimulation (DBS) is an established treatment for essential tremor (ET), with the ventral intermediate nucleus (Vim) of the thalamus and the posterior subthalamic area (PSA), including the zona incerta and dentato-rubro-thalamic tract (DRTT), serving as the primary stimulation targets. These structures lie along the cerebello-thalamo-cortical pathway but differ in anatomical location and fibre composition, potentially influencing clinical effects and side effect profiles. We aim to compare the anatomical and physiological considerations of Vim and PSA targeting in ET, explore the impact of pulse width modulation on the therapeutic window, and highlight the importance of a fibre-informed, anatomically guided approach to programming. PSA targeting, particularly toward the DRTT, may offer improved tremor control over Vim. While clinical studies suggest shorter pulse widths can widen the therapeutic window when defined by amplitude, modelling and neurophysiological data indicate that longer pulse widths may better engage target neural elements in the PSA. Variability in study design, anatomical target and stimulation parameters complicates direct comparison across trials. A nuanced understanding of target anatomy and neurophysiology may inform DBS programming to improve clinical outcomes. Based on biophysical and anatomical considerations, we propose an initial algorithm to guide DBS programming to substitute the conventional monopolar review.