Clinical deep brain stimulation strategies for orientation-selective pathway activation

This study investigated stimulation strategies to increase the selectivity of activating axonal pathways within the brain based on their orientations relative to clinical deep brain stimulation (DBS) lead implants.

Previous work has shown how varying electrode shape and controlling the primary electric field direction through preclinical electrode arrays can produce orientation-selective axonal stimulation. Here, we significantly extend those results using computational models to evaluate the degree to which clinical DBS leads can direct stimulus-induced electric fields and generate orientation-selective activation of fiber pathways in the brain. Orientation-selective pulse paradigms were evaluated in conceptual models and in patient-specific models of subthalamic nucleus (STN)-DBS for treating Parkinson's disease.

Single-contact monopolar or two-contact bipolar stimulation through clinical DBS leads with cylindrical electrodes primarily activated axons orientated parallel to the lead. Conversely, multi-contact monopolar stimulation with a cathode-leading pulse waveform selectively activated axons perpendicular to the DBS lead. Clinical DBS leads with segmented rows of electrodes and a single current source provided additional angular resolution for activating axons oriented 0°, ±22.5°, ±45°, ±67.5°, or 90° relative to the lead shaft. Employing multiple independent current sources to deliver unequal amounts of current through these leads further increased the angular resolution of activation relative to the lead shaft. The patient-specific models indicated that multi-contact cathode configurations, which are rarely used in clinical practice, could increase activation of the hyperdirect pathway collaterals projecting into STN (a putative therapeutic target), while minimizing direct activation of the corticospinal tract of internal capsule, which can elicit sensorimotor side-effects when stimulated.

When combined with patient-specific tissue anisotropy and patient-specific anatomical morphologies of neural pathways responsible for therapy and side effects, orientation-selective DBS approaches show potential to significantly improve clinical outcomes of DBS therapy for a range of existing and investigational clinical indications.