Abstract
Objective. 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. Approach. 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. Main results. 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. Significance. 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.
Highlights
Numerous individuals living with medication-refractory neurological and neuropsychiatric disorders have benefited from deep brain stimulation therapy (DBS), which is a treatment involving continuous or intermittent electrical stimulation through one or more leads of electrodes chronically implanted within the brain [1]
As an example of the importance of pathway-selective activation, DBS therapy for Parkinson’s disease (PD) often involves implanting a lead of electrodes in the dorsolateral subthalamic nucleus (STN) in order to target axonal pathways coursing approximately perpendicular to the DBS lead (e.g. STN efferents and the so-called hyperdirect pathway afferents)
Axons were radially mary motor cortex of the hemisphere ipsilateral to the DBS distributed adjacent to the DBS lead with axon angle reprelead, and a seed mask was generated within the ipsilateral internal capsule (IC), sented by sigma (σ)
Summary
Numerous individuals living with medication-refractory neurological and neuropsychiatric disorders have benefited from deep brain stimulation therapy (DBS), which is a treatment involving continuous or intermittent electrical stimulation through one or more leads of electrodes chronically implanted within the brain [1]. Deep brain targets of DBS therapy are embedded within functionally complex networks of axonal afferents, efferents, and fibers of passage that when stimulated can alleviate symptoms. Stimulation within these networks can induce adverse side effects [2, 3], with occurrence dependent upon the lead position and programmed stimulation settings. As an example of the importance of pathway-selective activation, DBS therapy for Parkinson’s disease (PD) often involves implanting a lead of electrodes in the dorsolateral subthalamic nucleus (STN) in order to target axonal pathways coursing approximately perpendicular to the DBS lead (e.g. STN efferents and the so-called hyperdirect pathway afferents). DBS therapy can require activation of multiple pathways with different axonal orientations relative to the lead of electrodes. Investigational stimulation of the subcallosal cingulate white matter for treatmentresistant depression is thought to require activation of three white matter tracts with different axonal orientations relative to each other: the forceps minor, the uncinate fasciculus, and the cingulum bundle for a sustained therapeutic effect [5]
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