Orientation-Selective Programming Strategies for Targeted Deep Brain Stimulation

Abstract

Deep Brain Stimulation (DBS) is a neurosurgical intervention that can be highly effective for treating several movement disorders, including Parkinson’s disease and Essential Tremor. However, the degree to which this therapy works depends on precisely targeting stimulation to key neural pathways within the brain and avoiding activation of neural pathways that produce side effects when stimulated. This thesis developed the theoretical and experimental framework for a novel ‘orientation selective stimulation’ (OSS) approach to more selectively target neural pathways within the brain. The approach was investigated in the context of directional DBS leads with electrodes segmented both along and around the lead body. Computational models revealed that steering the primary direction of the electric field along the axonal pathways of interest in patient-specific models of Parkinson’s disease increased the therapeutic window between activation of a therapeutic hyperdirect pathway while limiting activation of the internal capsule, which is known to produce involuntary muscle contractions. The OSS approach was investigated in a swine model of DBS where OSS was applied through a 16-channel segmented DBS lead implanted in the ventral lateral (VL) thalamus while the swine were imaged with whole-brain fMRI. The results showed that BOLD activity in motor and premotor cortex were tuned to the orientation of the electric field adjacent to the lead with maximal activation occurring when the electric field was aligned to the cortico-thalamocortical pathway. Finally, patient-specific models of ventral intermediate nucleus (VIM) DBS for Essential Tremor were developed and revealed that portions of the superior cerebellar peduncle terminating in the external and internal regions of the VIM were differentially associated with therapy and side effects, respectively. OSS paradigms increased activation of the external VIM afferents and reduced activation of the internal VIM afferents. An OSS approach to programming has important clinical significance to enhance patient care by increasing therapeutic windows and could provide the ability to more selectively activate an individual pathway and evaluate its role in aspects of DBS therapy on individual symptoms.