Browsing by Subject "Essential Tremor"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Experimental and Model-based Approaches to Directional Thalamic Deep Brain Stimulation
    (2016-09) Xiao, Joe
    Deep brain stimulation (DBS) is an effective surgical procedure for the treatment of several brain disorders. However, the clinical successes of DBS hinges on several factors. Here, we describe the development of tools and methodologies in the context of thalamic DBS for essential tremor (ET) to address three key challenges: 1) accurate localization of nuclei and fiber pathways for stimulation, 2) model-based programming of high-density DBS electrode arrays (DBSA) and 3) in vivo assessment of computational DBS model predictions. We approached the first challenge through a multimodal imaging approach, utilizing high-field (7T) susceptibility-weighted imaging and diffusion-weighted imaging data. A nonlinear image deformation algorithm was used in conjunction with probabilistic fiber tractography to segment individual thalamic sub-nuclei and reconstruct their afferent fiber pathways. We addressed the second challenge by developing subject-specific computational model-based algorithms built on maximizing population activating function values within a target region using convex optimization principles. The algorithms converged within seconds and only required as many finite-element simulations as the number of electrodes on the DBSA being modeled. For the third challenge, we recorded (in two non-human primates) unit-spike data from neurons in the vicinity of chronically implanted thalamic DBSAs before, during and after high-frequency stimulation. A novel entropy-based method was developed to quantify the degree and significance of stimulation-induced changes in neuronal firing pattern. Results indicated that neurons modulated by thalamic DBS were distributed and not confined to the immediate proximity of the active electrode. For those that were modulated by DBS, their responses increasingly shifted from firing rate modulation to firing pattern modulation with increased stimulation amplitude. Additionally, strong low-pass filtering effect was observed where <4% of DBS pulses produced phase-locked spikes in cells exhibiting significant excitatory firing pattern modulation. Finally, we quantified the spatial distribution of neurons modulated by DBS by developing a novel spherical statistical framework for analysis. Together, these tools and methodologies are poised to improve our understanding of DBS mechanisms and improve the efficacy and efficiency of DBS therapy.
  • Thumbnail Image
    Item
    Orientation-Selective Programming Strategies for Targeted Deep Brain Stimulation
    (2019-12) Slopsema, Julia
    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.