Browsing by Subject "essential tremor"

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    Characterization of the cortical electrophysiological effects of motor thalamic DBS and assessment of a pharmacological model for essential tremor
    (2021-02) Bello, Edward
    Deep brain stimulation (DBS) of the cerebellar-receiving area of motor thalamus has proven to be a highly effective neurosurgical treatment for Essential tremor (ET). Previous clinical studies, however, have also indicated that the overall efficacy and efficiency of the therapy can vary from patient to patient and that the physiological rationale for this outcome variability is not well understood. Functional imaging studies have shown that the pathological state of ET and thalamic DBS treatment each exert a distributed effect on the motor control network including the primary motor cortex (M1). What this effect is on the neuronal level in M1 is not known. Through a series of electrophysiological experiments in a large preclinical animal model, we investigated first how neuronal spike rates and patterns in M1 change during thalamic DBS and second how such changes might explain the clinical observations that (1) higher frequency pulse trains for thalamic DBS are more effective in suppressing tremor and (2) electrode contacts at the ventral pole of motor thalamus are more efficient at reducing tremor. Higher frequency thalamic DBS resulted in a mild increase in the population averaged neuronal spike rate in M1, a significant decrease in population-averaged spike pattern entropy, and a strong increase in the proportion of neurons with phase-locked spike activity. In contrast, high-frequency DBS through electrodes at the ventral pole of motor thalamus at low current amplitudes (in comparison to electrodes within motor thalamus proper) was found to predominantly affect phase-locked spike activity but not spike rate and spike-pattern entropy. Together, these data suggest that M1 phase-locked spike activity may be a useful biomarker for future studies seeking to develop and assess new approaches for optimizing DBS therapy for action and postural tremors. Toward this goal, we also characterized and assessed the suitability of the alkaloid harmaline in generating a robust and consistent tremor in a large preclinical animal for future translational efforts developing technology to help individuals living with ET.
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    Development of model-based and sensor-based programming techniques for optimizing directional deep brain stimulation therapy for movement disorders
    (2022-01) Brinda, AnneMarie
    Deep brain stimulation (DBS) therapy is a programmable neurosurgical intervention that can significantly improve quality of life for individuals with medication-refractory movement disorders, such as Essential Tremor and Parkinson’s Disease. However, clinical outcomes with DBS therapy still vary across patients, and the clinical time and effort necessary to program the stimulation settings to each patient’s symptoms presents practical challenges in the clinic. With the advent of directional lead technology and independent multi-channel current-controlled stimulation, the scope of possible DBS configurations is now substantially larger than it was even five years ago. This has greatly increased the time to determine the most effective electrode configuration, and in reality, much of the stimulation parameter space is left unexplored during a clinical visit. This thesis addressed the gap between the directional lead technology and its clinical implementation by developing three promising techniques to program directional DBS lead systems. The first programming technique involved developing subject-specific computational models of DBS based on individual MRI/CT scans. Comparing model predictions to clinical outcomes from patients with Essential Tremor revealed that lateral and medial parcellations of the motor-thalamic afferents of the cerebellothalamic tract were differentially associated with stimulation-induced therapy and side effects, respectively. Second, sensor-based evaluation of DBS in Essential Tremor patients revealed that directional contacts were superior to ring-mode contacts in providing optimized tremor reduction with reduced dysarthria. The third programming technique involved using neurophysiological feedback to guide the selection of which electrode(s) to use during DBS. In Parkinson’s disease, for example, stimulation through electrodes with higher resting-state beta-band oscillatory power in the subthalamic nucleus generally results in better clinical outcomes. Using a non-human primate model, we tracked how beta-band power changed spatially and temporally between intraoperative and chronic time points and showed that the strongest variability occurred within the first two weeks after lead implantation. This suggested that neurofeedback-based programming may be most consistent after the immune tissue response settles. Together, these results showed how model- and sensor-based programming techniques can limit the parameter space for programming directional DBS enabling more efficient and effective clinical outcomes in the future.