title: Advancing focused-ultrasound based treatment of essential tremor
Creators: name: Swytink-Binnema, Catherine Anne
Publisher: name: Schulich School of Engineering
Year: 2025
Subjects: subject: essential tremor
subject: ultrasound
subject: magnetic-resonance guided focused-ultrasound
subject: thalamotomy
subject: neuromodulation
subject: proprioception
subject: accelerometer
subject: electrophysiology
subject: Neuroscience
subject: Engineering--Biomedical

description: Focused ultrasound is emerging as a potentially powerful tool within the field of neuroscience, for both clinical and research applications. At high intensities, focused ultrasound can thermally lesion tissue with high spatial precision and, because ultrasound can pass through the skull, the lesioning can be done in a minimally invasive manner. When this ultrasound is combined with magnetic resonance scanners, the heating can be monitored in real time, leading to magnetic-resonance guided focused-ultrasound (MRgFUS). At lower intensities, however, ultrasound can elicit neuromodulation, i.e., a transient alteration of neuronal activity, also with high spatial specificity. The literature demonstrates the wide range of possible neuromodulatory effects, and also shows that these effects are dependent on the parameters of the applied ultrasound. The non-invasiveness and precision of focused ultrasound gives it advantages over current lesioning and neuromodulation tools. Ultrasound has already had a large impact on the treatment of essential tremor (ET). ET is the most common movement disorder and is characterized by postural and action tremor, typically in the upper limbs. Because ET interferes with many aspects of daily living, it can severely diminish quality-of-life. MRgFUS provides a surgical treatment for ET; the ventral intermediate (Vim) nucleus of the thalamus can be lesioned, interrupting the cerebello-thalamo-cortical pathway and relieving tremor. The overall goal of my work was to improve how focused ultrasound is used to treat ET, by improving the MRgFUS surgical workflow; by expanding our understanding of the impacts of these surgeries; and by investigating the parameter dependence of ultrasound neuromodulation, with the future aim of incorporating it into MRgFUS thalamotomies. First, I developed a method to quantify tremor intraoperatively. This method adds an objective element onto the current qualitative tremor assessments. Further, it provides a record of tremor progression during the surgery, data that are valuable as we explore the impact of intraoperative parameters on surgical outcomes. Second, proprioception and limb use were assessed following MRgFUS thalamotomy. Although I expected deficits because of the role of the Vim in kinesthesia, we measured no changes to proprioception. I did, however, find that, following the surgery, patients had a transient difficulty in using their treated arm and a transient preference for using their untreated arm, which confirmed previous anecdotal reports. These results suggest that, with respect to proprioception, there are mechanisms in place that compensate for Vim lesioning and also suggest that, although the surgery does impact movement, there is a compensation or relearning that occurs during the following months. Third, using a variety of parameter combinations, I assessed the impact of ultrasound on a well-characterized in vitro model of neuronal communication, acute hippocampal brain slices. I measured neither reliable neuromodulation nor changes to the expression of c-Fos, a marker of neuronal activity. Overall, this work advances how focused ultrasound is used to treat ET, but the results can extend beyond MRgFUS surgeries. An objective and quantitative tool to assess tremor can be used in a variety of clinical and research settings, the data on movement-related outcomes of MRgFUS thalamotomy can complement imaging studies, and the in vitro data, while negative, can inform directions for future research.