Clinical Research Directory

Effects of Stimulation Patterns of Deep Brain Stimulation

The purpose of this study is to measure the effects of non-regular temporal patterns of deep brain stimulation (DBS) on motor symptoms and neural activity in persons with Parkinson's disease (PD), essential tremor (ET), dystonia or multiple sclerosis (MS). These data will guide the design of novel stimulation patterns that may lead to more effective and reliable treatment with DBS. These data will also enable evaluation of current hypotheses on the mechanisms of action of DBS. Improving our understanding of the mechanisms of action of DBS may lead to full development of DBS as a treatment for Parkinson's disease and may lead to future applications of DBS.

Deep Brain Stimulation Surgery for Movement Disorders

Background: \- Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these areas helps to block the nerve signals that cause abnormal movements. Researchers also want to record the brain function of people with movement disorders during the surgery. Objectives: * To study how DBS surgery affects Parkinson s disease, dystonia, and tremor. * To obtain information on brain and nerve cell function during DBS surgery. Eligibility: \- People at least 18 years of age who have movement disorders, like Parkinson's disease, essential tremor, and dystonia. Design: * Researchers will screen patients with physical and neurological exams to decide whether they can have the surgery. Patients will also have a medical history, blood tests, imaging studies, and other tests. Before the surgery, participants will practice movement and memory tests. * During surgery, the stimulator will be placed to provide the right amount of stimulation for the brain. Patients will perform the movement and memory tests that they practiced earlier. * After surgery, participants will recover in the hospital. They will have a followup visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be programmed and adjusted over weeks to months to find the best settings. * Participants will return for followup visits at 1, 2, and 3 months after surgery. Researchers will test their movement, memory, and general quality of life. Each visit will last about 2 hours.

Radiofrequency (RF) Ablation Prospective Outcomes Study for Central Nervous System - RAPID for CNS

The objective of this study is to compile real-world outcomes of Boston Scientific commercially approved radiofrequency (RF) ablation systems used in the central nervous system (CNS) for use in functional neurosurgery.

Boston Scientific Registry of Deep Brain Stimulation for Treatment of Essential Tremor (ET)

To compile characteristics of real-world outcomes for Boston Scientific Corporation's commercially approved Deep Brain Stimulation (DBS) Systems, when used according to the applicable Directions for Use, for the treatment of Essential Tremor.

Cerebellar Research in Ultrasound Stimulation

Experiment 1: Modulation of Physiological Tremor in Healthy Volunteers Thirty healthy volunteers will undergo TUS targeting the dentate nucleus in a randomized, double-blinded crossover design. Tremor amplitude, induced by a 15 g weight, will be measured using an accelerometer, and EEG will assess neural oscillations and cerebello-thalamo-cortical connectivity. Stimulation will include short-term (1 minute on/off for 12 minutes) and long-term (30 minutes) protocols, as well as closed-loop TUS for phase-specific effects. This experiment aims to optimize stimulation parameters and explore the dentate nucleus's role in tremor generation. Experiment 2: Tremor Modulation in Essential Tremor Patients Thirty ET patients will receive TUS targeting the dentate nucleus with optimized parameters from Experiment 1 in a randomized crossover design. The best protocol from previous experiment will be tested here. Tremor amplitude and EEG will be recorded to assess short- and long-term effects of TUS on pathological tremor.

Deep Brain Stimulation (DBS) Retrospective Outcomes Study

The primary objective of this study is to characterize real-world clinical outcomes of Deep Brain Stimulation (DBS) using retrospective review of de-identified patient records.

EMBRACE Tremor BiFUS

This is a post-market (Phase IV) randomized, controlled, blinded, multicenter study with the aim to determine the added value of staged bilateral Exablate thalamotomy compared to a group of patients on previous unilateral treatment combined with local standard medical treatment.

Cortical-Basal Ganglia Speech Networks

In this research study the researchers want to learn more about brain activity related to speech perception and production.

RAD 1601: EDGE Radiosurgery for Intractable Essential Tremor and Tremor-Dominant Parkinson's Disease

To determine the efficacy of frameless Virtual Cone Radiosurgical Thalamotomy for medically refractory tremor resulting from either Essential Tremor or Tremor-Dominant Parkinson's Disease with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) in patients who are not candidates for deep brain stimulation (DBS).

Investigating Subcortical Contributions to Speech Sequencing in Deep Brain Stimulator Recipients

This study will examine how two important brain circuits - one involving the subthalamic nucleus (STN) and one involving the ventral intermediate nucleus of the thalamus (VIM) - contribute to learning and producing speech sequences. Participants will include two groups: 1. individuals with Parkinson's disease who have deep brain stimulation (DBS) devices targeting the STN and 2. individuals with essential tremor who have DBS devices targeting the VIM. Participants will complete speech tasks involving the learning and repetition of novel sound sequences. During some parts of the study, DBS stimulation will be temporarily turned on or off in a controlled research setting. This will allow researchers to examine how stimulation affects both the learning of new speech sequences and the production of previously learned sequences. All STN participants and most VIM participants will also be equipped with a cutting-edge DBS system, the Percept PC, which will enable the recording of deep brain activity during the tasks. The results of this study will improve our understanding of how different brain circuits support speech learning and production. In particular, this study will help to differentiate the roles of the STN and VIM in learning the ordering of speech sounds within a syllable from learning of speech sequences containing multiple syllables. This knowledge may help guide future approaches to optimizing DBS settings to improve both movement and speech outcomes in individuals with neurological disorders, as well as provide greater general insight into how these brain structures contribute to speech production and learning.

Ultrasound Neuromodulation in Essential Tremor

This study is being done to test whether low-intensity focused ultrasound (LIFU) (low energy sound waves) cause temporary changes in brain activity and behavior when directed at particular parts of the brain. By targeting LIFU to the parts of the brain thought to be responsible for essential tremor (ET), and measuring any associated improvement in tremor, the investigators hope to show that LIFU can be a useful tool for studying the brain circuits responsible for tremor and other brain disorders.

Magnetoencephalography (MEG) Pilot Study

The purpose of this research is to learn more about how the brain works in people with essential tremor, and how it changes after treatment with High-Intensity Focused Ultrasound (HiFU). Essential tremor is a movement disorder that causes shaking, usually in the hands, and can make everyday tasks difficult. HiFU is a treatment that uses focused sound waves to target a small area in the brain involved in tremor. In this study, the investigators aim to understand how this treatment affects the brain's networks by using safe, non-invasive tests such as brain imaging, brain wave recordings, and movement assessments.

Image-Guided DBS Programming

The objective of this study is to compare the effects of image-guided programming algorithm using various image segmentations vs standard clinical programming on reduction of tremor and patient satisfaction.

Analysis of Cutaneous Phosphorylated Alpha-Synuclein to Identify Patients at Risk of Progressing From Essential Tremor to Parkinson's Disease

Background and Rationale Essential tremor (ET) affects over 6 million Americans and approximately 5% of adults over age 60. Patients with ET have a 10-20 times higher risk of developing Parkinson's disease (PD) compared to age-matched populations, with approximately 1% converting to PD annually. Post-mortem studies reveal Lewy body pathology in some ET patients, suggesting a subset may have prodromal PD. Current diagnostic tools (DaTscan, SYNTap) are either insufficiently sensitive for early disease, too expensive, or too invasive for routine screening. The Syn-One Test offers a minimally invasive approach to detect phosphorylated α-synuclein (P-SYN) pathology in skin biopsies. Primary Objectives 1. Identify which ET patients have P-SYN pathology indicative of prodromal PD 2. Predict which patients are most likely to phenoconvert to PD

LIFUS For Neurological Disorders

Low intensity focused ultrasound (LIFUS) has the potential to be used as a means of non-invasive neuro-modulation. To this day, the use of LIFUS is under investigation. Studies in healthy subjects have shown that application of LIFUS to the motor region of the brain can mildly decrease neuron excitability in healthy controls. The purpose of the present study is to evaluate the effects of LIFUS on brain tissue excitability in patients with movement disorders in order to elucidate the therapeutic potential of LIFUS.

Dual Lead Thalamic Deep Brain Recording (DBR)-DBS Interface for Closed Loop Control of Severe Essential Tremor

This is a feasibility study based on physician-initiated Investigational Device Exemption (IDE) including intraoperative experiments and chronic testing of implanted dual thalamic DBS lead systems. This study will inform protocols for optimal use of implanted next-gen DBS systems for primarily tremor control in refractory essential tremor.If the approach appears to be successful, the pilot data generated will be used to base a future pivotal trial for FDA approval for enhanced tremor control and adaptive DBS (aDBS) functionality of DBS systems.

Long-Term Transcutaneous Stimulation and Essential Tremor: A PET Study

Essential tremor (ET) is the most common movement disorder in the United States and affects up to 5% of the population. ET patients experience involuntary shaking of the hands, head and/or voice that can range from mildly limiting to severely disabling. Treatment options are limited and there are currently no medications specifically designed to treat it, and medications that are prescribed to relieve tremors are often limited by either inadequate efficacy or intolerable side effects. A subset of essential tremor patients whose tremors are inadequately treated by medication choose to undergo deep brain stimulation (DBS) of the ventral intermediate thalamic nucleus. DBS has been shown to be highly effective for tremor suppression. However, DBS carries significant risks. As a result, a very small (less than 3%) percentage of essential tremor patients undergo DBS therapy. The medical technology company Cala Health has developed a wristband device (the Cala TWO) that offers individuals with essential tremor a novel non-pharmacological, non-invasive alternative, in the form of stimulation of peripheral nerves, to aid in hand tremor relief. This innovative form of therapy has the potential to have important health, quality of life, and economic benefits for essential tremor patients. The present pilot study (Aim 1) will assess the effectiveness of 3-month twice daily treatment with the Cala TWO device to aid in the relief of hand tremors in adult essential tremor subjects that have been approved to undergo deep brain stimulation surgery at Mayo Clinic - Rochester. This study is a prospective, within subject, non-significant risk study at Mayo Clinic - Rochester, enrolling approximately 20 subjects. A completely optional component of this study (Aim 2) is seeking to perform three standard PET/CT sessions on a subset of these subjects (n=10) at Mayo Clinic - Rochester to evaluate changes in brain metabolic activity as a result of 3 months treatment with the device. The first session would take place upon a subjects entry into the study (start of month 1) and prior to any treatment with the Cala device, a second the following day after a 40 minute treatment period with the Cala device, and a third session at the end of the third month. This study is a prospective, within subject, greater than minimum risk study.

Algorithms for Programming DBS Systems for ET

Deep brain stimulation (DBS) targeting the Vim thalamus (ventralis intermedius nucleus) is an FDA-approved neuromodulation therapy for treating postural and action tremor in individuals with essential tremor (ET). The success of this treatment, however, is highly dependent on the ability of clinicians to identify therapeutic stimulation settings through a laborious programming process. There is a strong and growing clinical need for new approaches to provide clinicians with more efficient guidance on how to titrate stimulation settings. This study will leverage subject-specific computational models that can predict neural activation of axonal pathways adjacent to the active electrode(s) and implicated in the therapeutic mechanisms of Vim-DBS to in turn guide clinicians with which stimulation settings are likely to be the most therapeutic on tremor.

Dual-Site Transcranial Magnetic Stimulation of the Supplementary Motor Area and Cerebellum for the Treatment of Essential Tremor.

Essential tremor is a common movement disorder that causes involuntary shaking, mainly during voluntary actions such as writing or holding objects. Recent research suggests that essential tremor is not caused by a single brain area, but by abnormal activity within a network that includes the cerebellum and motor areas of the brain. However, most non-invasive brain stimulation studies to date have targeted only one brain region and have shown inconsistent clinical benefits. This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the effects of a dual-site transcranial magnetic stimulation (rTMS) protocol targeting the supplementary motor area (SMA) and the cerebellum in patients with essential tremor that does not respond adequately to standard medications. The study is based on previous pilot data showing meaningful tremor reduction using combined stimulation of these two brain regions. Participants will receive five sessions of rTMS, consisting of low-frequency stimulation over the SMA followed by high-frequency stimulation over the cerebellum. The main hypothesis is that this combined approach will lead to an immediate and sustained improvement in action tremor of the dominant upper limb, measured up to four weeks after treatment. Secondary outcomes include quality of life, safety, side effects, and changes in brain excitability associated with tremor improvement.

3-D Tractography FUS Ablation for Essential Tremor

The investigators propose to advance Vim-FUSA (Ventral Intermediate Nucleus - Focused Ultrasound Ablation) with the support of 3-D tractography, a neuroimaging technique to visually represent nerve tracts within the brain. The investigators hypothesize that 3-D tractography Vim-FUSA will improve the Vim ablation compared to standard Vim-FUSA and prove safe and feasible in the clinical setting. The investigators also hypothesize that intraoperative magnetic resonance (i-MR) monitoring will differentiate ablated tissue from immediate perilesional edema and accurately predict the Vim-FUSA clinical outcomes.

Responsive Deep Brain Stimulator for Essential Tremor

Essential tremor is an incurable, degenerative brain disorder that results in increasingly debilitating tremor, and afflicts an estimated 7 million people in the US. In one study, 25% of essential tremor patients were forced to change jobs or take early retirement because of tremor. Essential tremor is directly linked to progressive functional impairment, social embarrassment, and even depression. The tremor associated with essential tremor is typically slow, involves the hands (and sometimes the head and voice), worsens with intentional movements, and is insidiously progressive over many years. Deep brain stimulation has emerged as a highly effective treatment for intractable, debilitating essential tremor. However, since the intention tremor of essential tremor is typically intermittent, and commonly absent at rest, the currently available continuous deep brain stimulation may be delivering unnecessary current to the brain that increases undesirable side effects such as slurred speech and walking difficulty, and hastens the depletion of device batteries, necessitating more frequent surgical procedures to replace spent pulse generators. The overall objective of this early feasibility study is to provide preliminary data on the safety and efficacy of "closed-loop" deep brain stimulation for intention tremor using novel deep brain stimulation devices capable of continuously sensing brain activity and delivering therapeutic stimulation only when necessary to suppress tremor.

Abbott DBS Post-Market Study of Outcomes for Indications Over Time

The purpose of this international study is to evaluate long-term safety and effectiveness of Abbott deep brain stimulation (DBS) systems for all indications, including Parkinson's disease, essential tremor or other disabling tremor and dystonia.

Neuromodulation Strategies for Treatment-Resistant Essential Tremor Using Chronos™ DBS

The goal of this observational study is to learn whether a new way of programming Deep Brain Stimulation (DBS) can improve and maintain tremor control in adults with essential tremor (ET) who stopped responding to standard DBS therapy. The main questions it aims to answer are: * 1\. Can advanced DBS settings, using varied stimulation patterns, frequencies, and pulses, restore tremor control in people with ET who lost benefit from standard Ventral Intermedius Deep Brain Stimulation (VIM-DBS)? * 2\. Do these advanced settings provide more stable, longer-lasting tremor improvement over time? Researchers will compare six different stimulation settings to see if any of them can improve tremor symptoms when standard DBS programming no longer works. Participants will: * Complete a clinic visit where they try six different DBS stimulation settings using specialized Chronos software. * Be randomly assigned to one of these settings to use at home. * Receive a follow-up phone call at 4 weeks to check on symptoms and device use. * Return to the clinic at 3 months for a full tremor evaluation. * Have the option to return for an additional follow-up visit at 1 year. This study will include 5 participants with essential tremor who previously lost benefit quickly after receiving standard VIM-DBS treatment.

Attention and Eye Movement in Parkinson's Disease

The goal of this observational and interventional study is to understand how therapeutic deep brain stimulation (DBS) affects attention, perception and cognition in participants with Parkinson's disease (PD) and essential tremor (ET). The main questions it aims to answer are: * Does impaired control of attention and eye movement in PD alter how social cues are perceived and interpreted? * Does therapeutic DBS improve or worsen attentional and perceptual deficits for social cues in PD and ET? * Can DBS be optimized to restore normal attentional control in PD while remaining an effective therapy for other aspects of the disorder. * What do parts of the brain targeted by DBS contribute to the control of attention? Using an eye tracking camera, investigators will study how participants with PD and ET look at and perceive facial expressions of emotion before and after starting DBS therapy, in comparison to a group of healthy participants without ET, PD or DBS. Participants with PD and ET will see and rate morphed facial expressions on a computer screen in three conditions: * Before starting DBS therapy (over approximately 1 hour). * In the operating room, during the standard procedure to implant DBS electrodes, while the participant is awake (for no more than 15 minutes). * After starting DBS therapy, with brief experimental changes of DBS stimulation level and frequency (over approximately 1 hour).