Essential Tremor

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.

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.

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

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.

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.

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.

Deep brain stimulation (DBS) is a surgical procedure for the treatment of Essential Tremor (ET). A novel approach to current DBS approaches is called coordinated reset DBS (CR-DBS) which uses different patterns of stimulation at lower currents and can address the limitations of traditional DBS that uses continuous high amplitude, high frequency stimulation. This study will evaluate the feasibility, safety and short-term efficacy of thalamic CR-DBS in upper extremity ET. The goal of this study is to evaluate the safety and short-term efficacy of thalamic CR- DBS in ET, including the acute (during CR-DBS) and carryover (following DBS cessation) effects, and compare these to those induced by clinically optimized T-DBS. To achieve our goal, a low-risk, two-phase clinical study will be conducted in patients with upper extremity (UE) ET. The first aim is to identify the spatial location and peak frequency of tremor related oscillatory activities in VIM (Phase I). The second aim is to compare the acute effects of thalamic CR-DBS to clinically optimized T-DBS (Phase II).

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.

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.

This open-label pilot study will evaluate the safety, tolerability, feasibility, and preliminary efficacy of repeated low-intensity focused ultrasound pulsation (LIFUP) targeting the ventral intermediate nucleus (Vim) of the thalamus in patients with Essential Tremor (ET). Twelve adults with clinically diagnosed ET will undergo six LIFUP treatment sessions over approximately two weeks using the BrainSonix BX Pulsar 1002 system. Tremor severity will be assessed using clinician-rated scales (TETRAS and FTM), patient-reported quality-of-life measures (QUEST), and objective accelerometry before and after treatment sessions, with additional follow-up visits at one and three months post-treatment. MRI scans will be performed at baseline and after the final treatment session to monitor safety. The study aims to characterize whether non-ablative focused ultrasound can safely and transiently modulate tremor-related thalamic circuits and provide preliminary evidence supporting future controlled trials of LIFUP for ET.

The purpose of this study is to collect electrophysiological data related to functional brain network changes in patients undergoing deep brain stimulation for the treatment of essential tremor. Participants will either 1) have electroencephalography (EEG) scalp electrodes placed, or 2) remain seated with their head inside of a magnetoencephalography (MEG) recording system, as resting-state and task-related data are acquired. Spontaneous electrophysiological activity will be recorded in both the eyes open and eyes closed conditions with the participant seated comfortably. These recordings will be repeated in the DBS OFF and DBS ON states, with the ON state involving specific settings identified as optimal, sub-optimal, or ineffective at achieving tremor control. They will also be repeated following the optional administration non-DBS tremor mitigation techniques, which may include one or more of the following: 1) cooling the limb, 2) oral administration of alprazolam, 3) oral consumption of ethanol (alcohol), or 4) peripheral nerve stimulation.

This study investigates the potential of phase-locked transcranial magnetic stimulation (TMS) as a non-invasive intervention for tremor in patients with Essential Tremor (ET) and Parkinson's Disease (PD). Tremor is a prevalent symptom that significantly impacts physical function and social participation. ET affects approximately 1% of the global population and worsens with age, while PD tremor is often less responsive to conventional dopaminergic therapy. Current treatments, including oral medications (propranolol, primidone), anticholinergics, and deep brain stimulation (DBS), are either limited by efficacy, side effects, or invasiveness. These challenges highlight the need for alternative, less invasive therapeutic options. The rationale for the study is based on the principle of phase-dependent neural modulation. Just as a swing's amplitude can be increased or decreased depending on when it is pushed, neural oscillations underlying tremor can theoretically be suppressed by precisely timed stimulation. Previous studies have shown that TMS over the motor cortex at tremor frequency (\~5 Hz) produces modest improvements in PD rest tremor. This study aims to enhance these effects by targeting amplitude-suppressing phases in the tremor cycle, potentially leading to greater and cumulative tremor reduction. The study has two components: Study 1 (Primary Objective): Determine whether phase-locked TMS can acutely reduce tremor. Participants (20 ET, 20 PD) will undergo two visits where tremor is recorded via inertial measurement units (IMUs) and surface EMG. TMS will be delivered over the motor cortex at or below active motor threshold, synchronized to the participant's tremor phase. The primary outcome is the change in tremor power during stimulation compared to no stimulation, measured objectively via IMU signals. Study 2 (Secondary Objective): Examine whether stimulation at the maximal tremor-suppressing phase, identified in Study 1, produces a larger reduction in tremor amplitude than stimulation at the minimal suppressing phase or sham stimulation. This will involve three additional sessions per participant, randomized for order, with outcomes assessed via IMU tremor power and participant-reported measures including the Quality of Life in Essential Tremor Questionnaire (QUEST), TETRAS, and Unified Parkinson's Disease Rating Scale (UPDRS). Study Design and Procedures: The design is a within-subject crossover. Participants may withhold tremor medications during visits to reduce confounding effects. EMG electrodes and IMU sensors will record tremor, while a figure-of-eight TMS coil will deliver phase-locked pulses. Phase-specific stimulation trains are applied for 3 seconds at intervals, with randomized order across multiple blocks. Study sessions last under two hours, including setup and post-stimulation recordings. Participants are recruited via self-referral or through DeNDRoN, screened for eligibility, and provide informed consent. Inclusion criteria require symptomatic ET or PD tremor, age ≥18, and ability to consent. Exclusion criteria include epilepsy, psychiatric illness, metal implants, pacemakers, or other conditions contraindicating TMS. Participants may withdraw at any time without penalty. Safety Measures: TMS and IMU recordings are low-risk, with potential minor effects including scalp tapping sensations, muscle twitches, or mild headaches, which are managed through monitoring and coil adjustment. Serious adverse events are defined, and procedures for reporting and auditing are established in accordance with UK regulations and Good Clinical Practice. Data Analysis: Tremor power will be quantified from IMU recordings using spectral analysis. Statistical comparisons between stimulation conditions and baseline will be conducted using paired t-tests or Wilcoxon tests. The study will employ validated software for randomization and analysis (SPSS, Matlab). Data will be pseudo-anonymized, securely stored, and archived for long-term research use. Ethical Considerations: The study follows the Declaration of Helsinki, Good Clinical Practice, and institutional approvals. Participants' privacy and data protection are ensured under GDPR standards. There are no commercial conflicts of interest, and participants are reimbursed for travel expenses. In summary, this research aims to evaluate the efficacy of phase-locked TMS as a non-invasive, targeted interventionfor tremor in ET and PD. By systematically stimulating the motor cortex at tremor-specific phases, the study seeks to establish a foundation for future minimally invasive treatments that could complement or replace existing pharmacological and surgical options.

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 non-PD movement disorders, including essential tremor (ET) and dystonia (DT). 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, ET and DT? * 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, ET and DT 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, DT or DBS. Participants with PD, ET and DT 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).

The goal of this proof-of-concept study is to examine the effects of a relatively new, non-invasive electrical current-based technique, transcranial temporal interference stimulation (tTIS), in patients with Essential Tremor (ET). TTIS is delivered via a Digitimer Ltd. stimulator, the "DS5 Isolated Bipolar Constant Current Stimulator." The method enables targeting deep cerebral structures to selectively modulate neurons. The structure of interest in the present study is the ventralis intermedius (VIM) of the thalamus, which plays a key role in tremor generation in people with essential tremor. Therefore, techniques targeting the VIM nucleus can potentially improve the tremor and the quality of life in the long term, as is the case with MRI-guided high-intensity focused ultrasound (MRgHIFU). Despite its efficiency, MRgHIFU can lead to side effects that could benefit from improved predictive modeling. In our proof-of-concept study, the investigators aim to examine whether tTIS of the VIM nucleus can alter tremor characteristics and, therefore, mimic the effects of MRgHIFU. This work would pave the way for future clinical trials to design prediction tools for MRgHIFU if the investigators can demonstrate the positive impact of tTIS.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.