Tremor Suppression Research Articles

Designs of Upper Limb Tremor Suppression Orthoses: Efficacy and Wearer's Comfort

Abstract Tremor is a rhythmic, involuntary oscillatory movement that significantly impacts various aspects of a patient's daily activities. The utilization of wearable tremor-suppressing orthoses has emerged as an efficacious and non-invasive treatment approach for managing tremors. This paper reviews recent advancements in upper limb tremor suppression orthoses, with the objective of laying a groundwork for future investigations. Through an analysis of the operational mechanisms, degrees of freedom, weight, and efficacy of tremor suppression across different orthotic designs, the following insights are gleaned: Disparities in operational mechanisms and the quantity of suppression directions are correlated with the device's weight, whereby weight emerges as a primary determinant influencing the comfort level of the orthoses. The interplay between the quantity and mass of quantity of suppression directions significantly influences the efficacy of orthoses equipment. Striking a balance among these three factors is poised to be a pivotal emphasis in forthcoming research endeavors. Furthermore, researchers are increasingly prioritizing the wearer's comfort in the evolution of these orthotic devices.

Frequency-Selective Suppression of Essential Tremor via Transcutaneous Spinal Cord Stimulation.

Essential tremor (ET) is a common debilitating condition, yet current treatments often fail to provide satisfactory relief. Transcutaneous spinal cord electrical stimulation (tSCS) has emerged as a potential noninvasive neuromodulation technique capable of disrupting the oscillatory activity underlying tremors. This study aimed to investigate the potential of tSCS to disrupt tremor in a frequency-dependent manner in a cohort of patients with ET. Eighteen patients with ET completed the study. The experiment consisted of 60-s postural tremor recording, during tSCS at tremor frequency, at 1 Hz, at 21 Hz, no stimulation, and trapezius stimulation. Tremor frequency and amplitude were analyzed and compared across the conditions. We found tremor amplitude reduction at tremor frequency stimulation significant only during the second half of the stimulation. The same stimulation resulted in the highest number of responders. tSCS at 1 Hz showed a trend toward decreased tremor amplitude in the latter half of stimulation. tSCS at 21 Hz did not produce any significant alterations in tremor, whereas trapezius stimulation exacerbated it. Notably, during tremor frequency stimulation, a subgroup of responders exhibited consistent synchronization between tremor phase and delivered stimulation, indicating tremor entrainment. Cervical tSCS holds promise for alleviating postural tremor in patients with ET when delivered at the subject's tremor frequency. The observed changes in tremor amplitude likely result from the modulation of spinal cord circuits by tSCS, which disrupts the oscillatory drive to muscles by affecting afferent pathways or spinal reflexes. However, the possibility of an interplay between spinal and supraspinal centers cannot be discounted. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Investigation of hand tremor suppression by a customized passive surgical support robot during internal limiting membrane peeling.

To construct a quantitative evaluation system for hand tremor during internal limiting membrane (ILM) peeling and investigate changes in hand tremor attributable to the use of the customized passive surgical support robot. This analytical and experimental study developed a hand tremor evaluation system that synchronizes three elements: surgical microscope images, an artificial eye module with a force sensor to simulate ILM peeling, and microforceps with an inertial measurement unit. Two surgeons used this system to measure hand tremor during ILM peeling with and without the robot. The horizontal, vertical, and combined vertical and horizontal components of hand tremor were 8.1 ± 6.1, 1.7 ± 1.8, and 8.5 ± 6.2 mG, respectively, in the no robot group. These components decreased to 7.2 ± 6.0, 1.5 ± 1.7, and 7.5 ± 6.1 mG, respectively, in the robot group. In particular, hand tremor was significantly suppressed by 11.9% for the horizontal component using the robot (p = 0.0006). The newly constructed system helps to quantitatively evaluate hand tremor during ILM peeling. The customized passive surgical support robot enables to decrease hand tremor during ILM peeling.

Responsive Versus Continuous Deep Brain Stimulation for Speech in Essential Tremor: A Pilot Study.

Responsive deep brain stimulation (rDBS) uses physiological signals to deliver stimulation when needed. rDBS is hypothesized to reduce stimulation-induced speech effects associated with continuous DBS (cDBS) in patients with essential tremor (ET). To determine if rDBS reduces cDBS speech-related side effects while maintaining tremor suppression. Eight ET participants with thalamic DBS underwent unilateral rDBS. Both speech evaluations and tremor severity were assessed across three conditions (DBS OFF, cDBS ON, and rDBS ON). Speech was analyzed using intelligibility ratings. Tremor severity was scored using the Fahn-Tolosa-Marin Tremor Rating Scale (TRS). During unilateral cDBS, participants experienced reduced speech intelligibility (P = 0.025) compared to DBS OFF. rDBS was not associated with a deterioration of intelligibility. Both rDBS (P = 0.026) and cDBS (P = 0.038) improved the contralateral TRS score compared to DBS OFF. rDBS maintained speech intelligibility without loss of tremor suppression. A larger prospective chronic study of rDBS in ET is justified. © 2024 International Parkinson and Movement Disorder Society.

Active Fabrics With Controllable Stiffness for Robotic Assistive Interfaces.

Assistive interfaces enable collaborative interactions between humans and robots. In contrast to traditional rigid devices, conformable fabrics with tunable mechanical properties have emerged as compelling alternatives. However, existing assistive fabrics actuated by fluidic or thermal stimuli struggle to adapt to complex body contours and are hindered by challenges such as large volumes after actuation and slow response rates. To overcome these limitations, inspiration is drawn from biological protective organisms combining hard and soft phases, and active assistive fabrics consisting of architectured rigid tiles interconnected with flexible actuated fibers are proposed. Through programmable tessellation of target body shapes into architectured tiles and controlling their interactions by the actuated fibers, the active fabrics can rapidly transition between soft compliant configurations and rigid states conformable to the body (>350 times stiffness change) while minimizing the device volume after actuation. The versatility of these active fabrics is demonstrated as exosuits for tremor suppression and lifting assistance,as body armors for impact mitigation, and integration withelectrothermal actuators for smart actuation with convenient folding capabilities. This work offers a practical framework for designing customizable active fabrics with shape adaptivity and controllable stiffness, suitable for applications in wearable exosuits, haptic devices, and medical rehabilitation systems.

Developing a wearable device for upper extremity tremors

Objective: This project aims to develop a wearable device to suppress both the essential and resting tremor and investigate its effectiveness. Materials and Methods: This study details the development and assessment of a wearable device for upper extremity tremors. The wearable device underwent a comprehensive design and a prototype was produced with a 3D-printer. To refine the functionality of the prototype, a motor that mimics tremor was attached to a 3D-printed prototype. Then, the printed prototype was applied to the hand model, and tested its effectiveness for tremor suppressing. The wearable device was further investigated on patients with essential tremor and Parkinson`s disease seeking treatment at Neurology Clinics. We recorded the tremor data and processed and visualized the recorded data by using the MatLab (version R2021a, MathWorks Inc., USA) software. Results: The wearable device effectively decreased the tremors both during the simulation phase and the patient testing phase. The data from the wearable device revealed a notable decrease in the amplitude of the tremor. This decrease signifies an achievement of tremor suppression. Conclusion: The prototype of the wearable device signifies a remarkable efficacy in tremor supression. It holds promise for being a potential solution to alleviate the tremor symptoms of essential tremor and Parkinson`s disease patients.

Impact of target depth on safety and efficacy outcomes in MR-guided focused ultrasound thalamotomy for tremor patients

OBJECTIVE Target depth, defined by the z-coordinate in the dorsoventral axis relative to the anterior commissure–posterior commissure axial plane of the MR-guided focused ultrasound (MRgFUS) lesion, is considered to be critical for tremor improvement and the occurrence of side effects such as gait impairment. However, although different z-coordinates are used in the literature, there are no comparative studies available with information on optimal lesion placement. This study aimed to compare two different MRgFUS lesion targets (z = +2 mm vs z = 0 mm) regarding efficacy and safety outcomes. METHODS The authors conducted a retrospective analysis of 52 patients with pharmacoresistant tremor disorders who received unilateral MRgFUS thalamotomy in the ventral intermediate nucleus for the first time between 2017 and 2022 by one neurosurgeon, with two different z-coordinates, either z = +2 mm (+2-mm group; n = 17) or z = 0 mm (0-mm group; n = 35), but otherwise identical parameters. Standardized video-recorded assessments of efficacy (including the Washington Heights-Inwood Genetic Study of Essential Tremor scale) and safety (using a standardized grading system) outcomes at baseline and at 6 months posttreatment were reviewed and compared. Moreover, overall patient satisfaction was extracted as documented by the examiner at 6 months. RESULTS Based on a multiple logistic regression analysis, the authors found that a more dorsal target with a z-coordinate of +2 mm as compared with 0 mm was associated with a higher incidence of any persistent side effect at 6 months (p = 0.02). Most consistently, sensory disturbances, although mild and nondisturbing in most cases, occurred more frequently in the +2-mm group (35% vs 11%, p = 0.007), while no significant differences were found for gait impairment (29% vs 35%) and arm ataxia (24% vs 11%). On the other hand, average tremor suppression was similar (63.6% vs 60.2%) between the groups. Here, higher efficacy was associated with a higher side effect burden in the 0-mm group but not in the +2-mm group. Despite the occurrence of side effects, general patient satisfaction was high (87% would undergo MRgFUS again) as most patients valued tremor suppression more. CONCLUSIONS A more ventral MRgFUS target of z = 0 mm seems to be associated with a more favorable safety and a comparable efficacy profile as compared with a more dorsal target of z = +2 mm, but prospective studies are warranted.

A Role for GABAA Receptor β3 Subunits in Mediating Harmaline Tremor Suppression by Alcohol: Implications for Essential Tremor Therapy.

Essential tremor patients may find that low alcohol amounts suppress tremor. A candidate mechanism is modulation of α6β3δ extra-synaptic GABAA receptors, that in vitro respond to non-intoxicating alcohol levels. We previously found that low-dose alcohol reduces harmaline tremor in wild-type mice, but not in littermates lacking δ or α6 subunits. Here we addressed whether low-dose alcohol requires the β3 subunit for tremor suppression. We tested whether low-dose alcohol suppresses tremor in cre-negative mice with intact β3 exon 3 flanked by loxP, and in littermates in which this region was excised by cre expressed under the α6 subunit promotor. Tremor in the harmaline model was measured as a percentage of motion power in the tremor bandwidth divided by overall motion power. Alcohol, 0.500 and 0.575 g/kg, reduced harmaline tremor compared to vehicle-treated controls in floxed β3 cre- mice, but had no effect on tremor in floxed β3 cre+ littermates that have β3 knocked out. This was not due to potential interference of α6 expression by the insertion of the cre gene into the α6 gene since non-floxed β3 cre+ and cre- littermates exhibited similar tremor suppression by alcohol. As α6β3δ GABAA receptors are sensitive to low-dose alcohol, and cerebellar granule cells express β3 and are the predominant brain site for α6 and δ expression together, our overall findings suggest alcohol acts to suppress tremor by modulating α6β3δ GABAA receptors on these cells. Novel drugs that target this receptor may potentially be effective and well-tolerated for essential tremor. We previously found with the harmaline essential tremor model that GABAA receptors containing α6 and δ subunits mediate tremor suppression by alcohol. We now show that β3 subunits in α6-expressing cells, likely cerebellar granule cells, are also required, indicating that alcohol suppresses tremor by modulating α6β3δ extra-synaptic GABAA receptors.

Magnetic Resonance-Guided Focused Ultrasound for Treatment of Essential Tremor: Ventral Intermediate Nucleus Ablation Alone or Additional Posterior Subthalamic Area Lesioning?

Magnetic resonance-guided focused ultrasound (MRgFUS) for treatment of essential tremor (ET) traditionally targets the ventral intermediate (Vim) nucleus. Recent strategies include a secondary lesion to the posterior subthalamic area (PSA). The aim was to compare lesion characteristics, tremor improvement, and adverse events (AE) between patients in whom satisfactory tremor suppression was achieved with lesioning of the Vim alone and patients who required additional lesioning of the PSA. Retrospective analysis of data collected from ET patients treated with MRgFUS at St Vincent's Hospital Sydney was performed. Clinical Rating Scale for Tremor (CRST), hand tremor score (HTS), and Quality of Life in Essential Tremor Questionnaire (QUEST) were collected pre- and posttreatment in addition to the prevalence of AEs. The lesion coordinates and overlap with the dentatorubrothalamic tract (DRTT) were evaluated using magnetic resonance imaging. Twenty-one patients were treated in Vim only, and 14 were treated with dual Vim-PSA lesions. Clinical data were available for 29 of the 35 patients (19 single target and 10 dual target). At follow-up (mean: 18.80 months) HTS, CRST, and QUEST in single-target patients improved by 57.97% (P < 0.001), 36.71% (P < 0.001), and 58.26% (P < 0.001), whereas dual-target patients improved by 68.34% (P < 0.001), 35.37% (P < 0.003), and 46.97% (P < 0.005), respectively. The Vim lesion of dual-target patients was further anterior relative to the posterior commissure (PC) (7.84 mm), compared with single-target patients (6.92 mm), with less DRTT involvement (14.85% vs. 23.21%). Dual-target patients exhibited a greater proportion of patients with acute motor AEs (100% vs. 58%); however, motor AE prevalence was similar in both groups at long-term follow-up (33% vs. 38%). Posterior placement of lesions targeting the Vim may confer greater tremor suppression. The addition of a PSA lesion, in patients with inadequate tremor control despite Vim lesioning, had a trend toward better long-term tremor suppression; however, this approach was associated with greater prevalence of gait disturbance in the short term.

Consistency is key: influence of skull density ratio distribution on the formation of clinically effective lesions and long-term tremor suppression following treatment with MR-guided focused ultrasound.

Skull density ratio (SDR) influences the permeability of the skull to the ultrasound waves used in magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of tremor. SDR values vary across the skull and the mean value is known to be predictive of sonication thermal increase. The aim of this investigation was to explore the effects of the SDR distribution on clinical outcomes following treatment with MRgFUS. Data from 61 patients with essential or dystonic tremor treated with MRgFUS targeting the ventral intermediate nucleus (Vim) were retrospectively analyzed. Tremor suppression was assessed using the Clinical Rating Scale for Tremor (CRST) and hand tremor score (HTS). Vim ablation volume was measured on the T1-weighted MR image acquired both at 1 day and 12 months after treatment. The numerical distribution of SDR values measured for each element in the ultrasound transducer was quantified by calculating the mean, standard deviation, skewness, entropy, and kurtosis of the SDR histogram. The effect of the SDR metrics on change in CRST and HTS was examined using a linear mixed-effects model. Additionally, the effect of the regional distribution of SDR values was explored in an element-wise analysis between patients with above- and below-average tremor suppression. A significant positive effect was found between SDR kurtosis and improvement in CRST (β = 0.33, p = 0.004) and HTS (β = 0.38, p < 0.001). The effect was found to be significant at 1 month posttreatment (CRST: β = 0.415, p = 0.008; HTS: β = 0.369, p = 0.016), and at the most recent clinical follow-up (CRST: β = 0.395, p < 0.001; HTS: β = 0.386, p < 0.001). One hundred seventy-one significant elements were identified in the element-wise analysis. The mean percentage difference from the mean SDR in these elements was associated with improvement in CRST (β = 0.27, p < 0.008) and HTS (β = 0.27, p < 0.015). Higher SDR kurtosis was associated with increased lesion volume at 12 months (p = 0.040) and less reduction in volume relative to the day-1 lesion volume (p = 0.007). Greater SDR kurtosis was associated with larger, more stable lesions at 12 months posttreatment and increased tremor suppression at long-term follow-up. SDR kurtosis may provide a more meaningful prognostic factor than the mean SDR.

Management of essential tremor deep brain stimulation-induced side effects.

Deep brain stimulation (DBS) is an effective surgical therapy for carefully selected patients with medication refractory essential tremor (ET). The most popular anatomical targets for ET DBS are the ventral intermedius nucleus (VIM) of the thalamus, the caudal zona incerta (cZI) and the posterior subthalamic area (PSA). Despite extensive knowledge in DBS programming for tremor suppression, it is not uncommon to experience stimulation induced side effects related to DBS therapy. Dysarthria, dysphagia, ataxia, and gait impairment are common stimulation induced side effects from modulation of brain tissue that surround the target of interest. In this review, we explore current evidence about the etiology of stimulation induced side effects in ET DBS and provide several evidence-based strategies to troubleshoot, reprogram and retain tremor suppression.

'Am I fixed, am I better now?': undergoing MR-guided focused ultrasound for essential tremor: an interpretative phenomenological analysis.

Essential tremor (ET) is characterised by postural and intentional tremor typically affecting the upper limbs, which can negatively impact functionality and quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a novel and promising non-invasive treatment for ET which offers instantaneous results. Using interpretative phenomenological analysis we explored the experience of undergoing MRgFUS in six ET patients as well as their experiences pre- and post-procedure. One-time, retrospective semi-structured interviews were conducted and six themes emerged: Life pre-treatment: "It's everyday tasks that get you down" and "Most people who understand, they are okay. Some people aren't"; MRgFUS: Treatment day: "Going into the unknown" and "There's no way I was going to press that button"; and Life post-treatment: "One is good. Two is better" and "Am I fixed, am I better now?." The findings point to a significant period of adjustment associated with living with ET and the effects of undergoing ET MRgFUS treatment. As ET progressed, participants struggled to cope with increasing symptoms and had to develop coping strategies to manage life with ET. The procedure itself was perceived as strange and extraordinary and despite some immediate adverse effects participants were determined to go through with it. Post procedure, all participants reported tremor suppression which was life changing. While some participants still felt burdened by ET, others expressed it took them a while to psychologically adjust to what essentially was their new body. This study has highlighted the need for patients to be supported at all stages of their ET journey.

Tremor Suppression Using Functional Electrical Stimulation.

Parkinson's disease (PD) and essential tremor are two major causes of pathological tremor among people over 60 years old. Due to the side effects and complications of traditional tremor management methods such as medication and deep brain surgery, non invasive tremor suppression methods have become more popular in recent years. Functional electrical stimulation (FES) is one of the methods used to reduce tremor in several studies. However, the effect of different FES parameters on tremor suppression and discomfort level, including amplitude, the number of pulses in each stimulation burst, frequency, and pulse width is yet to be studied for longer stimulation durations. Therefore, in this work, experiments were performed on 14 participants with PD to evaluate the effect of thirty seconds of out-of-phase electrical stimulation on wrist tremor at rest. Trials were conducted by varying the stimulation amplitude and the number of pulses while keeping the frequency and pulse width constant. Each test was repeated three times for each participant. The results showed an overall tremor suppression for 11 out of 14 participants and no average positive effects for three participants. It is concluded that despite the effectiveness of FES in tremor suppression, each set of FES parameters showed different suppression levels among participants due to the variability of tremor over time. Thus, for this method to be effective, an adaptive control system would be required to tune FES parameters in real time according to changes in tremor during extended stimulation periods.

Research on Tremor Suppression Strategies Under a Constant Current Peripheral Electrical Stimulation Device for Parkinson's Disease.

Tremor, a prevalent symptom in Parkinson's patients, is conventionally treated with medications and craniotomy. However, the associated side effects and high surgical costs pose challenges for some individuals. In this study, a lightweight constant current electrical stimulator was developed, which is driven by the FPGA to control the underlying logic and has multiple programmable stimulation parameters. Clinical experiments involving patients with Parkinson's-related resting tremor symptoms were conducted to assess the efficacy of peripheral electrical stimulation. Two Co-contraction Avoidance Stimulation (CAS) strategies targeting nerves and muscles were proposed to reduce tremors. Four Parkinson's disease (PD) patients were recruited to verify the effectiveness of these strategies. Kinematic data recorded by inertial sensors showed that the radial nerve and muscle intervention strategies reduced the average angular velocity amplitude of finger joints during resting tremor by 75.92% and 82.41%, respectively. Notably, under low-frequency pulse stimulation (100 Hz) focused on muscle interference, a low-intensity current of no more than 8 mA maintained a tremor suppression rate of 59.91% even 5 minutes post-stimulation. Based on the experimental results, it is concluded that the constant current electrical stimulator developed in this study can effectively suppress tremor under specific stimulation strategies. These findings have significant implications for the development of lightweight, wearable tremor suppression devices. The stimulator's adaptability, coupled with its precise control parameters, demonstrates promise for advancing non-invasive and cost-effective tremor management in Parkinson's patients.

An OpenSim-Based Closed-Loop Biomechanical Wrist Model for Subject-Specific Pathological Tremor Simulation.

A pathological tremor (PT) is an involuntary rhythmic movement of varying frequency and amplitude that affects voluntary motion, thus compromising individuals' independence. A comprehensive model incorporating PT's physiological and biomechanical aspects can enhance our understanding of the disorder and provide valuable insights for therapeutic approaches. This study aims to build a biomechanical model of pathological tremors using OpenSim's realistic musculoskeletal representation of the human wrist with two degrees of freedom. We implemented a Matlab/OpenSim interface for a forward dynamics simulation, which allows for the modeling, simulation, and design of a physiological H∞ closed-loop control. This system replicates pathological tremors similar to those observed in patients when their arm is extended forward, the wrist is pronated, and the hand is subject to gravity forces. The model was individually tuned to five subjects (four Parkinson's disease patients and one diagnosed with essential tremor), each exhibiting distinct tremor characteristics measured by an inertial sensor and surface EMG electrodes. Simulation agreement with the experiments for EMGs, central frequency, joint angles, and angular velocities were evaluated by Jensen-Shannon divergence, histogram centroid error, and histogram intersection. The model emulated individual tremor statistical characteristics, including muscle activations, frequency, variability, and wrist kinematics, with greater accuracy for the four Parkinson's patients than the essential tremor. The proposed model replicated the main statistical features of subject-specific wrist tremor kinematics. Our methodology may facilitate the design of patient-specific rehabilitation devices for tremor suppression, such as neural prostheses and electromechanical orthoses.

Multimodal Tremor Suppression of the Wrist Using FES and Electric Motors–A Simulation Study

Multimodal Tremor Suppression of the Wrist Using FES and Electric Motors–A Simulation Study

Search for Novel Therapies for Essential Tremor Based on Positive Modulation of α6-Containing GABAA Receptors.

Prior work using GABAA receptor subunit knockouts and the harmaline model has indicated that low-dose alcohol, gaboxadol, and ganaxolone suppress tremor via α6βδ GABAA receptors. This suggests that drugs specifically enhancing the action of α6βδ or α6βγ2 GABAA receptors, both predominantly expressed on cerebellar granule cells, would be effective against tremor. We thus examined three drugs described by in vitro studies as selective α6βδ (ketamine) or α6βγ2 (Compound 6, flumazenil) receptor modulators. In the first step of evaluation, the maximal dose was sought at which 6/6 mice pass straight wire testing, a sensitive test for psychomotor impairment. Only non-impairing doses were used to evaluate for anti-tremor efficacy in the harmaline model, which was assessed in wildtype and α6 subunit knockout littermates. Ketamine, in maximally tolerated doses of 2.0 and 3.5 mg/kg had minimal effect on harmaline tremor in both genotypes. Compound 6, at well-tolerated doses of 1-10 mg/kg, effectively suppressed tremor in both genotypes. Flumazenil suppressed tremor in wildtype mice at doses (0.015-0.05 mg/kg) far lower than those causing straight wire impairment, and did not suppress tremor in α6 knockout mice. Modulators of α6βδ and α6βγ2 GABAA receptors warrant attention for novel therapies as they are anticipated to be effective and well-tolerated. Ketamine likely failed to attain α6βδ-active levels. Compound 6 is an attractive candidate, but further study is needed to clarify its mechanism of action. The flumazenil results provide proof of principle that targeting α6βγ2 receptors represents a worthy strategy for developing essential tremor therapies. We tested for harmaline tremor suppression drugs previously described as in vitro α6βδ or α6βγ2 GABAA receptor-selective modulators. Well-tolerated flumazenil doses suppressed tremor in α6-wildtype but not α6-knockout mice. Compound 6 and ketamine failed to display this profile, likely from off-target effects. Selective α6 modulators hold promise as tremor therapy.

A Tremor Suppression and Noise Removal Algorithm for Microscopic Robot-Assisted Cataract Surgery

Ophthalmic surgery consists of a series of precise manipulations performed using a surgical microscope. A surgical robot with a master–slave paradigm is commonly adopted to improve the precision and guidance intelligence for ophthalmic surgery; however, the surgeon's hand tremor, misoperation, inherent characteristics of the robot, and environmental interference may cause tremors of the end-effector of the surgical manipulator, thus increasing the risk of soft tissue damage and poor prognosis for the patient. A symmetrical threshold noise reduction combiner (STIC) is proposed to suppress hand tremors and reduce environmental noise interference. Additionally, the inverse kinematic model of the eight-degrees-of-freedom surgical robot for cataract surgery is developed, with the constraints of continuous circular capsulorhexis manipulation. Simulation results show that the signal-to-noise ratio of the STIC is increased from 35.3907 to 57.0158 dB, whereas the maximum, average, standard deviation, and root mean square of the output of the STIC are decreased by 64.79%, 77.24%, 74.50%, and 75.86%, respectively. Three sets of in vitro experimental results show that these four indicators of the STIC performance are reduced by 59.73%, 76.57%, 57.23%, and 65.02%, respectively. These results validate the feasibility and effectiveness of the proposed method on hand tremor suppression and inherent high-frequency disturbance elimination, thereby enhancing the accuracy of the microsurgical operation.

Multivariable closed-loop control of deep brain stimulation for Parkinson’s disease

Objective. Closed-loop deep brain stimulation (DBS) methods for Parkinson’s disease (PD) to-date modulate either stimulation amplitude or frequency to control a single biomarker. While good performance has been demonstrated for symptoms that are correlated with the chosen biomarker, suboptimal regulation can occur for uncorrelated symptoms or when the relationship between biomarker and symptom varies. Control of stimulation-induced side-effects is typically not considered. Approach. A multivariable control architecture is presented to selectively target suppression of either tremor or subthalamic nucleus beta band oscillations. DBS pulse amplitude and duration are modulated to maintain amplitude below a threshold and avoid stimulation of distal large diameter axons associated with stimulation-induced side effects. A supervisor selects between a bank of controllers which modulate DBS pulse amplitude to control rest tremor or beta activity depending on the level of muscle electromyographic (EMG) activity detected. A secondary controller limits pulse amplitude and modulates pulse duration to target smaller diameter axons lying close to the electrode. The control architecture was investigated in a computational model of the PD motor network which simulated the cortico-basal ganglia network, motoneuron pool, EMG and muscle force signals. Main results. Good control of both rest tremor and beta activity was observed with reduced power delivered when compared with conventional open loop stimulation, The supervisor avoided over- or under-stimulation which occurred when using a single controller tuned to one biomarker. When DBS amplitude was constrained, the secondary controller maintained the efficacy of stimulation by increasing pulse duration to compensate for reduced amplitude. Dual parameter control delivered effective control of the target biomarkers, with additional savings in the power delivered. Significance. Non-linear multivariable control can enable targeted suppression of motor symptoms for PD patients. Moreover, dual parameter control facilitates automatic regulation of the stimulation therapeutic dosage to prevent overstimulation, whilst providing additional power savings.

Brief Submotor-Threshold Electrical Stimulation Applied Synchronously Over Wrist Flexor and Extensor Muscles does Not Suppress Essential Tremor, Independent of Stimulation Frequency.

Electrical stimulation of muscles below motoneuron threshold has shown potential as a low-cost and minimally invasive treatment for Essential Tremor (ET). Prior studies have stimulated wrist flexor and extensor muscles synchronously with diverging results, calling for further investigation. Also, prior studies have only used a narrow range of stimulation parameters, so stimulation parameters have not been optimized. Our purpose was to further investigate synchronous submotor stimulation and identify the effect of stimulation frequency on tremor suppression. We quantified the effect of brief, synchronous stimulation at 15 different frequencies from 10-150 Hz applied over wrist flexors and extensors on both tremor power and frequency in 20 ET patients. We compared tremor power and frequency from hand acceleration and sEMG between pre-, per-, and post-stimulation phases. Our stimulation paradigm did not result in significant tremor suppression or tremor frequency changes at any tested stimulation frequency, showing no significant interaction between phase and stimulation frequency for tremor power measured by either hand acceleration (p = 0.69) or sEMG (p = 0.07). Additionally, the effect of phase interacting with stimulation frequency on tremor frequency was statistically insignificant for acceleration (p = 0.64) and sEMG (p = 0.37). We conclude that brief synchronous submotor-threshold stimulation does not reduce tremor in ET patients, independent of stimulation frequency (from 10 to 150 Hz). Our results are consistent with the hypothesis that brief submotor-threshold stimulation suppresses tremor via reciprocal inhibition, which requires asynchronous stimulation. In contrast, it is hypothesized that synchronous stimulation might require longer stimulation durations to affect supraspinal tremor networks. We studied the effects of synchronous submotor electrical stimulation over wrist flexor and extensor muscles on Essential Tremor. Our results indicate that suppressing tremor with brief synchronous stimulation is ineffective. Based on recently hypothesized mechanisms of peripheral tremor suppression, we hypothesize that asynchronous stimulation or long-duration synchronous stimulation are more effective approaches to peripheral tremor suppression.