Controlling a motorized orthosis to follow elbow volitional movement: tests with individuals with pathological tremor.

BACKGROUND: There is a need for alternative treatment options for tremor patients who do not respond well to medications or surgery, either due to side effects or poor efficacy, or that are excluded from surgery. The study aims to evaluate feasibility of a voluntary-driven, speed-controlled tremor rejection approach with individuals with pathological tremor. The suppression approach was investigated using a robotic orthosis for suppression of elbow tremor. Importantly, the study emphasizes the performance in relation to the voluntary motion. METHODS: Nine participants with either Essential Tremor (ET) or Parkinson's disease (PD) were recruited and tested off medication. The participants performed computerized pursuit tracking tasks following a sinusoid and a random target, both with and without the suppressive orthosis. The impact of the Tremor Suppression Orthosis (TSO) at the tremor and voluntary frequencies was determined by the relative power change calculated from the Power Spectral Density (PSD). Voluntary motion was, in addition, assessed by position and velocity tracking errors. RESULTS: The suppressive orthosis resulted in a 94.4% mean power reduction of the tremor (p < 0.001) - a substantial improvement over reports in the literature. As for the impact to the voluntary motion, paired difference tests revealed no statistical effect of the TSO on the relative power change (p = 0.346) and velocity tracking error (p = 0.283). A marginal effect was observed for the position tracking error (p = 0.05). The interaction torque with the robotic orthosis was small (0.62 Nm) when compared to the maximum voluntary torque that can be exerted by adult individuals at the elbow joint. CONCLUSIONS: Two key contributions of this work are first, a recently proposed approach is evaluated with individuals with tremor demonstrating high levels of tremor suppression; second, the impact of the approach to the voluntary motion is analyzed comprehensively, showing limited inhibition. This study also seeks to address a gap in studies with individuals with tremor where the impact of engineering solutions on voluntary motion is unreported. This study demonstrates feasibility of the wearable technology as an effective treatment that removes tremor with limited impediment to intentional motion. The goal for such wearable technology is to help individuals with pathological tremor regain independence in activities affected by the tremor condition. Further investigations are needed to validate the technology.

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications.

OBJECTIVE: We propose, design and test a novel thin-film multichannel electrode that can be used for both recording from and stimulating a muscle in acute implants. APPROACH: The system is built on a substrate of polyimide and contains 12 recording and three stimulation sites made of platinum. The structure is 420 µm wide, 20 µm thick and embeds the recording and stimulation contacts on the two sides of the polyimide over an approximate length of 2 cm. We show representative applications in healthy individuals as well as tremor patients. The designed system was tested by a psychometric characterization of the stimulation contacts in six tremor patients and three healthy individuals determining the perception threshold and current limit as well as the success rate in discriminating elicited sensations (electrotactile feedback). Also, we investigated the possibility of using the intramuscular electrode for reducing tremor in one patient by electrical stimulation delivered with timing based on the electromyographic activity recorded with the same electrode. MAIN RESULTS: In the tremor patients, the current corresponding to the perception threshold and the current limit were 0.7 ± 0.2 and 1.4 ± 0.7 mA for the wrist flexor muscles and 0.4 ± 0.2 and 1.5 ± 0.7 mA for the extensors. In one patient, closed-loop stimulation resulted in a decrease of the tremor power >50%. In healthy individuals the perception threshold and current limits were 0.9 ± 0.6 and 2.1 ± 0.6 mA for the extensor carpi radialis muscle. The subjects could distinguish four or six stimulation patterns (two or three stimulation sites × two stimulation current amplitudes) with true positive rate >80% (two subjects) and >60% (one subject), respectively. SIGNIFICANCE: The proposed electrode provides a compact multichannel interface for recording electromyogram and delivering electrical stimulation in applications such as neuroprostheses for tremor suppression and closed-loop myoelectric prostheses.

Metabolic Positron Emission Tomography Response to Gamma Knife of the Ventral Intermediate Nucleus in Essential Tremor.

BACKGROUND: To understand the substrates of response and nonresponse and to identify potential biomarkers for the selection and follow-up of patients with essential tremor (ET) treated with Gamma Knife (Elekta AB, Stockholm, Sweden) of the ventral intermediate nucleus (GKVIM). OBJECTIVE: To characterize positron emission tomography (PET) changes in the metabolism of glucose and metabolic connectivity in patients with ET treated by GKVIM through observational study. METHODS: Forty-two patients with right ET were referred to 18F-fluorodesoxyglucose positron emission tomography (18F-FDG PET) imaging before and after left GKVIM. Statistical Parametric Mapping T-score map comparisons were performed between pre- and post-GKVIM groups and between clinical responders and nonresponders. Metabolic connectivity was evaluated by the interregional correlation analysis method. RESULTS: After GKVIM, patients with ET exhibited decreased left thalamic metabolism, which was associated with remote metabolic decreases in the right cerebellum, left temporal gyri, and bilateral frontal gyri (P < .05, family-wise error-corrected). Additionally, nonresponders (n = 7) showed metabolic decreases in the right temporo-occipital area (P < .005 corrected for cluster volume) after GKVIM. The metabolism in this area was already reduced in nonresponders before treatment in comparison to that in responders and was predictive of future response (sensitivity: 89%; specificity: 71%). In nonresponder patients, strong connectivity between the left thalamus and right temporo-occipital area was found before GKVIM and was lost after treatment, whereas this connectivity remained weak and stable in responders. CONCLUSION: These findings could lead to better knowledge of the variability in the metabolic PET profiles among patients with ET, particularly the integration of 18F-FDG PET imaging in the pretherapeutic evaluation of patients with refractory ET candidates for GKVIM.

Improvement of mouse controlling in Essential tremor by a tremor filter: A case report.

The interaction with electronic devices is crucial in our technological society. Hand kinetic tremor complicates mouse driving in Essential tremor patients. To solve this issue some technological solutions are available and accessible online. We present a 71-year-old patient with prominent mouse controlling tremor who improved with one of these systems.

Feasibility study: Effect of hand resistance exercise on handwriting in Parkinson's disease and essential tremor.

STUDY DESIGN: A single group, repeated measures design was used. INTRODUCTION: Tremor can lead to impaired hand function in patients with Parkinson's disease (PD) and essential tremor (ET). Difficulty with handwriting is a common complaint in these patients suffering from hand tremors. The effect of hand resistance exercise on handwriting is unknown. PURPOSE OF THE STUDY: To explore the influence of 6 weeks of home-based hand resistance exercise on handwriting in individuals with PD and ET. METHODS: Nine individuals with PD and 9 with ET participated in the study. The average age was 65.3 (6.0) years with an average disease duration of 7.8 years. Participants were instructed to perform a home-based, hand and arm resistance exercise program 3 times a week for 6 weeks. Samples of the area of handwriting and maximal grip strength were measured at baseline and after 6 weeks of exercise. The area of the handwriting sample and maximal grip strength measured before and after 6 weeks were compared. RESULTS: Mean grip strength of the participants with PD improved after 6 weeks of hand resistance exercise (P = .031), but grip strength did not change in ET (P = .091). The size of the handwriting samples (words and sentences) did not change after exercise in either participants with PD or ET. DISCUSSION: Micrographia in patients with PD and macrographia in patients with ET represent complex fine motor skills. More research is needed to understand what therapies could be effective in modifying the size and quality of handwriting. CONCLUSIONS: The purpose of this feasibility study was to explore the influence of home-based wrist resistance exercise on handwriting in individuals with PD and ET. Despite small gains in grip strength, the size of the handwriting samples (words and sentences) did not change for patients with PD or ET following a 6-week home-based hand resistance exercise program.

Taking on Essential Tremor: New Tools and Approaches Offer patients Increased Treatment Options.

Every year, Doris's primary care physician sends her to see a neurologist to check on her hand tremor, which has increasingly worsened over the past 20 years. Year in and year out, the neurologist asks her to draw a circle on a piece of paper. "The doctor looks at it, says 'Hmm,' and sends me home," Doris explains, adding that she gets no treatment, no recommendations, nothing except a request to schedule next year's appointment.

Online tremor suppression using electromyography and low-level electrical stimulation.

Tremor is one of the most prevalent movement disorders. There is a large proportion of patients (around 25%) in whom current treatments do not attain a significant tremor reduction. This paper proposes a tremor suppression strategy that detects tremor from the electromyographic signals of the muscles from which tremor originates and counteracts it by delivering electrical stimulation to the antagonist muscles in an out of phase manner. The detection was based on the iterative Hilbert transform and stimulation was delivered above the motor threshold (motor stimulation) and below the motor threshold (sensory stimulation). The system was tested on six patients with predominant wrist flexion/extension tremor (four with Parkinson disease and two with Essential tremor) and led to an average tremor reduction in the range of 46%-81% and 35%-48% across five patients when using the motor and sensory stimulation, respectively. In one patient, the system did not attenuate tremor. These results demonstrate that tremor attenuation might be achieved by delivering electrical stimulation below the motor threshold, preventing muscle fatigue and discomfort for the patients, which sets the basis for the development of an alternative treatment for tremor.

Robust controller for tremor suppression at musculoskeletal level in human wrist.

Tremor is a rhythmical and involuntary oscillatory movement of a body part and it is one of the most common movement disorders. Orthotic devices have been under investigation as a noninvasive tremor suppression alternative to medication or surgery. The challenge in musculoskeletal tremor suppression is estimating and attenuating the tremor motion without impeding the patient's intentional motion. In this research a robust tremor suppression algorithm was derived for patients with pathological tremor in the upper limbs. First the motion in the tremor frequency range is estimated using a high-pass filter. Then, by applying the backstepping method the appropriate amount of torque is calculated to drive the output of the estimator toward zero. This is equivalent to an estimation of the tremor torque. It is shown that the arm/orthotic device control system is stable and the algorithm is robust despite inherent uncertainties in the open-loop human arm joint model. A human arm joint simulator, capable of emulating tremorous motion of a human arm joint was used to evaluate the proposed suppression algorithm experimentally for two types of tremor, Parkinson and essential. Experimental results show 30-42 dB (97.5-99.2%) suppression of tremor with minimal effect on the intentional motion.

Dexterity training improves manual precision in patients affected by essential tremor.

OBJECTIVE: To evaluate the effect of a short-term dexterity-training program on muscle tremor and the performance of hand precision tasks in patients with essential tremor (ET). DESIGN: Three testing sessions: baseline, after 4 weeks without any interventions (control), and after 4 weeks of dexterity-training carried out 3 times per week. SETTING: Biomechanics research laboratory. PARTICIPANTS: Patients (N=8) with a diagnosis of ET. INTERVENTION: Training program consisted of 12 dexterity training sessions where each session comprised 4 tasks involving both goal-directed manual movements and hand postural exercises. MAIN OUTCOME MEASURES: Testing included an ET-specific quality of life questionnaire and postural and kinetic tremor assessments. Each training session was scored to evaluate the performance. RESULTS: After training, improvements were observed in the performance of the 2 goal-directed tasks (P<.01); however, postural and kinetic tremor did not change. CONCLUSIONS: This study suggests that dexterity training could be effective in increasing fine manual control during goal-directed movements, which are known to be the most compromised in this pathology. The absence of a decrease in tremor severity highlights the necessity for developing this novel training technique further, perhaps over a longer period of time. This study could provide guidelines for the prescription of self-directed and personalized home-based exercises and will offer clinicians a treatment that might be used as an adjuvant or an alternative to the classical pharmacotherapy.

Real-time two-dimensional asynchronous control of a computer cursor with a single subdural electrode.

OBJECTIVE: To test the feasibility of controlling a computer cursor asynchronously in two dimensions using one subdural electrode. DESIGN: Proof of concept study. SETTING: Acute care hospital in Toronto, Canada. PARTICIPANT: A 68-year-old woman with a subdural electrode implanted for the treatment of essential tremor (ET) using direct brain stimulation of the primary motor cortex (MI). INTERVENTIONS: Power changes in the electrocorticography signals were used to implement a "brain switch". To activate the switch the subject had to decrease the power in the 7-13 Hz frequency range using motor imagery of the left hand. The brain switch was connected to a system for asynchronous control of movement in two dimensions. Each time the user reduced the amplitude in the 7-13 Hz frequency band below an experimentally defined threshold the direction of cursor changed randomly. The new direction was always different from those previously rejected ensuring the convergence of the system on the desired direction. OUTCOME MEASURES: Training time, time and number of switch activations required to reach specific targets, information transfer rate. RESULTS: The user was able to control the cursor to specific targets on the screen after only 15 minutes of training. Each target was reached in 51.7 ± 40.2 seconds (mean ± SD) and after 9.4 ± 6.8 switch activations. Information transfer rate of the system was estimated to be 0.11 bit/second. CONCLUSION: A novel brain-machine interface for asynchronous two-dimensional control using one subdural electrode was developed.

Control of a neuroprosthesis for grasping using off-line classification of electrocorticographic signals: case study.

STUDY DESIGN: Proof of concept study to control a neuroprosthesis for grasping using identification of arm movements from ECoG signals. OBJECTIVE: To test the feasibility of using electrocorticographic (ECoG) signals as a control method for a neuroprosthesis for grasping. SETTING: Acute care hospital, Toronto Western Hospital and spinal cord injury (SCI) rehabilitation centre, Toronto Rehabilitation Institute, Lyndhurst Centre. Both hospitals are located in Toronto, Canada. METHODS: Two subjects participated in this study. The first subject had subdural electrodes implanted on the motor cortex for the treatment of essential tremor (ET). ECoG signals were recorded while the subject performed specific arm movements. The second subject had a complete SCI at C6 level (ASIA B score) and was fitted with a neuroprosthesis, capable of identifying arm movements from ECoG signals off-line, for grasping. To operate the neuroprosthesis, subject 2 issued a command that would trigger the release of a randomly selected ECoG signal recorded from subject 1, associated with a particular arm movement. The neuroprosthesis identified which arm movement was performed at the time of recording and used that information to trigger the stimulation sequence. A correct ECoG classification resulted in the neuroprosthesis producing the correct hand function (that is grasp and release). RESULTS: The neuroprosthesis classified ECoG signals correctly delivering the correct stimulation strategy with 94.5% accuracy. CONCLUSIONS: The feasibility of using ECoG signals as a control strategy for a neuroprosthesis for grasping was shown.

Evaluation of a wearable orthosis and an associated algorithm for tremor suppression.

We describe a wearable orthosis and an associated algorithm for the simultaneous assessment and treatment of essential tremor, one of the most common movement disorders in humans involving an overactivity of the olivo-cerebellar pathways. A motor providing effective viscosity is fixed on a wearable orthosis in the upper limbs. The motor is controlled by a personal computer with software processing in real time the position and rate of rotation of the joint detected by a chip gyroscope. The orthosis can be used in a monitoring mode and in an active mode. The range of tremor suppression of the signals above the orthosis operational limit ranges from about 3% (percentile 5) to about 79% (percentile 95) in relation to energy in the monitoring mode. Considering both postural and kinetic, the mean tremor energy decreased from 55.49 +/- 22.93 rad2 s(-3) in the monitoring mode to 15.66 +/- 7.29 rad2 s(-3) in the active mode. Medians of power reduction were below 60% for the wrist and the elbow. In addition to supplying new information on the interactions between kinematics, dynamics and tremor genesis, this non-invasive technique is an alternative to current therapies. This new approach will provide new insights into the understanding of motor control.

A novel quality of life instrument for deep brain stimulation in movement disorders.

OBJECTIVE: To develop a short instrument to examine quality of life (QoL) which specifically addresses patients with movement disorders treated by deep brain stimulation (DBS). DESIGN: The instrument was developed within an existing concept of a modular questionnaire (questions on life satisfaction: "general life satisfaction" QLS(M)-A, and "satisfaction with health" QLS(M)-G), in which each item is weighted according to its relative importance to the individual. METHODS: Items were generated by interviews with 20 DBS patients, followed by item reduction and scale generation, factor analysis to determine relevant and final questionnaire items, estimation of reliability, and validation based on the medical outcome study 36 item short form health survey (SF-36) and the EuroQol (EQ-5D) (data from 152 patients with Parkinson's disease, essential tremor, or idiopathic torsion dystonia, including 75 patients with DBS). RESULTS: Initial questionnaires were reduced to 12 items for a "movement disorder module" (QLS(M)-MD), and five items for a "deep brain stimulation module" (QLS(M)-DBS). Psychometric analysis revealed Cronbach's alpha values of of 0.87 and 0.73, and satisfactory correlation coefficients for convergent validity with SF-36 and EQ-5D. CONCLUSIONS: QLS(M)-MD and QLS(M)-DBS can evaluate quality of life aspects of DBS in movement disorders. Psychometric evaluation showed the questionnaires to be reliable, valid, and well accepted by the patients.

Identification of target areas for deep brain stimulation in human basal ganglia substructures based on median nerve sensory evoked potential criteria.

OBJECTIVE: In the interventional treatment of movement disorders, the thalamic ventral intermediate nucleus (VIM) and the subthalamic nucleus (STN) are the most relevant electrode targets for deep brain stimulation (DBS). This study tested the value of somatosensory evoked potentials (SEP) for the functional identification of VIM and STN. METHODS: Median nerve SEP were recorded from the final stimulation electrodes targeted at STN and VIM. Throughout the stereotactic procedure SEP were recorded during short electrode stops above STN/VIM and within the presumed target areas. After digital filtering, high and low frequency SEP components were analysed separately to parameterise both the 1000 Hz SEP burst and low frequency (<100 Hz) components. RESULTS: SEP recorded in the VIM target region could unequivocally be distinguished from SEP recorded in STN. The 1000 Hz burst signal was significantly larger in VIM than in STN without any overlap of amplitude values. In the low frequency band, a primary high amplitude negativity was obtained in VIM, contrasting with a low amplitude positivity in STN. SEP waveshapes in recordings above target positions resembled SEP obtained in STN. When entering VIM, a sharp amplitude increase was observed over a few millimetres only. CONCLUSIONS: Based on SEP criteria, the VIM target but not the STN region can be identified by typical SEP configuration changes, when penetrating the target zone. The approach is independent of the patient's cooperation and vigilance and therefore feasible in general anaesthesia. It provides an easy, reliable, and robust tool for the final assessment of electrode positions at the last instance during electrode implantation when eventual electrode revisions can easily be performed.

Functional outcomes after gamma knife thalamotomy for essential tremor and MS-related tremor.

Twelve patients with a median age of 75 years underwent gamma knife thalamotomy for essential tremor (ET) (n = 9) or MS-related tremor (n = 3). All 11 evaluable patients noted improvement in action tremor. Six of eight ET patients had complete tremor arrest, and the violent action tremor in all three patients with MS was improved. One patient developed transient arm weakness. Stereotactic radiosurgery for ET and MS-related tremor is safe and effective for patients who may be poor candidates for other procedures.