A pilot study of synergy-based FES for upper-extremity poststroke rehabilitation.

A previous study indicated that synergy-based functional electrical stimulation (FES) may improve instantaneous upper-limb motor performance for stroke survivors. However, it remains unclear whether the improvements will sustain over time to achieve functional gains associated with a task-oriented training (TOT). This pilot study was designed to investigate whether there is any promising sign of functional benefits. A TOT protocol with repeated forward and lateral reaching movements assisted by synergy-based FES was conducted in 16 patients (9 FES, 7 Sham) with post-stroke hemiparesis. FES stimuli were applied to 7 upper-extremity muscles of elbow and shoulder during patient movements. Envelopes of stimuli were individualized by re-composing the muscle synergies extracted from a healthy subject. After a five-day training for one hour each day, synergy-based FES induced higher increases in Fugl-Meyer scores (6.67 ± 5.20) than did the Sham (2.00 ± 2.38, p < 0.05). Peak velocity of forward reaching movements increased with a slope 73% steeper in FES group than Sham. In lateral reaching movements, the change in synergy similarity correlated with the change in elbow flexion for the FES group, but not the Sham group. Our results indicate that synergy-based FES therapy induced clinically traceable signs of improvements in poststroke motor performance. The muscle activation in patients also showed promising sign of alteration by FES. Results suggest that a larger scale clinical trial of synergy-based FES may be feasible towards an individualized therapeutic regimen.

Evaluation of multiple perceptual qualities of transcutaneous electrical nerve stimulation for evoked tactile sensation in forearm amputees.

Objective. Evoked tactile sensation (ETS) elicited by transcutaneous electrical nerve stimulation (TENS) is promising to convey digit-specific sensory information to amputees naturally and non-invasively. Fitting ETS-based sensory feedback to amputees entails customizing coding of multiple sensory information for each stimulation site. This study was to elucidate the consistency of percepts and qualities by TENS at multiple stimulation sites in amputees retaining ETS.Approach. Five transradial amputees with ETS and fourteen able-bodied subjects participated in this study. Surface electrodes with small size (10 mm in diameter) were adopted to fit the restricted projected finger map on the forearm stump of amputees. Effects of stimulus frequency on sensory types were assessed, and the map of perceptual threshold for each sensation was characterized. Sensitivity for vibration and buzz sensations was measured using distinguishable difference in stimulus pulse width. Rapid assessments for modulation ranges of pulse width at fixed amplitude and frequency were developed for coding sensory information. Buzz sensation was demonstrated for location discrimination relating to prosthetic fingers.Main results. Vibration and buzz sensations were consistently evoked at 20 Hz and 50 Hz as dominant sensation types in all amputees and able-bodied subjects. Perceptual thresholds of different sensations followed a similar strength-duration curve relating stimulus amplitude to pulse width. The averaged distinguishable difference in pulse width was 12.84 ± 7.23µs for vibration and 15.21 ± 6.47µs for buzz in able-bodied subjects, and 14.91 ± 10.54µs for vibration and 11.30 ± 3.42µs for buzz in amputees. Buzz coding strategy enabled five amputees to discriminate contact of individual fingers with an overall accuracy of 77.85%.Significance. The consistency in perceptual qualities of dominant sensations can be exploited for coding multi-modality sensory feedback. A fast protocol of sensory coding is possible for fitting ETS-based, non-invasive sensory feedback to amputees.

Automated functional electrical stimulation training system for upper-limb function recovery in poststroke patients.

BACKGROUND: This paper describes the design and test of an automated functional electrical stimulation (FES) system for poststroke rehabilitation training. The aim of automated FES is to synchronize electrically induced movements to assist residual movements of patients. METHODS: In the design of the FES system, an accelerometry module detected movement initiation and movement performed by post-stroke patients. The desired movement was displayed in visual game module. Synergy-based FES patterns were formulated using a normal pattern of muscle synergies from a healthy subject. Experiment 1 evaluated how different levels of trigger threshold or timing affected the variability of compound movements for forward reaching (FR) and lateral reaching (LR). Experiment 2 explored the effect of FES duration on compound movements. RESULTS: Synchronizing FES-assisted movements with residual voluntary movements produced more consistent compound movements. Matching the duration of synergy-based FES to that of patients could assist slower movements of patients with reduced RMS errors. CONCLUSIONS: Evidence indicated that synchronization and matching duration with residual voluntary movements of patients could improve the consistency of FES assisted movements. Automated FES training can reduce the burden of therapists to monitor the training process, which may encourage patients to complete the training.

The impact of evoked cutaneous afferents on voluntary reaching movement in patients with Parkinson's disease.

OBJECTIVE: Resting tremor may compound the effects of bradykinesia to further prolong the initiation of voluntary movement in patients with Parkinson's disease (PD). However, the interaction between resting tremor and voluntary movements in these PD patients has not been well understood. Recently, we demonstrated that cutaneous afferents evoked by surface stimulation of superficial radial nerve can inhibit resting tremor effectively. The inhibition appears to take effect via spinal interneuronal pathways. This study evaluates how evoked cutaneous afferents would impact the performance of voluntary movements in PD subjects when tremor is inhibited. APPROACH: Ten PD patients with tremor and eight age-matched control subjects were recruited to participate in this study. Both groups of subjects performed fast reaching movements, while cutaneous stimulation was delivered during reaching tasks on or off randomly. Kinematic performance, such as reaction time (RT), movement time (MT), and movement variability, as well as muscle synergy of tasks were evaluated and compared to assess the impact of evoked cutaneous afferents on movement performances. MAIN RESULTS: Results indicated that the cutaneous stimulation significantly reduced RT in PD patients by 17.7%; but had an insignificant effect on RT in control subjects. Cutaneous stimulation, however, caused a significantly longer MT both in control subjects (8.6%) and in PD subjects (15.7%). Movement variability was not significantly altered in both groups of subjects by the cutaneous stimulation. Muscle synergy analysis revealed that cutaneous stimulation affected the power spectral densities (PSD) of time profiles of muscle synergies more significantly than the vector patterns of synergies in both control subjects and PD subjects. SIGNIFICANCE: These findings provide evidence that tremor increases the RT of voluntary motor control in PD patients, and demonstrate that cutaneous stimulation reduces the RT of voluntary movements significantly, in addition to suppressing tremor, yet without interrupting voluntary control of movements.

Synergy-Based FES for Post-Stroke Rehabilitation of Upper-Limb Motor Functions.

Functional electrical stimulation (FES) is capable of activating muscles that are under-recruited in neurological diseases, such as stroke. Therefore, FES provides a promising technology for assisting upper-limb motor functions in rehabilitation following stroke. However, the full benefits of FES may be limited due to lack of a systematic approach to formulate the pattern of stimulation. Our preliminary work demonstrated that it is feasible to use muscle synergy to guide the generation of FES patterns.In this paper, we present a methodology of formulating FES patterns based on muscle synergies of a normal subject using a programmable multi-channel FES device. The effectiveness of the synergy-based FES was tested in two sets of experiments. In experiment one, the instantaneous effects of FES to improve movement kinematics were tested in three patients post ischemic stroke. Patients performed frontal reaching and lateral reaching tasks, which involved coordinated movements in the elbow and shoulder joints. The FES pattern was adjusted in amplitude and time profile for each subject in each task. In experiment two, a 5-day session of intervention using synergy-based FES was delivered to another three patients, in which patients performed task-oriented training in the same reaching movements in one-hour-per-day dose. The outcome of the short-term intervention was measured by changes in Fugl-Meyer scores and movement kinematics. Results on instantaneous effects showed that FES assistance was effective to increase the peak hand velocity in both or one of the tasks. In short-term intervention, evaluations prior to and post intervention showed improvements in both Fugl-Meyer scores and movement kinematics. The muscle synergy of patients also tended to evolve towards that of the normal subject. These results provide promising evidence of benefits using synergy-based FES for upper-limb rehabilitation following stroke. This is the first step towards a clinical protocol of applying FES as therapeutic intervention in stroke rehabilitation.

A Novel FES Strategy for Poststroke Rehabilitation Based on the Natural Organization of Neuromuscular Control.

The past decades have witnessed remarkable progress in neural technologies such as functional electrical stimulation (FES) and their applications in neurorehabilitation and neuromodulation. These advances are powered by new neuroscientific understandings of the organization and compositionality of neuromuscular control illuminating how muscle groups may be activated together as discrete units known as muscle synergies. These parallel developments have promoted novel approaches to clinical rehabilitation for neurological disorders that are insurmountable to current treatments. One such breakthrough is the evolution of FES as a therapeutic tool in poststroke rehabilitation with an interventional strategy particularly inspired by the concept that muscles in humans may be purposefully coordinated through neuromotor modules represented as muscle synergies. This paper will review recent advances in multichannel FES technology, its potential applications in poststroke rehabilitation, new findings that support the neurological basis of the muscle synergies for generating natural motor tasks, and the application of the muscle-synergy concept in poststroke assessment and rehabilitation of motor impairment. Finally, we will recommend future directions of development in relation to assistive FES and synergy-driven adaptive training for poststroke rehabilitation.

Customization of Synergy-Based FES for Post-Stroke Rehabilitation of Upper-Limb Motor Functions.

Functional Electrical Stimulation (FES) provides a promising technology for rehabilitation of upper-limb motor functions following stroke. It enables activation of individual muscles to assist restoration of impaired muscle synergies toward normal patterns. However, there lacks a systematic approach to optimize the FES stimulation patterns delivered to patients with stroke. Our preliminary work demonstrated that it is feasible to use muscle synergy patterns to guide the generation of FES patterns. Here, we present the methodology of customizing synergy-based FES using parameterized formulae with three strategies: weight-sensitive, variability-sensitive, and duration-sensitive. Each of them is comprised of two parameter sets, which represent different directions of parameter search. Two patients with ischemic stroke were recruited to participate in the preliminary test of these strategies. Preliminary results indicate that all strategies could increase the peak velocity in reaching movements, but only the "variability-sensitive" strategy restrained unwanted shoulder excursions. This pilot study demonstrates the feasibility to explore in the parameter space the directions, along which the clinical benefit of synergy-based FES can be tracked and continuously optimized.

Inhibition of Parkinsonian tremor with cutaneous afferent evoked by transcutaneous electrical nerve stimulation.

BACKGROUND: Recent study suggests that tremor signals are transmitted by way of multi-synaptic corticospinal pathway. Neurophysiological studies have also demonstrated that cutaneous afferents exert potent inhibition to descending motor commands by way of spinal interneurons. We hypothesize in this study that cutaneous afferents could also affect the transmission of tremor signals, thus, inhibit tremor in patients with PD. METHODS: We tested this hypothesis by activating cutaneous afferents in the dorsal hand skin innervated by superficial radial nerve using transcutaneous electrical nerve stimulation (TENS). Eight patients with PD having tremor dominant symptom were recruited to participate in this study using a consistent experimental protocol for tremor inhibition. Resting tremor and electromyogram (EMG) of muscles in the upper extremity of these subjects with PD were recorded, while surface stimulation was applied to the dorsal skin of the hand. Fifteen seconds of data were recorded for 5 s prior to, during and post stimulation. Power spectrum densities (PSDs) of tremor and EMG signals were computed for each data segment. The peak values of PSDs in three data segments were compared to detect evidence of tremor inhibition. RESULTS: At stimulation intensity from 1.5 to 1.75 times of radiating sensation threshold, apparent suppressions of tremor at wrist, forearm and upper arm and in the EMGs were observed immediately at the onset of stimulation. After termination of stimulation, tremor and rhythmic EMG bursts reemerged gradually. Statistical analysis of peak spectral amplitudes showed a significant difference in joint tremors and EMGs during and prior to stimulation in all 8 subjects with PD. The average percentage of suppression was 61.56% in tremor across all joints of all subjects, and 47.97% in EMG of all muscles. The suppression appeared to occur mainly in distal joints and muscles. There was a slight, but inconsistent effect on tremor frequency in the 8 patients with PD tested. CONCLUSIONS: Our results provide direct evidence that tremor in the upper extremity of patients with PD can be inhibited to a large extent with evoked cutaneous reflexes via surface stimulation of the dorsal hand skin area innervated by the superficial radial nerve.

Development of network-based multichannel neuromuscular electrical stimulation system for stroke rehabilitation.

Neuromuscular electrical stimulation (NMES) is a promising assistive technology for stroke rehabilitation. Here we present the design and development of a multimuscle stimulation system as an emerging therapy for people with paretic stroke. A network-based multichannel NMES system was integrated based on dual bus architecture of communication and an H-bridge current regulator with a power booster. The structure of the system was a body area network embedded with multiple stimulators and a communication protocol of controlled area network to transmit muscle stimulation parameter information to individual stimulators. A graphical user interface was designed to allow clinicians to specify temporal patterns and muscle stimulation parameters. We completed and tested a prototype of the hardware and communication software modules of the multichannel NMES system. The prototype system was first verified in nondisabled subjects for safety, and then tested in subjects with stroke for feasibility with assisting multijoint movements. Results showed that synergistic stimulation of multiple muscles in subjects with stroke improved performance of multijoint movements with more natural velocity profiles at elbow and shoulder and reduced acromion excursion due to compensatory trunk rotation. The network-based NMES system may provide an innovative solution that allows more physiological activation of multiple muscles in multijoint task training for patients with stroke.

Characterization of evoked tactile sensation in forearm amputees with transcutaneous electrical nerve stimulation.

OBJECTIVE: The goal of this study is to characterize the phenomenon of evoked tactile sensation (ETS) on the stump skin of forearm amputees using transcutaneous electrical nerve stimulation (TENS). APPROACH: We identified the projected finger map (PFM) of ETS on the stump skin in 11 forearm amputees, and compared perceptual attributes of the ETS in nine forearm amputees and eight able-bodied subjects using TENS. The profile of perceptual thresholds at the most sensitive points (MSPs) in each finger-projected area was obtained by modulating current amplitude, pulse width, and frequency of the biphasic, rectangular current stimulus. The long-term stability of the PFM and the perceptual threshold of the ETS were monitored in five forearm amputees for a period of 11 months. MAIN RESULTS: Five finger-specific projection areas can be independently identified on the stump skin of forearm amputees with a relatively long residual stump length. The shape of the PFM was progressively similar to that of the hand with more distal amputation. Similar sensory modalities of touch, pressure, buzz, vibration, and numb below pain sensation could be evoked both in the PFM of the stump skin of amputees and in the normal skin of able-bodied subjects. Sensory thresholds in the normal skin of able-bodied subjects were generally lower than those in the stump skin of forearm amputees, however, both were linearly modulated by current amplitude and pulse width. The variation of the MSPs in the PFM was confined to a small elliptical area with 95% confidence. The perceptual thresholds of thumb-projected areas were found to vary less than 0.99 × 10(-2) mA cm(-2). SIGNIFICANCE: The stable PFM and sensory thresholds of ETS are desirable for a non-invasive neural interface that can feed back finger-specific tactile information from the prosthetic hand to forearm amputees.

Design of a high voltage stimulator chip for a stroke rehabilitation system.

This paper describes the design of an 8-channel high voltage stimulator chip for rehabilitation of stroke patients through surface stimulation, which requires high stimulation currents and high compliance voltage. The chip gets stimulation control data through its Serial Peripheral Interface (SPI), and can accordingly generate biphasic stimulation currents with different amplitudes, duration, frequencies and polarities independently for each channel. The current driver is implemented with thick oxide devices with a supply voltage up to 90V. The chip is designed in a 0.35εm X-FAB high voltage process.

Effects of acute sacral neuromodulation on bladder reflex in complete spinal cord injury rats.

BACKGROUND: Neurogenic bladder associated with spinal cord injury (SCI) often results in serious disruption of lower urinary tract function. Compared to conventional therapies, sacral neuromodulation (SNM) may offer an alternative, non-destructive treatment for SCI patients with bladder dysfunction. Understanding bladder reflex changes following SCI and the effects of SNM may yield new insights for innovative use of this promising technique. Using a SCI rat model developed in this study, we investigated: 1) the bladder responses with different grades of bladder filling in intact and SCI rats; and 2) the effects of acute SNM on bladder reflex responses in SCI rats. METHODS: An SCI rat model with overactive bladder was developed and evaluated in this study to examine the effects of acute SNM on bladder reflex in complete SCI rats. Twelve adult female Sprague-Dawley rats were divided into three groups; group I: spinally intact rats (N = 4), group II: transected (T9-T10) rats (N = 4), i.e., SCI rats, and group III: SCI rats with SNM treatment (N = 4). All rats were anesthetized and set up for continuous saline infusion. Cystometric parameters, including contraction period, contraction duration, bladder peak pressure, and number of uninhibited contractions, were analyzed and compared between groups and between conditions with and without SNM treatment for SCI rats. RESULTS: In the intact rats, the frequency of bladder contraction was dependent upon the rate of bladder filling, while the spinal transected rats exhibited large fluctuation and demonstrated different patterns in response to saline infusion. Moreover, the bladder in SCI rats demonstrated an increased contraction period and a decreased contraction strength compared to the intact rats (all p < 0.05). In SCI rats under acute SNM treatment, bladder contraction period and duration tended to become longer, and the bladder peak pressure was decreased. The accumulating evidence indicated that acute SNM had inhibiting effects for bladder overactivity following SCI. CONCLUSION: The spinal rat model developed in this study was suitable to investigate the effect of sacral neural stimulation on micturition reflex. The results of present study demonstrated that the micturition reflex can be modulated by sacral neural stimulation.

Nuclear translocation of calpain-2 regulates propensity toward apoptosis in cardiomyocytes of tail-suspended rats.

The compensatory increase in catecholamine release does not reverse orthostatic intolerance after returning from a long-term spaceflight, but it is unclear whether high dose of catecholamine induces cardiac damage. The tail-suspended rat model was used to simulate the effects of weightlessness on the heart. Apoptotic rates in the left ventricular myocardium did not increase in 4-week of tail-suspended rats compared with the synchronous control. On the contrary, isoproterenol (intraperitoneal injection) and 1-day recovery from the 4-week tail-suspension increased apoptotic rates in the myocardium. Propranolol and PD150606 inhibited cardiomyocyte apoptosis in the recovery group. PD150606 and calpain-2 knockdown also blocked isoproterenol-induced cardiomyocyte apoptosis in tail-suspended rats. The activity and nuclear translocation of calpain-2 increased, but the expression of calpain-1, calpain-2, and calpastatin was unchanged in the myocardium of tail-suspended rats. The Ser-16-phosphorylated phospholamban of the nuclear envelope was higher in tail-suspended rats than in the control rats under isoproterenol stimulation. Isoproterenol treatment also induced a large intranuclear Ca(2+) transient of cardiomyocytes in tail-suspended rats. These results suggest that high-dose isoproterenol phosphorylates phospholamban of the nuclear envelope and increases intranuclear Ca(2+) transient. Larger intranuclear Ca(2+) further activates nuclear calpain-2 and hence induces cardiomyocyte apoptosis.

Expression of ghrelin and its receptor GHS-R in the hypothalamus and gastrointestinal tract in rats with chronic renal failure / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of ghrelin and its receptor, growth hormone secretagogue receptor (GHS-R), in the hypothalamus and gastrointestinal tract in rats with chronic renal failure (CRF) and explore their relationship with the disorder of gastrointestinal tract motility.</p><p><b>METHODS</b>SD rats were randomly divided into sham-operated group (n=8) and CRF group (n=16), and in the latter group, the rats were subjected to 5/6 nephrectomy to induce CRF. Real-time PCR and immunohistochemical staining were used to detect the distribution of mRNA and protein of ghrelin and GHS-R in the gastric fundus, duodenum, and hypothalamus.</p><p><b>RESULTS</b>The rats in the CRF group showed a significantly higher expression of ghrelin mRNA and protein in the gastric fundus but a lower expression in the hypothalamus than those in the sham-operated group (P<0.01), but the expression in the duodenum was similar between the two groups (P>0.05). The expression of GHS-R mRNA and protein in the gastric fundus was significantly higher in the CRF group than in the sham-operated group (P<0.01), while in the hypothalamus and duodenum, the expression was significantly lower in the CRF group (P<0.01).</p><p><b>CONCLUSION</b>The different distribution patterns of ghrelin and GHS-R in the tissues may be an important pathological basis of gastrointestinal motility disorder in CRF.</p>

Stability analysis for postural control in a two-joint limb system.

The stability behavior of a multi-joint limb with electrically activated muscles provides important clues for postural control of motor tasks. The stability property of the musculoskeletal system can be characterized with its eigenvalues evaluated at operating postures in the workspace. A planar arm model with shoulder and elbow joints and three pairs of antagonistic muscles was constructed in ADAMS. Stability behavior of shoulder and elbow joints was analyzed using the loci of eigenvalues in the s-plane. In the analysis of open-loop cocontraction of antagonist muscles with increasing activation from 5% to 100%, the eigenvalues of the shoulder and elbow joints were confined within the left half of the s-plane in a stripe of +/- j 0.5, and moved toward left onto the real axis. The shoulder eigenvalues were generally nearer to the imaginary axis than the elbow ones, indicating a more oscillatory behavior at the shoulder joint than that at the elbow joint. The effects of joint configuration evaluated within the workspace from 40 degrees to 110 degrees for the elbow and from 40 degrees to 120 degrees for the shoulder showed that the elbow eigenvalues were more prone to configuration changes, particularly elbow angles. We also developed a simulation paradigm for sampled data FES control systems that contain a mixture of continuous time components and sampling and hold effects. This simulation paradigm is useful for realistic simulation of local feedback controller performance.