The use of potential biasing and biphasic, asymmetric current pulse waveforms to maximize the charge-injection capacity of activated iridium oxide (AIROF) microelectrodes used for neural stimulation ...is described. The waveforms retain overall zero net charge for the biphasic pulse, but employ an asymmetry in the current and pulse widths of each phase, with the second phase delivered at a lower current density for a longer period of time than the leading phase. This strategy minimizes polarization of the AIROF by the charge-balancing second phase and permits the use of a more positive anodic bias for cathodal-first pulsing or a more negative cathodic bias for anodal-first pulsing to maximize charge injection. Using 0.4-ms cathodal-first pulses, a maximum charge-injection capacity of 3.3 mC/cm/sup 2/ was obtained with an 0.6-V bias (versus Ag|AgCl) and a pulse asymmetry of 1:8 in the cathodal and anodal pulse widths. For anodal-first pulsing, a maximum charge capacity of 9.6 mC/cm/sup 2/ was obtained with an asymmetry of 1:3 at an 0.1-V bias. These measurements were made in vitro in carbonate-buffered saline using microelectrodes with a 2000 /spl mu/m/sup 2/ surface area.
Multi-site studies in stroke rehabilitation are important for determining whether a technology and/or treatment can be successfully administered by sites other than the originating site and with ...similar positive outcomes. This study is the first multi-site clinical trial of a novel intervention for post-stroke upper limb rehabilitation called contralaterally controlled functional electrical stimulation (CCFES). Previous pilot and single-site studies showed positive effects of CCFES on upper limb impairment and hand dexterity in stroke survivors. The main purpose of this study is to confirm and demonstrate the efficacy of CCFES in a larger group of most likely responders across multiple clinical sites.
Up to 129 stroke survivors with moderate to severe upper extremity hemiparesis at 4 clinical trial sites will be randomized to CCFES, cyclic neuromuscular electrical stimulation (cNMES), or task-oriented-training (TOT). Participants will receive 12 weeks of group-specific therapy. Blinded assessments of upper limb impairment and activity limitation, quality of life, and neurophysiology will be used to compare outcomes at baseline, after treatment, and up to 6 months post-treatment. The primary endpoint is change in dexterity from baseline to 6 months post-treatment.
Loss of hand function following stroke is a major rehabilitation problem affecting millions of people per year globally. More effective rehabilitation therapies are needed to restore hand function in these individuals. This study will determine whether CCFES therapy produces greater improvements in upper extremity function than cNMES or TOT, and will begin to elucidate the different mechanisms underlying each of the three treatments. This multi-site study is a critical step in advancing a novel method of rehabilitation toward clinical translation and widespread dissemination.
ClinicalTrials.gov NCT03574623 . Registered prior to first enrollment; July 2, 2018.
Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate ...their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing cholinergic interneurons with simultaneous detection of dopamine release at carbon-fiber microelectrodes in striatal slices. We reveal that activation of cholinergic interneurons by light flashes that cause only single action potentials in neurons from a small population triggers dopamine release via activation of nicotinic receptors on dopamine axons. This event overrides ascending activity from dopamine neurons and, furthermore, is reproduced by activating ChR2-expressing thalamostriatal inputs, which synchronize cholinergic interneurons in vivo. These findings indicate that synchronized activity in cholinergic interneurons directly generates striatal dopamine signals whose functions will extend beyond those encoded by dopamine neuron activity.
► Striatal ACh input to dopamine axons directly evokes dopamine release via nAChRs ► DA release is triggered by synchrony amongst cholinergic interneurons (ChIs) ► ChI-driven DA release overrides ascending input from dopamine neurons ► ACh interneurons and their inputs are potential targets for treatment of DA disorders
Dopamine neuron activity is assumed to be the principal driver of striatal dopamine release. Here, Threlfell et al. reveal that activity in a group of striatal interneurons or their thalamic inputs powerfully drives dopamine release from axons, bypassing dopamine neurons.
Muscle atrophy and deconditioning are common complications in patients on prolonged mechanical ventilation (PMV). There are few studies that reviewed the effects of electrical muscle stimulation in ...this population. The purpose of this study was to examine the effects of electrical muscle stimulation on muscle function and hospitalization outcomes in subjects with PMV.
Subjects on mechanical ventilation for ≥21 d were randomly assigned to the electrical muscle stimulation group (
= 16) or the control group (
= 17). The electrical muscle stimulation group received daily muscle electrical stimulation for 30 min/session for 10 d. The measurement of muscle strength (by medical research council MRC scale), leg circumference, and physical functional status (by Functional Independence Measure FIM scores) were performed before and after completion of the study. The length of stay in respiratory care center of subjects were recorded.
After electrical muscle stimulation, there was no difference in pulmonary function between the electrical muscle stimulation and control groups. Significantly increased in MRC points was found in the electrical muscle stimulation group after intervention (2 1-7 points vs 2 1-3.5 points, respectively,
= .034). No difference in MRC points was found between baseline and post-measurement in the control group (11-2 points vs 11-2.5 points, respectively,
> .99). At the end of the study, leg circumference in control group significantly decreased when compared with baseline (47.5 ± 8.3 cm vs 44.6 ± 5.7 cm, respectively,
= .004) and remained unchanged in the EMS group. However, no significant differences were found between the electrical muscle stimulation and control groups. There was no difference in physical functional status and hospital stay between the electrical muscle stimulation and control groups.
Electrical muscle stimulation enhanced muscle strength in subjects who received PMV. Electrical muscle stimulation can be considered a preventive strategy for muscle weakness in patients who receive PMV. (ClinicalTrials.gov registration NCT02227810.).
Purpose We report the long-term efficacy and safety of percutaneous tibial nerve stimulation with the Urgent® PC Neuromodulation System for overactive bladder after 3 years of therapy. Materials and ...Methods Fifty participants in the randomized, double-blind SUmiT (Sham Effectiveness in Treatment of Overactive Bladder Symptoms) Trial who met the primary effectiveness end point after 12 weekly percutaneous tibial nerve stimulation treatments were enrolled in this prospective study to assess long-term outcomes with percutaneous tibial nerve stimulation. STEP (Sustained Therapeutic Effects of Percutaneous Tibial Nerve Stimulation) Study patients were prescribed a fixed schedule 14-week tapering protocol followed by a personal treatment plan aimed at sustaining overactive bladder symptom improvement. Overactive bladder and quality of life questionnaires were completed every 3 months and 3-day voiding diaries were completed every 6 months. Results A total of 29 patients completed the 36-month protocol and received a median of 1.1 treatments per month after a 14-week treatment tapering protocol. A Bayesian model estimated that 77% (95% CI 64–90) of patients maintained moderate or marked improvement in overactive bladder symptoms at 3 years. Compared to baseline, median voids per day decreased from 12.0 (IQR 10.3–13.7) to 8.7 (IQR 7.3–11.3), nighttime voids per night decreased from 2.7 (IQR 1.7–3.3) to 1.7 (IQR 1.0–2.7) and urge incontinence episodes per day decreased from 3.3 (IQR 0.7–6.0) to 0.3 (IQR 0.0–1.0) (all p <0.0001). All quality of life parameters remained markedly improved from baseline through 3 years (all p <0.0001). One patient experienced 2 mild treatment related adverse events of bleeding at the needle site during followup. Conclusions Most STEP participants with an initial positive response to 12 weekly percutaneous tibial nerve stimulation treatments safely sustained overactive bladder symptom improvement to 3 years with an average of 1 treatment per month.
To study the possible predictive value of drug-induced sleep endoscopy (DISE) in assessing therapeutic response to implanted upper airway stimulation (UAS) for obstructive sleep apnea (OSA).
During ...DISE, artificial sleep is induced by midazolam and/or propofol, and the pharyngeal collapse patterns are visualized using a flexible fiberoptic nasopharyngoscope. The level (palate, oropharynx, tongue base, hypopharynx/epiglottis), the direction (anteroposterior, concentric, lateral), and the degree of collapse (none, partial, or complete) were scored in a standard fashion.
We report on the correlation between DISE results and therapy response in 21 OSA patients (apnea-hypopnea index AHI 38.5 ± 11.8/h; body mass index BMI 28 ± 2 kg/m(2), age 55 ± 11 y, 20 male/1 female) who underwent DISE before implantation of a UAS system. Statistical analysis revealed a significantly better outcome with UAS in patients (n = 16) without palatal complete concentric collapse (CCC), reducing AHI from 37.6 ± 11.4/h at baseline to 11.1 ± 12.0/h with UAS (p < 0.001). No statistical difference was noted in AHI or BMI at baseline between the patients with and without palatal CCC. In addition, no predictive value was found for the other DISE collapse patterns documented.
The absence of palatal CCC during DISE may predict therapeutic success with implanted UAS therapy. DISE can be recommended as a patient selection tool for implanted UAS to treat OSA.
Epiretinal prostheses aim at electrically stimulating the inner most surviving retinal cells-retinal ganglion cells (RGCs)-to restore partial sight to the blind. Recent tests in patients with ...epiretinal implants have revealed that electrical stimulation of the retina results in the percept of color of the elicited phosphenes, which depends on the frequency of stimulation. This paper presents computational results that are predictive of this finding and further support our understanding of the mechanisms of color encoding in electrical stimulation of retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. This provides, for the first time, a directly applicable "amplitude-frequency" stimulation strategy to "encode color" in future retinal prosthetics through a predictive computational tool to selectively target small bistratified cells, which have been shown to contribute to "blue-yellow" color opponency in the retinal circuitry. The presented results are validated with experimental data reported in the literature and correlated with findings in blind patients with a retinal prosthetic implant collected by our group.
The study aim was to identify and analyze intramuscular electrically sensitive points. Electrically sensitive points are herein defined as positions, which allow muscles stimulation with a minimum ...possible fatigue for a maximum amount of time. A multichannel array electrode was used which could be interesting to retain the function of larynx muscle after paralysis. Eight array electrodes were implanted in the triceps brachii muscle of four rats. While being under anesthesia, the animals were intramuscularly stimulated at 16 different positions. Sihler’s staining technique was used to make visible the nerves routes and the intramuscular position of the individual electrode plate. The positions of the motor end plates were determined by means of multichannel-electromyography. The positions that allow longest stimulation periods are located close to the points where the nerves enter the muscle. Stimulation at the position of the motor end plates does not result in stimulation periods above average. Locations initially causing strong muscle contractions are not necessarily identical to the ones allowing long stimulation periods. The animal model identified the stimulation points for minimal possible muscle fatigue stimulation as being located close to the points of entrance of the nerve into the muscle. Stimulation causing an initially strong contraction response is no indication of optimal location of the stimulation electrode in terms of chronic stimulation. The array electrode of this study could be interesting as a stimulation electrode for a larynx pacemaker.
•The mechanism of electro-synthesis with neutral red in E. coli was identified.•Neutral red reduces menaquinone in the inner membrane.•Resulting menaquinol drives anaerobic respiration with multiple ...electron acceptors.•Sans electron acceptor, menaquinol reduces the arcB redox sensor.•Reduced arcB causes transcriptional changes that alter metabolite profiles.
The aim of this work was to elucidate the mechanism of mediated microbial electrosynthesis via neutral red from an electrode to fermenting Escherichia coli cultures in a bioelectrochemical system. Chemical reduction of NAD+ by reduced neutral red did not occur as predicted. Instead, neutral red was shown to reduce the menaquinone pool in the inner bacterial membrane. The reduced menaquinone pool altered fermentative metabolite production via the arcB redox-sensing cascade in the absence of terminal electron acceptors. When the acceptors DMSO, fumarate, or nitrate were provided, as many as 19% of the electrons trapped in the reduced acceptors were derived from the electrode. These results demonstrate the mechanism of neutral red-mediated microbial electrosynthesis during fermentation as well as how neutral red enables microbial electrosynthesis of reduced terminal electron acceptors.
Sacral neuromodulation (SNM) is a well-established treatment for overactive bladder (OAB) and non-obstructive urinary retention (NOR). During test stimulation, the lead is positioned along the third ...sacral nerve, which ideally results in a response in all four contact points (active electrodes). However, it is unclear whether the position of the lead (depth, angle, deflection) and the number of active electrodes is related to the outcome of SNM.
All patients who underwent test stimulation using the tined lead between January 2011 and September 2016 were included in this retrospective study. Success was defined as >50% improvement in voiding diary parameters compared to baseline. The correlation between lead position and outcome of test stimulation was evaluated. The lead position was determined by evaluating the depth, angle and deflection with respect to the sacral foramen. Binary logistic regression was used in order to determine the predictive value of these factors.
We included 189 patients of whom 105 were diagnosed with OAB and 84 with NOR. After a SNM test period of 4 weeks, 111 patients (59%) were successful and received a permanent implant. The position of the lead and the number of active electrodes did not predict success of test stimulation in neither the OAB group nor the NOR. However, lateral deflection of the lead was associated with finding more active electrodes (p = 0.01).
In our study, the position of the lead or the number of active electrodes did not predict the outcome of SNM test stimulation. However, the impact of lead positioning and number of active electrodes on long-term outcome remains to be proven.
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