Novel Electrode Designs for Electrotactile Stimulation of the Finger: A Comparative Assessment.

Electrotactile stimulation can be an attractive technology to restore tactile feedback in different application scenarios (e.g., virtual and augmented reality, tele-manipulation). This technology allows designing compact solutions with no mechanical elements that can integrate a high-density matrix of stimulation points. The present study introduced four novel multi-pad finger-electrode designs with different arrangements (two matrix and two circular) and shapes of active pads (producing sensation) and reference pads (ideally, no sensation produced below the pad). The electrodes were used to investigate the subjects' ability to spatially discriminate active pads within phalanges individually (6-9 pads) as well as across the full finger (18-19 pads). The tests were conducted in 12 subjects and the results showed that all designs led to high success rates when applied to the fingertip (70-81%). When tested on the full finger, the matrix and circular designs were characterized with similar performance (54-57%), and when the phalanges were analyzed individually, the spatial discrimination was best at the fingertip. Additionally, new approaches for faster amplitude calibration were proposed and tested, demonstrating that calibration duration can be reduced by approximately 40% compared to the standard approach of calibrating single pads individually. Finally, discrimination tests of dynamic tactile patterns were conducted using circular and matrix designs on the fingertip and full finger, respectively. The tests showed that the different patterns generated by the two arrangements could be clearly discriminated, especially in the case of full-finger matrix-style patterns. The present study, therefore, provides several important insights that are relevant when delivering tactile feedback to the finger using an electrotactile interface.

Optimization of Protocols Using Neuromuscular Electrical Stimulation for Paralyzed Lower-Limb Muscles to Increase Energy Expenditure in People With Spinal Cord Injury.

OBJECTIVE: The aim of this study was to evaluate whether using surface neuromuscular electrical stimulation (NMES) for paralyzed lower-limb muscles results in an increase in energy expenditure and whether the number of activated muscles and duty cycle affect the potential increase. DESIGN: This was a cross-sectional study. RESULTS: Energy expenditure during all NMES protocols was significantly higher than the condition without NMES (1.2 ± 0.2 kcal/min), with the highest increase (+51%; +0.7 kcal/min, 95% confidence interval, 0.3-1.2) for the protocol with more muscles activated and the duty cycle with a shorter rest period. A significant decrease in muscle contraction size during NMES was found with a longer stimulation time, more muscles activated, or the duty cycle with a shorter rest period. CONCLUSION: Using NMES for paralyzed lower-limb muscles can significantly increase energy expenditure compared with sitting without NMES, with the highest increase for the protocol with more muscles activated and the duty cycle with a shorter rest period. Muscle fatigue occurred significantly with the more intense NMES protocols, which might cause a lower energy expenditure in a longer protocol. Future studies should further optimize the NMES parameters and investigate the long-term effects of NMES on weight management in people with SCI.

Assessment of neuromuscular electrical stimulation effect on contralateral quadriceps muscle.

BACKGROUND: In the field of rehabilitation, the acute application of neuromuscular electrical stimulation (NMES) causes not only peripheral muscle contraction but also involve the central nervous system by the transient increase in spinal motor neuron and cortical activity. Therefore it has been used in several fields of rehabilitation. Previous studies used surface electromyography to assess this effect. But we conducted our study to assess the effect of NMES on contralateral quadriceps muscle in normal individuals using another method needle electromyography. METHODS: A study carried out on 20 normal males, who were subjected to (i) NMES Training Program for 60 min for the right quadriceps muscle. (ii) Assessment of EMG activity for rectus femoris muscle (RF) on the contralateral side. An assessment was done for minimal volition and maximal volition or interference pattern analysis, this assessment was done twice: before the start of NMES and during the session. RESULTS: EMG of voluntary activity (Minimal volition) and Maximum voluntary activity analysis for RF muscles showed increased duration (in millisecond), amplitude (in millivolt) (P < 0.01), increased activity in turn per second, amplitude/turn (M) (uV) compared to the result before NMES application. CONCLUSION: Our study provides a new evident date that the acute NMES application to the contralateral quadriceps muscles, leads to significant facilitation of the maximal voluntary power in the ipsilateral muscles through activation of efferent neural control. This facilitating effect of motor neurons in the contralateral muscles is likely due to the complex combination interaction between spinal and supraspinal control. TRIAL REGISTRATION: Trial registration: PACTR202010887172053.

Biomechanical Assessment of Post-Stroke Patients' Upper Limb before and after Rehabilitation Therapy Based on FES and VR.

Stroke is a medical condition characterized by the rapid loss of focal brain function. Post-stroke patients attend rehabilitation training to prevent the degeneration of physical function and improve upper limb movements and functional status after stroke. Promising rehabilitation therapies include functional electrical stimulation (FES), exergaming, and virtual reality (VR). This work presents a biomechanical assessment of 13 post-stroke patients with hemiparesis before and after rehabilitation therapy for two months with these three methods. Patients performed two tests (Maximum Forward Reach and Apley Scratching) where maximum angles, range of motion, angular velocities, and execution times were measured. A Wilcoxon test was performed (p = 0.05) to compare the variables before and after the therapy for paretic and non-paretic limbs. Significant differences were found in range of motion in flexion-extension, adduction-abduction, and internal-external rotation of the shoulder. Increases were found in flexion-extension, 17.98%, and internal-external rotation, 18.12%, after therapy in the Maximum Forward Reach Test. For shoulder adduction-abduction, the increase found was 20.23% in the Apley Scratching Test, supporting the benefits of rehabilitation therapy that combines FES, exergaming, and VR in the literature.

Assessment of sacral spinal excitability using stimulus-response curves of the bulbocavernosus reflex.

OBJECTIVE: To analyze and quantify sacral spinal excitability through bulbocavernosus reflex (BCR) stimulus-response curves. METHODS: Thirty subjects with upper motor neuron lesions (UMN) and nine controls were included in this prospective, monocentric study. Sacral spinal excitability was assessed using stimulus-response curves of the BCR, modeled at different bladder filling volumes relative to the desire to void (as defined by the International Continence Society) during a cystometry. Variations in α (i.e. the slope of the stimulus-response curve) were considered as an indicator of the modulation of sacral spinal excitability. RESULTS: In all subjects, α increased during bladder filling suggesting the modulation of spinal sacral excitability during the filling phase. This increase was over 30% in 96.7% of neurological subjects and 88.9% of controls. The increase was higher before the first sensation to void in the neurological population (163.15%), compared to controls, (29.91%), p < 0.001. CONCLUSIONS: We showed the possibility of using BCR stimulus-response curves to characterize sacral spinal response with an amplification of this response during bladder filling as well as a difference in this response amplification in patients with UMN in comparison with a control group. SIGNIFICANCE: BCR, through stimulus-response curves, might be an indicator of pelvic-perineal exaggerated reflex response and possibly a tool for evaluating treatment effectiveness.

Protocolo Clínico e Diretrizes Terapêuticas da miastenia gravis / Clinical Protocol and Therapeutic Guidelines for myasthenia gravis

CONTEXTO: Os PCDT são documentos que visam garantir o melhor cuidado de saúde diante do contexto brasileiro e dos recursos disponíveis no SUS. Podem ser utilizados como materiais educativos aos profissionais de saúde, auxílio administrativo aos gestores, regulamentação da conduta assistencial perante o Poder Judiciário e explicitação de direitos aos usuários do SUS. Os PCDT são os documentos oficiais do SUS que estabelecem critérios para o diagnóstico de uma doença ou agravo à saúde; tratamento preconizado, com os medicamentos e demais produtos apropriados, quando couber; posologias recomendadas; mecanismos de controle clínico; e acompanhamento e verificação dos resultados terapêuticos a serem seguidos pelos gestores do SUS. Os PCDT devem incluir recomendações de condutas, medicamentos ou produtos para as diferentes fases evolutivas da doença ou do agravo à saúde de que se tratam, bem como aqueles indicados em casos de perda de eficácia e de surgimento de intolerância ou reação adversa relevante, provocadas pelo medicamento, produto ou procedimento de primeira escolha. A lei reforçou a análise baseada em evidências científicas para a elaboração dos protocolos, destacando os critérios de eficácia, segurança, efetividade e custo-efetividade para a formulação das recomendações sobre intervenções em saúde. Para a constituição ou alteração dos PCDT, a Portaria GM n° 2.009 de 2012 instituiu na Conitec uma Subcomissão Técnica de Avaliação de PCDT, com as competências de definir os temas para novos protocolos, acompanhar sua elaboração, avaliar as recomendações propostas e as evidências científicas apresentadas, além da revisão periódica dos PCDT vigentes, em até dois anos. A Subcomissão Técnica de Avaliação de PCDT é composta por representantes de Secretarias do Ministério da Saúde interessadas na elaboração de diretrizes clínicas: Secretaria de Atenção Primária à Saúde, Secretaria de Atenção Especializada à Saúde, Secretaria de Vigilância em Saúde, Secretaria Especial de Saúde Indígena e Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Após concluídas as etapas de definição do tema e escopo do PCDT, de busca, seleção e análise de evidências científicas e consequente definição das recomendações, a aprovação do texto é submetida à apreciação do Plenário da Conitec, com posterior disponibilização deste documento para contribuição de sociedade, por meio de consulta pública (CP) pelo prazo de 20 dias, antes da deliberação final e publicação. A consulta pública é uma importante etapa de revisão externa dos PCDT. O Plenário da Conitec é o fórum responsável pelas recomendações sobre a constituição ou alteração de PCDT, além dos assuntos relativos à incorporação, exclusão ou alteração das tecnologias no âmbito do SUS, bem como sobre a atualização da Relação Nacional de Medicamentos Essenciais (RENAME). É composto por treze membros, um representante de cada Secretaria do Ministério da Saúde ­ sendo o indicado pela Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) o presidente do Plenário ­ e um representante de cada uma das seguintes instituições: ANVISA, Agência Nacional de Saúde Suplementar - ANS, Conselho Nacional de Saúde - CNS, Conselho Nacional de Secretários de Saúde - CONASS, Conselho Nacional de Secretarias Municipais de Saúde - CONASEMS e Conselho Federal de Medicina - CFM. Cabe à Secretaria-Executiva, exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE), a gestão e a coordenação das atividades da Conitec. Conforme o Decreto n° 7.646 de 2011, o Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde deverá submeter o PCDT à manifestação do titular da Secretaria responsável pelo programa ou ação a ele relacionado antes da sua publicação e disponibilização à sociedade. APRESENTAÇÃO: A proposta de atualização do PCDT de Miastenia Gravis é uma demanda que cumpre o Decreto nº 7.508 de 28 de junho de 2011 e as orientações previstas no artigo 26º e o parágrafo único, sobre a responsabilidade do Ministério da Saúde de atualizar os Protocolos Clínicos e Diretrizes Terapêuticas. Este PCDT apresenta a atualização da versão publicada em 2015, com inclusão do exame complementar de diagnóstico dosagem sérica de anticorpos de acetilcolina (anti-AChR). DELIBERAÇÃO INICIAL: Os membros da Conitec presentes na 88ª Reunião do Plenário, realizada nos dias 07, 08 e 09 de julho de 2020, deliberaram para que o tema fosse submetido à consulta pública com recomendação preliminar favorável à publicação deste Protocolo. CONSULTA PÚBLICA: A Consulta Pública nº 27/2020 foi realizada entre os dias 21 de julho a 10 de agosto de 2020. A seguir é apresentado o resumo da análise das contribuições recebidas, ressaltando-se que foram consideradas apenas as encaminhadas no período estipulado e por meio do sítio eletrônico da Conitec. Os dadosforam avaliados quantitativa e qualitativamente, considerando asseguintes etapas: a) leitura de todas as contribuições, b) identificação e categorização das ideias centrais, e c) discussão acerca das contribuições. Foram recebidas ao todo 34 contribuições. A grande maioria dos participantes (n= 33; 97%) classificou a proposta de PCDT como boa ou muito boa na avaliação geral.

Reliability and agreement of a dynamic quadriceps incremental test for the assessment of neuromuscular function.

The quadriceps-intermittent-fatigue (QIF) test assesses knee extensors strength, endurance and performance fatigability in isometric condition. We aimed to assess reliability and agreement for this test in dynamic conditions and with the use of transcranial magnetic stimulation. On two separate sessions, 20 young adults (25 ± 4 yr, 10 women) performed stages of 100 knee extensors concentric contractions at 120°/s (60° range-of-motion) with 10% increments of the initial maximal concentric torque until exhaustion. Performance fatigability across the test was quantified as maximal isometric and concentric torque loss, and its mechanisms were investigated through the responses to transcranial magnetic and electrical stimulations. Reliability and agreement were assessed using ANOVAs, coefficients of variation (CVs) and intra-class correlation coefficients (ICCs) with 95% CI. Good inter-session reliability and high agreement were found for number of contractions [489 ± 75 vs. 503 ± 95; P = 0.20; ICC = 0.85 (0.66; 0.94); CV = 5% (3; 7)] and total work [11,285 ± 4,932 vs. 11,792 ± 5838 Nm.s; P = 0.20; ICC = 0.95 (0.87; 0.98); CV = 8% (5; 11)]. Poor reliability but high agreement were observed for isometric [-33 ± 6 vs. -31 ± 7%; P = 0.13; ICC = 0.47 (0.05; 0.75); CV = 6% (4;8)] and concentric [-20 ± 11% vs. -19 ± 9%; P = 0.82; ICC = 0.26 (-0.22; 0.63); CV = 9% (6; 12)] torque loss. The dynamic QIF test represents a promising tool for neuromuscular evaluation in isokinetic mode.

Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients: a randomized controlled feasibility study and pooled analysis.

BACKGROUND: Expiratory muscle weakness leads to difficult ventilator weaning. Maintaining their activity with functional electrical stimulation (FES) may improve outcome. We studied feasibility of breath-synchronized expiratory population muscle FES in a mixed ICU population ("Holland study") and pooled data with our previous work ("Australian study") to estimate potential clinical effects in a larger group. METHODS: Holland: Patients with a contractile response to FES received active or sham expiratory muscle FES (30 min, twice daily, 5 days/week until weaned). Main endpoints were feasibility (e.g., patient recruitment, treatment compliance, stimulation intensity) and safety. Pooled: Data on respiratory muscle thickness and ventilation duration from the Holland and Australian studies were combined (N = 40) in order to estimate potential effect size. Plasma cytokines (day 0, 3) were analyzed to study the effects of FES on systemic inflammation. RESULTS: Holland: A total of 272 sessions were performed (active/sham: 169/103) in 20 patients (N = active/sham: 10/10) with a total treatment compliance rate of 91.1%. No FES-related serious adverse events were reported. Pooled: On day 3, there was a between-group difference (N = active/sham: 7/12) in total abdominal expiratory muscle thickness favoring the active group [treatment difference (95% confidence interval); 2.25 (0.34, 4.16) mm, P = 0.02] but not on day 5. Plasma cytokine levels indicated that early FES did not induce systemic inflammation. Using a survival analysis approach for the total study population, median ventilation duration and ICU length of stay were 10 versus 52 (P = 0.07), and 12 versus 54 (P = 0.03) days for the active versus sham group. Median ventilation duration of patients that were successfully extubated was 8.5 [5.6-12.2] versus 10.5 [5.3-25.6] days (P = 0.60) for the active (N = 16) versus sham (N = 10) group, and median ICU length of stay was 10.5 [8.0-14.5] versus 14.0 [9.0-19.5] days (P = 0.36) for those active (N = 16) versus sham (N = 8) patients that were extubated and discharged alive from the ICU. During ICU stay, 3/20 patients died in the active group versus 8/20 in the sham group (P = 0.16). CONCLUSION: Expiratory muscle FES is feasible in selected ICU patients and might be a promising technique within a respiratory muscle-protective ventilation strategy. The next step is to study the effects on weaning and ventilator liberation outcome. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03453944. Registered 05 March 2018-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03453944 .

Mechanomyography-based assessment during repetitive sit-to-stand and stand-to-sit in two incomplete spinal cord-injured individuals.

Standing up and sitting down movements are important prerequisites to achieve functional independence in everyday life of spinal cord injury (SCI) patients. Thus, mechanomyography (MMG) was proposed as a safe monitoring tool to evaluate muscle function performance of these activities. Two incomplete SCI participants performed repetitive sit-to-stand (SitTS) and stand-to-sit (StandTS) until fatigued challenge. Three sets of these activities were completed with MMG sensors attached over the quadriceps muscles of both legs. A 5-min rest was allocated between each set, totalling 399 trials of SitTS and StandTS activities. There was a significant difference between MMG's mean root mean square maximum (RMSmax) in SitTS and StandTS activities (p = 0.014). The mean values of RMSmax and root mean square average (RMSave) on the right leg were detected to be significantly higher compared to those of the left leg during these activities (p < 0.05). In the frequency domain, MMG's mean power frequency (MPF) proved to be significantly higher at the beginning compared to the end of the three sets of both activities (p = 0.000). These muscle performances during both activities can be verified based on the analysis of MMG behaviour in time and frequency domains. Furthermore, this study indicated that MMG can be used as a monitoring tool to identify muscle fatigue throughout a prolonged event.

Quantitative Assessment of Changes in Muscle Contractility Due to Fatigue During NMES: An Ultrasound Imaging Approach.

OBJECTIVE: This paper investigates an ultrasound imaging-based non-invasive methodology to quantitatively assess changes in muscle contractility due to the fatigue induced by neuromuscular electrical stimulation (NMES). METHODS: Knee extension experiments on human participants were conducted to record synchronized isometric knee force data and ultrasound images of the electrically stimulated quadriceps muscle. The data were first collected in a pre-fatigue stage and then in a post-fatigue stage. Ultrasound images were processed using a contraction rate adaptive speckle tracking algorithm. A two-dimensional strain measure field was constructed based on the muscle displacement tracking results to quantify muscle contractility. RESULTS: Analysis of the strain images showed that, between the pre-fatigue and post-fatigue stages, there was a reduction in the strain peaks, a change in the strain peak distribution, and a decrease in an area occupied by the large positive strain. CONCLUSION: The results indicate changes in muscle contractility due to the NMES-induced muscle fatigue. SIGNIFICANCE: Ultrasound imaging with the proposed methodology is a promising tool for a direct NMES-induced fatigue assessment and facilitates new strategies to alleviate the effects of the NMES-induced fatigue.

Quantitative electrical pain threshold assessment in the lower urinary tract.

AIMS: Assessing the reliability of electrical pain threshold (PT) and evaluating the impact of stimulation frequency at different locations in the healthy lower urinary tract (LUT). METHODS: Ninety subjects (age: 18.3-35.8 years, 40 females, 50 males) were randomly allocated to one stimulation site (bladder dome [BD], trigone, proximal, membranous (only males), or distal urethra). Using 0.5 Hz/1.1 Hz/1.6 Hz electrical stimulation (square wave, pulse width:1 ms), current perception thresholds (CPTs), PTs and tolerance thresholds were assessed at two visits. Analyses were performed using linear mixed models, intraclass correlation coefficients (ICC) and Bland-Altman method. RESULTS: PTs vary in relation to stimulation frequency, location and between genders. PT decreased with higher stimulation frequency. The highest PTs were measured at the BD and membranous urethra with males reporting higher PTs than females. Reliability of PT assessments according to ICC was good to excellent across all frequencies, locations, and genders (ICC = 0.61-0.97), except for BD and distal urethra in females showing poor to fair reliability (BD: all frequencies, distal urethra: 0.5 Hz). CONCLUSIONS: PTs can be safely and reliably assessed from bladder and urethral locations. Semi-objective PT assessment may provide additional information on functionality and sensitivity of the LUT slow fiber afferents and complement findings from urodynamic investigations and CPT assessments. In conclusion, the developed methodology may open new opportunities for using electrical stimulation paradigms for LUT PT assessments and diagnostics. All this allows a more precise, location-specific characterization of pain origin and pain reaction towards therapy.

Impact of Fungiform Papillae Count on Taste Perception and Different Methods of Taste Assessment and their Clinical Applications: A comprehensive review.

Fungiform papillae are raised lingual structures which contain taste buds and thus play an important role in taste perception. These structures vary in number due to their relative sensitivity to a range of systemic and local factors which affect the dorsum of the tongue. Taste sensation can be measured using both chemical and electrical methods; however, the number of fungiform papillae has a direct effect on chemogustometric and electrogustometric values during evaluation. This review provides a general overview of fungiform papillae, their quantification methods and the various factors which may affect these structures. In addition, numerous methods of recording taste sensation and their clinical applications are highlighted.

Assessment and preservation of liquid and frozen-thawed Black crested mangabey (Lophocebus aterrimus) spermatozoa obtained by transrectal ultrasonic-guided massage of the accessory sex glands and electroejaculation.

The Black Crested Mangabey (Lophocebus aterrimus) is an African monkey listed as Near Threatened by the IUCN and in captivity the population is limited to 34 males. The aim of this study was to evaluate two Black Crested Mangabey males, maintained in captivity in a zoological garden and suspected of infertility, with a complete examination of their genital tract using ultrasonography, followed by recovery of semen using transrectal ultrasonic massage of the accessory sexual glands (TUMASG) and electroejaculation. One male had small testicular and accessory sex gland sizes indicative of senile hypoplasia. The other male was suspected of infertility. Four semen samples were obtained. Fresh semen was initially evaluated, diluted in Refrigeration Medium Test Yolk buffer, cooled at 15 °C and cryopreserved. Endocrine profiles (testosterone, oestradiol, FSH, LH, cortisol), prostatic specific antigen and semen variables (volume, concentration, motility by CASA, viability and acrosome status using flow cytometry, morphology, morphometry utilising TEM) were evaluated in raw, cooled and cryopreserved samples. There was no detrimental effect of cooling or cryopreservation on sperm viability and acrosomal integrity. Similar percentages of viable and acrosome-intact spermatozoa were present in cooled (for 6 h) and frozen-thawed semen samples (75.1% compared with 69.0%, P > 0.05), while progressive motility was greater in cooled, compared with frozen-thawed samples (81.5% compared with 67.3%). This study was the first in which there was evaluation of sperm variables in this species and, although this study is limited by the number of animals it provides background information for further studies using assisted reproductive technologies.

Trigeminal nociceptive function and oral somatosensory functional and structural assessment in patients with diabetic peripheral neuropathy.

This case-control study primarily compared the trigeminal nociceptive function, the intraoral somatosensory profile and possible structural nerve changes between diabetic peripheral neuropathy (DPN, n = 12) patients and healthy participants (n = 12). The nociceptive blink reflex (nBR) was recorded applying an electrical stimulation over the entry zone of the right supraorbital (V1R), infraorbital (V2R) and mental (V3R) and left infraorbital (V2L) nerves. The outcomes were: individual electrical sensory (I0) and pain thresholds (IP); root mean square (RMS), area-under-the-curve (AUC) and onset latencies of R2 component of the nBR. Furthermore, a standardized full battery of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) or  nerve fibre length density (NFLD) assessment were performed, respectively, on the distal leg and oral mucosa. As expected, all patients had altered somatosensory sensitivity and lower IENFD in the lower limb. DPN patients presented higher I0, IP, RMS and AUC values (p < 0.050), lower warm detection thresholds (WDT) (p = 0.004), higher occurrence of paradoxical heat sensation (PHS) (p = 0.040), and a lower intraoral NFLD (p = 0.048) than the healthy participants. In addition, the presence of any abnormal intraoral somatosensory finding was more frequent in the DPN patients when compared to the reference group (p = 0.013). Early signs of trigeminal nociceptive facilitation, intraoral somatosensory abnormalities and loss of intraoral neuronal tissue can be detected in DPN patients.

A control-theoretic system identification framework and a real-time closed-loop clinical simulation testbed for electrical brain stimulation.

OBJECTIVE: Closed-loop electrical brain stimulation systems may enable a precisely-tailored treatment for neurological and neuropsychiatric disorders by controlling the stimulation based on neural activity feedback in real time. Developing model-based closed-loop systems requires a principled system identification framework to quantify the effect of input stimulation on output neural activity by learning an input-output (IO) dynamic model from data. Further, developing these systems needs a realistic clinical simulation testbed to design and validate the closed-loop controllers derived from the IO models before testing in human patients. APPROACH: First, we design a control-theoretic system identification framework to build dynamic IO models for neural activity that are amenable to closed-loop control design. To enable tractable model-based control, we use a data-driven linear state-space IO model that characterizes the effect of input on neural activity in terms of a low-dimensional hidden neural state. To learn the model parameters, we design a novel input waveform-a pulse train modulated by stochastic binary noise (BN) parameters-that we show is optimal for collecting informative IO datasets in system identification and conforms to clinical safety requirements. Second, we further extend this waveform to a generalized BN (GBN)-modulated waveform to reduce the required system identification time. Third, to enable extensive testing of system identification and closed-loop control, we develop a real-time closed-loop clinical hardware-in-the-loop (HIL) simulation testbed using the [Formula: see text] microelectrode recording and stimulation device, which incorporates stochastic noises, unknown disturbances and stimulation artifacts. Using this testbed, we implement both the system identification and the closed-loop controller by taking control of mood in depression as an example. RESULTS: Testbed simulation results show that the closed-loop controller designed from IO models identified with the BN-modulated waveform achieves tight control, and performs similar to a controller that knows the true IO model of neural activity. When system identification time is limited, performance is further improved using the GBN-modulated waveform. SIGNIFICANCE: The system identification framework with the new BN-modulated waveform and the clinical HIL simulation testbed can help develop future model-based closed-loop electrical brain stimulation systems for treatment of neurological and neuropsychiatric disorders.

In vitro assessment of the differences in retinal ganglion cell responses to intra- and extracellular electrical stimulation.

OBJECTIVE: To compare responses of retinal ganglion cells (RGCs) to intracellular and extracellular electrical stimulation of varying frequency and amplitude. APPROACH: In vitro patch clamp was used to record the responses of RGCs to sinusoidal current stimulation of varying frequency and amplitude. The results were simulated using the Neuron software package. MAIN RESULTS: The stimulation frequency yielding the greatest response was higher for extracellular stimulation compared to intracellular stimulation in the same cells (256 Hz versus 64 Hz). In fact, at the high end of the frequency range, where extracellular stimulation was highly efficacious, no responses could be generated using intracellular stimulation. A region in the amplitude-frequency stimulation space was identified where OFF-RGCs could be preferentially stimulated over ON-RGCs. We found that the inability of RGCs to respond at high frequencies of intracellular stimulation is likely the result of the axon acting as a low pass filter. SIGNIFICANCE: There is no direct translation of the results obtained with intracellular stimulation to those that employ extracellular stimulation.

Assessment of the H-reflex using two synchronized magnetic stimulators in order to increase stimulus durations: A comparison with electrical stimulation.

Magnetic nerve stimulation (MNS) may be a less painful alternative to electrical nerve stimulation (ENS) for Hoffmann reflex (H-reflex) measurement, however standard MNS (sMNS) techniques utilize a short stimulus duration, thereby limiting its use for H-reflex assessment. This limitation may be partly overcome by coupling two magnetic stimulators to increase the pulse duration (coupled MNS: cMNS). The aim of this study was to test this assumption by comparing the H-reflex characteristics evoked by ENS, sMNS and cMNS. Thirteen healthy volunteers were tested with ENS and both MNS in the prone position. Maximal soleus H-reflex (Hmax) and M-wave (Mmax) amplitudes were measured to compute the Hmax/Mmax ratio. Hmax was evoked at rest and during both isometric submaximal (10%MVC) and maximal plantar-flexions (MVC). At rest, MNS techniques underestimated Hmax (ENS: 8.32 ±â€¯2.73 mV; sMNS: 6.85 ±â€¯2.29 mV; cMNS: 7.48 ±â€¯2.23 mV; p < 0.05). In contrast, no difference was observed for Hmax/Mmax (ENS: 0.59 ±â€¯0.17; sMNS: 0.45 ±â€¯0.28; cMNS: 0.47 ±â€¯0.29; p = 0.11). sMNS, cMNS and ENS similarly detected Hmax facilitation during MVC (ENS: +120 ±â€¯248%; sMNS: +228 ±â€¯350%; cMNS: +162 ±â€¯180% of the rest value; p = 0.344). Owing to their shorter stimulus duration, both MNS techniques underestimated the Hmax compared to ENS. However, when the gold standard ENS technique cannot be used, coupled MNS may be recommended since it provides better H-reflex characteristic assessment than standard MNS due to its longer stimulus duration.

Sodium-potassium pump assessment by submaximal electrical nerve stimulation.

OBJECTIVE: Sodium-potassium pump dysfunction in peripheral nerve is usually assessed by determining axonal hyperpolarization following maximal voluntary contraction (MVC) or maximal electrical nerve stimulation. As MVC may be unreliable and maximal electrical stimulation too painful, we assessed if hyperpolarization can also be induced by submaximal electrical nerve stimulation. METHODS: In 8 healthy volunteers different submaximal electrical stimulus trains were given to the median nerve at the wrist, followed by 5 min assessment of thresholds for compound muscle action potentials of 20%, 40% or 60% of maximal. RESULTS: Threshold increase after submaximal electrical nerve stimulation was most prominent after an 8 Hz train of at least 5 min duration evoking submaximal CMAPs of 60%. It induced minimal discomfort and was not painful. Threshold increase after MVC was not significantly higher than this stimulus train. CONCLUSIONS: Submaximal electrical stimulation evokes activity dependent hyperpolarization in healthy test subjects without causing significant discomfort. SIGNIFICANCE: Sodium-potassium pump function may be assessed using submaximal electrical stimulation.

Towards a Complete In Silico Assessment of the Outcome of Cochlear Implantation Surgery.

Cochlear implantation (CI) surgery is a very successful technique, performed on more than 300,000 people worldwide. However, since the challenge resides in obtaining an accurate surgical planning, computational models are considered to provide such accurate tools. They allow us to plan and simulate beforehand surgical procedures in order to maximally optimize surgery outcomes, and consequently provide valuable information to guide pre-operative decisions. The aim of this work is to develop and validate computational tools to completely assess the patient-specific functional outcome of the CI surgery. A complete automatic framework was developed to create and assess computationally CI models, focusing on the neural response of the auditory nerve fibers (ANF) induced by the electrical stimulation of the implant. The framework was applied to evaluate the effects of ANF degeneration and electrode intra-cochlear position on nerve activation. Results indicate that the intra-cochlear positioning of the electrode has a strong effect on the global performance of the CI. Lateral insertion provides better neural responses in case of peripheral process degeneration, and it is recommended, together with optimized intensity levels, in order to preserve the internal structures. Overall, the developed automatic framework provides an insight into the global performance of the implant in a patient-specific way. This enables to further optimize the functional performance and helps to select the best CI configuration and treatment strategy for a given patient.

Palpebral portion of the orbicularis oculi muscle to repetitive nerve stimulation testing: A potential assessment indicator in patients with generalized myasthenia gravis.

Repetitive nerve stimulation (RNS) is a valuable diagnostic method for myasthenia gravis (MG). However, its association with clinical severity was scarcely studied. We reviewed medical records and retrospectively enrolled 121 generalized MG patients. Sensitivity of different muscles to RNS and clinical scoring systems was evaluated. RNS testing revealed facial muscles have the highest positive rate, followed by proximal muscles and distal muscles, with the palpebral portion of the orbicularis oculi muscle most sensitive. Amplitude decrement of compound muscle action potential (CMAP) in the palpebral portion of the orbicularis oculi muscle is related to quantitative myasthenia gravis (QMG) scores, MG-specific manual muscle testing (MMT) scores and myasthenia gravis-related activities of daily living (MG-ADL) scores. We suggest that RNS testing of the palpebral portion of the orbicularis oculi muscle is a potential assessment indicator in patients with generalized MG.