Porcine Model of Cerebral Ischemic Stroke Utilizing Intracortical Recordings for the Continuous Monitoring of the Ischemic Area.

PURPOSE: Our aim was to use intracortical recording to enable the tracking of ischemic infarct development over the first few critical hours of ischemia with a high time resolution in pigs. We employed electrophysiological measurements to obtain quick feedback on neural function, which might be useful for screening, e.g., for the optimal dosage and timing of agents prior to further pre-clinical evaluation. METHODS: Micro-electrode arrays containing 16 (animal 1) or 32 electrodes (animal 2-7) were implanted in the primary somatosensory cortex of seven female pigs, and continuous electrical stimulation was applied at 0.2 Hz to a cuff electrode implanted on the ulnar nerve. Ischemic stroke was induced after 30 min of baseline recording by injection of endothelin-1 onto the cortex adjacent to the micro-electrode array. Evoked responses were extracted over a moving window of 180 s and averaged across channels as a measure of cortical excitability. RESULTS: Across the animals, the cortical excitability was significantly reduced in all seven 30 min segments following endothelin-1 injection, as compared to the 30 min preceding this intervention. This difference was not explained by changes in the anesthesia, ventilation, end-tidal CO2, mean blood pressure, heart rate, blood oxygenation, or core temperature, which all remained stable throughout the experiment. CONCLUSIONS: The animal model may assist in maturing neuroprotective approaches by testing them in an accessible model of resemblance to human neural and cardiovascular physiology and body size. This would constitute an intermediate step for translating positive results from rodent studies into human application, by more efficiently enabling effective optimization prior to chronic pre-clinical studies in large animals.

The Use of the Velocity Selective Recording Technique to Reveal the Excitation Properties of the Ulnar Nerve in Pigs.

Decoding information from the peripheral nervous system via implantable neural interfaces remains a significant challenge, considerably limiting the advancement of neuromodulation and neuroprosthetic devices. The velocity selective recording (VSR) technique has been proposed to improve the classification of neural traffic by combining temporal and spatial information through a multi-electrode cuff (MEC). Therefore, this study investigates the feasibility of using the VSR technique to characterise fibre type based on the electrically evoked compound action potentials (eCAP) propagating along the ulnar nerve of pigs in vivo. A range of electrical stimulation parameters (amplitudes of 50 µA-10 mA and pulse durations of 100 µs, 500 µs, 1000 µs, and 5000 µs) was applied on a cutaneous and a motor branch of the ulnar nerve in nine Danish landrace pigs. Recordings were made with a 14 ring MEC and a delay-and-add algorithm was used to convert the eCAPs into the velocity domain. The results revealed two fibre populations propagating along the cutaneous branch of the ulnar nerve, with mean velocities of 55 m/s and 21 m/s, while only one dominant fibre population was found for the motor branch, with a mean velocity of 63 m/s. Because of its simplicity to provide information on the fibre selectivity and direction of propagation of nerve fibres, VSR can be implemented to advance the performance of the bidirectional control of neural prostheses and bioelectronic medicine applications.

A Multiday Evaluation of Real-Time Intramuscular EMG Usability with ANN.

Recent developments in implantable technology, such as high-density recordings, wireless transmission of signals to a prosthetic hand, may pave the way for intramuscular electromyography (iEMG)-based myoelectric control in the future. This study aimed to investigate the real-time control performance of iEMG over time. A novel protocol was developed to quantify the robustness of the real-time performance parameters. Intramuscular wires were used to record EMG signals, which were kept inside the muscles for five consecutive days. Tests were performed on multiple days using Fitts' law. Throughput, completion rate, path efficiency and overshoot were evaluated as performance metrics using three train/test strategies. Each train/test scheme was categorized on the basis of data quantity and the time difference between training and testing data. An artificial neural network (ANN) classifier was trained and tested on (i) data from the same day (WDT), (ii) data collected from the previous day and tested on present-day (BDT) and (iii) trained on all previous days including the present day and tested on present-day (CDT). It was found that the completion rate (91.6 ± 3.6%) of CDT was significantly better (p < 0.01) than BDT (74.02 ± 5.8%) and WDT (88.16 ± 3.6%). For BDT, on average, the first session of each day was significantly better (p < 0.01) than the second and third sessions for completion rate (77.9 ± 14.0%) and path efficiency (88.9 ± 16.9%). Subjects demonstrated the ability to achieve targets successfully with wire electrodes. Results also suggest that time variations in the iEMG signal can be catered by concatenating the data over several days. This scheme can be helpful in attaining stable and robust performance.

Ethical Assessment and Reflection in Research and Development of Non-Conformité Européene Marked Medical Devices.

Today there are multiple implantable medical devices on the market. The type of implants that interface the body's tissues has been considered to have particular strong ethical implications. This article describes a development of a novel practice for ethical assessment and reflection within medical device research and development of non-CE marked medical devices, taking the perspective of both the ethicist and the researcher. The research case was an EU funded project where the aim was to develop and compare the efficiency of invasive and non-invasive technological medical devices to create meaningful sensations as a novel therapy for phantom limb pain. An Independent Ethical Advisor (IEA) with a regulatory and advisory role was assigned to the project, allowing us to investigate the projects deliberate incorporation of ethics. In the article we suggest and applied a novel framework based on action research for combining ethical assessment with building ethical reflection. The case analyse five different activities / elements: 1) the use of informed consent; 2) a survey amongst the research partners; 3) a workshop session; 4) observation of consortium meetings; and 5) an interview with a participating patient.

A New Rat Model of Seizures Suitable for Screening Antiepileptic Electrical Stimulation Therapies.

The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spike-and-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures.

Optimal Vagus Nerve Stimulation Frequency for Suppression of Spike-and-Wave Seizures in Rats.

Vagus nerve stimulation (VNS) is used as an adjunctive therapy for drug-resistant epilepsy and results in a 50% seizure reduction in up to 50% of treated patients. The VNS frequency used in the clinic today is in the range of 10-30 Hz. The evidence for choosing the stimulation frequency is limited, and little knowledge is available on the effect of other VNS frequencies. Deep brain, trigeminal nerve, or spinal cord stimulation studies have suggested the use of stimulation frequencies above 80 Hz for seizure control. Therefore, our objective for the present study was to investigate if VNS using frequencies higher than those currently used in the clinic could be more effective in attenuating seizures. Spike-and-wave (SW) discharges were induced in 11 rats, which then were subjected to VNS sessions applied at the frequencies of 10, 30, 80, 130, and 180 Hz combined with control intervals without stimulation. The anticonvulsive effect of VNS was evaluated by comparing the normalized mean power (nMP) and frequency (nMSF) of the SW discharges derived from intracortical recordings collected during the stimulation and control intervals. Compared with the control intervals, all the tested VNS frequencies significantly reduced the nMP (in the range of 9-21%). However, we found that 130 and 180 Hz VNS induced a 50% larger attenuation of seizures than that achieved by 30 Hz VNS. In addition, we found that 80, 130, and 180 Hz VNS induced a significant reduction of the nMSF, that is by 5, 7, and 8%, respectively. These results suggest that a VNS stimulation frequency in the range of 130-180 Hz may be more effective in inhibiting seizures than the 30 Hz VNS applied in the clinic today.

The Effect of Spinal Cord Stimulation on Epileptic Seizures.

OBJECTIVE: Spinal cord stimulation (SCS) has been applied to relieve chronic pain for decades. Recent studies suggested that SCS also might alleviate epileptic seizures, but the most effective stimulation parameters are not known. The objective of this work was to investigate the role of SCS frequency in alleviating spike-and-wave (SW) discharges induced in rats by pentylenetetrazole (PTZ) infusion. MATERIALS AND METHODS: The SW discharges were induced in nine rats. An epidural electrode was placed in the spinal canal at the cervical level. SCS was delivered at four frequencies (30, 80, 130 and 180 Hz) and compared with control intervals without stimulation. The effect was evaluated by analyzing electrocorticographic and intracortical (IC) signals. The means of normalized SW spike power (mSP) and frequency (mSF) were derived from the IC recordings and used to estimate the seizure severity. RESULTS: Compared with the control intervals, SCS conducted at 30 Hz significantly increased the mSP and mSF indicating an increase of the SW spiking activity; 80 Hz did not induce significant changes of the features. In contrast, 130- and 180-Hz SCS reduced both mSP and mSF significantly indicating a reduction of the SW spiking activity. CONCLUSIONS: The present results showed that 130-Hz and 180-Hz SCS reduced the SWs power and frequency which may indicate an anticonvulsive effect of these SCS frequencies, whereas 30-Hz SCS induced the opposite effects and, therefore, may be proconvulsive.

Simulation of a Real-Time Brain Computer Interface for Detecting a Self-Paced Hitting Task.

OBJECTIVES: An invasive brain-computer interface (BCI) is a promising neurorehabilitation device for severely disabled patients. Although some systems have been shown to work well in restricted laboratory settings, their utility must be tested in less controlled, real-time environments. Our objective was to investigate whether a specific motor task could be reliably detected from multiunit intracortical signals from freely moving animals in a simulated, real-time setting. MATERIALS AND METHODS: Intracortical signals were first obtained from electrodes placed in the primary motor cortex of four rats that were trained to hit a retractable paddle (defined as a "Hit"). In the simulated real-time setting, the signal-to-noise-ratio was first increased by wavelet denoising. Action potentials were detected, and features were extracted (spike count, mean absolute values, entropy, and combination of these features) within pre-defined time windows (200 ms, 300 ms, and 400 ms) to classify the occurrence of a "Hit." RESULTS: We found higher detection accuracy of a "Hit" (73.1%, 73.4%, and 67.9% for the three window sizes, respectively) when the decision was made based on a combination of features rather than on a single feature. However, the duration of the window length was not statistically significant (p = 0.5). CONCLUSION: Our results showed the feasibility of detecting a motor task in real time in a less restricted environment compared to environments commonly applied within invasive BCI research, and they showed the feasibility of using information extracted from multiunit recordings, thereby avoiding the time-consuming and complex task of extracting and sorting single units.

The Influence of Vagus Nerve and Spinal Cord Stimulation on the Ictal Fast Ripple Activity in a Spike-and-Wave Rat Model of Seizures.

OBJECTIVES: Fast ripple (FR) activity has received increasing attention as a potential epileptic marker. The current knowledge on how neurostimulation affects FRs is, however, very limited. In this study, we assess the influence of the vagus nerve stimulation (VNS) and spinal cord stimulation (SCS) frequency on ictal FRs associated with spike-and-wave (SW) seizures. METHODS: SW discharges were induced and maintained by an infusion of pentylenetetrazol in rat. During ongoing SW seizures, SCS was conducted at 30, 80, 130, and 180 Hz and VNS at 10, 30, 80, 130, and 180 Hz. The FRs were derived from intracortical recordings and the FR rate was used for quantifying the level of FR activity. RESULTS: The FR rate was significantly correlated (r = 0.81) with the level of total pentylenetetrazol dose. Compared with no stimulation intervals, SCS conducted at 80, 130, and 180 Hz significantly reduced the normalized FR rate by 24, 38, and 44%, respectively. Similarly, VNS conducted at 30, 80, 130, and 180 Hz significantly reduced the normalized FR rate by 23, 40, 61, and 65%, respectively. CONCLUSIONS: In the present model of sustained SW seizures, the FR rate was proportional with the severity of the SW seizures. Both SCS and VNS attenuated the FR rate and this attenuation was consistently strongest at the higher stimulation frequencies. Our results suggest that SCS may induce some of the same antiepileptic effects as VNS.

Subchronic stimulation performance of transverse intrafascicular multichannel electrodes in the median nerve of the Göttingen minipig.

This work evaluated the subchronic stimulation performance of an intraneural multichannel electrode (transverse intrafascicular multichannel electrode, TIME) in a large human-sized nerve. One or two TIMEs were implanted in the right median nerve above the elbow joint in four pigs for a period of 32 to 37 days (six TIMEs in total). The ability of the contact sites to recruit five muscles in the forelimb was assessed via their evoked electromyographic responses. Based on these responses, a selectivity index was defined. Four TIMEs were able to selectively recruit a subset of muscles throughout the implantation period. The required recruitment current significantly increased, while there was a tendency for the recruitment selectivity to decrease over time. Histological assessment showed that all TIMEs remained inside the nerve and that they were located between fascicles. The average thickness of the encapsulation of the electrode was estimated to be 115.4 ± 51.5 µm (mean ± SD). This study demonstrates the feasibility of keeping the TIME electrodes fixed and functional inside a large polyfascicular human-sized nerve in a subchronic setting.

Human ability in identification of location and pulse number for electrocutaneous stimulation applied on the forearm.

BACKGROUND: The need of a sensory feedback system that would improve users' acceptance in prostheses is generally recognized. Feedback of hand opening and position are among the most important concerns of prosthetic users. To address the two concerns, this study investigated the human capability to identify pulse number and location when electrical stimulation applied on the forearm skin. The pulse number may potentially be used to encode the opening of prosthetic hands and stimulation location to encode finger position. METHODS: Ten able-bodied subjects participated in the study. Three electrodes were placed transversely across the ventral forearm spatially encoding three fingers (i.e., thumb, index, and middle finger). Five different pulse numbers (1, 4, 8, 12, and 20) encoded five levels of hand opening. The study consisted of three experiments. In the three experiments, each after a training session, the subjects were required to identify among: (a) five stimulation locations, (b) five pulse numbers, or (c) ten paired combinations of location and pulse number, respectively. The subjects' performance in the three identification tasks was evaluated. RESULTS: The main results included: 1) the overall identification rate for stimulation location was 92.2 ± 6.2%, while the success rate in two-site stimulation was lower than one-site stimulation; 2) the overall identification rate for pulse number was 90.8 ± 6.0%, and the subjects showed different performance in identification of the five pulse numbers; 3) the overall identification rate decreased to 80.2 ± 11.7% when the subjects were identifying paired parameters. CONCLUSIONS: The results indicated that the spatial (location) and temporal (pulse number) identification performance are promising in electrocutaneous stimulation on the forearm. The performance degraded when both parameters had to be identified likely due to increased cognitive load resulting from multiple tasks. Utilizing the proposed coding strategy in practical prosthetic hands remains to be investigated for clinical evaluation of its feasibility.

Morphology and morphometry of the ulnar nerve in the forelimb of pigs.

The knowledge of the morphology and morphometry of peripheral nerves is essential for developing neural interfaces and understanding nerve regeneration in basic and applied research. Currently, the most adopted animal model is the rat, even though recent studies have suggested that the neuroanatomy of large animal models is more comparable to humans. The present knowledge of the morphological structure of large animal models is limited; therefore, the present study aims to describe the morphological characteristics of the Ulnar Nerve (UN) in pigs. UN cross-sections were taken from seven Danish landrace pigs at three distinct locations: distal UN, proximal UN and at the dorsal cutaneous branch of the UN (DCBUN). The nerve diameter, fascicle diameter and number, number of fibres and fibre size were quantified. The UN diameter was larger in the proximal section compared to the distal segment and the DCBUN. The proximal branch also had a more significant number of fascicles (median: 15) than the distal (median: 10) and the DCBUN (median: 11) segments. Additionally, the mean fascicle diameter was smaller at the DCBUN (mean: 165 µm) than at the distal (mean: 197 µm) and proximal (mean: 199 µm) segments of the UN. Detailed knowledge of the microscopical structure of the UN in pigs is critical for further studies investigating neural interface designs and computational models of the peripheral nervous system.

Referred Sensation Areas in Bilateral Upper Limb Amputee.

Phantom limb pain (PLP) following amputation considerably reduces the quality of life, given a difficult to treat pain of highly variate profile. The loss of sensory input induces a complex pattern of neuroplastic changes of the sensory neural pathways and their central projections. Referred sensation areas (RSAs) may occur on the stump as a consequence of amputation, providing a direct path towards the altered central sensory projections. Modulated electrical stimulation of RSAs was investigated in a long-term experiment in the case of a 62 years-old participant with bilateral upper limb amputation due to traumatic injury. RSAs were investigated using mechanical (vibration and pressure) and electrical stimuli over five sessions within a five weeks period. Further test of sensations induced by steady state and modulated electrical stimuli was performed during additional 4 sessions. Location and features of RSAs were highly dependent on the type of stimulus and time of delivery between sessions.Clinical Relevance- The case study presents a variety of types and locations of the sensation induced by electrical and mechanical stimuli that may eventually be used as artificially generated sensory input as individualized alternative form of therapy for PLP alleviation. Furthermore, possible multichannel stimulus delivery on RSAs on both arms and the cross-over effect of the bilateral amputation in perception of the induced sensation in the opposite phantom hand may be considered in dedicated design of an experimental setup that may possibly help investigation of mechanisms for PLP.

On determining the mechanical nociceptive threshold in pigs: a reliability study.

Background: A pressure algometer is a valuable tool for assessing the mechanical nociceptive threshold (MNT) in clinical pain studies. Recent research has turned to large animal models of pain because of the closer anatomy and physiology to humans. Although the reliability and usefulness of the MNT have been extensively validated in humans, similar data from large animals is still sparse. Objective: Therefore, the aim of the current study was to evaluate the reliability (within- and between-session) of MNT in the forelimb of pigs using a pressure algometer. Methods: Nine animals were used (23-40 kg), and MNTs were measured at both the right and left limbs at three different sessions, with three repetitions per session. The intraclass correlation coefficient (ICC) was used as a metric for relative reliability. The standard error of measurement (SEM) and coefficient of variation (CV) was used to assess absolute reliability. Systematic bias was also evaluated. Results: The average ICC was found to be 0.71 and 0.45 for the between-session and within-session, respectively. CV ranged from 17.9% to 20.5%, with a grand average of 19.1%. The grand average SEM was 249.5 kPa (16.6%). No systematic differences were found for the MNT between sessions, which suggests that there was no habituation to the stimulus. Conclusion: The reliability indices obtained in this study are comparable to results obtained in other species or anatomical regions and substantiate the use of the pressure algometer as a valuable tool to investigate the nociceptive system in pigs and translation to the human nociceptive withdrawal reflex.

Alteration in Cortical Activity and Perceived Sensation Following Modulated TENS.

Over the last decades, conventional transcutaneous electrical nerve stimulation (TENS) has been utilized as an efficient rehabilitation intervention for alleviation of chronic pain, including phantom limb pain (PLP). However, recently the literature has increasingly focused on alternative temporal stimulation patterns such as pulse width modulation (PWM). While the effect of non-modulated high frequency (NMHF) TENS on somatosensory (SI) cortex activity and sensory perception has been studied, the possible alteration following PWM TENS at the SI has not yet been explored. Therefore, we investigated the cortical modulation by PWM TENS for the first time and conducted a comparative analysis with the conventional TENS pattern. We recorded sensory evoked potentials (SEP) from 14 healthy subjects before, immediately, and 60 min after TENS interventions (PWM and NMHF). The results revealed suppression of SEP components, theta, and alpha band power simultaneously associated with the perceived intensity reduction when the single sensory pulses applied ipsilaterally to the TENS side. The reduction of N1 amplitude, theta, and alpha band activity occurred immediately after both patterns remained at least 60 min. However, the P2 wave was suppressed right after PWM TENS, while NMHF could not induce significant reduction immediately after the intervention phase. As such, since PLP relief has been shown to be correlated with inhibition at somatosensory cortex, we, therefore, believe that the result of this study provides further evidence that PWM TENS may also be potential therapeutic intervention for PLP reduction. Future studies on PLP patients with PWM TENS sessions is needed to validate our result.

From pulse width modulated TENS to cortical modulation: based on EEG functional connectivity analysis.

Modulation in the temporal pattern of transcutaneous electrical nerve stimulation (TENS), such as Pulse width modulated (PWM), has been considered a new dimension in pain and neurorehabilitation therapy. Recently, the potentials of PWM TENS have been studied on sensory profiles and corticospinal activity. However, the underlying mechanism of PWM TENS on cortical network which might lead to pain alleviation is not yet investigated. Therefore, we recorded cortical activity using electroencephalography (EEG) from 12 healthy subjects and assessed the alternation of the functional connectivity at the cortex level up to an hour following the PWM TENS and compared that with the effect of conventional TENS. The connectivity between eight brain regions involved in sensory and pain processing was calculated based on phase lag index and spearman correlation. The alteration in segregation and integration of information in the network were investigated using graph theory. The proposed analysis discovered several statistically significant network changes between PWM TENS and conventional TENS, such as increased local strength and efficiency of the network in high gamma-band in primary and secondary somatosensory sources one hour following stimulation. Our findings regarding the long-lasting desired effects of PWM TENS support its potential as a therapeutic intervention in clinical research.

Gamma-band enhancement of functional brain connectivity following transcutaneous electrical nerve stimulation.

Objective.Transcutaneous electrical nerve stimulation (TENS) has been suggested as a possible non-invasive pain treatment. However, the underlying mechanism of the analgesic effect of TENS and how brain network functional connectivity (FC) is affected following the use of TENS is not yet fully understood. The purpose of this study was to investigate the effect of high-frequency TENS on the alteration of functional brain network connectivity and the corresponding topographical changes, besides perceived sensations.Approach.Forty healthy subjects participated in this study. Electroencephalography (EEG) data and sensory profiles were recorded before and up to an hour following high-frequency TENS (100 Hz) in sham and intervention groups. Brain source activity from EEG data was estimated using the LORETA algorithm. In order to generate the functional brain connectivity network, the Phase Lag Index was calculated for all pair-wise connections of eight selected brain areas over six different frequency bands (i.e.δ, θ, α, ß, γ, and 0.5-90 Hz).Main results.The results suggested that the FC between the primary somatosensory cortex (SI) and the anterior cingulate cortex, in addition to FC between SI and the medial prefrontal cortex, were significantly increased in the gamma-band, following the TENS intervention. Additionally, using graph theory, several significant changes were observed in global and local characteristics of functional brain connectivity in gamma-band.Significance.Our observations in this paper open a neuropsychological window of understanding the underlying mechanism of TENS and the corresponding changes in functional brain connectivity, simultaneously with alteration in sensory perception.

Effect of Modulated TENS on Corticospinal Excitability in Healthy Subjects.

Conventional transcutaneous electrical nerve stimulation (TENS) has been reported to effectively alleviate chronic pain, including phantom limb pain (PLP). Recently, literature has focused on modulated TENS patterns, such as pulse width modulation (PWM) and burst modulation (BM), as alternatives to conventional, non-modulated (NM) sensory neurostimulation to increase the efficiency of rehabilitation. However, there is still limited knowledge of how these modulated TENS patterns affect corticospinal (CS) and motor cortex activity. Therefore, our aim was to first investigate the effect of modulated TENS patterns on CS activity and corticomotor map in healthy subjects. Motor evoked potentials (MEP) elicited by transcranial magnetic stimulation (TMS) were recorded from three muscles before and after the application of TENS interventions. Four different TENS patterns (PWM, BM, NM 40 Hz, and NM 100 Hz) were applied. The results revealed significant facilitation of CS excitability following the PWM intervention. We also found an increase in the volume of the motor cortical map following the application of the PWM and NM (40 Hz). Although PLP alleviation has been reported to be associated with an enhancement of corticospinal excitability, the efficiency of the PWM intervention to induce pain alleviation should be validated in a future clinical study in amputees with PLP.

A Comparison of Delay-and-Add and Maximum Likelihood Estimation for Velocity-Selective Recording Using Multi-Electrode Cuffs.

Extracting information from the peripheral nervous system with implantable devices remains a significant challenge that limits the advancement of closed-loop neural prostheses. Linear electrode arrays can record neural signals with both temporal and spatial selectivity, and velocity selective recording using the delay-and-add algorithm can enable classification based on fibre type. The maximum likelihood estimation method also measures velocity and is frequently used in electromyography but has never been applied to electroneurography. Therefore, this study compares the two algorithms using in-vivo recordings of electrically evoked compound action potentials from the ulnar nerve of a pig. The performance of these algorithms was assessed using the velocity quality factor (Q-factor), computational time and the influence of the number of channels. The results show that the performance of both algorithms is significantly influenced by the number of channels in the recording array, with accuracies ranging from 77% with only two channels to 98% for 11 channels. Both algorithms were comparable in accuracy and Q-factor for all channels, with the delay-and-add having a slight advantage in the Q-factor.

Impacts of selected stimulation patterns on the perception threshold in electrocutaneous stimulation.

BACKGROUND: Consistency is one of the most important concerns to convey stable artificially induced sensory feedback. However, the constancy of perceived sensations cannot be guaranteed, as the artificially evoked sensation is a function of the interaction of stimulation parameters. The hypothesis of this study is that the selected stimulation parameters in multi-electrode cutaneous stimulation have significant impacts on the perception threshold. METHODS: The investigated parameters included the stimulated location, the number of active electrodes, the number of pulses, and the interleaved time between a pair of electrodes. Biphasic, rectangular pulses were applied via five surface electrodes placed on the forearm of 12 healthy subjects. RESULTS: Our main findings were: 1) the perception thresholds at the five stimulated locations were significantly different (p < 0.0001), 2) dual-channel simultaneous stimulation lowered the perception thresholds and led to smaller variance in perception thresholds compared to single-channel stimulation, 3) the perception threshold was inversely related to the number of pulses, and 4) the perception threshold increased with increasing interleaved time when the interleaved time between two electrodes was below 500 µs. CONCLUSIONS: To maintain a consistent perception threshold, our findings indicate that dual-channel simultaneous stimulation with at least five pulses should be used, and that the interleaved time between two electrodes should be longer than 500 µs. We believe that these findings have implications for design of reliable sensory feedback codes.