Selective intrafascicular stimulation of myelinated and unmyelinated nerve fibers through a longitudinal electrode: A computational study.

Carbon nanotube (CNT) fiber electrodes have demonstrated exceptional spatial selectivity and sustained reliability in the context of intrafascicular electrical stimulation, as evidenced through rigorous animal experimentation. A significant presence of unmyelinated C fibers, known to induce uncomfortable somatosensory experiences, exists within peripheral nerves. This presence poses a considerable challenge to the excitation of myelinated Aß fibers, which are crucial for tactile sensation. To achieve nuanced tactile sensory feedback utilizing CNT fiber electrodes, the selective stimulation of Aß sensory afferents emerges as a critical factor. In confronting this challenge, the present investigation sought to refine and apply a rat sciatic-nerve model leveraging the capabilities of the COMSOL-NEURON framework. This approach enables a systematic evaluation of the influence exerted by stimulation parameters and electrode geometry on the activation dynamics of both myelinated Aß and unmyelinated C fibers. The findings advocate for the utilization of current pulses featuring a pulse width of 600 µs, alongside the deployment of CNT fibers characterized by a diminutive diameter of 10 µm, with an exclusively exposed cross-sectional area, to facilitate reduced activation current thresholds. Comparative analysis under monopolar and bipolar electrical stimulation conditions revealed proximate activation thresholds, albeit with bipolar stimulation exhibiting superior fiber selectivity relative to its monopolar counterpart. Concerning pulse waveform characteristics, the adoption of an anodic-first biphasic stimulation modality is favored, taking into account the dual criteria of activation threshold and fiber selectivity optimization. Consequently, this investigation furnishes an efficacious stimulation paradigm for the selective activation of touch-related nerve fibers, alongside provisioning a comprehensive theoretical foundation for the realization of natural tactile feedback within the domain of prosthetic hand applications.

System-level biological effects of extremely low-frequency electromagnetic fields: an in vivo experimental review.

During the past decades, the potential effects of extremely low-frequency electromagnetic fields (ELF-EMFs) on human health have gained great interest all around the world. Though the International Commission on Non-Ionizing Radiation Protection recommended a 100 µT, and then a 200 µT magnetic field limit, the long-term effects of ELF-EMFs on organisms and systems need to be further investigated. It was reported that both electrotherapy and possible effects on human health could be induced under ELF-EM radiation with varied EM frequencies and fields. This present article intends to systematically review the in vivo experimental outcome and the corresponding mechanisms to shed some light on the safety considerations of ELF-EMFs. This will further advance the subsequent application of electrotherapy in human health.

Spatial Attention Modulates Neuronal Interactions between Simple and Complex Cells in V1.

Visual perception is profoundly modulated by spatial attention, which can selectively prioritize goal-related information. Previous studies found spatial attention facilitated the efficacy of neuronal communication between visual cortices with hierarchical organizations. In the primary visual cortex (V1), there is also a hierarchical connection between simple (S) and complex (C) cells. We wonder whether and how spatial attention modulates neuronal communication within V1, especially for neuronal pairs with heterogeneous visual input. We simultaneously recorded the pairs' activity from macaque monkeys when they performed a spatial-attention-involved task, then applied likelihood-based Granger causality analysis to explore attentional modulation of neuronal interactions. First, a significant attention-related decrease in Granger causality was found in S-C pairs, which primarily displayed in the S-to-C feedforward connection. Second, the interaction strength of the feedforward connection was significantly higher than that of the feedback under attend toward (AT) conditions. Although information flow did not alter as the attentional focus shifted, the strength of communications between target- and distractor-stimuli-covered neurons differed only when attending to complex cells' receptive fields (RFs). Furthermore, pairs' communications depended on the attentional modulation of neurons' firing rates. Our findings demonstrate spatial attention does not induce specific information flow but rather amplifies directed communication within V1.

A system of real-time neural recording and stimulation and its potential application in blood pressure modulation.

Hypertension is one of the most prevalent chronic diseases that affects more than 20% of the adult population worldwide, but fortunately, most of their blood pressure can be effectively controlled via drug treatment. However, there still remains 5-30% of patients clinically who do not respond well to conventional medication, while the non-drug treatments currently existing are struggling with major drawbacks like irreversible nerve damage, huge side effects, and even non-effectiveness. In this study, based on the physiological regulation mechanism of blood pressure and state-of-the-art neuromodulation technique, we worked along with the vagus nerve stimulation scheme, developed, and explored whether and how a real-time neural recording and stimulation system could provide an insight into self-adaptive modulation in the blood pressure, in the hope to crack a crevice in the closed-loop treatment for resistant hypertension. Unlike traditional neuromodulation devices, additional signal recording and real-time wireless transmission functions are added to the same device to realize the features of a dynamic monitor and modulator. The system is tested both in vitro and in vivo, showing decent electrical performance of 8 kHz sampling rate and flexible stimulation outputs which sufficiently covers our needs in manipulating neural activities of interest. A relatively stable drop in the blood pressure resulting from stimulation was observed and specific patterns in the vagus nerve signals relating to blood pressure could also be primarily identified. This laid a solid foundation for further studies on the final realization of closed-loop automatic adjustment for resistive hypertension treatment.

Spatial Attention Modulates Spike Count Correlations and Granger Causality in the Primary Visual Cortex.

The influence of spatial attention on neural interactions has been revealed even in early visual information processing stages. It resolves the process of competing for sensory information about objects perceived as targets and distractors. However, the attentional modulation of the interaction between pairs of neurons with non-overlapping receptive fields (RFs) is not well known. Here, we investigated the activity of anatomically distant neurons in two behaving monkeys' primary visual cortex (V1), when they performed a spatial attention task detecting color change. We compared attentional modulation from the perspective of spike count correlations and Granger causality among simple and complex cells. An attention-related increase in spike count correlations and a decrease in Granger causality were found. The results showed that spatial attention significantly influenced only the interactions between rather than within simple and complex cells. Furthermore, we found that the attentional modulation of neuronal interactions changed with neuronal pairs' preferred directions differences. Thus, we found that spatial attention increased the functional communications and competing connectivities when attending to the neurons' RFs, which impacts the interactions only between simple and complex cells. Our findings enrich the model of simple and complex cells and further understand the way that attention influences the neurons' activities.

Objective neuromodulation basis for intrafascicular artificial somatosensation through carbon nanotube yarn electrodes.

BACKGROUND: Intrafascicular electrical stimulation has been extensively adopted to achieve sensory feedback for limb amputees. Axon-like carbon nanotube yarn (CNTy) electrodes with both promising flexibility and spatial selectivity index (SSI) can be fascinating alternatives to generate artificial somatosensation. NEW METHOD: Here we systematically disclose objective neuromodulation basis for artificial somatosensation through intrafascicular CNTy electrodes. CNTy electrodes with different exposed lengths were utilized for electrically stimulating tibial nerves in twelve rats. Somatosensory evoked potentials (SEPs) were recorded synchronously using an epidural thirty-channel electrode array. Spatiotemporal characteristics of SEPs were analyzed as current pulse amplitude (PA), pulse width (PW) and pulse frequency (PF) varied. RESULTS: The current thresholds at 1 Hz exhibit the lowest means when compared with those at 4 and 8 Hz for most CNTy electrodes (20/28). For all the electrodes, amplitudes of SEPs and activated areas of perceptive fields increase with PWs and PAs rising, and decrease remarkably with PFs from 1 to 8 Hz. Latencies of P1 and N1 of SEP peaks gradually reduced with PWs and PAs advancing. Considering high SSIs, relatively stable current thresholds, wider variation ranges of sensory magnitudes and optimal stability of perceptive fields, the L-200 µm electrodes are preferable for neuromodulation with PFs of 1 - 8 Hz, PWs of 100 - 800 µs and PAs of 2 - 64 µA. COMPARISON WITH EXISTING METHODS: New-type CNTy electrodes possess both promising flexibility and SSI when compared with other neural interfaces. We systematically explore objective neuromodulation basis for artificial somatosensation through CNTy electrodes for the first time. CONCLUSIONS: Significantly higher SSIs, lower current and charge thresholds exist for CNTy electrodes in comparison with other peripheral-nerve interfaces. This study can, for the first time, lay a solid neuromodulation foundation for CNTy electrodes to achieve fine sensory feedback.

Computational Modeling of Spatially Selective Retinal Stimulation With Temporally Interfering Electric Fields.

Retinal electrical stimulation is a widely utilized method to restore visual function for patients with retinal degenerative diseases. Transcorneal electrical stimulation (TES) represents an effective way to improve the visual function due to its potential neuroprotective effect. However, TES with single electrode fails to spatially and selectively stimulate retinal neurons. Herein, a computational modeling method was proposed to explore the feasibility of spatially selective retinal stimulation via temporally interfering electric fields. An eyeball model with multiple electrodes was constructed to simulate the interferential electric fields with various electrode montages and current ratios. The results demonstrated that the temporal interference (TI) stimulation would gradually generate an increasingly localized high-intensity region on retina as the return electrodes moved towards the posterior of the eyeball and got closer. Additionally, the position of the convergent region could be modulated by regulating the current ratio of different electrode channels. The TI strategy with multisite and steerable stimulation can stimulate local retinal region with certain convergence and a relatively large stimulation range, which would be a feasible approach for the spatially selective retinal neuromodulation.

Mediating different-diameter Aß nerve fibers using a biomimetic 3D TENS computational model.

BACKGROUND: Significant progress has been made over the last 50 years in the design, development and testing of transcutaneous electrical nerve stimulation (TENS) in mediating different levels of tactile sensations. However, without knowing how best to stimulate the nerve fibers, the elicited sensation quality will always remain poor and unnatural. NEW METHOD: A new biomimetic 3D TENS computational model is developed to quantify the neural activation mechanism with varied surface electrodes. This model includes seven-layered anatomical structure of the forearm and biophysically-detailed myelinated Aß fibers. The Aß-fiber diameters from 1.5 - 7.5 µm were randomly distributed beneath the skin to mimic the physiologically-realistic fiber population. The arithmetic averaging algorithm and Gaussian filter were adopted to identify the sensation center and to quantify sensation intensities under different stimulation conditions. RESULTS: Fibers larger than 4.5 µm can usually be activated producing tactile sensations such as light touch, pressure, buzz, and vibration. While, fibers with diameters of 3.5 and 3 µm can only be excited at uncomfortable numb and pain sensations. The resulted modelling predictions match the recent psychophysical experimental data. COMPARISON WITH EXISTING METHOD(S): The new TENS model is more physiologically-realistic by introducing a detailed morphological information and key ionic mechanisms in nerve fibers. CONCLUSIONS: Our results indicate that TENS may be a promising method to target functionally-distinct neural pathways in an effort to improve the elicited tactile sensations quality with electrical stimulation. This work provides a promising platform of discovering neural mechanisms under TENS.

A Three-Dimensional Microelectrode Array to Generate Virtual Electrodes for Epiretinal Prosthesis Based on a Modeling Study.

Despite many advances in the development of retinal prostheses, clinical reports show that current retinal prosthesis subjects can only perceive prosthetic vision with poor visual acuity. A possible approach for improving visual acuity is to produce virtual electrodes (VEs) through electric field modulation. Generating controllable and localized VEs is a crucial factor in effectively improving the perceptive resolution of the retinal prostheses. In this paper, we aimed to design a microelectrode array (MEA) that can produce converged and controllable VEs by current steering stimulation strategies. Through computational modeling, we designed a three-dimensional concentric ring-disc MEA and evaluated its performance with different stimulation strategies. Our simulation results showed that electrode-retina distance (ERD) and inter-electrode distance (IED) can dramatically affect the distribution of electric field. Also the converged VEs could be produced when the parameters of the three-dimensional MEA were appropriately set. VE sites can be controlled by manipulating the proportion of current on each adjacent electrode in a current steering group (CSG). In addition, spatial localization of electrical stimulation can be greatly improved under quasi-monopolar (QMP) stimulation. This study may provide support for future application of VEs in epiretinal prosthesis for potentially increasing the visual acuity of prosthetic vision.

Discrimination and Recognition of Phantom Finger Sensation Through Transcutaneous Electrical Nerve Stimulation.

Tactile sensory feedback would make a significant contribution to the state-of-the-art prosthetic hands for achieving dexterous manipulation over objects. Phantom finger sensation, also called referred sensation of lost fingers, can be noninvasively evoked by transcutaneous electrical nerve stimulation (TENS) of the phantom finger territories (PFTs) near the stump for upper-limb amputees. As such, intuitive sensations pertaining to lost fingers could be non-invasively generated. However, the encoding of stimulation parameters into tactile sensations that can be intuitively interpreted by the users remains a significant challenge. Further, how discriminative such artificial tactile sensation with TENS of the PFTs is still unknown. In this study, we systematically characterized the tactile discrimination across different phantom fingers on the stump skin by TENS among six subjects. Charge-balanced and biphasic stimulating current pulses were adopted. The pulse amplitude (PA), the pulse frequency (PF) and the pulse width (PW) were modulated to evaluate the detection threshold, perceived touch intensity, and the just-noticeable difference (JND) of the phantom finger sensation. Particularly, the recognition of phantom fingers under simultaneous stimulation was assessed. The psychophysical experiments revealed that subjects could discern fine variations of stimuli with comfortable sensation of phantom fingers including D1 (phantom thumb), D2 (phantom index finger), D3 (Phantom middle finger), and D5 (Phantom pinky finger). With respect to PA, PF, and PW modulations, the detection thresholds across the four phantom fingers were achieved by the method of constant stimuli based on a two-alternative forced-choice (2AFC) paradigm. For each modulation, the perceived intensity, which was indexed by skin indentations on the contralateral intact finger pulp, reinforced gradually with enhancing stimuli within lower-intensity range. Particularly, the curve of the indentation depth vs. PF almost reached a plateau with PF more than 200 Hz. Moreover, the performance of phantom finger recognition deteriorated with the increasing number of phantom fingers under simultaneous TENS. For one, two and four stimulating channels, the corresponding recognition rate of an individual PFT were respective 85.83, 67.67, and 46.44%. The results of the present work would provide direct guidelines regarding the optimization of stimulating strategies to deliver artificial tactile sensation by TENS for clinical applications.

An optimized content-aware image retargeting method: toward expanding the perceived visual field of the high-density retinal prosthesis recipients.

OBJECTIVE: Retinal prosthesis devices have shown great value in restoring some sight for individuals with profoundly impaired vision, but the visual acuity and visual field provided by prostheses greatly limit recipients' visual experience. In this paper, we employ computer vision approaches to seek to expand the perceptible visual field in patients implanted potentially with a high-density retinal prosthesis while maintaining visual acuity as much as possible. APPROACH: We propose an optimized content-aware image retargeting method, by introducing salient object detection based on color and intensity-difference contrast, aiming to remap important information of a scene into a small visual field and preserve their original scale as much as possible. It may improve prosthetic recipients' perceived visual field and aid in performing some visual tasks (e.g. object detection and object recognition). To verify our method, psychophysical experiments, detecting object number and recognizing objects, are conducted under simulated prosthetic vision. As control, we use three other image retargeting techniques, including Cropping, Scaling, and seam-assisted shrinkability. MAIN RESULTS: Results show that our method outperforms in preserving more key features and has significantly higher recognition accuracy in comparison with other three image retargeting methods under the condition of small visual field and low-resolution. SIGNIFICANCE: The proposed method is beneficial to expand the perceived visual field of prosthesis recipients and improve their object detection and recognition performance. It suggests that our method may provide an effective option for image processing module in future high-density retinal implants.

Chronic interfacing with the autonomic nervous system using carbon nanotube (CNT) yarn electrodes.

The ability to reliably and safely communicate chronically with small diameter (100-300 µm) autonomic nerves could have a significant impact in fundamental biomedical research and clinical applications. However, this ability has remained elusive with existing neural interface technologies. Here we show a new chronic nerve interface using highly flexible materials with axon-like dimensions. The interface was implemented with carbon nanotube (CNT) yarn electrodes to chronically record neural activity from two separate autonomic nerves: the glossopharyngeal and vagus nerves. The recorded neural signals maintain a high signal-to-noise ratio (>10 dB) in chronic implant models. We further demonstrate the ability to process the neural activity to detect hypoxic and gastric extension events from the glossopharyngeal and vagus nerves, respectively. These results establish a novel, chronic platform neural interfacing technique with the autonomic nervous system and demonstrate the possibility of regulating internal organ function, leading to new bioelectronic therapies and patient health monitoring.

A 3D Computational Model of Transcutaneous Electrical Nerve Stimulation for Estimating Aß Tactile Nerve Fiber Excitability.

Tactile sensory feedback plays an important role in our daily life. Transcutaneous electrical nerve stimulation (TENS) is widely accepted to produce artificial tactile sensation. To explore the underlying mechanism of tactile sensation under TENS, this paper presented a novel 3D TENS computational model including an active Aß tactile nerve fiber (TNF) model and a forearm finite element model with the fine-layered skin structure. The conduction velocity vs. fiber diameter and strength-duration relationships in this combined TENS model matched well with experimental data. Based on this validated TENS model, threshold current variation were further investigated under different stimulating electrode sizes with varied fiber diameters. The computational results showed that the threshold current intensity increased with electrode size, and larger nerve fibers were recruited at lower current intensities. These results were comparable to our psychophysical experimental data from six healthy subjects. This novel 3D TENS model would further guide the floorplan of the surface electrodes, and the stimulating paradigms for tactile sensory feedback.

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.

Effects of different three-dimensional electrodes on epiretinal electrical stimulation by modeling analysis.

BACKGROUND: Epiretinal prostheses have been greatly successful in helping restore the vision of patients blinded by retinal degenerative diseases. The design of stimulating electrodes plays a crucial role in the performance of epiretinal prostheses. The objective of this study was to investigate, through computational modeling analysis, the effects on the excitation of retinal ganglion cells (RGCs) when different three-dimensional (3-D) electrodes were placed in the epiretinal space. METHODS: 3-D finite element models of retinal electrical stimulation were created in COMSOL using a platinum microelectrode, a vitreous body, multi-layered retinal tissue, and retinal pigment epithelium (RPE). Disk and non-planar electrodes with different 3-D structures were used in the epiretinal electrical stimulation. In addition, a multi-RGC model including ionic mechanisms was constructed in NEURON to study the excitability of RGCs in response to epiretinal electrical stimulation by different types of electrodes. Threshold current, threshold charge density, and the activated RGC area were the three key factors used to evaluate the stimulating electrode's performance. RESULTS: As the electrode-retina distance increased, both threshold current and threshold charge density showed an approximately linear relationship. Increasing the disk electrode's diameter resulted in an increase in threshold current and a decrease in threshold charge density. Non-planar electrodes evoked different activation responses in RGCs than the disk electrode. Concave electrodes produced superior stimulation localization and electrode safety while convex electrodes performed relatively poorly. CONCLUSIONS: Investigation of epiretinal electrical stimulation using different 3-D electrodes would further the optimization of electrode design and help improve the performance of epiretinal prostheses. The combination of finite element analysis in COMSOL and NEURON software provides an efficient way to evaluate the influences of various 3-D electrodes on epiretinal electrical stimulation. Non-planar electrodes had larger threshold currents than disk electrodes. Of the five types of electrodes, concave hemispherical electrodes may be the ideal option, considering their superior stimulation localization and electrode safety.

3D finite element modeling of epiretinal stimulation: Impact of prosthetic electrode size and distance from the retina.

PURPOSE: A novel 3-dimensional (3D) finite element model was established to systematically investigate the impact of the diameter (Φ) of disc electrodes and the electrode-to-retina distance on the effectiveness of stimulation. METHODS: The 3D finite element model was established based on a disc platinum stimulating electrode and a 6-layered retinal structure. The ground electrode was placed in the extraocular space in direct attachment with sclera and treated as a distant return electrode. An established criterion of electric-field strength of 1000 Vm-1 was adopted as the activation threshold for RGCs. RESULTS: The threshold current (TC) increased linearly with increasing Φ and electrode-to-retina distance and remained almost unchanged with further increases in diameter. However, the threshold charge density (TCD) increased dramatically with decreasing electrode diameter. TCD exceeded the electrode safety limit for an electrode diameter of 50 µm at an electrode-to-retina distance of 50 to 200 µm. The electric field distributions illustrated that smaller electrode diameters and shorter electrode-to-retina distances were preferred due to more localized excitation of RGC area under stimulation of different threshold currents in terms of varied electrode size and electrode-to-retina distances. Under the condition of same-amplitude current stimulation, a large electrode exhibited an improved potential spatial selectivity at large electrode-to-retina distances. CONCLUSIONS: Modeling results were consistent with those reported in animal electrophysiological experiments and clinical trials, validating the 3D finite element model of epiretinal stimulation. The computational model proved to be useful in optimizing the design of an epiretinal stimulating electrode for prosthesis.

Spatial characteristics of evoked potentials elicited by a MEMS microelectrode array for suprachoroidal-transretinal stimulation in a rabbit.

BACKGROUND: Suprachoroidal-transretinal stimulation (STS) can potentially restore vision. This study investigated the spatial characteristics of cortical electrical evoked potentials (EEPs) elicited by STS. METHODS: A 4 × 4 thin-film platinum microelectrode stimulating array (200 µm electrode diameter and 400 µm center-to-center distance) was fabricated by a micro-electro-mechanical systems (MEMS) techniques and implanted into the suprachoroidal space of albino rabbits. RESULTS: The current threshold to elicit reliable EEPs by a single electrode was 41.6 ± 12.6 µA, corresponding to a 66.2 ± 20.1 µC · cm(-2) charge density per phase, which was lower than the reported safety limits. Spatially differentiated cortical responses could be evoked by STS through different rows or columns of electrical stimulation; furthermore, shifts in the location of the maximum cortical activities were consistent with cortical visuotopic maps; increasing the number of simultaneously stimulating electrodes increased the response amplitudes of EEPs and expanded the spatial spread as well. In addition, long-term implantation and electrical stimulation of the MEMS electrode array in suprachoroidal space are necessary to evaluate systematically the safety and biocompatibility of this approach. CONCLUSIONS: This study indicates that the STS approach by a MEMS-based platinum electrode array is a feasible alternative for visual restoration, and relatively high spatial discrimination may be achieved.

A simulation of current focusing and steering with penetrating optic nerve electrodes.

OBJECTIVE: Current focusing and steering are both widely used to shape the electric field and increase the number of distinct perceptual channels in neural stimulation, yet neither technique has been used for an optic nerve (ON)-based visual prosthesis. In order to evaluate the effects of current focusing and steering in penetrative stimulation, we built an integrated computational model to simulate and investigate the influence of stimulating parameters on ON fibre recruitment. APPROACH: Finite element models with extremely fine meshes were first established to compute the 3D electric potential distribution under different stimulating parameters. Then the external electric potential was fed to randomized multi-compartment cable models to predict the distribution of fibres generating an action potential. Finally a statistical process was conducted to quantify the recruitment region. MAIN RESULTS: The simulation results show that a two-electrode mode is superior to a three-electrode mode in current steering. The three-electrode mode performs poorly in current focusing, albeit the localized recruitment from both configurations implies that current focusing might be unnecessary in penetrative ON stimulation. SIGNIFICANCE: This study provides useful information for the optimized design of penetrating ON electrodes and stimulating strategies. The Monte Carlo style computation paradigm is designed to simulate neural responses of an ensemble of ON fibres, which can be immediately transferred to other similar problems.

[In-vitro electrochemical stability evaluation of a flexible MEMS microelectrode].

Three-electrode testing method was used to investigate the effect of temperature on electrode impedance, and the pH shifts in saline solution resulting from the electrical stimulation were also determined. Experiments in PBS (phosphate buffered solution) solution showed that the electrode impedance was almost invariable at the human body temperature range (35 degrees C-40 degrees C). And the experiments in unbuffered saline solution showed that pH shifts decreased from 0.03 to 0.005 when the frequency of biphasic charged-balanced pulses increased from 1 Hz to 100 Hz. Even stimulated by monophasic pulses (frequency is 15 Hz, amplitude is 50 microA), the stimulus-induced pH shift of electrode only varies 0.15 (anodic pulse current increased 0.15 and cathodic pulse current decreased 0.15).

In vitro and in vivo evaluation of a photosensitive polyimide thin-film microelectrode array suitable for epiretinal stimulation.

BACKGROUND: Epiretinal implants based on microelectro-mechanical system (MEMS) technology with a polyimide (PI) material are being proposed for application. Many kinds of non-photosensitive PIs have good biocompatibility and stability as typical MEMS materials for implantable electrodes. However, the effects of MEMS microfabrication, sterilization and implantation using a photosensitive polyimide (PSPI) microelectrode array for epiretinal electrical stimulation has not been extensively examined. METHODS: A novel PSPI (Durimide 7510) microelectrode array for epiretinal electrical stimulation was designed, fabricated based on MEMS processing and microfabrication techniques. The biocompatibility of our new microelectrode was tested in vitro using an MTT assay and direct contact tests between the microelectrode surface and cells. Electrochemical impedance characteristics were tested based on a three-electrode testing method. The reliability and stability was evaluated by a chronic implantation of a non-functional array within the rabbit eye. Histological examination and SEM were performed to monitor possible damage of the retina and microelectrodes. Electrically evoked potentials (EEPs) were recorded during the acute stimulation of the retina. RESULTS: The substrate was made of PSPI and the electrode material was platinum (Pt). The PSPI microelectrode array showed good biocompatibility and appropriate impedance characteristics for epiretinal stimulation. After a 6-month epiretinal implantation in the eyes of rabbits, we found no local retinal toxicity and no mechanical compression caused by the array. The Pt electrodes adhesion to the PSPI remained stable. A response to electrical stimuli was with recording electrodes lying on the visual cortex. CONCLUSION: We provide a relevant design and fundamental characteristics of a PSPI microelectrode array. Strong evidences on testing indicate that implantation is safe in terms of mechanical pressure and biocompatibility of PSPI microelectrode arrays on the retina. The dual-layer process we used proffers considerable advantages over the more traditional single-layer approach and can accommodate much many electrode sites. This lays the groundwork for a future, high-resolution retinal prosthesis with many more electrode sites based on the flexible PSPI thin film substrate.