Electrically-evoked Potentials Research Articles

Classification of electrically-evoked potentials in the parkinsonian subthalamic nucleus region

Electrically evoked compound action potentials (ECAPs) generated in the subthalamic nucleus (STN) contain features that may be useful for titrating deep brain stimulation (DBS) therapy for Parkinson’s disease. Delivering a strong therapeutic effect with DBS therapies, however, relies on selectively targeting neural pathways to avoid inducing side effects. In this study, we investigated the spatiotemporal features of ECAPs in and around the STN across parameter sweeps of stimulation current amplitude, pulse width, and electrode configuration, and used a linear classifier of ECAP responses to predict electrode location. Four non-human primates were implanted unilaterally with either a directional (n = 3) or non-directional (n = 1) DBS lead targeting the sensorimotor STN. ECAP responses were characterized by primary features (within 1.6 ms after a stimulus pulse) and secondary features (between 1.6 and 7.4 ms after a stimulus pulse). Using these features, a linear classifier was able to accurately differentiate electrodes within the STN versus dorsal to the STN in all four subjects. ECAP responses varied systematically with recording and stimulating electrode locations, which provides a subject-specific neuroanatomical basis for selecting electrode configurations in the treatment of Parkinson’s disease with DBS therapy.

The influence of stimulating electrode conditions on electrically evoked potentials and resistance in suprachoroidal transretinal stimulation.

To determine the influence of stimulating electrode conditions on the amplitudes and latencies of electrically evoked potentials (EEPs) and the resistance at the electrode-tissue interface in the suprachoroidal transretinal stimulation (STS) system. Experimental study. A scleral pocket (3 × 5 mm) was created just over the visual streak in anesthetized pigmented rabbits (weight, 1.9-2.7 kg), and STS stimulating electrodes were implanted into the pocket. Measurements were obtained with stimulating electrodes of different lengths (0.3 or 0.5 mm) and different surface characteristics (smooth or porous). EEPs elicited with a fixed current under each set of electrode conditions were recorded; three measurement sessions were performed for each rabbit. The resistance at each electrode-tissue interface was measured. The latencies and amplitudes of the EEPs did not differ significantly with changes in the height and surface characteristics of the stimulating electrodes, but the resistances at the electrode-tissue interface differed significantly (P = 0.001; the resistance values for the 0.3-mm-long electrode with a porous surface was 5.24 ± 0.67 kΩ and with the 0.3- and 0.5-mm-long electrodes with smooth surfaces were 7.63 ± 0.12 kΩ and6.77 ± 0.20 kΩ). Being shorter did not affect the EEPs of the stimulating electrodes with a porous surface while decreasing the resistance at the electrode-tissue interface.

Monitoring Cortical Response and Electrode-Retina Impedance Under Epiretinal Stimulation in Rats.

Retinal prosthesis can restore partial vision in patients with retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Epiretinal prosthesis is one of three therapeutic approaches, which received regulatory approval several years ago. The thresholds of an epiretinal stimulation is partly determined by the size of the physical gap between the electrode and the retina after implantation. Precise positioning of epiretinal stimulating electrode array is still a challenging task. In this study, we demonstrate an approach to positioning epiretinal prostheses for an optimal response at the cortical output by monitoring both the impedance at the electrode-retina interface and the evoked-potential at the cortical level. We implanted a single-channel electrode on the epiretinal surface in adult rats, acutely, guided by both the impedance at the electrode-retina interface and by electrically evoked potentials (EEPs) in the visual cortex during retinal stimulation. We observe that impedance monotonously increases with decreasing electrode-retina distance, but that the strongest cortical responses were achieved at intermediate impedance levels. When the electrode penetrates the retina, the impedance keeps increasing. The effect of stimulation on the retina changes from epiretinal paradigm to intra-retinal paradigm and a decrease in cortical activation is observed. It is found that high impedance is not always favorable to elicit best cortical responses. Histopathological results showed that the electrode was placed at the intra-retinal space at high impedance value. These results show that monitoring impedance at the electrode-retina interface is necessary but not sufficient in obtaining strong evoked-potentials at the cortical level. Monitoring the cortical EEPs together with the impedance can improve the safety of implantation as well as efficacy of stimulation in the next generation of retinal implants.

Electrically Evoked Potentials Are Reduced Compared to Axon Numbers in Rhodopsin P347L Transgenic Rabbits With Severe Photoreceptor Degeneration.

To determine the relationship between the amplitudes of the electrically evoked potentials (EEPs) and the number of optic nerve axons at a late stage of retinal degeneration in rhodopsin P347L transgenic (Tg) rabbits, a model of retinitis pigmentosa. Six eyes of six wild-type (WT) (43.8 ± 7.5 months of age) and six eyes of six Tg (40.3 ± 2.6 months of age) rabbits were studied. The EEPs were elicited by 1 to 5 mA of transcorneal electrical stimulation. The first positive wave, the P1 component, was analyzed. After euthanasia, the number of axons in the optic nerve was counted. The threshold current to elicit a P1 was significantly higher in Tg rabbits than WT rabbits. The amplitude of P1 elicited by 5 mA in Tg rabbits was about 24% of that in WT rabbits (P < 0.01). The number of axons in the optic nerve of Tg rabbits was reduced to about 59% of that of WT rabbits (P < 0.01). The correlation between the axon number and the amplitude of the P1 in Tg and WT rabbits was not significant. The mean ratio of the P1 amplitude/axon in Tg rabbits was decreased to 53% of that in WT rabbits (P < 0.05). The degree of reduction in the EEP in Tg rabbits is more severe than the reduction in the number of optic nerve axons. The use of transcorneal electrical stimulation to determine the suitable candidates for prosthesis at the end-stage of retinitis pigmentosa may underestimate the condition of the optic nerves.

Electrophysiological evaluation of a chronically implanted electrode for suprachoroidal transretinal stimulation in rabbit eyes.

In this study, we aimed to determine the electrophysiological efficacy, safety, and electrical stability of a chronically implanted electrode for suprachoroidal transretinal stimulation (STS) in rabbit eyes. A platinum microelectrode was implanted into the scleral pocket of rabbit eyes (n = 5) and followed-up for 6months. To evaluate the electrophysiological efficacy, electrically evoked potentials (EEPs) were measured every month after implantation. To evaluate safety, fundus examinations, fluorescein angiograms, electroretinograms (ERGs), and visually evoked potentials (VEPs) were measured before and every month after the implantation. At the end of the experiment, histological examination of retinal tissue beneath the site of the electrode was performed. To evaluate electrical stability, the resistance of the circuit was measured every month after implantation. EEPs could be elicited from the STS electrodes at all testing times. The mean threshold current to evoke EEPs was 186.4 ± 47.0µA at 6months after implantation. There was no significant change in the threshold over the follow-up period. The resistance of the circuit was significantly increased at 1months after implantation, with no further increase at 6months. There was no statistically significant change in the relative amplitudes and implicit times of a- and b-waves of ERGs and VEPs. No intraocular infection, inflammation, or vitreoretinal proliferation was observed in any eye. Histological examination revealed no retinal damage beneath the electrode. We conclude that chronically implanted electrodes for STS appear to be effective, safe, and electrically stable.

Properties of electrically evoked potentials activated by optic nerve stimulation with penetrating electrodes of different modes in rabbits.

To investigate the effect of different stimulation modes on cortical electrically evoked potentials (EEPs) by intraorbital optic nerve (ON) stimulation with penetrating electrodes. A stimulating electrode array with three electrodes arranged linearly was inserted into the ON along its axis. EEPs were recorded using a 4 × 4 silver-ball electrode array in response to monopolar and bipolar stimulation mode, respectively. The simultaneous monopolar stimulation mode had a lower threshold than the individual monopolar stimulation mode, but elicited smaller cortical response when a fixed charge was injected. The threshold of the bipolar stimulation mode was comparable to that of individual monopolar stimulation mode. The response to the smaller spacing (150μm) bipolar stimulation mode was similar in amplitude to that of the individual monopolar stimulation mode, but spread wider. The larger spacing (500μm) bipolar stimulation mode elicited stronger and wider response than the individual monopolar stimulation mode. For the individual monopolar stimulation mode, stimulation with different electrodes can be differentiated even when the spacing of the two electrodes was 150μm. For ON stimulation with penetrating electrodes, the monopolar stimulation mode could induce more localized cortical responses than the bipolar stimulation mode with comparable threshold and had a high stimulation selectivity. These findings may provide valuable information for the design of stimulation strategy of the penetrative ON visual prosthesis.

Surgical feasibility and biocompatibility of wide-field dual-array suprachoroidal-transretinal stimulation prosthesis in middle-sized animals.

To investigate the safety and efficacy of a newly-developed wide-field dual-array suprachoroidal-transretinal stimulation (STS) prosthesis in middle-sized animals. The prosthesis consisted of two arrays with 50 to 74 electrodes. To test the feasibility of implanting the prosthesis and its efficacy, the prosthesis was implanted for 14days into two rabbits. Optical coherence tomography (OCT) and ophthalmoscopy were performed 7 and 14days after the implantation. Then the rabbits were euthanized, eyes were enucleated, and the posterior segment of the eye was examined histologically. In a second experiment, the arrays were implanted into two cats, and their ability to elicit neural responses was determined by electrically evoked potentials (EEPs) at the chiasm and by optical imaging of the retina. All arrays were successfully implanted, and no major complications occurred during the surgery or during the 2-week postoperative period. Neither OCT nor ophthalmoscopy showed any major complications or instability of the arrays. Histological evaluations showed only mild cellular infiltration and overall good retinal preservation. Stimulation of the retina by the arrays evoked EEPs recorded from the chiasm. Retinal imaging showed that the electrical pulses from the arrays altered the retinal images indicating an activation of retinal neurons. The thresholds were as low as 100μA for a chiasm response and 300μA for the retinal imaging. Implantation of a newly-developed dual-array STS prosthesis for 2weeks in rabbits was feasible surgically, and safe. The results of retinal imaging showed that the dual-array system was able to activate retinal neurons. We conclude that the dual-array design can be implanted without complication and is able to activate retinal neurons and optic nerve axons.

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

Suprachoroidal-transretinal stimulation (STS) can potentially restore vision. This study investigated the spatial characteristics of cortical electrical evoked potentials (EEPs) elicited by STS. 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. 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. 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.

Retinal origin of electrically evoked potentials in response to transcorneal alternating current stimulation in the rat.

Little is known about the physiological mechanisms underlying the reported therapeutic effects of transorbital alternating current stimulation (ACS) in vision restoration, or the origin of the recorded electrically evoked potentials (EEPs) during such stimulation. We examined the issue of EEP origin and electrode configuration for transorbital ACS and characterized the physiological responses to CS in different structures of the visual system. We recorded visually evoked potentials (VEPs) and EEPs from the rat retina, visual thalamus, tectum, and visual cortex. The VEPs were evoked by light flashes and EEPs were evoked by electric stimuli delivered by two electrodes placed either together on the same eye or on the eyeball and in the neck. Electrically evoked potentials and VEPs were recorded before and after bilateral intraorbital injections of tetrodotoxin that blocked retinal ganglion cell activity. Tetrodotoxin abolished VEPs at all levels in the visual pathway, confirming successful blockage of ganglion cell activity. Tetrodotoxin also abolished EEPs and this effect was independent of the stimulating electrode configurations. Transorbital electrically evoked responses in the visual pathway, irrespective of reference electrode placement, are initiated by activation of the retina and not by passive conductance and direct activation of neurons in other visual structures. Thus, placement of stimulating electrodes exclusively around the eyeball may be sufficient to achieve therapeutic effects.

Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis

Objective. The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. Approach. A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. Main results. The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm−2). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. Significance. Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.

Lateral geniculate body evoked potentials elicited by visual and electrical stimulation.

PurposeBlind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli.MethodsFor visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 µA.ResultsOur experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred.ConclusionsEEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.

Penetrating electrode stimulation of the rabbit optic nerve: parameters and effects on evoked cortical potentials

Stimulus parameters, in particular pulse shape, are an important consideration in the application of electrical stimulation when experimentally testing a visual prosthesis. We changed the biphasic pulse shape of several asymmetric charge-balanced pulses to investigate their effect on optic nerve (ON) stimulation and the recorded cortical response. Monopolar platinum-iridium electrodes were implanted into the rabbit's ON behind the eyeball. Electrical evoked potentials (EEPs) were recorded with silver ball electrodes placed on the cortex, and the results quantified. Our results indicate that changing the shape of cathodic-first charge-balanced biphasic pulse (CA) while maintaining charge balance could reduce the current thresholds for stimulation. When stimulated at the same charge density, the stimulus having high-amplitude short-duration (HASD) cathodic phase produced a higher amplitude response, with a larger spatial spread but with a lower current threshold compared with other stimuli. Adding an inter-phase gap between the two phases of the stimulus increased the EEP amplitude, but was saturated at a gap of ∼0.2 ms; this was most obvious with CA stimulation, which was able to elicit a larger cortical response than that elicited by asymmetrical charge-balanced stimulus pulses with HASD cathodic phase, in contrast to CA without a gap. As the stimulating frequency increased, the amplitudes of the EEP components elicited by CA monotonically decreased. The fastest component (P0) was present with stimulating frequencies as high as 80 Hz, while the slower P1 and P2 disappeared with stimulating frequencies higher than 40 and 20 Hz, respectively. A CA stimulus waveform with an inter-phase gap of 0.2 ms was more efficacious for ON stimulation than other stimulus combinations, and therefore should result in less tissue damage, minimal electrode etching, and lower power consumption if used in a visual prosthesis.

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

BackgroundEpiretinal 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.MethodsA 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.ResultsThe 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.ConclusionWe 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.

Fabrication and In vivo Evaluation of Poly(3,4-ethylenedioxythiophene) Stimulus Electrodes for Fully Implantable Retinal Prosthesis

The development of poly(3,4-ethylenedioxythiophene) (PEDOT) stimulus electrodes and the relationship between the electrical stimulation of a rabbit retina and electrically evoked potential (EEP) were studied in detail. We fabricated implantable flexible cables with Pt, IrOx, and PEDOT electrodes and evaluated the electrochemical impedances (EIs) and charge injection capacities (CICs) of such electrodes. From the result, we confirmed that PEDOT electrodes have both lower EIs and larger CICs than Pt and IrOx electrodes. In addition, we performed in vivo experiments with PEDOT electrodes and clarified the relationships between the electrical stimulation of the rabbit retina and EEP. It is highly probable that visual restoration will be realized safely with PEDOT electrodes.

Performance of conducting polymer electrodes for stimulating neuroprosthetics

Objective. Recent interest in the use of conducting polymers (CPs) for neural stimulation electrodes has been growing; however, concerns remain regarding the stability of coatings under stimulation conditions. These studies examine the factors of the CP and implant environment that affect coating stability. The CP poly(ethylene dioxythiophene) (PEDOT) is examined in comparison to platinum (Pt), to demonstrate the potential performance of these coatings in neuroprosthetic applications. Approach. PEDOT is coated on Pt microelectrode arrays and assessed in vitro for charge injection limit and long-term stability under stimulation in biologically relevant electrolytes. Physical and electrical stability of coatings following ethylene oxide (ETO) sterilization is established and efficacy of PEDOT as a visual prosthesis bioelectrode is assessed in the feline model. Main results. It was demonstrated that PEDOT reduced the potential excursion at a Pt electrode interface by 72% in biologically relevant solutions. The charge injection limit of PEDOT for material stability was found to be on average 30× larger than Pt when tested in physiological saline and 20× larger than Pt when tested in protein supplemented media. Additionally stability of the coating was confirmed electrically and morphologically following ETO processing. It was demonstrated that PEDOT-coated electrodes had lower potential excursions in vivo and electrically evoked potentials (EEPs) could be detected within the visual cortex. Significance. These studies demonstrate that PEDOT can be produced as a stable electrode coating which can be sterilized and perform effectively and safely in neuroprosthetic applications. Furthermore these findings address the necessity for characterizing in vitro properties of electrodes in biologically relevant milieu which mimic the in vivo environment more closely.

Brain State-Dependence of Electrically Evoked Potentials Monitored With Head-Mounted Electronics

Inferring changes in brain connectivity is critical to studies of learning-related plasticity and stimulus-induced conditioning of neural circuits. In addition, monitoring spontaneous fluctuations in connectivity can provide insight into information processing during different brain states. Here, we quantified state-dependent connectivity changes throughout the 24-h sleep-wake cycle in freely behaving monkeys. A novel, head-mounted electronic device was used to electrically stimulate at one site and record evoked potentials at other sites. Electrically evoked potentials (EEPs) revealed the connectivity pattern between several cortical sites and the basal forebrain. We quantified state-dependent changes in the EEPs. Cortico-cortical EEP amplitude increased during slow-wave sleep, compared to wakefulness, while basal-cortical EEP amplitude decreased. The results demonstrate the utility of using portable electronics to document state-dependent connectivity changes in freely behaving primates.

Automated single-trial assessment of laser-evoked potentials as an objective functional diagnostic tool for the nociceptive system

ObjectiveTo assess the clinical usefulness of an automated analysis of event-related potentials (ERPs). MethodsNociceptive laser-evoked potentials (LEPs) and non-nociceptive somatosensory electrically-evoked potentials (SEPs) were recorded in 37 patients with syringomyelia and 21 controls. LEP and SEP peak amplitudes and latencies were estimated using a single-trial automated approach based on time-frequency wavelet filtering and multiple linear regression, as well as a conventional approach based on visual inspection. ResultsThe amplitudes and latencies of normal and abnormal LEP and SEP peaks were identified reliably using both approaches, with similar sensitivity and specificity. Because the automated approach provided an unbiased solution to account for average waveforms where no ERP could be identified visually, it revealed significant differences between patients and controls that were not revealed using the visual approach. ConclusionThe automated analysis of ERPs characterized reliably and objectively LEP and SEP waveforms in patients. SignificanceThe automated single-trial analysis can be used to characterize normal and abnormal ERPs with a similar sensitivity and specificity as visual inspection. While this does not justify its use in a routine clinical setting, the technique could be useful to avoid observer-dependent biases in clinical research.

Evaluation of a MEMS-Based Dual Metal-Layer Thin-Film Microelectrode Array for Suprachoroidal Electrical Stimulation

A double metal-layer thin-film platinum microelectrode array was fabricated for implantation between sclera and choroid based on MEMS processing techniques and photosensitive polyimide material. The array was composed of 60 stimulating sites (6 × 10) and four selectable returning electrodes. The diameter of each stimulating electrode was 350 μ m with a center-to-center spacing of 750 μm. The transient voltage responses of the electrode to current pulse stimulation indicated a charge-injection capacity greater than 52.1 μ C/cm (2) . Acute in vivo animal experiments showed that the implicit time of electrically evoked potentials (EEPs) was 17.09±1.45 ms at a threshold current of 25.55 ±5.43 μA for a full-row of simultaneously stimulated electrodes (i.e., current applied simultaneously to each of the 10 electrodes). Individual electrode stimulation threshold was 48.57 ±6.90 μA. The corresponding threshold charge densities were 13.28 ±2.82 μC/cm (2) and 25.24 ±3.59 μC/cm (2) , respectively. The spatial spread of the maximally recorded P1 response in the EEPs indicated a correspondence between the retinal stimulation site and the focal response location in the cortex. This method of array fabrication is suitable for acute suprachoroidal stimulation, and has a potential use for the fabrication of a visual prosthesis.

Implantation of a newly developed direct optic nerve electrode device for artificial vision in rabbits

The purpose of this study was to investigate the surgical procedures involved in the implantation of a newly developed direct optic nerve electrode device for inducing artificial vision. The electrode device comprised seven wire stimulation electrodes and a return electrode (diameter 50μm), one manipulation rod (diameter 100μm), and a cylindrical silicone board (diameter 2.0mm). The stimulation electrodes and the manipulation rod protruded through the board to allow implantation of the electrode tips into the optic disc of the rabbit eye. The surgical procedures required to insert the device into the vitreous cavity and implant the device into the optic disc were evaluated. When the electrodes were stimulated, electrically evoked potentials (EEPs) were recorded at the visual cortex. The electrode device was inserted into the vitreous cavity with no damage using a trocar through a scleral incision. The device was easily manipulated using vitreoretinal forceps in the vitreous cavity, and the electrode tips were implanted into the optic disc in a single insertion after vitrectomy. When electrical stimulation was applied, EEPs were recorded from all electrode pairs. The newly developed electrode device was inserted into the eye and implanted into the optic nerve disc smoothly and safely, suggesting that these surgical procedures are useful for our artificial vision system.

Using independent component analysis to remove artifacts in visual cortex responses elicited by electrical stimulation of the optic nerve

In visual prosthesis research, electrically evoked potentials (EEPs) can be elicited by one or more biphasic current pulses delivered to the optic nerve (ON) through penetrating electrodes. Multi-channel EEPs recorded from the visual cortex usually contain large stimulus artifacts caused by instantaneous electrotonic current spread through the brain tissue. These stimulus artifacts contaminate the EEP waveform and often make subsequent analysis of the underlying neural responses difficult. This is particularly serious when investigating EEPs in response to electrical stimulation with long duration and multi-pulses. We applied independent component analysis (ICA) to remove these electrical stimulation-induced artifacts during the development of a visual prosthesis. Multi-channel signals were recorded from visual cortices of five rabbits in response to ON electrical stimulation with various stimulus parameters. ON action potentials were then blocked by lidocaine in order to acquire cortical potentials only including stimulus artifacts. Correlation analysis of reconstructed artifacts by ICA and artifacts recorded after blocking the ON indicates successful removal of artifacts from electrical stimulation by the ICA method. This technique has potential applications in studies designed to optimize the electrical stimulation parameters used by visual prostheses.