Role of dominant motivation in producing the effects of electric stimulation of hypothalamo-limbic structures

The experiments were made on cats with electrodes chronically implanted in the hypothalamus and the amygdala. The effects of electrical stimulation of the points from which the food reactions were initially evoked, were transformed into an avoidance reaction, if stimulation was applied in surroundings where the animals had previously received pain stimuli. Defensive reactions to stimulation of the hypothalamus and amygdala changed to alimentary reactions if the same stimulation was presented to hungry cats in conditions of repetitive feeding. A conclusion has been drawn that the elements of the hypothalamo-limbic structures have plastic properties and may be involved in different forms of behaviour, depending on current motivation and learning.     

Interaction between neurons of the frontal cortex and hippocampus during the realization of choice of food reinforcement quality in cats

Six cats were subjected to the procedure of appetitive instrumental conditioning (with light as a conditioned stimuls) by the method of the "active choice" of reinforcement quality. Short-delay conditioned bar-press responses were rewarded with bread-meat mixture, and the delayed responses were reinforced by meat. The animals differed in behavior strategy: four animals preferred the bar-pressing with a long delay (the so-called "self-control" group), and two cats preferred the bar-pressing with a short delay (the so-called "impulsive" group). Multiunit activity in the frontal cortex and hippocampus (CA3) was recorded via chronically implanted nichrome wire semimicroelectrodes. An interaction between the neighboring neurons in the frontal cortex and hippocampus (within local neural networks) and between the neurons of the frontal cortex and hippocampus (distributed neural networks in frontal-hippocampal and hippocampal-frontal directions) was evaluated by means of statistical crosscorrelation analysis of spike trains. Crosscorrelations between neuronal spike trains in the delay range of 0-100 ms were explored. It was shown that the number of crosscorrelations between the neuronal discharges both in the local and distributed networks was significantly higher in the "self-control" cats. It was suggested that the local and distributed neural networks of the frontal cortex and hippocampus are involved in the system of brain structures which determine the behavioral strategy of animals in the "self-control" group.     

Response of cortical evoked potentials to electric stimulation of the acoustic nerve in animals with damaged cochlea

Evoked potentials of the auditory cortex during the electrical stimulation of the cochlea were studied in acute experiments on cats. A series of electric pulses of short duration and different frequency delivered to the streptomycin-damaged cochlea were used as a stimulus. It has been shown that an amplitude and latency of electrical cortex responses depended on the number of pulses in series and on the interpulse intervals. Amplitudes of evoked responses increased with the growth of the number of stimuli. Latent periods changed in a narrower stimulation frequency band. Dependence of the induced potentials' amplitude growth on the increase in the number of electric pulses changed as a result of the two-fold enhancement of the stimulation amplitude.     

The possibility of elaborating conditioned reflexes on the basis of emotional reactions evoked by electrical stimulation of limbic structures]

In experiments on cats with chronically implanted electrodes a conditioned stimulus (200 c/s tone) was paired with electrical stimulation of limbic structures, which produces pronounced emotional behaviour: defensive, aggressive, alimentary or drinking reactions. It has been shown that conditioned reactions are not elaborated on the basis of electrical stimulation, which activates alimentary, drinking or aggressive behaviour. Neither is a conditioned reflex formed to the combination of sound and stimulation of the brain structures, which inhibits alimentary behaviour. A distinct conditioned fear reaction sets in as a result of combination of sound and electrical stimulation of brain structures, which evoke defensive behaviour. The data obtained are analyzed in the light of the significance of natural requirements of the organism for the elaboration of conditioned reflexes.     

Modifications of acoustic habituation by interruption of visual input in quipazine treated cats

The influence of interruption of the visual input on acoustic habituation was studied in cats before and following the administration of quipazine, 3 mg/kg iv. The characteristics of acoustic habituation were analyzed through the magnitude and temporal course of multiunit activity (MUA) responses elicited in the mesencephalic reticular formation (MRF) by repetitive acoustic stimuli (70 db, 50 Hz trains of 2 sec duration) in 6 freely moving cats with cortical electrodes over the parietal cortex and bipolar electrodes chronically implanted in MRF and basolateral amygdala (AMN). The cats were submitted to repetitive acoustic stimulation during one 30 min period before, and three 30 min periods after drug administration in the following conditions: a) with unmasked eyes; b) with masked eyes by means of dark contact lenses. Persistent attentive behavior, catatonic attitudes, hypersynchronous (6 Hz, 100-150 microV) EEG activity and significant increase of spontaneous MUA in FRM and AMN were induced by quipazine both in the cats tested with unmasked and with masked eyes. This increase of MUA was higher immediately following drug administration and progressively decreased, although MUA values remained significantly higher than controls 110 min after quipazine administration. Acoustic habituation, evidenced through the progressive decrease of MUA responses of MRF to acoustic stimuli, was observed before quipazine administration when the cats were tested with unmasked and with masked eyes; as well as in cats tested with unmasked eyes following drug administration. However, the MUA responses to acoustic stimuli did not decrease in cats with masked eyes during acoustic stimulation periods 0-30 min and 40-70 min after quipazine administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of cortical ablations on the turning response evoked by stimulation of the pulvinar-lateralis posterior nucleus complex in the cat

The role played by the cerebral cortex on turning responses elicited by electrical stimulation of P-LP was studied in 9 chronic cats. In three animals the sensorimotor cortex was bilaterally ablated and the threshold values for inducing a turning response were determined. None of the cats showed abnormal threshold values. In six cats the cerebral cortical area known to have reciprocal anatomical connections with P-LP was unilaterally removed. Seven days after surgery, 50% of the electrodes gave no responses; 25% evoked responses with high thresholds and 25% with normal thresholds. One month after surgery the percentages were: 14, 18 and 68 respectively. Histological findings show important fiber and neuronal degeneration in P-LP. It is postulated that this area of the cerebral cortex plays, a facilitatory role on the P-LP ability to induce turning response and that the recovery of this ability can be explained by the development of P-LP denervation supersensitivity.     

Effects of bromocryptine on hepatic blood volume responses to hepatic nerve stimulation in cats

Arterial pressures, portal pressures, and hepatic blood volumes were recorded after hepatic denervation in cats anesthetized with pentobarbital. Bromocryptine (50 micrograms/kg) lowered arterial pressure but did not significantly change portal pressure or hepatic blood volume. However, both portal pressure and hepatic blood volume responses to hepatic nerve stimulation were significantly depressed after bromocryptine especially at low frequencies of stimulation. Responses to intraportal infusions of norepinephrine were significantly impaired only at the highest dose. The inhibitory effect of bromocryptine on the neural responses may, therefore, involve a presynaptic inhibition of norepinephrine release, but the mechanism requires further study. These data provide further support for the hypothesis that drugs which impair hepatic venous responses to sympathetic stimuli cause significant impairment of postural reflexes and orthostatic hypotension during clinical use.     

Whole Cell Patch Clamp for Investigating the Mechanisms of Infrared Neural Stimulation

It has been demonstrated in recent years that pulsed, infrared laser light can be used to elicit electrical responses in neural tissue, independent of any further modification of the target tissue. Infrared neural stimulation has been reported in a variety of peripheral and sensory neural tissue in vivo, with particular interest shown in stimulation of neurons in the auditory nerve. However, while INS has been shown to work in these settings, the mechanism (or mechanisms) by which infrared light causes neural excitation is currently not well understood. The protocol presented here describes a whole cell patch clamp method designed to facilitate the investigation of infrared neural stimulation in cultured primary auditory neurons. By thoroughly characterizing the response of these cells to infrared laser illumination in vitro under controlled conditions, it may be possible to gain an improved understanding of the fundamental physical and biochemical processes underlying infrared neural stimulation.     

Photobiomodulation by diffusing optical fiber on spinal cord: A feasibility study in piglet model

Previous studies on spinal cord injury (SCI) have confirmed that percutaneous photobiomodulation (PBM) therapy can ameliorate immunoinflammatory responses at sites of injury, accelerate nerve regeneration, suppress glial scar formation and promote the subsequent recovery of locomotor function. The current study was performed to evaluate a large‐animal model employing implanted optical fibers to accurately irradiate targeted spinal segments. The method's feasibility and irradiation parameters that do not cause phototoxic reaction were determined, and the methodology of irradiating the spinal cord with near‐infrared light was investigated in detail. A diffusing optical fiber was implanted above the T9 spinal cord of Bama miniature pigs and used to transfer near‐infrared light (810 nm) onto the spinal cord surface. After daily irradiation with 200, 300, 500 or 1000 mW for 14 days, both sides of the irradiated area of the spinal cord were assessed for temperature changes. The condition of the spinal cord and the position of optical fiber were investigated by magnetic resonance imaging (MRI), and different parameters indicating temperature increases or phototoxicity were measured on the normal spinal cord surface due to light irradiation (ie, heat shock responses, inflammatory reactions and neuronal apoptosis), and the animals' lower‐limb neurological function and gait were assessed during the irradiation process. The implanted device was stable inside the freely moving animals, and light energy could be directly projected onto the spinal cord surface. The screening of different irradiation parameters preliminary showed that direct irradiation onto the spinal cord surface at 200 and 300 mW did not significantly increase the temperature, stress responses, inflammatory reactions and neural apoptosis, whereas irradiation at 500 mW slightly increased these parameters, and irradiation at 1000 mW induced a significant temperature increase, heat shock, inflammation and apoptosis responses. HE staining of spinal cord tissue sections did not reveal any significant structural changes of the tissues compared to the control group, and the neurological function and gait of all irradiated animals were normal. In this study, we established an in‐vivo optical fiber implantation method, which might be safe and stable and could be used to directly project light energy onto the spinal cord surface. This study might provide a new perspective for clinical applications of PBM in acute SCI.     

Fiber-optic Implantation for Chronic Optogenetic Stimulation of Brain Tissue

Elucidating patterns of neuronal connectivity has been a challenge for both clinical and basic neuroscience. Electrophysiology has been the gold standard for analyzing patterns of synaptic connectivity, but paired electrophysiological recordings can be both cumbersome and experimentally limiting. The development of optogenetics has introduced an elegant method to stimulate neurons and circuits, both in vitro¹ and in vivo^2,3. By exploiting cell-type specific promoter activity to drive opsin expression in discrete neuronal populations, one can precisely stimulate genetically defined neuronal subtypes in distinct circuits^4-6. Well described methods to stimulate neurons, including electrical stimulation and/or pharmacological manipulations, are often cell-type indiscriminate, invasive, and can damage surrounding tissues. These limitations could alter normal synaptic function and/or circuit behavior. In addition, due to the nature of the manipulation, the current methods are often acute and terminal. Optogenetics affords the ability to stimulate neurons in a relatively innocuous manner, and in genetically targeted neurons. The majority of studies involving in vivo optogenetics currently use a optical fiber guided through an implanted cannula^6,7; however, limitations of this method include damaged brain tissue with repeated insertion of an optical fiber, and potential breakage of the fiber inside the cannula. Given the burgeoning field of optogenetics, a more reliable method of chronic stimulation is necessary to facilitate long-term studies with minimal collateral tissue damage. Here we provide our modified protocol as a video article to complement the method effectively and elegantly described in Sparta et al.⁸ for the fabrication of a fiber optic implant and its permanent fixation onto the cranium of anesthetized mice, as well as the assembly of the fiber optic coupler connecting the implant to a light source. The implant, connected with optical fibers to a solid-state laser, allows for an efficient method to chronically photostimulate functional neuronal circuitry with less tissue damage⁹ using small, detachable, tethers. Permanent fixation of the fiber optic implants provides consistent, long-term in vivo optogenetic studies of neuronal circuits in awake, behaving mice¹⁰ with minimal tissue damage.     

Mechanisms of stepping rhythm formation in decerebrated and chronic spinal cats under epidural stimulation

A study was made of the stepping pattern formation in decerebrated and in chronic spinal cats during epidural stimulation (ES). The hindlimb stepping performance depended on the parameters of ES and afferent input. At non-optimal ES parameters, no stepping was induced, only muscle reflexes followed the stimulation rhythm. Optimized ES (3–5 Hz, 50–100 μA for decerebrated and 20–30 Hz, 150–250 μA for spinal cats) evoked coordinated stepping movements at a natural rate (0.8–1 Hz) accompanied by electromyographic burst activity of the corresponding muscles. In decerebrated cats, the bursts are formed owing to modulation of early responses and the late polysynaptic activity. In chronic spinal cats, this process is mainly due to amplitude modulation of the early responses. Formation of the stepping pattern in decerebrated cats involves spinal interneurons responsible for the polysynaptic activity, which allows its correction based on processing the afferent signals. Activation of this system in chronic spinal cats can be realized by afferent stimulation alone, without ES.     

Behavioral determination of stimulus pair discrimination of auditory acoustic and electrical stimuli using a classical conditioning and heart-rate approach

Acute animal preparations have been used in research prospectively investigating electrode designs and stimulation techniques for integration into neural auditory prostheses, such as auditory brainstem implants and auditory midbrain implants. While acute experiments can give initial insight to the effectiveness of the implant, testing the chronically implanted and awake animals provides the advantage of examining the psychophysical properties of the sensations induced using implanted devices. Several techniques such as reward-based operant conditioning, conditioned avoidance, or classical fear conditioning have been used to provide behavioral confirmation of detection of a relevant stimulus attribute. Selection of a technique involves balancing aspects including time efficiency (often poor in reward-based approaches), the ability to test a plurality of stimulus attributes simultaneously (limited in conditioned avoidance), and measure reliability of repeated stimuli (a potential constraint when physiological measures are employed). Here, a classical fear conditioning behavioral method is presented which may be used to simultaneously test both detection of a stimulus, and discrimination between two stimuli. Heart-rate is used as a measure of fear response, which reduces or eliminates the requirement for time-consuming video coding for freeze behaviour or other such measures (although such measures could be included to provide convergent evidence). Animals were conditioned using these techniques in three 2-hour conditioning sessions, each providing 48 stimulus trials. Subsequent 48-trial testing sessions were then used to test for detection of each stimulus in presented pairs, and test discrimination between the member stimuli of each pair. This behavioral method is presented in the context of its utilisation in auditory prosthetic research. The implantation of electrocardiogram telemetry devices is shown. Subsequent implantation of brain electrodes into the Cochlear Nucleus, guided by the monitoring of neural responses to acoustic stimuli, and the fixation of the electrode into place for chronic use is likewise shown.     

Chronic stimulation of the septal area for the relief of intractable pain

Although brain stimulation techniques have changed the treatment of pain, their rationale has not yet been fully proved, and their clinical results are still frequently erratic or contradictory. In an attempt to provide alternate sites for stimulation, 10 patients were, in addition to conventional targets, chronically implanted at the septal area. Satisfactory relief of dysesthetic pain was induced by septal stimulation in 60% of the cases overall, without untoward effects. The follow-up ranged from 1 to 42 months. The available data conceivably suggest other mechanisms than the presumed exclusive activation of opiomimetic structures. They also seem to indicate that the septal area may be a suitable target for chronic stimulation.     

The effect of acute and chronic administration of timolol on cardiac sympathetic neural discharge, arrhythmia, and beta adrenergic receptor density associated with coronary occlusion in the cat

The effect of timolol (5 mg/kg, p.o., b.i.d. 7 or 14 days) on cardiac beta adrenergic receptor density, the times to arrhythmia (AR) and death (D), heart rate, mean arterial blood pressure, and postganglionic cardiac sympathetic neural discharge after acute coronary occlusion in cats was examined. In the control animals, receptor densities in the left and right atria did not differ, but were lower than the right ventricle. Left ventricle and septum receptor densities were higher, with the left ventricle the highest. The importance of the gradation of beta receptors with increasing density from base to apex appears to be its relation to cardiac contractile function. Occlusion in cats not treated with timolol did not alter the cardiac beta receptor densities. After timolol for 7 or 14 days, no occlusion, receptor density increased in left ventricle and septum although the increase was only significant after 14 days. A comparison of the beta adrenergic receptor densities in cats pretreated with timolol for 7 or 14 days with or without occlusion revealed that, in general, a decrease (p greater than 0.05) occurred for the occlusion group. Timolol decreased heart rate and blood pressure prior to occlusion. The mean times to AR and D were not significantly increased by either dosing regimen of timolol, although the trend was for an increase in the time to D after 7 days of timolol and an increase in the time to AR and D after 14 days of timolol. When compared with data obtained in saline cats, chronic timolol produced minimal changes in postganglionic cardiac sympathetic neural discharge. Timolol given chronically (p.o.) or acutely (5 mg/kg, i.v. given 15 min prior to occlusion) also did not prevent the cardiac sympathetic discharge associated with the development of AR. The time to AR and D in the acutely treated cats was increased but not significantly. Since cardiac sympathetic neural discharge increased as blood pressure fell in the control period but did not increase after occlusion in the timolol treated animals, the combination of timolol and occlusion may have modified neural discharge via an action on the baroreceptor mechanism. That chronic administration of timolol produces an effect not present in cats in which only occlusion was done is supported by the observation that chronic treatment produced an occlusion-induced decrease in beta adrenergic receptor density.(ABSTRACT TRUNCATED AT 400 WORDS)     

Steroid anaesthesia: alphadione depresses multiunit activity in the mesencephalic reticular formation

Cortical EEG and multiunit activity (MUA) of the mesencephalic reticular formation (MRF), area hypothalami anterior (AH) and the nucleus amygdalae basalis (AMY) were studied before and after different doses of alphadione (Althesin) and hexobarbitone (Evipan-Natrium) given to cats with chronically implanted electrodes. Non-anaesthetic doses of alphadione (0.15 ml/kg; 0.3 ml/kg; 0.6 ml/kg and 1.2 ml/kg i.p.) had sedative effects decreasing selectively the MUA in the MRF. In doses of 2.0 ml/kg, 2.4 ml/kg and 3.0 ml/kg i.p., alphadione induced anaesthesia which was associated with a rapid decrease of MUA in the MRF and by a gradual decrease of activity in the AH and AMY. The i.p. dose of 3.0 ml/kg abolished MUA responses of the reticular formation to acoustic, visual and somatic stimulation but failed to block responses to pain. Deep anaesthesia with lasting analgesia could be maintained by i.v. infusion (0.075 ml/kg/min). This procedure blocked the responsiveness to painful stimulation while pharyngeal and laryngeal reflexes were maintained. Hexobarbitone in a dose of 20.0 mg/kg i.p. did not produce anaesthesia in the cat. Administration of 40.0 mg/kg i.p. resulted in a rapid decrease of MUA in the MRF, AH and AMY, MUA responses to each stimulation were abolished and the pharyngeal reflex was blocked.     

Modulation of Nociceptive Responses by Electrical Stimulation of the Nucleus Raphe Dorsalis and Midbrain Substantia Grisea Centralis in Cat

In chronic experiments on 20 awake cats, we studied modulation of nociceptive responses to intense noxious stimulation of the skin of the hindlimb (electrical cutaneous stimulation, ECS) after electrical stimulation of some parts of the brainstem had been applied through chronically implanted electrodes. The stimulated structures were as follows: the nucleus raphe dorsalis, RD, and the dorsolateral zone of the rostral section or the ventrolateral zone of the middle section of the midbrain central gray matter (substantia grisea centralis, SGC), dl SGC and vl SGC, respectively. Freely moving animals were subjected to ECS applied either in isolation or against the background of stimulation of one of the above-mentioned brainstem structures. Integral intensity of nociceptive responses was scored on a four-point scale. In this case, the characteristics of the motor (drawing back of the leg and generalized motor reactions, i.e., change in the posture, episodes of pace, etc.), autonomic (changes in the heart rate, respiratory rate, and respiration depth), and emotional (vocalization, reactions of anxiety and aggression) components of the nociceptive response were taken into account. The strength of standard isolated ECS was selected such that it caused a nociceptive response of the level 3. The same ECS strength, but applied against the background of preliminary stimulation of the vl SGC, in 85% of the tests caused the development of a significantly more intense response (level 4). Under the influence of ECS against the background of stimulation of the dl SGC or RD, in the overwhelming majority of cases, only level-1 responses developed. To obtain a nociceptive level-3 response against the background of stimulation of the dl SGC and RD, the ECS strength should be increased at least twice. Isolated vl SGC stimulation caused nociceptive responses, which as a whole corresponded to level 2. Control isolated stimulation of the dl SGC and RD either did not result in any noticeable behavioral change or evoked minimum responses. We conclude that the SGC with respect to the nociceptive/antinociceptive systems is heterogeneous; the vl SGC should be considered the nociceptive zone, while the dl SGC and RD should be considered the antinociceptive brainstem zones.     

Motor effects of electrical and cholinergic stimulation of the cat's dorsal hippocampus

The effect of electrical stimulation of the dorsal hippocampus was studied in 17 adult cats with implanted electrodes and those effects of carbachol and dioxolane in a group of ten adult cats with a cannula and electrodes implanted in the above cited structure. Electrical stimulation induced a contralateral head-eye-body turning response in 3 cats (17.6%), only when it was associated with afterdischarge. On the other hand the cholinergic agonists evoked contralateral head-eye-body turning in nine out of ten cats in whom the injections were administered into the hippocampus. The fact that dioxolane, an exclusive muscarinic agonist evoked this behavior and that atropine sulfate blocked this response, favours the postulation that turning is due to activation of muscarinic receptors inside the dorsal hippocampus. Comparison was done between the hippocampal group with a group similarly studied with electrodes implanted in the pulvinar-lateralis posterior nucleus complex (P-LP), and in the caudate nucleus, in which the electrical stimulation evoked contralateral head-eye-body turning response without any EEG activation.     

Auditory brain stem responses to monoaural stimulation registered in symmetrical areas of cat's brain cortex

In five anaesthetized cats (Nembutal 35 mg/kg) with 14 chronically implanted recording epidural electrodes the auditory brain stem responses (ABR) to monoaural stimulation (click) in symmetrical areas of the brain cortex were recorded. Each ABR to acoustic stimulus of sufficient intensity is formed by a complex of alternating five positive (P1-P5) and four negative (N1-N4) peaks; two further small peaks often follow on this complex. The amplitude of ABR peaks N3, P4, N4 and P5 to monoaural stimulation in symmetrical areas of cat's cortex was always higher in records from the hemisphere contralateral to the stimulated ear than in records from the ipsilateral one. The amplitude of P3 ABR peak behaved to the contrary--it was higher on ipsilateral hemisphere. On the other hand the amplitude of ABR peaks P1, N1, P2 and N2 to monoaural stimulation in symmetrical areas of the brain cortex showed no degree of lateralization in our experimental animals. The present findings support indirectly the presumption that each peak of the ABR is generated by a particular acoustic brain stem structure.     

Cochlear implants: the view from the brain

The cochlear implant arguably is the most successful neural prosthesis. Studies of the responses of the central auditory system to prosthetic electrical stimulation of the cochlea are revealing the success with which electrical stimulation of a deaf ear can mimic acoustic stimulation of a normal-hearing ear. Understanding of the physiology of central auditory structures can lead to improved restoration of hearing with cochlear implants. In turn, the cochlear implant can be exploited as an experimental tool for examining central hearing mechanisms isolated from the effects of cochlear mechanics and transduction.     

Chronic Electrical Stimulation with a Suprachoroidal Retinal Prosthesis: A Preclinical Safety and Efficacy Study

Purpose

To assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.

Methods

Seven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.

Results

All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.

Conclusions

Chronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.