Angelica Perez Fornos

Temporal Properties of Visual Perception on Electrical Stimulation of the Retina

PURPOSE To investigate the elementary temporal properties of electrically evoked percepts in blind patients chronically implanted with an epiretinal prosthesis. METHODS Nine subjects were presented with isolated stimuli of variable duration and pulse rate. Stimulation amplitude was set to the upper comfortable level and a group of 2 × 2 adjacent electrodes was simultaneously activated. First, subjects were asked to verbally describe their visual perception paying particular attention to the time-course of brightness. Then, in subsequent trials, they described the brightness time dependence using a joystick while auditory feedback of joystick position was provided. RESULTS All subjects described a bright, well-localized percept at stimulus onset. Only one subject reported such a bright, well-localized visual sensation during an entire 10-second stimulation trial. For the remaining eight subjects, it faded more or less rapidly (in four cases <0.5 second) and was often followed by a percept described as less bright, poorly localized, and having different color. Only initial percepts at stimulation onset seemed bright and localized enough to reconstruct a patterned image. Changing stimulation pulse rate influenced the time course of perception only in some cases but the effect was not systematic. CONCLUSIONS Percepts differed considerably across subjects, probably because of the considerable variations in the progression and remodeling processes associated with the disease. Appropriate coding of a patterned image under such conditions appears challenging. Further research of the underlying mechanisms of visual perception upon electrical stimulation of the retina is required to optimize stimulation paradigms and to better establish patient selection criteria.

Artificial balance: restoration of the vestibulo-ocular reflex in humans with a prototype vestibular neuroprosthesis

The vestibular system plays a crucial role in the multisensory control of balance. When vestibular function is lost, essential tasks such as postural control, gaze stabilization, and spatial orientation are limited and the quality of life of patients is significantly impaired. Currently, there is no effective treatment for bilateral vestibular deficits. Research efforts both in animals and humans during the last decade set a solid background to the concept of using electrical stimulation to restore vestibular function. Still, the potential clinical benefit of a vestibular neuroprosthesis has to be demonstrated to pave the way for a translation into clinical trials. An important parameter for the assessment of vestibular function is the vestibulo-ocular reflex (VOR), the primary mechanism responsible for maintaining the perception of a stable visual environment while moving. Here we show that the VOR can be artificially restored in humans using motion-controlled, amplitude modulated electrical stimulation of the ampullary branches of the vestibular nerve. Three patients received a vestibular neuroprosthesis prototype, consisting of a modified cochlear implant providing vestibular electrodes. Significantly higher VOR responses were observed when the prototype was turned ON. Furthermore, VOR responses increased significantly as the intensity of the stimulation increased, reaching on average 79% of those measured in healthy volunteers in the same experimental conditions. These results constitute a fundamental milestone and allow us to envision for the first time clinically useful rehabilitation of patients with bilateral vestibular loss.

Simulation of artificial vision: IV. Visual information required to achieve simple pointing and manipulation tasks

Retinal prostheses attempt to restore some amount of vision to totally blind patients. Vision evoked this way will be however severely constrained because of several factors (e.g., size of the implanted device, number of stimulating contacts, etc.). We used simulations of artificial vision to study how such restrictions of the amount of visual information provided would affect performance on simple pointing and manipulation tasks. Five normal subjects participated in the study. Two tasks were used: pointing on random targets (LEDs task) and arranging wooden chips according to a given model (CHIPs task). Both tasks had to be completed while the amount of visual information was limited by reducing the resolution (number of pixels) and modifying the size of the effective field of view. All images were projected on a 10 degrees x 7 degrees viewing area, stabilised at a given position on the retina. In central vision, the time required to accomplish the tasks remained systematically slower than with normal vision. Accuracy was close to normal at high image resolutions and decreased at 500 pixels or below, depending on the field of view used. Subjects adapted quite rapidly (in less than 15 sessions) to performing both tasks in eccentric vision (15 degrees in the lower visual field), achieving after adaptation performances close to those observed in central vision. These results demonstrate that, if vision is restricted to a small visual area stabilised on the retina (as would be the case in a retinal prosthesis), the perception of several hundreds of retinotopically arranged phosphenes is still needed to restore accurate but slow performance on pointing and manipulation tasks. Considering that present prototypes afford less than 100 stimulation contacts and that our simulations represent the most favourable visual input conditions that the user might experience, further development is required to achieve optimal rehabilitation prospects.

Reading with a Simulated 60-Channel Implant

First generation retinal prostheses containing 50–60 electrodes are currently in clinical trials. The purpose of this study was to evaluate the theoretical upper limit (best possible) reading performance attainable with a state-of-the-art 60-channel retinal implant and to find the optimum viewing conditions for the task. Four normal volunteers performed full-page text reading tasks with a low-resolution, 60-pixel viewing window that was stabilized in the central visual field. Two parameters were systematically varied: (1) spatial resolution (image magnification) and (2) the orientation of the rectangular viewing window. Performance was measured in terms of reading accuracy (% of correctly read words) and reading rates (words/min). Maximum reading performances were reached at spatial resolutions between 3.6 and 6 pixels/char. Performance declined outside this range for all subjects. In optimum viewing conditions (4.5 pixels/char), subjects achieved almost perfect reading accuracy and mean reading rates of 26 words/min for the vertical viewing window and of 34 words/min for the horizontal viewing window. These results suggest that, theoretically, some reading abilities can be restored with actual state-of-the-art retinal implant prototypes if “image magnification” is within an “optimum range.” Future retinal implants providing higher pixel resolutions, thus allowing for a wider visual span might allow faster reading rates.

First functional rehabilitation via vestibular implants

The vestibular system is part of themultisensory balance sense, which is responsible for postural control, gaze stabilization, and spatial orientation. In particular, the vestibulo-ocular reflex (VOR) is responsible for generating compensatory eyemovements relative to headmovements while moving. In patients with a bilateral loss of vestibular function, the VOR is absent or very weak. As a consequence, such patients complain about oscillopsia, the illusory perception of movement of the visual surroundings in dynamic situations. The direct functional consequence of this is an abnormal decrease of visual acuity when in movement (Lambert et al., 2010; Guinand et al., 2012), which translates into difficulty in reading signs and recognizing faces while walking. This considerably contributes to a significant impairment of the quality of life of affected patients. Currently, there is no evidence of an effective treatment for these patients. The idea of electrically stimulating the vestibular system emerged about a decade ago and is based on a concept very similar to that of cochlear implants. Briefly, such a system would use inertial sensors (i.e. a gyroscope and/or accelerometer) to detect motion information. Such information is translated into a pattern of neural excitation code by an external signal processor. This pattern is wirelessly transmitted to an implanted stimulator which finally delivers the corresponding patterns of electrical stimulation via electrodes implanted near the vestibular structures in the neural system. The translation of the cochlear implant concept into a device suitable for stimulating the vestibular system requires two steps: (1) adaptation of the electrode topology to the neural target to be stimulated, and (2) transformation of the pertinent input signal (in this case motion) into a signal that can be processed by the audio processor of a standard cochlear implant. Today, both steps have been completed. A modified cochlear implant providing 1–3 extracochlear electrodes was developed in collaboration with MED-EL (Innsbruck, Austria). Our research group has developed the necessary interfaces to capture the signal coming from a gyroscope and use it to modulate the stimulation signals delivered by the cochlear implant stimulator (Geneva University Hospitals: Device and method for electrical stimulation of neural or muscular tissue; 2013-01-30; European Patent Application 13153300.2-1652). A number of studies have contributed to establish the feasibility of the idea of restoring semicircular canal function via electrical stimulation in animal models. At the same time, several important steps have been taken towards the development of a system allowing for the chronic stimulation of the vestibular system in human patients. For example, special extralabyrinthine (Kos et al., 2006) and intralabyrinthine (Van de Berg et al., 2012) surgical techniques have been developed and the feasibility of electrical stimulation of vestibular structures has been demonstrated both in acute (Guyot et al., 2011a) and chronic configurations (Guyot et al., 2011b). To date, seven volunteer patients with a profound bilateral vestibular loss have received a custom-modified cochlear implant in which one or three electrodes are in contact with the vestibular structures (see Table 1). In addition, since hearing loss due to the implantation of electrodes near the vestibular system remains an important concern, patients were also profoundly deaf in the implanted ear. Two patients (BVL1 and BVL2) were implanted using the intralabyrinthine approach (Van de Berg et al., 2012) in Maastricht (Ethics committee protocol NL36777.068.11/METC 11-2-031). Five patients (BVL3–BVL7) were implanted using the extralabyrinthine approach (Kos et al., 2006) in Geneva (Ethics Committee protocol NAC 11-080). Correspondence to: Marco Pelizzone, Department of Otorhinolaryngology, Head and Neck Surgery, Geneva University Hospital, Geneva, Switzerland. Email: marco.pelizzone@hcuge.ch

A Real-Time Research Platform to Study Vestibular Implants With Gyroscopic Inputs in Vestibular Deficient Subjects

Researchers have succeeded in partly restoring damaged vestibular functionality in several animal models. Recently, acute interventions have also been demonstrated in human patients. Our previous work on a vestibular implant for humans used predefined stimulation patterns; here we present a research tool that facilitates motion-modulated stimulation. This requires a system that can process gyroscope measurements and send stimulation parameters to a hybrid vestibular-cochlear implant in real-time. To match natural vestibular latencies, the time from sensor input to stimulation output should not exceed 6.5 ms. We describe a system based on National Instruments CompactRIO platform that can meet this requirement and also offers floating point precision for advanced transfer functions. It is designed for acute clinical interventions, and is sufficiently powerful and flexible to serve as a development platform for evaluating prosthetic control strategies. Amplitude and pulse frequency modulation to predetermined functions or sensor inputs have been validated. The system has been connected to human patients, who each have received a modified MED-EL cochlear implant for vestibular stimulation, and patient tests are ongoing.

Restoring Visual Acuity in Dynamic Conditions with a Vestibular Implant

Vestibular implants are devices designed to rehabilitate patients with a bilateral vestibular loss (BVL). These patients lack a properly functioning vestibulo-ocular reflex (VOR), which impairs gaze stabilization abilities and results in an abnormal loss of visual acuity (VA) in dynamic situations (i.e., severely limiting the patients ability to read signs or recognize faces while walking). We previously demonstrated that the VOR can be artificially restored in a group of BVL patients fitted with a prototype vestibular implant. This study was designed to investigate whether these promising results could be translated to a close-to-reality task, significantly improving VA abilities while walking. Six BVL patients previously implanted with a vestibular implant prototype participated in the experiments. VA was determined using Sloan letters displayed on a computer screen, in four conditions: (1) with the patient standing still without moving (static), (2) while the patient was walking on a treadmill at constant speed with the vestibular implant prototype turned off (systemOFF), (3) while the patient was walking on a treadmill at constant speed with the vestibular implant prototype turned on providing coherent motion information (systemONmotion), and (4) a “placebo” condition where the patient was walking on a treadmill at constant speed with the vestibular implant prototype turned on providing reversed motion information (systemONsham). The analysis (one-way repeated measures analysis of variance) revealed a statistically significant effect of the test condition [F(3, 12) = 30.5, p < 0.001]. Significant decreases in VA were observed with the systemOFF condition when compared to the static condition (Tukey post-hoc p < 0.001). When the vestibular implant was turned on, delivering pertinent motion information (systemONmotion) the VA improved to close to normal values. The improvement disappeared in the placebo condition (systemONsham) and VA-values also dropped significantly in this condition (Tukey post-hoc p < 0.001). These results are a significant step forward in the field, demonstrating for the first time in humans that gaze stabilization abilities can be restored with a vestibular implant prototype. The vestibular implant shows considerable promise of being the first-ever effective therapeutic alternative for patients with a BVL in the near future.

Simultaneous development of 2 oral languages by child cochlear implant recipients.

Objective To study the development French as a mainstream language by children with a cochlear implant who belong to non-French speaking families. Study Design Matched pairs comparison of postoperative hearing perception and speech development data of monolingual and bilingual children with cochlear implants. Setting University medical center. Patients Fourteen congenital profoundly deaf children. Seven were exclusively French speaking and seven bilingual (French-Portuguese, Arab, Turkish, or Serbo-Croatian) children. Interventions Cochlear implantation before the age of 5 ½ years. Main Outcome Measures Subjects were evaluated using standard hearing perception and oral language development tests. Results Both monolingual and bilingual groups obtained excellent hearing perception results with the cochlear implant. Monolingual children showed oral language development results equivalent to those of normal hearing children of the same age, except for the morpho-syntax test where they were slightly below average. Bilingual children scored below average in all oral language development tests. Conclusion Despite the excellent hearing perception obtained with cochlear implants, the acquisition of a second language at home seems to slow down the development of the French mainstream language. Comparison of our results with those of previous studies indicates that bilingual children require intensive and correct input in both languages. Parents’ involvement in rehabilitation efforts also appears as an important factor for successful oral language development.

The vestibular implant: A probe in orbit around the human balance system

The primary goal of the vestibular implant is to restore the vestibular function in patients with a disabling bilateral vestibular loss for whom there is currently no available treatment. The prototype developed by our team is a hybrid system consisting of a modified cochlear implant incorporating additional vestibular electrodes. Therefore, in addition of delivering sound information it is also capable of delivering motion information to the central nervous system using electrical stimulation. To date, thirteen patients have been implanted with such vestibular implant prototypes. For ethical reasons, only deaf ears were implanted and all patients experienced a clinical benefit from the hearing rehabilitation. The recent demonstration of partial restoration of the vestibulo-ocular and the vestibulo-collic reflexes in implanted patients suggests that gaze stabilization and postural control, fundamental functions of the balance system, can be artificially restored using a vestibular implant. This allows us to glimpse a useful clinical application in a near future. In parallel, we show how the vestibular implant provides a unique opportunity to explore the integration of the vestibular sensory input into the multisensory, multimodal balance system in humans, since it is able to selectively stimulate the vestibular system.

The Video Head Impulse Test to Assess the Efficacy of Vestibular Implants in Humans

The purpose of this study was to evaluate whether it is possible to restore the high-frequency angular vestibulo-ocular reflex (aVOR) in patients suffering from a severe bilateral vestibulopathy (BV) and implanted with a vestibular implant prototype. Three patients (S1–3) participated in the study. They received a prototype vestibular implant with one to three electrode branches implanted in the proximity of the ampullary branches of the vestibular nerve. Five electrodes were available for electrical stimulation: one implanted in proximity of the left posterior ampullary nerve in S1, one in the left lateral and another one in the superior ampullary nerves in S2, and one in the right lateral and another one in the superior ampullary nerves in S3. The high-frequency aVOR was assessed using the video head impulse test (EyeSeeCam; EyeSeeTec, Munich, Germany), while motion-modulated electrical stimulation was delivered via one of the implanted vestibular electrodes at a time. aVOR gains were compared to control measurements obtained in the same patients when the device was not activated. In three out of the five tested electrodes the aVOR gain increased monotonically with increased stimulation strength when head impulses were delivered in the plane of the implanted canal. In these cases, gains ranging from 0.4 to values above 1 were measured. A “reversed” aVOR could also be generated when inversed stimulation paradigms were used. In most cases, the gain for excitatory head impulses was superior to that recorded for inhibitory head impulses, consistent with unilateral vestibular stimulation. Improvements of aVOR gain were generally accompanied by a concomitant decrease of corrective saccades, providing additional evidence of an effective aVOR. High inter-electrode and inter-subject variability were observed. These results, together with previous research, demonstrate that it is possible to restore the aVOR in a broad frequency range using motion-modulated electrical stimulation of the vestibular afferents. This provides additional encouraging evidence of the possibility of achieving a useful rehabilitation alternative for patients with BV in the near future.