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1.  Preliminary 6 Month Results from the Argus™ II Epiretinal Prosthesis Feasibility Study 
Conference Proceedings  2009;2009:4566-4568.
The Argus™ II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.
doi:10.1109/IEMBS.2009.5332695
PMCID: PMC3337704  PMID: 19963839
2.  The Detection of Motion by Blind Subjects With the Epiretinal 60-Electrode (Argus II) Retinal Prosthesis 
JAMA ophthalmology  2013;131(2):183-189.
Objective
To investigate the ability of 28 blind subjects implanted with a 60-electrode Argus II (Second Sight Medical Products Inc) retinal prosthesis system to detect the direction of a moving object.
Methods
Blind subjects (bare light perception or worse in both eyes) with retinitis pigmentosa were implanted with the Argus II prosthesis as part of a phase 1/2 feasibility study at multiple clinical sites worldwide. The experiment measured their ability to detect the direction of motion of a high-contrast moving bar on a flatscreen monitor in 3 conditions: with the prosthesis system on and a 1-to-1 mapping of spatial information, with the system off, and with the system on but with randomly scrambled spatial information.
Results
Fifteen subjects (54%) were able to perform the task significantly better with their prosthesis system than they were with their residual vision, 2 subjects had significantly better performance with their residual vision, and no difference was found for 11 subjects. Of the 15 better-performing subjects, 11 were available for follow-up testing, and 10 of them had significantly better performance with normal rather than with scrambled spatial information.
Conclusions
This work demonstrates that blind subjects implanted with the Argus II retinal prosthesis were able to perform a motion detection task they could not do with their native vision, confirming that electrical stimulation of the retina provides spatial information from synchronized activation of multiple electrodes.
doi:10.1001/2013.jamaophthalmol.221
PMCID: PMC3924899  PMID: 23544203
3.  The Argus II epiretinal prosthesis system allows letter and word reading and long-term function in patients with profound vision loss 
Background
Retinal prosthesis systems (RPS) are a novel treatment for profound vision loss in outer retinal dystrophies. Ideal prostheses would offer stable, long-term retinal stimulation and reproducible spatial resolution in a portable form appropriate for daily life.
Methods
We report a prospective, internally controlled, multicentre trial of the Argus II system. Twenty-eight subjects with light perception vision received a retinal implant. Controlled, closed-group, forced-choice letter identification, and, open-choice two-, three- and four-letter word identification tests were carried out.
Results
The mean±SD percentage correct letter identification for 21 subjects tested were: letters L, T, E, J, F, H, I, U, 72.3±24.6% system on and 17.7±12.9% system off; letters A, Z, Q, V, N, W, O, C, D, M, 55.0±27.4% system on and 11.8%±10.7% system off, and letters K, R, G, X, B, Y, S, P, 51.7±28.9% system on and 15.3±7.4% system off. (p<0.001 for all groups). A subgroup of six subjects was able to consistently read letters of reduced size, the smallest measuring 0.9 cm (1.7°) at 30 cm, and four subjects correctly identify unrehearsed two-, three- and four-letter words. Average implant duration was 19.9 months.
Conclusions
Multiple blind subjects fitted with the Argus II system consistently identified letters and words using the device, indicating reproducible spatial resolution. This, in combination with stable, long-term function, represents significant progress in the evolution of artificial sight.
doi:10.1136/bjophthalmol-2012-301525
PMCID: PMC3632967  PMID: 23426738
4.  Reading Visual Braille with a Retinal Prosthesis 
Retinal prostheses, which restore partial vision to patients blinded by outer retinal degeneration, are currently in clinical trial. The Argus II retinal prosthesis system was recently awarded CE approval for commercial use in Europe. While retinal prosthesis users have achieved remarkable visual improvement to the point of reading letters and short sentences, the reading process is still fairly cumbersome. This study investigates the possibility of using an epiretinal prosthesis to stimulate visual braille as a sensory substitution for reading written letters and words. The Argus II retinal prosthesis system, used in this study, includes a 10 × 6 electrode array implanted epiretinally, a tiny video camera mounted on a pair of glasses, and a wearable computer that processes the video and determines the stimulation current of each electrode in real time. In the braille reading system, individual letters are created by a subset of dots from a 3 by 2 array of six dots. For the visual braille experiment, a grid of six electrodes was chosen out of the 10 × 6 Argus II array. Groups of these electrodes were then directly stimulated (bypassing the camera) to create visual percepts of individual braille letters. Experiments were performed in a single subject. Single letters were stimulated in an alternative forced choice (AFC) paradigm, and short 2–4-letter words were stimulated (one letter at a time) in an open-choice reading paradigm. The subject correctly identified 89% of single letters, 80% of 2-letter, 60% of 3-letter, and 70% of 4-letter words. This work suggests that text can successfully be stimulated and read as visual braille in retinal prosthesis patients.
doi:10.3389/fnins.2012.00168
PMCID: PMC3504310  PMID: 23189036
retina; epiretinal prosthesis; sensory substitution; retinitis pigmentosa; blindness; perception; degeneration; sight restoration
5.  Detection, eye–hand coordination and virtual mobility performance in simulated vision for a cortical visual prosthesis device 
Journal of neural engineering  2009;6(3):035008.
In order to assess visual performance using a future cortical prosthesis device, the ability of normally sighted and low vision subjects to adapt to a dotted ‘phosphene’ image was studied. Similar studies have been conduced in the past and adaptation to phosphene maps has been shown but the phosphene maps used have been square or hexagonal in pattern. The phosphene map implemented for this testing is what is expected from a cortical implantation of the arrays of intracortical electrodes, generating multiple phosphenes. The dotted image created depends upon the surgical location of electrodes decided for implantation and the expected cortical response. The subjects under tests were required to perform tasks requiring visual inspection, eye–hand coordination and way finding. The subjects did not have any tactile feedback and the visual information provided was live dotted images captured by a camera on a head-mounted low vision enhancing system and processed through a filter generating images similar to the images we expect the blind persons to perceive. The images were locked to the subject’s gaze by means of video-based pupil tracking. In the detection and visual inspection task, the subject scanned a modified checkerboard and counted the number of square white fields on a square checkerboard, in the eye–hand coordination task, the subject placed black checkers on the white fields of the checkerboard, and in the way-finding task, the subjects maneuvered themselves through a virtual maze using a game controller. The accuracy and the time to complete the task were used as the measured outcome. As per the surgical studies by this research group, it might be possible to implant up to 650 electrodes; hence, 650 dots were used to create images and performance studied under 0% dropout (650 dots), 25% dropout (488 dots) and 50% dropout (325 dots) conditions. It was observed that all the subjects under test were able to learn the given tasks and showed improvement in performance with practice even with a dropout condition of 50% (325 dots). Hence, if a cortical prosthesis is implanted in human subjects, they might be able to perform similar tasks and with practice should be able to adapt to dotted images even with a low resolution of 325 dots of phosphene.
doi:10.1088/1741-2560/6/3/035008
PMCID: PMC3902177  PMID: 19458397
6.  Use of the Argus II Retinal Prosthesis to Improve Visual Guidance of Fine Hand Movements 
Purpose.
We studied the capabilities of the Argus II retinal prosthesis for guiding fine hand movement, and demonstrated and quantified guidance improvement when using the device over when not using the device for progressively less predictable trajectories.
Methods.
A total of 21 patients with retinitis pigmentosa (RP), remaining vision no more than bare light perception, and an implanted Argus II epiretinal prostheses used a touchscreen to trace white paths on black backgrounds. Sets of paths were divided into three categories: right-angle/single-turn, mixed-angle/single-turn, and mixed-angle/two-turn. Subjects trained on paths by using prosthetic vision and auditory feedback, and then were tested without auditory feedback, with and without prosthetic vision. Custom software recorded position and timing information for any contact that subjects made with the screen. The area between the correct path and the trace, and the elapsed time to trace a path were used to evaluate subject performance.
Results.
For right-angle/single-turn sets, average tracing error was reduced by 63% and tracing time increased by 156% when using the prosthesis, relative to residual vision. With mixed-angle/single-turn sets, error was reduced by 53% and time to complete tracing increased by 184%. Prosthesis use decreased error by 38% and increased tracing time by 252% for paths that incorporated two turns.
Conclusions.
Use of an epiretinal visual prosthesis can allow RP patients with no more than bare light perception to guide fine hand movement visually. Further, prosthetic input tends to make subjects slower when performing tracing tasks, presumably reflecting greater effort. (ClinicalTrials.gov number, NCT00407602.)
A total of 21 blind retinitis pigmentosa patients used retinal prostheses to visually guide their hands to trace high-contrast paths of varying complexities. Prosthesis use decreased performance error by an average of 60% and increased time to complete the task by an average of 211%. Use of an epiretinal visual prosthesis can allow RP patients with no more than bare light perception to visually guide fine hand movement. Further, prosthetic input tends to make subjects slower when performing tracing tasks, presumably reflecting greater effort.
doi:10.1167/iovs.12-9536
PMCID: PMC3416020  PMID: 22661464
7.  Spatial and temporal characteristics of V1 microstimulation during chronic implantation of a microelectrode array in a behaving macaque 
Journal of neural engineering  2012;9(6):065003.
Objective
It has been hypothesized that a vision prosthesis capable of evoking useful visual percepts can be based upon electrically stimulating the primary visual cortex (V1) of a blind human subject via penetrating microelectrode arrays. As a continuation of earlier work, we examined several spatial and temporal characteristics of V1 microstimulation.
Approach
An array of 100 penetrating microelectrodes was chronically implanted in V1 of a behaving macaque monkey. Microstimulation thresholds were measured using a two-alternative forced choice detection task. Relative locations of electrically-evoked percepts were measured using a memory saccade-to-target task.
Main results
The principal finding was that two years after implantation we were able to evoke behavioural responses to electric stimulation across the spatial extent of the array using groups of contiguous electrodes. Consistent responses to stimulation were evoked at an average threshold current per electrode of 204 ± 49 µA (mean ± std) for groups of four electrodes and 91 ± 25 µA for groups of nine electrodes. Saccades to electrically-evoked percepts using groups of nine electrodes showed that the animal could discriminate spatially distinct percepts with groups having an average separation of 1.6 ± 0.3 mm (mean ± std) in cortex and 1.0 ± 0.2 degrees in visual space.
Significance
These results demonstrate chronic perceptual functionality and provide evidence for the feasibility of a cortically-based vision prosthesis for the blind using penetrating microelectrodes.
doi:10.1088/1741-2560/9/6/065003
PMCID: PMC3521049  PMID: 23186948
8.  Tactile/proprioceptive integration during arm localization is intact in individuals with Parkinson’s disease 
Neuroscience letters  2009;470(1):38.
It has been theorized that sensorimotor processing deficits underlie Parkinson’s disease (PD) motor impairments including movement under proprioceptive control. However, it is possible that these sensorimotor processing deficits exclude tactile/proprioception sensorimotor integration: prior studies show improved movement accuracy in PD with endpoint tactile feedback, and good control in tactile-driven precision-grip tasks.
To determine whether tactile/proprioceptive integration in particular is affected by PD, nine subjects with PD (off-medication, UPDRS motor=19-42) performed an arm-matching task without visual feedback. In some trials one arm touched a static tactile cue that conflicted with dynamic proprioceptive feedback from biceps brachii muscle vibration. This sensory conflict paradigm has characterized tactile/proprioceptive integration in healthy subjects as specific to the context of tactile cue mobility assumptions and the intention to move the arm.
We found that the individuals with PD had poorer arm-matching acuracy than age-matched control subjects. However, PD-group accuracy improved with tactile feedback. Furthermore, sensory conflict conditions were resolved in the same context-dependent fashion by both subject groups. We conclude that the somatosensory integration mechanism for prioritizing tactile and proprioception feedback in this task are not disrupted by PD, and are not related to the observed proprioceptive deficits.
doi:10.1016/j.neulet.2009.12.051
PMCID: PMC2814986  PMID: 20036715
Parkinson’s disease; proprioception; touch; sensory integration
9.  Frequency and Amplitude Modulation Have Different Effects on the Percepts Elicited by Retinal Stimulation 
To restore functional form vision, epiretinal prostheses have been implanted in blind human subjects to electrically elicit percepts. These findings suggest that frequency modulation may be the best way to produce percepts that range widely in brightness while minimizing loss of spatial resolution.
Purpose.
In an effort to restore functional form vision, epiretinal prostheses that elicit percepts by directly stimulating remaining retinal circuitry were implanted in human subjects with advanced retinitis pigmentosa RP). In this study, manipulating pulse train frequency and amplitude had different effects on the size and brightness of phosphene appearance.
Methods.
Experiments were performed on a single subject with severe RP (implanted with a 16-channel epiretinal prosthesis in 2004) on nine individual electrodes. Psychophysical techniques were used to measure both the brightness and size of phosphenes when the biphasic pulse train was varied by either modulating the current amplitude (with constant frequency) or the stimulating frequency (with constant current amplitude).
Results.
Increasing stimulation frequency always increased brightness, while having a smaller effect on the size of elicited phosphenes. In contrast, increasing stimulation amplitude generally increased both the size and brightness of phosphenes. These experimental findings can be explained by using a simple computational model based on previous psychophysical work and the expected spatial spread of current from a disc electrode.
Conclusions.
Given that amplitude and frequency have separable effects on percept size, these findings suggest that frequency modulation improves the encoding of a wide range of brightness levels without a loss of spatial resolution. Future retinal prosthesis designs could benefit from having the flexibility to manipulate pulse train amplitude and frequency independently (clinicaltrials.gov number, NCT00279500).
doi:10.1167/iovs.11-8401
PMCID: PMC3292357  PMID: 22110084
10.  Viewing and feeling touch modulates hand position for reaching 
Neuropsychologia  2011;49(5):1287-1293.
Action requires knowledge of our body location in space. Here we asked if interactions with the external world prior to a reaching action influence how visual location information is used. We investigated if the temporal synchrony between viewing and feeling touch modulates the integration of visual and proprioceptive body location information for action. We manipulated the synchrony between viewing and feeling touch in the Rubber Hand Illusion paradigm prior to participants performing a ballistic reaching task to a visually specified target. When synchronous touch was given, reaching trajectories were significantly shifted compared to asynchronous touch. The direction of this shift suggests that touch influences the encoding of hand position for action. On the basis of this data and previous findings, we propose that the brain uses correlated cues from passive touch and vision to update its own position for action and experience of self-location.
doi:10.1016/j.neuropsychologia.2011.02.012
PMCID: PMC3086579  PMID: 21320514
Parietal Cortex; Touch; Action; Human Body; Body Location; Rubber Hand Illusion
11.  Attentional selection of location and modality in vision and touch modulates low-frequency activity in associated sensory cortices 
Journal of Neurophysiology  2012;107(9):2342-2351.
Selective attention allows us to focus on particular sensory modalities and locations. Relatively little is known about how attention to a sensory modality may relate to selection of other features, such as spatial location, in terms of brain oscillations, although it has been proposed that low-frequency modulation (α- and β-bands) may be key. Here, we investigated how attention to space (left or right) and attention to modality (vision or touch) affect ongoing low-frequency oscillatory brain activity over human sensory cortex. Magnetoencephalography was recorded while participants performed a visual or tactile task. In different blocks, touch or vision was task-relevant, whereas spatial attention was cued to the left or right on each trial. Attending to one or other modality suppressed α-oscillations over the corresponding sensory cortex. Spatial attention led to reduced α-oscillations over both sensorimotor and occipital cortex contralateral to the attended location in the cue-target interval, when either modality was task-relevant. Even modality-selective sensors also showed spatial-attention effects for both modalities. The visual and sensorimotor results were generally highly convergent, yet, although attention effects in occipital cortex were dominant in the α-band, in sensorimotor cortex, these were also clearly present in the β-band. These results extend previous findings that spatial attention can operate in a multimodal fashion and indicate that attention to space and modality both rely on similar mechanisms that modulate low-frequency oscillations.
doi:10.1152/jn.00973.2011
PMCID: PMC3362245  PMID: 22323628
multisensory; magnetoencephalography; oscillations; alpha; beta; visual; somatosensory; prestimulus
12.  Interim Results from the International Trial of Second Sight’s Visual Prosthesis 
Ophthalmology  2012;119(4):779-788.
Purpose
This study evaluates the Argus™ II Retinal Prosthesis System in blind subjects with severe outer retinal degeneration.
Design
The study design is a single arm, prospective, multicenter clinical trial.
Participants
Thirty subjects were enrolled in the United States and Europe between 6 June 2007 and 11 August 2009. All subjects were followed for a minimum of six months and up to 2.7 years.
Methods
The electronic stimulator and antenna of the implant was sutured onto the sclera using an encircling silicone band. Next, a pars plana vitrectomy was performed and the electrode array and cable were introduced into the eye via a pars plana sclerotomy. The microelectrode array was then tacked to the epiretinal surface.
Main Outcome Measures
The primary safety endpoint for the trial was the number, severity, and relation of adverse events. Principal performance endpoints were assessments of visual function as well as performance on orientation and mobility tasks.
Results
Subjects performed statistically better with system ON vs. OFF in the following tasks: object localization (96% of subjects); motion discrimination (57%); and discrimination of oriented gratings (23%). The best recorded visual acuity to date is 20/1260. Subjects’ mean performance on Orientation and Mobility tasks was significantly better when the System was ON vs. OFF.
Seventy percent of the patients did not have any serious adverse events (SAEs). The most common SAE reported was either conjunctival erosion or dehiscence over the extraocular implant and was successfully treated in all subjects except in one which required explantation of the device without further complications.
Conclusions
The long-term safety results of Second Sight’s retinal prosthesis system are acceptable and the majority of subjects with profound visual loss perform better on visual tasks with system than without.
doi:10.1016/j.ophtha.2011.09.028
PMCID: PMC3319859  PMID: 22244176
13.  Impact of Simulated Central Scotomas on Visual Search in Natural Scenes 
Purpose
In performing search tasks, the visual system encodes information across the visual field at a resolution inversely related to eccentricity and deploys saccades to place visually interesting targets upon the fovea where resolution is highest. The serial process of fixation, punctuated by saccadic eye movements, continues until the desired target has been located. Loss of central vision restricts the ability to resolve the high spatial information of a target, interfering with this visual search process. We investigate oculomotor adaptations to central visual field loss with gaze-contingent artificial scotomas.
Methods
Spatial distortions were placed at random locations in 25° square natural scenes. Gaze-contingent artificial central scotomas were updated at the screen rate (75Hz) based on a 250Hz eyetracker. Eight subjects searched the natural scene for the spatial distortion and indicated its location using a mouse-controlled cursor.
Results
As the central scotoma size increased, the mean search time increased [F(3,28)= 5.27, p= .05] and the spatial distribution of gaze points during fixation increased significantly along the x [F(3,28)= 6.33, p= .002] and y [F(3,28)= 3.32, p= .034] axes. Oculomotor patterns of fixation duration, saccade size and saccade duration did not change significantly, regardless of scotoma size.
Conclusions
There is limited automatic adaptation of the oculomotor system following simulated central vision loss.
doi:10.1097/OPX.0b013e318267a914
PMCID: PMC3432450  PMID: 22885785
scotoma; saccade; fixation; eyetracking; visual search
14.  Facilitating conversation through self-initiated augmentative communication treatment. 
We examined the conversational skills of 2 adult males with severe motor and speech deficits resulting from cerebral palsy. A multiple baseline design across subjects was used to determine the effectiveness of an intervention strategy designed to teach them to use an augmentative communication system (Touch Talker) independently. The dependent measure was the number of conversation initiations relative to conversation reactions during spontaneous communication across baseline and treatment. The treatment included specific training on using the augmentative system to participate in communication. Once the intervention began, the production of conversation initiations accelerated at a rapid rate. The treatment program was effective in training the subjects to use the augmentative system to increase conversation participation. These results demonstrate that training on the operation of the device alone is not sufficient to ensure improvement in conversation performance, and that it is important to incorporate direct conversational treatment when providing instruction on the use of augmentative communication systems for severely speech-impaired individuals.
doi:10.1901/jaba.1991.24-369
PMCID: PMC1279580  PMID: 1890052
15.  Toward Wide-Field Retinal Prosthesis 
Journal of neural engineering  2009;6(3):035002.
The purpose of this article is to present a wide field electrode array that may increase the field of vision in patients implanted with a retinal prosthesis.
Mobility is often impaired in patients with low vision, particularly in those with peripheral visual loss. Studies on low vision patients as well as simulation studies on normally sighted individuals have indicated a strong correlation between the visual field and mobility. In addition, it has been shown that increased visual field is associated with a significant improvement in visual acuity and object discrimination. Current electrode arrays implanted in animals or human vary in size; however, the retinal area covered by the electrodes has a maximum projected visual field of about 10°. We have designed wide field electrode arrays that could potentially provide a visual field of 34°, which may significantly improve the mobility. Tests performed on a mechanical eye model showed that it was possible to fix flexible polyimide dummy electrode arrays of 10 mm wide onto the retina using a single retinal tack. They also showed that the arrays could conform to the inner curvature of the eye. Surgeries on an enucleated porcine eye model demonstrated feasibility of implantation of 10 mm wide arrays through a 5 mm eye wall incision.
doi:10.1088/1741-2560/6/3/035002
PMCID: PMC2861858  PMID: 19458405
Wide field; electrode array; retinal prosthesis; visual field; mobility; retinitis pigmentosa; age related macular degeneration
16.  Speeded Reaching Movements around Invisible Obstacles 
PLoS Computational Biology  2012;8(9):e1002676.
We analyze the problem of obstacle avoidance from a Bayesian decision-theoretic perspective using an experimental task in which reaches around a virtual obstacle were made toward targets on an upright monitor. Subjects received monetary rewards for touching the target and incurred losses for accidentally touching the intervening obstacle. The locations of target-obstacle pairs within the workspace were varied from trial to trial. We compared human performance to that of a Bayesian ideal movement planner (who chooses motor strategies maximizing expected gain) using the Dominance Test employed in Hudson et al. (2007). The ideal movement planner suffers from the same sources of noise as the human, but selects movement plans that maximize expected gain in the presence of that noise. We find good agreement between the predictions of the model and actual performance in most but not all experimental conditions.
Author Summary
In everyday, cluttered environments, moving to reach or grasp an object can result in unintended collisions with other objects along the path of movement. Depending on what we run into (a priceless Ming vase, a crotchety colleague) we can suffer serious monetary or social consequences. It makes sense to choose movement trajectories that trade off the value of reaching a goal against the consequences of unintended collisions along the way. In the research described here, subjects made speeded movements to touch targets while avoiding obstacles placed along the natural reach trajectory. There were explicit monetary rewards for hitting the target and explicit monetary costs for accidentally hitting the intervening obstacle. We varied the cost and location of the obstacle across conditions. The task was to earn as large a monetary bonus as possible, which required that reaches curve around obstacles only to the extent justified by the location and cost of the obstacle. We compared human performance in this task to that of a Bayesian movement planner who maximized expected gain on each trial. In most conditions, but not all, movement strategies were close to optimal.
doi:10.1371/journal.pcbi.1002676
PMCID: PMC3447970  PMID: 23028276
17.  Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects 
Purpose
The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device.
Methods
Electrode–retina and electrode–fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode–retina distance, electrode–fovea distance, and monocular light threshold) were quantified using regression.
Results
Regression analysis showed a significant correlation between electrical threshold and electrode–retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode–retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005).
Conclusions
Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount.
Translational Relevance
Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that employ smaller diameter electrodes. (clinicaltrials.gov identifier: NCT00407602)
doi:10.1167/tvst.2.4.1
PMCID: PMC3763895  PMID: 24049718
retinal prosthesis; retinal degeneration; retinitis pigmentosa
18.  Flexible, task-dependent use of sensory feedback to control hand movements 
We tested whether changing accuracy demands for simple pointing movements leads humans to adjust the feedback control laws that map sensory signals from the moving hand to motor commands. Subjects made repeated pointing movements in a virtual environment to touch a button whose shape varied randomly from trial-to-trial – between squares, rectangles oriented perpendicular to the movement path and rectangles oriented parallel to the movement path. Subjects performed the task on a horizontal table, but saw the target configuration and a virtual rendering of their pointing finger through a mirror mounted between a monitor and the table. On a one-third of trials, the position of the virtual finger was perturbed by ±1 cm either in the movement direction or perpendicular to the movement direction when the finger passed behind an occluder. Subjects corrected quickly for the perturbations despite not consciously noticing them; however, they corrected almost twice as much for perturbations aligned with the narrow dimension of a target than for perturbations aligned with the long dimension. These changes in apparent feedback gain appeared in the kinematic trajectories soon after the time of the perturbations, indicating that they reflect differences in the feedback control law used throughout the duration of movements. The results indicate that the brain adjusts its feedback control law for individual movements “on-demand” to fit task demands. Simulations of optimal control laws for a two-joint arm show that accuracy demands alone, coupled with signal dependent noise lead to qualitatively the same behavior.
doi:10.1523/JNEUROSCI.3522-09.2011
PMCID: PMC3047484  PMID: 21273407
Feedback; optimal control; motor control; pointing; online control
19.  Children with Developmental Coordination Disorder Benefit from Using Vision in Combination with Touch Information for Quiet Standing 
Gait & posture  2011;34(2):183-190.
In two experiments, the ability to use multisensory information (haptic information, provided by lightly touching a stationary surface, and vision) for quiet standing was examined in typically developing (TD) children, adults, and in 7-year-old children with Developmental Coordination Disorder (DCD). Four sensory conditions (no touch/no vision, with touch/no vision, no touch/with vision, and with touch/with vision) were employed. In experiment 1, we tested 4-, 6- and 8-year-old TD children and adults to provide a developmental landscape for performance on this task. In experiment 2, we tested a group of 7-year-old children with DCD and their age-matched TD peers. For all groups, touch robustly attenuated standing sway suggesting that children as young as 4 years old use touch information similarly to adults. Touch was less effective in children with DCD compared to their TD peers, especially in attenuating their sway velocity. Children with DCD, unlike their TD peers, also benefited from using vision to reduce sway. The present results suggest that children with DCD benefit from using vision in combination with touch information for standing control possibly due to their less well developed internal models of body orientation and self-motion. Internal model deficits, combined with other known deficits such as postural muscles activation timing deficits, may exacerbate the balance impairment in children with DCD.
doi:10.1016/j.gaitpost.2011.04.007
PMCID: PMC3130081  PMID: 21571533
Developmental Coordination Disorder (DCD); Standing Balance Multisensory; Light Touch; Vision
20.  Spatial working memory for locations specified by vision and audition: Testing the amodality hypothesis 
Spatial working memory can maintain representations from vision, hearing, and touch, representations referred to here as spatial images. The present experiment addressed whether spatial images from vision and hearing that are simultaneously present within working memory retain modality-specific tags or are amodal. Observers were presented with short sequences of targets varying in angular direction, with the targets in a given sequence being all auditory, all visual, or a sequential mixture of the two. On two thirds of the trials, one of the locations was repeated, and observers had to respond as quickly as possible when detecting this repetition. Ancillary detection and localization tasks confirmed that the visual and auditory targets were perceptually comparable. Response latencies in the working memory task showed small but reliable costs in performance on trials involving a sequential mixture of auditory and visual targets, as compared with trials of pure vision or pure audition. These deficits were statistically reliable only for trials on which the modalities of the matching location switched from the penultimate to the final target in the sequence, indicating a switching cost. The switching cost for the pair in immediate succession means that the spatial images representing the target locations retain features of the visual or auditory representations from which they were derived. However, there was no reliable evidence of a performance cost for mixed modalities in the matching pair when the second of the two did not immediately follow the first, suggesting that more enduring spatial images in working memory may be amodal.
doi:10.3758/s13414-012-0311-2
PMCID: PMC3482114  PMID: 22552825
21.  Water-Induced Finger Wrinkles Do Not Affect Touch Acuity or Dexterity in Handling Wet Objects 
PLoS ONE  2014;9(1):e84949.
Human non-hairy (glabrous) skin of the fingers, palms and soles wrinkles after prolonged exposure to water. Wrinkling is a sympathetic nervous system-dependent process but little is known about the physiology and potential functions of water-induced skin wrinkling. Here we investigated the idea that wrinkling might improve handling of wet objects by measuring the performance of a large cohort of human subjects (n = 40) in a manual dexterity task. We also tested the idea that skin wrinkling has an impact on tactile acuity or vibrotactile sensation using two independent sensory tasks. We found that skin wrinkling did not improve dexterity in handling wet objects nor did it affect any aspect of touch sensitivity measured. Thus water-induced wrinkling appears to have no significant impact on tactile driven performance or dexterity in handling wet or dry objects.
doi:10.1371/journal.pone.0084949
PMCID: PMC3885627  PMID: 24416318
22.  Touch in primary care consultations: qualitative investigation of doctors’ and patients’ perceptions 
The British Journal of General Practice  2013;63(609):e283-e290.
Background
Good communication skills are integral to successful doctor–patient relationships. Communication may be verbal or non-verbal, and touch is a significant component, which has received little attention in the primary care literature. Touch may be procedural (part of a clinical task) or expressive (contact unrelated to a procedure/examination).
Aim
To explore GPs’ and patients’ experiences of using touch in consultations.
Design and setting
Qualitative study in urban and semi-rural areas of north-west England.
Method
Participating GPs recruited registered patients with whom they felt they had an ongoing relationship. Data were collected by semi-structured interviews and subjected to constant comparative qualitative analysis.
Results
All participants described the importance of verbal and non-verbal communication in developing relationships. Expressive touch was suggested to improve communication quality by most GPs and all patients. GPs reported a lower threshold for using touch with older patients or those who were bereaved, and with patients of the same sex as themselves. All patient responders felt touch on the hand or forearm was appropriate. GPs described limits to using touch, with some responders rarely using anything other than procedural touch. In contrast, most patient responders believed expressive touch was acceptable, especially in situations of distress. All GP responders feared misinterpretation in their use of touch, but patients were keen that these concerns should not prevent doctors using expressive touch in consultations.
Conclusion
Expressive touch improves interactions between GPs and patients. Increased educational emphasis on the conscious use of expressive touch would enhance clinical communication and, hence, perhaps patient wellbeing and care.
doi:10.3399/bjgp13X665251
PMCID: PMC3609476  PMID: 23540485
communication skills; consultations; non-verbal communication; primary health care; qualitative research; touch
23.  Line versus representational bisections in unilateral spatial neglect 
OBJECTIVES—To clarify the mechanisms of left unilateral spatial neglect found in the bisection of lines after cueing to the left end point and to determine whether neglect occurs for the mental representation of a line.
METHODS—A new representational bisection task was developed to eliminate the influence of the right segment of the physical line that would attract attention. Eight patients with typical left unilateral spatial neglect underwent line and representational bisection tasks on a computer display with a touch panel. In the line bisection with cueing, they bisected a line after touching the left end point. In the representational bisection, the patients were presented with a line until they touched the left end point. On the blank display, they pointed to the subjective midpoint of the erased line. The performances of the two bisection tasks were compared when the length and position of stimulus lines were varied.
RESULTS—The rightward errors in the representational bisection were greater than or equivalent to those in the line bisection with cueing. The effect of line length in which the errors became greater for the longer lines was equally found in the line bisection with cueing and the representational bisection. This was confirmed in the condition where the right end point was placed at a fixed position and the line length was varied.
CONCLUSIONS—After cueing to the left end point, rightward bisection errors of patients with neglect are not caused by overattention to the right segment of the physical line. Left neglect occurs mainly for the mental representation formed at the time of cueing or seeing the whole extent of a line.


doi:10.1136/jnnp.69.6.745
PMCID: PMC1737171  PMID: 11080226
24.  TMS of posterior parietal cortex disrupts visual tactile multisensory integration 
The European journal of neuroscience  2010;31(10):1783-1790.
Functional neuroimaging studies have implicated a number of brain regions, especially the posterior parietal cortex (PPC), as being potentially important for visual–tactile multisensory integration. However, neuroimaging studies are correlational and do not prove the necessity of a region for the behavioral improvements that are the hallmark of multisensory integration. To remedy this knowledge gap, we interrupted activity in the PPC, near the junction of the anterior intraparietal sulcus and the postcentral sulcus, using MRI-guided transcranial magnetic stimulation (TMS) while subjects localized touches delivered to different fingers. As the touches were delivered, subjects viewed a congruent touch video, an incongruent touch video, or no video. Without TMS, a strong effect of multisensory integration was observed, with significantly better behavioral performance for discrimination of congruent multisensory touch than for unisensory touch alone. Incongruent multisensory touch produced a smaller improvement in behavioral performance. TMS of the PPC eliminated the behavioral advantage of both congruent and incongruent multisensory stimuli, reducing performance to unisensory levels. These results demonstrate a causal role for the PPC in visual–tactile multisensory integration. Taken together with converging evidence from other studies, these results support a model in which the PPC contains a map of space around the hand that receives input from both the visual and somatosensory modalities. Activity in this map is likely to be the neural substrate for visual–tactile multisensory integration.
doi:10.1111/j.1460-9568.2010.07193.x
PMCID: PMC2994715  PMID: 20584182
hand; intraparietal sulcus; IPS; somatosensory; vision
25.  Spontaneous Spatial Mapping of Learned Sequence in Chimpanzees: Evidence for a SNARC-Like Effect 
PLoS ONE  2014;9(3):e90373.
In the last couple of decades, there has been a growing number of reports on space-based representation of numbers and serial order in humans. In the present study, to explore evolutionary origins of such representations, we examined whether our closest evolutionary relatives, chimpanzees, map an acquired sequence onto space in a similar way to humans. The subjects had been trained to perform a number sequence task in which they touched a sequence of “small” to “large” Arabic numerals presented in random locations on the monitor. This task was presented in sessions that also included test trials consisting of only two numerals (1 and 9) horizontally arranged. On half of the trials 1 was located to the left of 9, whereas on the other half 1 was to the right to 9. The Chimpanzees' performance was systematically influenced by the spatial arrangement of the stimuli; specifically, they responded quicker when 1 was on the left and 9 on the right compared to the other way around. This result suggests that chimpanzees, like humans, spontaneously map a learned sequence onto space.
doi:10.1371/journal.pone.0090373
PMCID: PMC3958337  PMID: 24643044

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