- •Visual Prosthetics
- •Preface
- •Acknowledgments
- •Contents
- •Contributors
- •1.1 The Visual System as an Engineering Compromise
- •1.2 An Overview of Human Visual System Architecture
- •1.2.1 Architecture and Basic Function of the Eye
- •1.2.2 Layout of the Retino-Cortical Pathway
- •1.2.3 Layout of the Subcortical Pathways
- •1.3 An Overview of Human Visual Function
- •1.3.1 Roles of Central (Foveal) Vision
- •1.3.2 Roles of Peripheral Vision
- •1.3.3 Roles of Dark-Adapted Vision
- •1.3.4 A Few Remarks Regarding Visual Development
- •1.4 Prospects for Prosthetic Vision Restoration
- •References
- •2.1 Introduction
- •2.2 Retina
- •2.2.1 Anatomy
- •2.2.2 Physiology and Receptive Fields
- •2.4.1 Anatomy
- •2.4.2 Physiology and Receptive Fields
- •2.6 The Role of Spatiotemporal Edges in Early Vision
- •2.7 The Role of Corners in Early Vision
- •2.7.1 Overview
- •2.8 Effects of Fixational Eye Movements in Early Visual Physiology and Perception
- •2.8.1 Overview
- •2.8.2 Neural Adaptation and Visual Fading
- •2.8.3 Microsaccades in Visual Physiology and Perception
- •References
- •3.1 Introduction
- •3.2 Background
- •3.3 Retinal Disease and Its Diversity
- •3.4 Retinal Remodeling
- •3.5 Retinal Circuitry
- •3.6 Retinal Circuitry Revision
- •3.7 Implications for Bionic Rescue
- •3.8 Implications for Biological Rescue
- •3.9 Final Remarks
- •References
- •4.1 Introduction
- •4.4 What Are the Limits to This Cortical Plasticity?
- •4.5 Possible Mechanisms Behind Brain Plasticity
- •4.6 Modulation of Brain Plasticity: Recent Developments
- •4.7 Neuroplasticity and Other Neuroprostheses Efforts
- •4.8 A Look at What Is Ahead
- •References
- •5.1 Introduction
- •5.2 Vision Changes Experienced by RP Patients
- •5.2.1 Overview
- •5.2.2 Visual Field Loss in RP
- •5.2.3 Changes in Color Vision and Glare Sensitivity in RP
- •5.2.4 Vision Fluctuations in RP
- •5.3 Visual Changes in Patients with Advanced Macular Degeneration
- •5.3.1 Changes Due to Wet AMD or Choroidal Neovascularization
- •5.3.2 Changes Due to Dry AMD or Geographic Atrophy
- •5.4 Charles Bonnet Syndrome
- •5.4.1 Overview
- •5.4.2 Complexity of Visual Hallucinations in CBS
- •5.4.3 Predictors and Alleviating Factors for CBS
- •5.5 Filling-In Phenomena (Perceptual Completion)
- •5.6 Remapping of Primary Visual Cortex in Patients with Central Scotomas from Macular Disease
- •5.7 The Preferred Retinal Locus for Fixation
- •5.8 Photopsias
- •5.8.1 Photopsias in RP
- •5.8.2 Photopsias in AMD and Other Ocular Diseases
- •5.9 Concluding Remarks
- •References
- •6.1 Introduction
- •6.2 Electrode–Electrolyte Interface
- •6.3 Electrode Material
- •6.3.1 Electrode Characterization
- •6.4 Overview of Electrode Materials for Neural Stimulation
- •6.5 Overview of Extracellular Stimulation
- •6.6 Safe Stimulation of Tissue
- •6.6.1 Mechanisms of Neural Injury
- •6.6.2 Parameters for Safe Stimulation
- •6.6.3 Stimulation Induced Injury in the Retina
- •References
- •7.1 Introduction
- •7.2 Power and Data Transmission
- •7.2.1 Wireline Connection
- •7.2.2 Inductive Coils
- •7.2.3 Serial Optical Telemetry
- •7.2.4 Photodiode Array-Based Prostheses
- •7.2.5 Thermal Safety Considerations
- •7.2.6 Conclusions: Comparing the Different Approaches
- •7.3 Tissue Response to a Subretinal Implant
- •7.3.1 Flat Implants
- •7.3.2 Chamber Implants
- •7.3.3 Pillar Arrays
- •7.4 Damage to Retinal Tissue from Electrical Stimulation
- •7.4.1 Effect of Pulse Duration
- •7.4.2 Electrode Size
- •7.5 Concluding Remarks
- •References
- •8.1 Introduction
- •8.2 Quasistatic Numerical Methods: The Admittance Method
- •8.2.1 Layered Retinal Model
- •8.2.2 Equivalent Electric Circuit
- •8.3 Three-Dimensional Activation Function Calculation
- •8.4 Safety of Implant
- •8.5 Conclusion
- •References
- •9.1 Pathophysiology of Retinal Degeneration
- •9.2.1 Outer Plexiform Layer
- •9.2.2 Inner Plexiform Layer
- •9.2.2.1 Bipolar Cell Excitation of Retinal Ganglion Cells
- •9.2.2.2 Amacrine Cell Modulation of Signal Processing
- •9.2.2.3 Inhibitory Transmitters
- •9.2.2.4 Acetylcholine and Dopamine
- •9.2.2.5 Neuropeptides
- •9.2.2.6 Putative neurotransmitters for retinal prosthesis
- •9.3 Neurophysiological Changes in Retinal Degeneration
- •9.4 Rationale for a Neurotransmitter-Based Retinal Prosthesis
- •9.4.1 Limitations of Electrical Stimulation
- •9.5 Technical Considerations and Design Approaches
- •9.5.1 Operating Principles for a Neurotransmitter-Based Retinal Prosthesis
- •9.5.2 Establishing a Retinal Prosthesis/Synaptic Interface
- •9.5.2.1 The Proximity Requirement
- •9.5.2.2 Convective Delivery of Neurotransmitters Via Microfluidics
- •9.5.2.3 Functionalized Surfaces for Neurotransmitter Stimulation
- •9.5.2.4 Synaptic Requirements for l-Glutamate Mediated Neuronal Stimulation
- •9.6 Summary
- •References
- •10.1 Introduction
- •10.2 Pioneering Experiments
- •10.2.1 Stimulation with No Chromophores
- •10.2.2 Azo Chromophores
- •10.3 Current Research
- •10.3.1 Caged Neurotransmitters
- •10.3.2 Pore Blocker and Photoisomerization
- •10.3.3 The Channelrhodopsins
- •10.3.4 Melanopsin
- •10.4 Synthetic Chromophores and Artificial Sight
- •References
- •11.1 Background
- •11.2 Physical Structure of Intracortical Electrodes
- •11.3 Charge Injection Using Intracortical Electrodes
- •11.3.1 The Intracortical Electrode as a Transducer
- •11.3.2 Charge Injection Limits
- •11.4 Intracortical Electrode Coatings
- •11.5 Characterization of Intracortical Electrodes
- •11.5.1 Cyclic Voltammetry
- •11.5.2 Electrode Stimulation Voltage Waveforms
- •11.5.3 Non-ideal Access Resistance Behavior
- •11.5.4 Non-linear Electrode Polarization
- •11.5.5 Determining Electrode Safety
- •11.6 Contrasts of In Vitro and In Vivo Behavior
- •11.7 Alternative Coatings for Improving Intracortical Electrodes
- •11.7.1 SIROF
- •11.7.2 PEDOT
- •11.7.3 Carbon Nanotube Coatings
- •11.8 Conclusion
- •References
- •12.1 Introduction
- •12.2 Responses of RGCs to Electrical Stimulation in Normal Retina
- •12.2.1 Epiretinal Stimulation
- •12.2.1.1 Target of Stimulation
- •12.2.1.2 The Site of Spike Initiation in RGCs
- •12.2.1.3 Threshold vs. Stimulating Electrode Diameter
- •12.2.1.4 Spatial Extent of Activation
- •12.2.1.5 Selective Activation
- •12.2.1.6 Temporal Response Properties
- •12.2.2 Subretinal Stimulation
- •12.2.2.1 Target of Stimulation
- •12.2.2.2 Threshold vs. Polarity of Stimulation Pulse
- •12.2.2.3 Spatial Extent of Activation
- •12.2.2.4 Temporal Response Properties
- •12.2.2.5 Dynamics of the Retinal Response
- •12.4 Responses of RGCs to Electrical Stimulation in Degenerate Retina
- •12.4.1 Epiretinal Stimulation
- •12.4.2 Subretinal Stimulation
- •12.4.2.1 Response Properties of RGCs
- •12.4.2.2 Activation Thresholds of RGCs
- •12.5 Cortical Responses to Retinal Stimulation
- •12.5.1 Spatial Properties Revealed by Cortical Measurements
- •12.5.2 Local Field Potentials
- •12.5.3 Elicited Responses Are Focal
- •12.5.4 Cortical Measurements Reveal Electrode Interactions
- •12.5.5 Temporal Responsiveness in Cortex
- •12.6 Suggestions for Future Studies
- •References
- •13.1 Introduction
- •13.2 General Considerations for Acute Retinal Stimulation Experiments
- •13.3 Surgical Technique
- •13.4 Threshold Measurements
- •13.5 Spatial Resolution and Pattern Perception
- •13.6 Temporal Resolution
- •13.7 Subretinal Versus Epiretinal Stimulation
- •13.8 Less Invasive Stimulation Procedures
- •13.9 Conclusions and Outlook
- •References
- •14.1 Introduction
- •14.2 Overview of Chronic Retinal Implant Technologies
- •14.2.1 The Retinal Implant AG Microphotodiode Prosthesis
- •14.2.2 The Intelligent Retinal Implant System
- •14.2.3 Second Sight Medical Products, Inc. A16 System
- •14.3 Thresholds on Individual Electrodes
- •14.3.1 Single Pulse Thresholds Using the SSMP System
- •14.3.2 Pulse Train Integration and Temporal Sensitivity
- •14.4 Suprathreshold Brightness
- •14.4.1 Brightness Using the Retinal Implant AG System
- •14.4.2 Brightness Using the Intelligent Medical Implant System
- •14.4.3 Brightness Using the SSMP A16 System
- •14.5 Spatial Vision
- •14.5.1 Spatial Vision with the Retinal Implant AG System
- •14.5.2 Spatial Vision with the Intelligent Medical Implant System
- •14.5.3 Spatial Vision with the SSMP A16 System
- •14.6 Models to Guide Electrical Stimulation Protocols
- •14.7 Conclusions
- •References
- •15.1 Background
- •15.2 Cortical Surface Stimulation
- •15.3 Intracortical Microstimulation
- •15.4 Optic Nerve Stimulation
- •15.5 What Is Known and What Needs to Be Done
- •15.6 Current Research Efforts
- •15.6.1 Optic Nerve Stimulation
- •15.6.2 Cortical Surface Stimulation
- •15.6.3 Intracortical Stimulation of Visual Cortex
- •15.6.4 CORTIVIS Program
- •15.6.5 Lateral Geniculate Stimulation
- •15.7 Microelectrode Arrays and Stimulation Hardware
- •15.7.1 Miniature Cameras
- •15.7.2 Animal Models
- •15.7.3 Image Processing and Phosphene Mapping
- •15.8 Conclusion
- •References
- •16.1 Introduction
- •16.2 Simulation Techniques and Basic Parameters
- •16.2.1 Gaze Tracking and Image Stabilization
- •16.2.2 Filter Engine Parameters
- •16.2.2.1 Raster Spatial Properties
- •16.2.2.2 Dot Spatial Properties
- •16.2.2.3 Temporal Properties
- •16.2.2.4 Dynamic Background Noise
- •16.2.2.5 Input Filtering/Windowing, Image Enhancement
- •16.3 Optotype Resolution and Reading
- •16.3.1 Visual Acuity
- •16.3.2 Reading
- •16.4 Face and Object Recognition
- •16.5 Visually Guided Behavior
- •16.5.1 Hand–Eye Coordination
- •16.5.2 Wayfinding
- •16.6 Visual Tracking
- •16.7 Computational Simulations
- •16.8 Conclusion
- •References
- •17.1 Introduction
- •17.2 Situating Image Analysis
- •17.3 The Experimental Framework
- •17.4 Tracking a Low-Resolution Target
- •17.5 Discussion
- •17.6 Conclusion
- •References
- •18.1 Introduction
- •18.2 Representation of Visual Space on the Visual Cortex
- •18.3 Cortical Stimulation Studies
- •18.4 Variability in Occipital Cortex
- •18.5 Phosphene Map Estimation
- •18.6 Psychophysical Studies with the Estimated Maps
- •References
- •19.1 Importance of Mapping
- •19.3 The Computer Era: Refining the Pointing Method of Phosphene Mapping
- •19.4 Verbal Mapping
- •19.5 Mapping Studies Using Subject Drawings
- •19.6 Recent Simulation Studies Using Phosphene Mapping
- •19.6.1 Tactile Simulations at Shanghai Jiao Tong University
- •19.6.2 Simulations in Our Laboratory
- •19.7 Concluding Remarks on Phosphene Mapping Techniques
- •References
- •20.1 Introduction
- •20.2 Principles for Assessment of Prosthetic Vision
- •20.2.1 Experimental Design
- •20.2.2 The Importance of Pre-operative Testing
- •20.2.3 Post-operative Assessment
- •20.2.4.1 Potential Approaches
- •20.2.4.2 Avoidance of Bias
- •20.2.4.3 Criteria for Sound Testing
- •20.2.4.4 Forced Choice Procedures
- •20.2.4.5 Response Time
- •20.2.4.6 Task (Perceptual) Learning
- •20.2.4.7 Establishing Criteria for Meaningful Change
- •20.2.4.8 Light Level
- •20.3 Vision Assessment in Prosthesis Recipients: Overview
- •20.3.1 Visual Function Assessment: Overview
- •20.3.2 Visual Performance Assessment: Overview
- •20.3.2.1 Measured Visual Performance
- •20.3.2.2 Self-Reported Visual Performance
- •20.4 Visual Function Assessment
- •20.4.1 Candidate Measures
- •20.4.1.1 Contrast Sensitivity (Contrast Detection)
- •20.4.1.2 Contrast Discrimination
- •20.4.1.3 Motion Perception
- •20.4.1.4 Depth Perception
- •20.4.2 Tests Used in Prosthesis Trials
- •20.4.3 Tests that Have Been Designed for Use with Prostheses
- •20.4.4 Vision Tests for Very Low Vision
- •20.5 Visual Performance Assessment
- •20.5.1 Measured Performance
- •20.5.2 Self-Reported Performance (Questionnaires)
- •20.6 Summary
- •References
- •21.1 Concepts of Functional Vision and Rehabilitation
- •21.1.1 Application to Orientation and Mobility
- •21.1.2 Application for Activities of Daily Living
- •21.1.3 Patient Lifestyle and Expectations
- •21.1.4 Congenital and Adventitious Vision Loss
- •21.2 Evaluation and Intervention with Prosthetic Vision
- •21.2.1 Evaluation
- •21.2.2 Intervention
- •21.3 Measuring Functional Outcomes
- •21.4 The Future
- •References
- •Author Index
- •Subject Index
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function through the migration process, for 6 weeks after implantation, and that there is excellent apposition between neuronal cell bodies and electrode tips [9].
In summary, the best proximity between electrodes and target cells in the inner retina is achieved using three-dimensional implants that utilize retinal plasticity for intimate integration of the inner retina with the implant. An implant with a multitude of voids allows retinal cell bodies and cell processes to migrate into the voids within 72 h after implantation, and appears to be stable at least up to 6 weeks post-op.
7.4 Damage to Retinal Tissue from Electrical Stimulation
Understanding the safe limits of electrical stimulation of neural tissue is critically important for maintaining a stable interface between the retina and the prosthesis. Some studies along these lines have been performed with cortical stimulation in cats, using charge-balanced 400 ms pulses at 50 Hz over the course of 7 h, and analyzed by histology [39]. It was determined that charge per phase and charge density were cofactors that determined cellular damage in different regimes. However, no detailed understanding has been achieved regarding dependence of the damage threshold on pulse duration, electrode size, distance from the electrode and number of pulses. This section explores these dependences using chick retina, validated with a limited number of experiments on mammalian retina in vitro.
Electrical stimulation was biphasic, with the same duration in both phases, leading with the cathodal phase. All durations mentioned below refer to time per phase. Cellular damage was assessed using propidium iodide (PI), a normally cell impermeable molecule that becomes fluorescent upon binding to nucleic acids [70]. PI was added to the medium prior to the treatment and dye fluorescence was assessed 15 min after the electrical pulse. Causes of cellular damage may include the direct effect of electric field, thermal damage from the applied current, or toxic products from the electrochemical reactions at the electrode–electrolyte interface. Our estimations of Joule heating within the pulse durations and currents used in our experiments indicated that this effect is negligible – temperature rise did not exceed 0.02°C, significantly lower than thermal damage thresholds [10]. Glass pipettes pulled to various tip diameters were used as stimulating electrodes. This design allowed large platinum wire bundles inside the pipette to have low current density on the metal surface to avoid generation of gas inside the capillary, while having high current densities at the electrode tip.
Damage thresholds were established for pulse durations in the range of 6 ms/ phase to 6 ms/phase, and for electrode diameters of 0.1–1 mm. All plots include two points for each setting: a maximum safe value and a minimum damaging level, evaluated 5–15 min after the insult.
As shown in Fig. 7.7, the damage threshold decreased with the number of pulses, stabilizing after 100 exposures at approximately 15% of the single pulse value. This level remained stable up to the maximum number of pulses tested – 7,500 exposures at 25 Hz. The pulse duration was 600 ms in these measurements.
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Fig. 7.7 Retinal damage threshold current density as a function of the number of pulses, applied during 5 min, normalized to a single exposure damage threshold. After approximately 50 pulses, the damage threshold reaches a constant level. A pipette of 1 mm in diameter was used in these measurements with a 600 ms pulse duration. Figure reprinted from [10], with permission; © 2009 IEEE
Fig. 7.8 Strength-duration dependence of the damage thresholds on the retina. (○) Measured on the chick retina with single shots (open symbols) and with sustained repetitive exposures (● solid symbols). Current density relates to pulse duration t roughly as t−0.5, which is characteristic of electroporation [69, 70]. For comparison, (´) represents the damage thresholds of the porcine retina by single pulses in vitro and (D) presents chronic damage thresholds on the rabbit retina measured in vivo [13]. Figure reprinted from [10], with permission; © 2009 IEEE
7.4.1 Effect of Pulse Duration
Pulse duration was varied between 6 ms and 6 ms using a large electrode (1 mm) for single and repeated exposures. As shown in Fig. 7.8, the damage thresholds scale with pulse length as approximately 1/√t, or more exactly t−0.48 for chronic
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stimulation (7,500 pulses), and t−0.41 for single exposures. Two additional measurements have been performed with single exposures on porcine retina to validate the chick model; they are presented with the X. For comparison we also plot the in vivo result of chronic retinal stimulation in rabbits (D) [71].
The approximate scaling of the strength–duration curves as t−0.5 is characteristic of electroporation [41, 42], indicating that cellular damage is produced by the opening of pores in the cell membrane. Though cells can recover from the transient occurrence of these pores, it is unlikely that the cell would be able to sustain this abnormal state chronically. The scaling also indicates that neither charge, nor charge density, q = j∙t, are conserved along the strength–duration curve. It used to be believed that charge and charge density per phase were the two determinants of damage threshold [39].
7.4.2 Electrode Size
The dependence of damage threshold on electrode size was investigated using 600 ms biphasic pulses on chick retina with electrode size ranging from 0.1 to 1 mm. As shown in Fig. 7.9, damage threshold current density is nearly constant with large electrodes (diameter greater than 300 mm). With smaller electrodes the current increases, asymptotically approaching a 1/d2 dependence, indicating a constant current regime characteristic of a point source. This asymptotic constant current value was about 140 mA for a 600 ms pulse duration.
The strength–duration relationship for large and small pipettes (0.115 and 1.0 mm) are compared in Fig. 7.10 with the retinal stimulation thresholds published by Jensen et al. [24]. The inset plot depicts the safe dynamic range of retinal
Fig. 7.9 Dependence of the threshold current density on pipette diameter for sustained exposures on chick retina with pulse duration of 0.6 ms/phase. The solid line represents the current density at the tissue, calculated using the model of a disk electrode separated from the retina by 125 mm. On electrodes smaller than 200 mm, the current density scales as 1/d2, corresponding to a constant current of 139 mA. Figure reprinted from [10], with permission; © 2009 IEEE