- •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
12 The Response of Retinal Neurons to Electrical Stimulation |
249 |
tyrosine kinase gene Mertk, which results in the failure of the outer segments of photoreceptors to be phagocytosed and eventually causing the death of photoreceptors [5, 34]. Degeneration of photoreceptors in RCS rat is slower than that in rd1 mouse. Only ~1/3 of photoreceptors are lost by P30. However, by P75 only scattered photoreceptors are present [37].
Pu et al. [38] reported that RGCs in RCS rats show an increased level of baseline spiking and by P47 (before complete degeneration of photoreceptors) were predominately OFF cells. Similar findings were reported in the rd1 mouse retina [52] where baseline spiking levels went from <1 Hz in RGCs of normal, wild type mice to as high as 20 Hz in retinas from rd1 mice. Furthermore, Stasheff [52] found that ~2/3 of rd1 RGCs exhibited rhythmic bursts (peaks at ~6 and ~12 Hz) of activity. As in the RCS rat retina, Stasheff [52] reported that ON and OFF responses are differentially affected in early stages of retinal degeneration rd1 mouse retina. Light-evoked ON responses in rd1 RGCs at P14-P15 were reduced more than OFF responses, and unlike OFF responses many of the ON responses showed an increased latency.
From patch-clamp recordings, Margolis et al. [29] reported rhythmic spike activity (frequency of ~10 Hz) in rd1 mouse retinas of P36-P50. The spike bursting was present in older mice as well, although the frequency of the bursts decreased 2-3-fold. Margolis et al. further showed that the rhythmic bursting was not generated intrinsically in RGCs but was due to strong, aberrant synaptic input. Intrinsic electrical properties of (morphologically identified) ON and OFF RGCs in rd1 mouse retinas were similar to those in wild-type mouse retinas.
The hyperactivity and bursting activity in RGCs indicates that new strategies for prosthetic stimulation of the retina may be necessary. For example, higher spiking levels may be needed to obtain an adequate signal to noise ratio. Alternatively, it may be necessary to develop stimulation strategies that reduce the level of baseline activity in order for the brain to be able to understand the signal leaving the retina. However, it is important to first determine whether increased spiking levels and bursts of activity are present clinically (in patients) before new stimulation strategies are developed.
12.4 Responses of RGCs to Electrical Stimulation in Degenerate Retina
The prosthetic must ultimately function in patients with retinal degenerative disease and therefore stimulation methods for clinical use must be tailored to these types of retinas. While many studies have examined the structural changes that occur as part of the degenerative process (Chap. 3), the corresponding physiological changes are not as well known. It is important to understand how the anatomical and physiological changes in degenerate retina will affect the response to electrical stimulation. In this section, we explore the few studies that have looked at the electrophysiological properties of RGCs in degenerate retina as well as those that have looked at the responses of RGCs in these retinas to electrical stimulation.