Visual restoration after decades of blindness is now becoming possible by means of retinal and cortical prostheses, as well as emerging stem cell and gene therapeutic approaches. After restoring visual perception, however, a key question remains. Are there optimal means and methods for retraining the visual cortex to process visual inputs, and for learning or relearning to “see”? Up to this point, it has been largely assumed that if the sensory loss is visual, then the rehabilitation focus should also be primarily visual. However, the other senses play a key role in visual rehabilitation due to the plastic repurposing of visual cortex during blindness by audition and somatosensation, and also to the reintegration of restored vision with the other senses. I will present multisensory neuroimaging results, cortical thickness changes, as well as behavioral outcomes for patients with Retinitis Pigmentosa (RP), which causes blindness by destroying photoreceptors in the retina. These patients have had their vision partially restored by the implantation of a retinal prosthesis, which electrically stimulates still viable retinal ganglion cells in the eye. Our multisensory and structural neuroimaging and behavioral results suggest a new, holistic concept of visual rehabilitation that leverages rather than neglects audition, somatosensation, and other sensory modalities.

Photoreceptor loss is the primary cause behind vision impairment and blindness in diseases such as retinitis pigmentosa and age-related macular degeneration. However, the death of rods and cones allows retinoids to permeate the inner retina, causing retinal ganglion cells to become spontaneously hyperactive, severely reducing the signal-to-noise ratio, and creating interference in the communication between the surviving retina and the brain. Treatments aimed at blocking or reducing hyperactivity improve vision initiated from surviving photoreceptors and could enhance the signal fidelity generated by vision restoration methodologies.

Ophthalmology is ideally placed to benefit from recent advances in artificial intelligence. It is a highly image-based specialty and provides unique access to the microvascular circulation and the central nervous system. This talk will demonstrate diverse applications of machine learning and deep learning techniques in ophthalmology, including in age-related macular degeneration (AMD), the leading cause of blindness in industrialized countries, and cataract, the leading cause of blindness worldwide. This will include deep learning approaches to automated diagnosis, quantitative severity classification, and prognostic prediction of disease progression, both from images alone and accompanied by demographic and genetic information. The approaches discussed will include deep feature extraction, label transfer, and multi-modal, multi-task training. Cluster analysis, an unsupervised machine learning approach to data classification, will be demonstrated by its application to geographic atrophy in AMD, including exploration of genotype-phenotype relationships. Finally, mediation analysis will be discussed, with the aim of dissecting complex relationships between AMD disease features, genotype, and progression.

Previous studies have shown that blind individuals outperform sighted controls in a variety of auditory tasks; however, only few studies have investigated blind listeners’ speaker identification abilities. In addition, existing studies in the area show conflicting results. The presented empirical investigation with 153 blind (74 of them congenitally blind) and 153 sighted listeners is the first of its kind and scale in which long-term memory effects of blind listeners’ speaker identification abilities are examined. For the empirical investigation, all listeners were evenly assigned to one of nine subgroups (3 x 3 design) in order to investigate the influence of two parameters with three levels, respectively, on blind and sighted listeners’ speaker identification performance. The parameters were a) time interval; i.e. a time interval of 1, 3 or 6 weeks between the first exposure to the voice to be recognised (familiarisation) and the speaker identification task (voice lineup); and b) signal quality; i.e. voice recordings were presented in either studio-quality, mobile phone-quality or as recordings of whispered speech. Half of the presented voice lineups were target-present lineups in which the previously heard target voice was included. The other half consisted of target-absent lineups which contained solely distractor voices. Blind individuals outperformed sighted listeners only under studio quality conditions. Furthermore, for blind and sighted listeners no significant performance differences were found with regard to the three investigated time intervals of 1, 3 and 6 weeks. Blind as well as sighted listeners were significantly better at picking the target voice from target-present lineups than at indicating that the target voice was absent in target-absent lineups. Within the blind group, no significant correlations were found between identification performance and onset or duration of blindness. Implications for the field of forensic phonetics are discussed.

We examine consciousness from the perspective of theoretical computer science (TCS), a branch of mathematics concerned with understanding the underlying principles of computation and complexity, including the implications and surprising consequences of resource limitations. We propose a formal TCS model, the Conscious Turing Machine (CTM). The CTM is influenced by Alan Turing's simple yet powerful model of computation, the Turing machine (TM), and by the global workspace theory (GWT) of consciousness originated by cognitive neuroscientist Bernard Baars and further developed by him, Stanislas Dehaene, Jean-Pierre Changeux, George Mashour, and others. However, the CTM is not a standard Turing Machine. It’s not the input-output map that gives the CTM its feeling of consciousness, but what’s under the hood. Nor is the CTM a standard GW model. In addition to its architecture, what gives the CTM its feeling of consciousness is its predictive dynamics (cycles of prediction, feedback and learning), its internal multi-modal language Brainish, and certain special Long Term Memory (LTM) processors, including its Inner Speech and Model of the World processors. Phenomena generally associated with consciousness, such as blindsight, inattentional blindness, change blindness, dream creation, and free will, are considered. Explanations derived from the model draw confirmation from consistencies at a high level, well above the level of neurons, with the cognitive neuroscience literature. Reference. L. Blum and M. Blum, "A theory of consciousness from a theoretical computer science perspective: Insights from the Conscious Turing Machine," PNAS, vol. 119, no. 21, 24 May 2022. https://www.pnas.org/doi/epdf/10.1073/pnas.2115934119

My research uses electrophysiological techniques to evaluate normal retinal function, dysfunction caused by blinding retinal diseases and the restoration of function using a variety of therapeutic strategies. We can use our understanding or normal retinal function and disease-related changes to construct optimal therapeutic strategies and evaluate how they ameliorate the effects of disease. Retinitis pigmentosa (RP) is a family of blinding eye diseases caused by photoreceptor degeneration. The absence of the cells that for this primary signal leads to blindness. My interest in RP involves the evaluation of therapies to restore vision: replacing degenerated photoreceptors either with: (1) new stem or other embryonic cells, manipulated to become photoreceptors or (2) prosthetics devices that replace the photoreceptor signal with an electronic signal to light. Glaucoma is caused by increased intraocular pressure and leads to ganglion cell death, which eliminates the link between the retinal output and central visual processing. We are parsing out of the effects of increased intraocular pressure and aging on ganglion cells. Congenital Stationary Night Blindness (CSNB) is a family of diseases in which signaling is eliminated between rod photoreceptors and their postsynaptic targets, rod bipolar cells. This deafferents the retinal circuit that is responsible for vision under dim lighting. My interest in CSNB involves understanding the basic interplay between excitation and inhibition in the retinal circuit and its normal development. Because of the targeted nature of this disease, we are hopeful that a gene therapy approach can be developed to restore night vision. My work utilizes rodent disease models whose mutations mimic those found in human patients. While molecular manipulation of rodents is a fairly common approach, we have recently developed a mutant NIH miniature swine model of a common form of autosomal dominant RP (Pro23His rhodopsin mutation) in collaboration with the National Swine Resource Research Center at University of Missouri. More genetically modified mini-swine models are in the pipeline to examine other retinal diseases.

John DowlingJohn E. Dowling received his AB and PhD from Harvard University. He taught in the Biology Department at Harvard from 1961 to 1964, first as an Instructor, then as assistant professor. In 1964 he moved to Johns Hopkins University, where he held an appointment as associate professor of Ophthalmology and Biophysics. He returned to Harvard as professor of Biology in 1971, was the Maria Moors Cabot Professor of Natural Sciences from 1971-2001, Harvard College professor from 1999-2004 and is presently the Gordon and Llura Gund Professor of Neurosciences. Dowling was chairman of the Biology Department at Harvard from 1975 to 1978 and served as associate dean of the faculty of Arts and Sciences from 1980 to 1984. He was Master of Leverett House at Harvard from 1981-1998 and currently serves as president of the Corporation of The Marine Biological Laboratory in Woods Hole. He is a Fellow of the American Academy of Arts and Sciences, a member of the National Academy of Sciences and a member of the American Philosophical Society. Awards that Dowling received include the Friedenwald Medal from the Association of Research in Ophthalmology and Vision in 1970, the Annual Award of the New England Ophthalmological Society in 1979, the Retinal Research Foundation Award for Retinal Research in 1981, an Alcon Vision Research Recognition Award in 1986, a National Eye Institute's MERIT award in 1987, the Von Sallman Prize in 1992, The Helen Keller Prize for Vision Research in 2000 and the Llura Ligget Gund Award for Lifetime Achievement and Recognition of Contribution to the Foundation Fighting Blindness in 2001. He was granted an honorary MD degree by the University of Lund (Sweden) in 1982 and an honorary Doctor of Laws degree from Dalhousie University (Canada) in 2012. Dowling's research interests have focused on the vertebrate retina as a model piece of the brain. He and his collaborators have long been interested in the functional organization of the retina, studying its synaptic organization, the electrical responses of the retinal neurons, and the mechanisms underlying neurotransmission and neuromodulation in the retina. Dowling became interested in zebrafish as a system in which one could explore the development and genetics of the vertebrate retina about 20 years ago. Part of his research team has focused on retinal development in zebrafish and the role of retinoic acid in early eye and photoreceptor development. A second group has developed behavioral tests to isolate mutations, both recessive and dominant, specific to the visual system.

The Manookin lab is investigating the structure and function of neural circuits within the retina and developing techniques for treating blindness. Many blinding diseases, such as retinitis pigmentosa, cause death of the rods and cones, but spare other cell types within the retina. Thus, many techniques for restoring visual function following blindness are based on the premise that other cells within the retina remain viable and capable of performing their various roles in visual processing. There are more than 80 different neuronal types in the human retina and these form the components of the specialized circuits that transform the signals from photoreceptors into a neural code responsible for our perception of color, form, and motion, and thus visual experience. The Manookin laboratory is investigating the function and connectivity of neural circuits in the retina using a variety of techniques including electrophysiology, calcium imaging, and electron microscopy. This knowledge is being used to develop more effective techniques for restoring visual function following blindness.

Electronic interfaces to the retina represent an exciting development in science, engineering, and medicine – an opportunity to exploit our knowledge of neural circuitry and function to restore or even enhance vision. However, although existing devices demonstrate proof of principle in treating incurable blindness, they produce limited visual function. Some of the reasons for this can be understood based on the precise and specific neural circuitry that mediates visual signaling in the retina. Consideration of this circuitry suggests that future devices may need to operate at single-cell, single-spike resolution in order to mediate naturalistic visual function. I will show large-scale multi-electrode recording and stimulation data from the primate retina indicating that, in some cases, such resolution is possible. I will also discuss cases in which it fails, and propose that we can improve artificial vision in such conditions by incorporating our knowledge of the visual system in bi-directional devices that adapt to the host neural circuitry. Finally, I will introduce the Stanford Artificial Retina Project, aimed at developing a retinal implant that more faithfully reproduces the neural code of the retina, and briefly discuss the implications for scientific investigation and for other neural interfaces of the future.