1 2 1. Introduction The loss of eyesight can be the most impactful incident of a lifetime, and is associated with radical changes in life-style, impaired autonomy and increased risk for depression and even suicide (De Leo et al., 1999). For these reasons, the restoration of vision to the blind has been a centuries-old aspiration in the field of medicine. Over the past decades some promising progress has been made in the development of visual neuroprostheses that supply a functional form of visual perception through electrical stimulation of neurons in the visual pathway (Bak et al., 1990; Barry et al., 2023; Brindley & Lewin, 1968; Chen et al., 2020; Dobelle & Mladejovsky, 1974; Fernández et al., 2021; Humayun et al., 2003; Kelly et al., 2011; Keserü et al., 2012; Lowery et al., 2015; MenzelSevering et al., 2012; Oswalt et al., 2021; Panetsos et al., 2011; Pezaris & Reid, 2007; Stingl et al., 2013). The artificially created prosthetic percept is relatively elementary compared to natural vision, but the expectations are that visual prosthetics will re-enable many visually-guided activities of daily living, supporting self-dependence and improving the users’ quality of life (Beyeler & Sanchez-Garcia, 2022; Fernández et al., 2020). There are many challenges ahead for the development of visual prostheses. Besides the technical hurdles for creating a safe and durable interface with the visual cortex (e.g., see Fernández and Botella, 2018), there are many remaining questions regarding the encoding of visual signals into the brain. For instance, what information should be conveyed to create an interpretable visual percept that can support daily life visually-guided activities? In what manner is the functional quality of the prosthetic vision influenced by contextual parameters such as the visual environment or design features of the implant? How can the encoding of visual information be evaluated, optimized and tailored to deal with this multitude of contextual parameters? These questions form the basis of the research in this dissertation. 1.1. Background 1.1.1. Core components and mechanism of action Although there are distinct variations among different prosthetic designs, they generally follow the same principles of operation. The functioning of visual prostheses can be understood from the constituent main components: acameracaptures information from the surroundings. Amobile computer processes the camera frames, and calculates an electrical stimulation protocol. Theneural interface receives the stimulation protocol and accordingly activates populations of neurons in the visual pathway using electrical stimulation (seeBox1for a visualization). 1.1.2. Phosphene perception The electrical activation of visual neurons induces the visual experience of a localized light flash, called phosphene - a percept similar to ‘seeing stars’ after a sneeze or standing up too quickly. Importantly, visual prostheses make use of the topological organization of the visual system: the location of electrical stimulation in the brain influences the visual location where the phosphene is perceived. By stimulation of a subset of electrodes at different locations, one can activate a controlled subset of neural populations, resulting in a specific pattern of phosphenes. This basic pattern of phosphenes can be used to create an informative representation of the visual surrounding (seeFigure1.1).
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