, 2005 and Dobelle, 2000). The attractiveness of visual cortex as the stimulation site for a visual prosthesis

is based on several factors. Firstly the large surface area of visual cortex and the cortical magnification TGF beta inhibitor factor combine to render it more amenable to implanting large numbers of electrodes in cortical areas subserving central vision (Daniel and Whitteridge, 1961 and Harvey and Dumoulin, 2011), potentially offering a higher-resolution visual experience than either LGN or retinal implants. Secondly, the stereotactic implantation of small occipital cortical electrode arrays is a relatively straightforward procedure compared to implanting deep LGN electrodes or microarrays onto, or under the retina. Lastly, the utility of direct cortical stimulation extends to all causes of visual impairment in

patients with late blindness due to retinal or optic nerve disease or injury. Cortical visual prosthesis research therefore has enormous Cabozantinib order potential for future treatment of visual impairment, and three research groups known to us report ongoing plans, either in the scientific literature or via their institutional websites, to develop a cortical visual prosthesis (Table 1). Many other research groups are conducting research within the general domain of neural prosthetics, much of which may translate to a cortical visual prosthesis. A number of these studies are covered throughout this review. Visual cortex electrical stimulation has a rich history spanning almost a century, beginning with the early 20th century observations of Löwenstein and Borchardt (1918), who stimulated the occipital cortex of soldiers with occipital bullet wounds. Research involving

such patients provided a wealth of data, with Krause and Förster subsequently demonstrating that stable, punctate phosphenes could be elicited by electrical stimulation of occipital cortex (Förster, 1929, Krause, 1924 and Krause Etofibrate and Schum, 1931). These studies also confirmed that the retinotopic map of visual cortex was roughly equivalent to that proposed by Inouye and Holmes, who examined visual field defects of soldiers with occipital bullet wounds and concluded that the occipital pole subserved central vision (Glickstein and Whitteridge, 1987 and Holmes and Lister, 1916). After Penfield׳s extensive mapping studies (Penfield, 1947) and Button and Putnam׳s rudimentary but groundbreaking attempts to provide visual perception to four blind volunteers (Button and Putnam, 1962 and Button, 1958), the first attempt to produce a genuinely functional visual prosthesis was made by Brindley and Lewin (1968). Their implant was a significant advance on Button and Putnam׳s four stainless steel wires, consisting of an array of eighty 1 mm2 platinum electrodes embedded in a silicon substrate and molded to the recipient׳s occipital cortex.