, 2012). Taken together, these studies suggest that while stimulation-induced efficacy of individual electrodes may be preserved over a period of months, the chronic tissue response to penetrating electrodes may require reconfiguration of stimulus parameters to maintain device efficacy over time. An obvious drawback to increasing the number of concurrently stimulated electrodes in particular is the potential for a gradual reduction in the resolution

of the resulting phosphene map. Davis et al. (2012) reported Ipilimumab ic50 that the precision of saccades to percepts elicited with multiple-electrode groups was less than those to photic stimuli, suggesting that the percepts elicited with larger groups of electrodes were larger. However, the same authors point out that a previous study (Bradley et al., 2005) also showed inferior precision of saccades to percepts elicited by stimulation with single electrodes compared to photic stimuli. In that study Bradley et al.

(2005) suggested that this loss of precision Ganetespib supplier may be the result of differences in the way electrically-evoked percepts are committed to short-term memory, a question that remains unresolved. Additional considerations in the context of chronic stimulation include the risk of stimulation-induced alterations in neuronal excitability. From a safety perspective, the risks of seizure induction cannot be understated. Parker et al. (2011) noted that simultaneous stimulation of 72 cortical (-)-p-Bromotetramisole Oxalate electrodes at 25 µA induced a tonic seizure in cats. Given this observation of a seizure in an animal model, and previous reports of seizures in human recipients of cortical surface implants (Naumann, 2012 and Pudenz, 1993), it is pertinent to discuss the risk of cortical kindling. Cortical kindling

describes the evolution of electrical stimulus response from the expected transient increase in neuronal firing, to the development of after discharges and eventually seizures with no increase in stimulus current (Goddard et al., 1969). This phenomenon is readily observed in the amygdale (Goddard et al., 1969), and the susceptibility of visual cortex to kindling is of direct relevance to the long-term safety of a cortical visual prosthesis. Previous studies have demonstrated the development of neuronal afterdischarges or generalized seizure progression (kindling) in the visual cortex of cats (Pollen, 1977 and Wada et al., 1989), rabbits (Jibiki et al., 1988) and primates (Goddard et al., 1969 and Poggio et al., 1956). Comparing the susceptibilities of the amygdala and visual cortex to kindling in cats, Wada et al. (1989) noted that visual cortex required much higher currents to elicit afterdischarges.