, 1989). Wada׳s observations in cats are consistent with the earlier macaque studies of Poggio et al. (1956), in which repeated stimulation of occipital cortex produced less frequent and shorter visual cortical afterdischarges, and with less subcortical progression than other parts of the brain. Bartlett et al. (1977) also noted that even with high current (5.0 mA) stimulus of TSA HDAC mouse macaque visual cortex, afterdischarges did not propagate beyond 6 mm from the site of stimulation. The influence of long-term blindness on the susceptibility of visual cortex to the development of seizures and/or kindling following long-term electrical stimulation is poorly understood. Examining

the susceptibility of visual cortex to kindling in immature and adult cats, Moneta and Singer (1986) noted that the developing visual cortex had a higher afterdischarge threshold and was more resistant to the kindling effect. In discussing potential mechanisms for the observed reduction in cortical excitability Ibrutinib in vitro in kittens, the authors postulated that visual input may antagonize any kindling response (Moneta and Singer, 1986). Importantly, in the blind human subject, there would be no such visual input, potentially

increasing the risk of a kindling response. Clearly this is an area requiring further research. Seizure risk mitigation may be achieved with anticonvulsant medications such as phenytoin, which is known to suppress both neuronal afterdischarges in cats by raising the threshold current for their elicitation (Pollen, 1977 and Wada et al., 1990), in addition to suppressing kindled seizures (Wada et al., 1990). Alternatives include sodium valproate, which second has been shown to elevate afterdischarge threshold and prevent convulsions in a rat model of amygdala kindling (Salt et al., 1980).

There is little data on the prevention of kindled occipital seizures in humans, however occipital epilepsies generally respond equally well to a wide range of antiepileptics, although if a photosensitive component is present, then sodium valproate may be more effective (Taylor et al., 2003). Whether or not photosensitive epilepsy is a more appropriate model for kindled visual cortex seizures is a subject that requires further investigation. One possible seizure risk mitigation strategy proposed by Parker et al. (2011) was the interleaving of stimuli, maximizing the distance between any two individual, or groups of stimulated electrodes. This may have the added benefit of reducing another undesired side-effect of chronic stimulation, being the depression of neuronal excitability that is seen following 7 h of constant stimulation and may persist for several days (McCreery et al., 1997 and McCreery et al., 2002).