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Neural changes related to learning of the meaning of Chinese characters in English speakers were examined using functional magnetic resonance imaging (fMRI). We examined item specific learning effects for trained characters, but also the generalization of semantic knowledge to novel transfer characters that shared a semantic radical (part of a character that gives a clue to word meaning, e.g. water for lake) with trained characters. Behavioral results show that acquired semantic knowledge improves performance for both trained and transfer characters. Neuroimaging results show that the left fusiform gyrus plays a central role in the visual processing of orthographic information in characters. The left superior parietal cortex seems to play a crucial role in learning the visual-spatial aspects of the characters because it shows learning related decreases for trained characters, is correlated with behavioral improvement from early to late in learning for the trained characters, and is correlated with better long-term retention for the transfer characters. The inferior frontal gyrus seems to be associated with the efficiency of retrieving and manipulating semantic representations because there are learning related decreases for trained characters and this decrease is correlated with greater behavioral improvement from early to late in learning.