Semantic priming, a well-established technique to study conceptual representation, has thus far produced variable fMRI results, both regarding the type of priming effects and their correlation with brain activation. The aims of the current study were (a) to investigate two types of semantic relations—categorical versus associative—under controlled processing conditions and (b) to investigate whether categorical and associative relations between words are correlated with response enhancement or response suppression. We used fMRI to examine neural correlates of semantic priming as subjects performed a lexical decision task with a long SOA (800 msec). Four experimental conditions were compared: categorically related trials (couch–bed), associatively related trials (couch–pillow), unrelated trials (couch–bridge), and nonword trials (couch–sibor). We found similar behavioral priming effects for both categorically and associatively related pairs. However, the neural priming effects differed: Categorically related pairs resulted in a neural suppression effect in the right MFG, whereas associatively related pairs resulted in response enhancement in the left IFG. A direct contrast between them revealed activation for categorically related trials in the right insular lobe. We conclude that perceptual and functional similarity of categorically related words may lead to response suppression within right-lateralized frontal regions that represent more retrieval effort and the recruitment of a broader semantic field. Associatively related pairs that require a different processing of the related target compared to the prime may lead to the response enhancement within left inferior frontal regions. Nevertheless, the differences between associative and categorical relations might be parametrical rather than absolutely distinct as both relationships recruit similar regions to a different degree.

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