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Here we designed 2 types of novel stimuli\u2014\u201cnovel useful and novel useless,\u201d adapted from \u201cfamiliar useful\u201d designs taken from daily life\u2014to demonstrate how the left and right medial temporal lobe (MTL) respond to novel designs of different usefulness. Taking the \u201cfamiliar useful\u201d design as a baseline, we found that the right MTL showed increased activation in response to \u201cnovel useful\u201d designs, followed by \u201cnovel useless\u201d ones, while the left MTL only showed increased activation in response to \u201cnovel useful\u201d designs. Calculating an asymmetry index suggests that usefulness processing is predominant in the left MTL, whereas the right MTL is predominantly involved in novelty processing. Moreover, the left parahippocampal gyrus (PHG) showed stronger functional connectivity with the anterior cingulate cortex when responding to \u201cnovel useless\u201d designs. In contrast, the right PHG showed stronger connectivity with the amygdala, midbrain, and hippocampus. Critically, multivoxel representational similarity analyses revealed that the left MTL was more effective than the right MTL at distinguishing the usefulness differences in novel stimuli, while representational patterns in the left PHG positively predicted the post-behavior evaluation of \u201ctruly creative\u201d products. These findings suggest an apparent dissociation of the left and right MTL in integrating the novelty and usefulness information and novel associative processing during creativity evaluation, respectively. Our results provide novel insights into a longstanding and controversial question in creativity research by demonstrating functional lateralization of the MTL in processing novel associations.<\/jats:p>","DOI":"10.1093\/cercor\/bhac129","type":"journal-article","created":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T20:11:32Z","timestamp":1646770292000},"page":"1186-1206","source":"Crossref","is-referenced-by-count":22,"title":["Functional lateralization of the medial temporal lobe in novel associative processing during creativity evaluation"],"prefix":"10.1093","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7089-6397","authenticated-orcid":false,"given":"Jingyuan","family":"Ren","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University , Beijing 100048, China"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen, 6525 EN, 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3962-5804","authenticated-orcid":false,"given":"Sarah F","family":"Schoch","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , Nijmegen, 6525 EN, Netherlands"},{"name":"Center of Competence Sleep & Health Zurich, University of Zurich , Z\u00fcrich 8091, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1859-2150","authenticated-orcid":false,"given":"Shaozheng","family":"Qin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cognitive Neuroscience and Learning & IDG\/McGovern Institute for Brain Research, Faculty of Psychology at Beijing Normal University , Beijing 100875, China"},{"name":"Chinese Institute for Brain Research , Beijing 102206, 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