RESEARCH ARTICLE The function of medial temporal lobe and posterior middle temporal gyrus in forming creative associations Ze Zhang 1 | Lulu Liu 1,2 | Yue Li 1 | Tengteng Tan 1 | Kazuhisa Niki 3,4 | Jing Luo 1,5 1 Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China 2 Graduate School of Chinese Academy of Agricultural Sciences, Beijing, China 3 Human Informatics Research Institute, Advanced Industrial Science and Technology, Tsukuba, Japan 4 Keio University Graduate School of Human Relations, Keio University, Tokyo, Japan 5 Department of Psychology, Shaoxing University, Shaoxing, China Correspondence Jing Luo, Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, 100048, China. Email: luoj@psych.ac.cn Funding information Beijing Brain Initiative of Beijing Municipal Science & Technology Commission; Capacity Building for Sci-Tech Innovation-Fundamental Scientific Research Funds, Grant/Award Numbers: 047-19530050133, 025-185305000; National Natural Science Foundation of China, Grant/Award Numbers: 31671124, 31871093 Abstract Although the function of the hippocampus and adjacent medial temporal lobe (MTL) areas in forming associations is generally recognized, how MTL contributes to form creative associations that could result in novel and appropriate functions or meanings remains unclear. In this study, we compared highly creative combinations (HCCs) of two objects (e.g., that of “lifejacket” and “distress signal device”) that resulted in genuine innovative designs comprising additionally unprecedented functions (the “1+1>2” effects) with the lowly creative combinations (LCCs, e.g., the combi- nation of “set-top box” and “jewelry box”) that resulted in nothing more than simple “1+1=2” effects. The event-related functional magnetic resonance imaging (fMRI) study found that during the “early binding phase,” when the combinations of the two objects were initially encoded, the right parahippocampus was more intensively activated during the encoding of HCC relative to LCC trials. However, during the “late integration phase,” when participants finally formed a holistic mental represen- tation of new products based on the two-object combinations, both HCCs and LCCs were found to be associated with significantly increased hippocampal and para- hippocampal activation relative to the baseline condition, but at a similar level. In this “late integration phase,” the functional areas appeared to be more intensively activated in HCCs relative to LCCs located in the posterior middle temporal gyrus (pMTG), the area known to mediate category-related processing. Consistently, our supplementary behavioral study found that, relative to LCCs, HCCs had a higher possibility of resulting in some new conceptual expansions that differed from each of the original two objects that constituted the combinations. These findings indicate that the formation of creative combinations not only require MTL-based novel association-formation, but also pMTG-based novel concept-expansion. KEYWORDS association formation, conceptual expansion, creativity, hippocampus, medial temporal lobe (MTL), posterior middle temporal gyrus (pMTG) 1 | INTRODUCTION Creativity refers to making something that is novel as well as appro- priate, useful, or valuable (Barron, 1955; Runco & Jaeger, 2012). Neuroscience studies have found that widely distributed brain areas Ze Zhang and Lulu Liu contributed equally to this work. Received: 28 November 2019 Revised: 27 June 2020 Accepted: 16 July 2020 DOI: 10.1002/hipo.23253 Hippocampus. 2020;1–11. wileyonlinelibrary.com/journal/hipo © 2020 Wiley Periodicals LLC 1