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This study aimed to investigate the hippocampal\u2013cortical connectivity and the metabolic interactions between neurons and astrocytes to elucidate the underlying mechanisms of EE\u2010induced memory improvement after stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rats were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham surgery and housed in standard environment or EE for 30\u2009days. Memory function was examined by Morris water maze (MWM) test. Magnetic resonance imaging (MRI) was conducted to detect the structural and functional changes. [<jats:sup>18<\/jats:sup>F]\u2010fluorodeoxyglucose (FDG) positron emission tomography (PET) was conducted to detect brain energy metabolism. PET\u2010based brain connectivity and network analysis was performed to study the changes of hippocampal\u2013cortical connectivity. Astrocyte\u2010neuron metabolic coupling, including gap junction protein connexin 43 (Cx43), glucose transporters (GLUTs), and monocarboxylate transporters (MCTs), was detected by histological studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed EE promoted memory function improvement, protected structure integrity, and benefited energy metabolism after stroke. More importantly, EE intervention significantly increased functional connectivity between the hippocampus and peri\u2010hippocampal cortical regions, and specifically regulated the level of Cx43, GLUTs and MCTs in the hippocampus and cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results revealed the three\u2010phase enriched environment paradigm enhanced hippocampal\u2013cortical connectivity plasticity and ameliorated post\u2010stroke memory deficits. These findings might provide some new clues for the development of EE and thus facilitate the clinical transformation of EE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.14466","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:31:15Z","timestamp":1695799875000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Combination of fMRI and PET reveals the beneficial effect of three\u2010phase enriched environment on post\u2010stroke memory deficits by enhancing plasticity of brain connectivity between hippocampus and peri\u2010hippocampal cortex"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4279-717X","authenticated-orcid":false,"given":"Yun","family":"Lu","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Capital Medical University  Beijing China"},{"name":"Beijing Key Lab of TCM Collateral Disease Theory Research 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