biostudies-literatureValk SLNIMH NIH HHSNIH HHSCIHR2341https://www.ebi.ac.uk/biostudies/studies/S-EPMC9085871biostudies-literatureUnknown13(1)Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relatiNature communicationsGenetic and phylogenetic uncoupling of structure and function in human transmodal cortex.PMC9085871S10 OD023696R01 MH083246RF1 MH123163R01 MH074457FDN-154298R01 MH081218U54 MH091657R21 MH084126R01 MH094639Bethlehem RAISmallwood JYeo BTTEickhoff SBBayrak SValk SLMasouleh SKKochunov PBernhardt BCMargulies DRoyer JVos de Wael RXu TPaquola CPark BYfalseGenetic and phylogenetic uncoupling of structure and function in human transmodal cortex.Brain structure scaffolds intrinsic function, supporting cognition and ultimately behavioral flexibility. However, it remains unclear how a static, genetically controlled architecture supports flexible cognition and behavior. Here, we synthesize genetic, phylogenetic and cognitive analyses to understand how the macroscale organization of structure-function coupling across the cortex can inform its role in cognition. In humans, structure-function coupling was highest in regions of unimodal cortex and lowest in transmodal cortex, a pattern that was mirrored by a reduced alignment with heritable connectivity profiles. Structure-function uncoupling in macaques had a similar spatial distribution, but we observed an increased coupling between structure and function in association cortices relati2022-01-01T00:00:00Z2022 May2025-04-04T07:47:23.448Z2025-04-04T07:47:23.448ZS-EPMC90858713553445410.1038/s41467-022-29886-1