A middle ground where executive control meets semantics: the neural substrates of semantic control are topographically sandwiched between the multiple-demand and default-mode systems

Rocco Chiou*, Elizabeth Jefferies, John Duncan, Gina F. Humphreys, Matthew A. Lambon Ralph

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Semantic control is the capability to operate on meaningful representations, selectively focusing on certain aspects of meaning while purposefully ignoring other aspects based on one’s behavioral aim. This ability is especially vital for comprehending figurative/ambiguous language. It remains unclear why and how regions involved in semantic control seem reliably juxtaposed alongside other functionally specialized regions in the association cortex, prompting speculation about the relationship between topography and function. We investigated this issue by characterizing how semantic control regions topographically relate to the default-mode network (associated with memory and abstract cognition) and multiple-demand network (associated with executive control). Topographically, we established that semantic control areas were sandwiched by the default-mode and multi-demand networks, forming an orderly arrangement observed both at the individual and group level. Functionally, semantic control regions exhibited “hybrid” responses, fusing generic preferences for cognitively demanding operation (multiple-demand) and for meaningful representations (default-mode) into a domain-specific preference for difficult operation on meaningful representations. When projected onto the principal gradient of human connectome, the neural activity of semantic control showed a robustly dissociable trajectory from visuospatial control, implying different roles in the functional transition from sensation to cognition. We discuss why the hybrid functional profile of semantic control regions might result from their intermediate topographical positions on the cortex.

Original languageEnglish
Pages (from-to)4512-4526
Number of pages15
JournalCerebral Cortex
Issue number8
Publication statusPublished - 20 Sept 2022

Bibliographical note

Funding Information:
This research was funded by an MRC programme grant and intramural funding to MALR (MR/R023883/1; MC_UU_00005/18), a Sir Henry Wellcome Fellowship (201381/Z/16/Z) to RC, and a European Research Council Grant (771863 #x2013; FLEXSEM) to EJ.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press.

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