A tale of two gradients: Differences between the left and right hemispheres predict semantic cognition

Tirso Gonzalez Alam, Beth Jefferies, Brontë McKeown, Zhiyao Gao, Jonathan Smallwood, Boris C Bernhardt, Reinder Vos de Wael, Daniel S Margulies

Research output: Contribution to journalArticlepeer-review


Decomposition of whole-brain functional connectivity patterns reveals a principal gradient that captures the separation of sensorimotor cortex from heteromodal regions in the default mode network (DMN). Functional homotopy is strongest in sensorimotor areas, and weakest in heteromodal cortices, suggesting there may be differences between the left and right hemispheres (LH/RH) in the principal gradient, especially towards its apex. This study characterised hemispheric differences in the position of large-scale cortical networks along the principal gradient, and their functional significance. We collected resting-state fMRI and semantic, working memory and non-verbal reasoning performance in 175+ healthy volunteers. We then extracted the principal gradient of connectivity for each participant, tested which networks showed significant hemispheric differences on the gradient, and regressed participants’ behavioural efficiency in tasks outside the scanner against interhemispheric gradient differences for each network. LH showed a higher overall principal gradient value, consistent with its role in heteromodal semantic cognition. One frontotemporal control subnetwork was linked to individual differences in semantic cognition: when it was nearer heteromodal DMN on the principal gradient in LH, participants showed more efficient semantic retrieval – and this network also showed a strong hemispheric difference in response to semantic demands but not working memory load in a separate study. In contrast, when a dorsal attention subnetwork was closer to the heteromodal end of the principal gradient in RH, participants showed better visual reasoning. Lateralization of function may reflect differences in connectivity between control and heteromodal regions in LH, and attention and visual regions in RH.
Original languageEnglish
Pages (from-to)623-654
Number of pages24
JournalBrain structure & function
Early online date12 Sept 2021
Publication statusE-pub ahead of print - 12 Sept 2021

Bibliographical note

© The Author(s) 2021


  • Gradients
  • Intrinsic Connectivity
  • Laterality
  • fMRI
  • Semantic Cognition
  • Hemispheric Specialization

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