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.

The semantic network is thought to include multiple components, including heteromodal conceptual representations and semantic control processes that shape retrieval to suit the circumstances. Much of this network is strongly left-lateralised; however, work to date has not considered whether separable components of semantic cognition have different degrees of lateralisation. This study examined intrinsic connectivity of four regions implicated in heteromodal semantic cognition, identified using large scale meta-analyses: two sites which have been argued to act as heteromodal semantic hubs in anterior temporal lobe (ATL) and angular gyrus (AG); and two sites implicated in semantic control in inferior frontal (IFG) and posterior middle temporal gyri (pMTG). We compared the intrinsic connectivity of these sites in left hemisphere (LH) and right hemisphere (RH), and linked individual differences in the strength of within- and between-hemisphere connectivity from left-lateralised seeds to performance on semantic tasks, in a sample of 196 healthy volunteers. ATL showed more symmetrical patterns of intrinsic connectivity than the other three sites. The connectivity between IFG and pMTG was stronger in the LH than the RH, suggesting that the semantic control network is strongly left-lateralised. The degree of hemispheric lateralisation also predicted behaviour: participants with stronger intrinsic connectivity within the LH had better semantic performance, while those with stronger intrinsic connectivity between left pMTG and homotopes of semantic regions in the RH performed more poorly on judgements of weak associations, which require greater control. Stronger connectivity between left AG and visual cortex was also linked to poorer perceptual performance. Overall, our results show that hemispheric lateralisation is particularly important for the semantic control network, and that this lateralisation has contrasting functional consequences for the retrieval of dominant and subordinate aspects of knowledge

We frequently guide our decisions about when and how to act based on the meanings of perceptual inputs: we might avoid treading on a flower, but not on a leaf. However, most research on response inhibition has used simple perceptual stimuli devoid of meaning. In two Go/No-Go experiments, we examined whether the neural mechanisms supporting response inhibition are influenced by the relevance of meaning to the decision, and by presentation modality (whether concepts were presented as words or images). In an on-line fMRI experiment, we found common regions for response inhibition across perceptual and conceptual decisions. These included the bilateral intraparietal sulcus and the right inferior frontal sulcus, whose neural responses have been linked to diverse cognitive demands in previous studies. In addition, we identified a cluster in ventral lateral occipital cortex that was sensitive to the modality of input, with a stronger response to No-Go than Go trials for meaningful images, compared to words with the same semantic content. In a second experiment, using resting-state fMRI, we explored how individual variation in the intrinsic connectivity of these activated regions related to variation in behavioural performance. Participants who showed stronger connectivity between common inhibition regions and limbic areas in medial temporal and subgenual anterior cingulate cortex were better at inhibition when this was driven by the meaning of the items. In addition, regions with a specific role in picture inhibition were more connected to a cluster in the thalamus/caudate for participants who were better at performing the picture task outside of the scanner. Together these studies indicate that the capacity to appropriately withhold action depends on interactions between common control regions, which are important across multiple types of input and decision, and other brain regions linked to specific inputs (i.e., visual features) or representations (e.g., memory).