The default mode network in cognition: a topographical perspective.

The default mode network (DMN) is a set of widely distributed brain regions in the parietal, temporal and frontal cortex. These regions often show reductions in activity during attention-demanding tasks but increase their activity across multiple forms of complex cognition, many of which are linked to memory or abstract thought. Within the cortex, the DMN has been shown to be located in regions furthest away from those contributing to sensory and motor systems. Here, we consider how our knowledge of the topographic characteristics of the DMN can be leveraged to better understand how this network contributes to cognition and behaviour.

Distinctive and Complementary Roles of Default Mode Network Subsystems in Semantic Cognition.

The default mode network (DMN) typically deactivates to external tasks, yet supports semantic cognition. It comprises medial temporal (MT), core, and frontotemporal (FT) subsystems, but its functional organization is unclear: the requirement for perceptual coupling versus decoupling, input modality (visual/verbal), type of information (social/spatial), and control demands all potentially affect its recruitment. We examined the effect of these factors on activation and deactivation of DMN subsystems during semantic cognition, across four task-based human functional magnetic resonance imaging (fMRI) datasets, and localized these responses in whole-brain state space defined by gradients of intrinsic connectivity. FT showed activation consistent with a central role across domains, tasks, and modalities, although it was most responsive to abstract, verbal tasks; this subsystem uniquely showed more "tuned" states characterized by increases in both activation and deactivation when semantic retrieval demands were higher. MT also activated to both perceptually coupled (scenes) and decoupled (autobiographical memory) tasks and showed stronger responses to picture associations, consistent with a role in scene construction. Core DMN consistently showed deactivation, especially to externally oriented tasks. These diverse contributions of DMN subsystems to semantic cognition were related to their location on intrinsic connectivity gradients: activation was closer to the sensory-motor cortex than deactivation, particularly for FT and MT, while activation for core DMN was distant from both visual cortex and cognitive control. These results reveal distinctive yet complementary DMN responses: MT and FT support different memory-based representations that are accessed externally and internally, while deactivation in core DMN is associated with demanding, external semantic tasks.

The Brain's Topographical Organization Shapes Dynamic Interaction Patterns That Support Flexible Behavior Based on Rules and Long-Term Knowledge.

Adaptive behavior relies both on specific rules that vary across situations and stable long-term knowledge gained from experience. The frontoparietal control network (FPCN) is implicated in the brain's ability to balance these different influences on action. Here, we investigate how the topographical organization of the cortex supports behavioral flexibility within the FPCN. Functional properties of this network might reflect its juxtaposition between the dorsal attention network (DAN) and the default mode network (DMN), two large-scale systems implicated in top-down attention and memory-guided cognition, respectively. Our study tests whether subnetworks of FPCN are topographically proximal to the DAN and the DMN, respectively, and how these topographical differences relate to functional differences: the proximity of each subnetwork is anticipated to play a pivotal role in generating distinct cognitive modes relevant to working memory and long-term memory. We show that FPCN subsystems share multiple anatomical and functional similarities with their neighboring systems (DAN and DMN) and that this topographical architecture supports distinct interaction patterns that give rise to different patterns of functional behavior. The FPCN acts as a unified system when long-term knowledge supports behavior but becomes segregated into discrete subsystems with different patterns of interaction when long-term memory is less relevant. In this way, our study suggests that the topographical organization of the FPCN and the connections it forms with distant regions of cortex are important influences on how this system supports flexible behavior.

Individual word representations dissociate from linguistic context along a cortical unimodal to heteromodal gradient.

Language comprehension involves multiple hierarchical processing stages across time, space, and levels of representation. When processing a word, the sensory input is transformed into increasingly abstract representations that need to be integrated with the linguistic context. Thus, language comprehension involves both input-driven as well as context-dependent processes. While neuroimaging research has traditionally focused on mapping individual brain regions to the distinct underlying processes, recent studies indicate that whole-brain distributed patterns of cortical activation might be highly relevant for cognitive functions, including language. One such pattern, based on resting-state connectivity, is the 'principal cortical gradient', which dissociates sensory from heteromodal brain regions. The present study investigated the extent to which this gradient provides an organizational principle underlying language function, using a multimodal neuroimaging dataset of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) recordings from 102 participants during sentence reading. We found that the brain response to individual representations of a word (word length, orthographic distance, and word frequency), which reflect visual; orthographic; and lexical properties, gradually increases towards the sensory end of the gradient. Although these properties showed opposite effect directions in fMRI and MEG, their association with the sensory end of the gradient was consistent across both neuroimaging modalities. In contrast, MEG revealed that properties reflecting a word's relation to its linguistic context (semantic similarity and position within the sentence) involve the heteromodal end of the gradient to a stronger extent. This dissociation between individual word and contextual properties was stable across earlier and later time windows during word presentation, indicating interactive processing of word representations and linguistic context at opposing ends of the principal gradient. To conclude, our findings indicate that the principal gradient underlies the organization of a range of linguistic representations while supporting a gradual distinction between context-independent and context-dependent representations. Furthermore, the gradient reveals convergent patterns across neuroimaging modalities (similar location along the gradient) in the presence of divergent responses (opposite effect directions).

Default mode network shows distinct emotional and contextual responses yet common effects of retrieval demands across tasks.

The default mode network (DMN) lies towards the heteromodal end of the principal gradient of intrinsic connectivity, maximally separated from the sensory-motor cortex. It supports memory-based cognition, including the capacity to retrieve conceptual and evaluative information from sensory inputs, and to generate meaningful states internally; however, the functional organisation of DMN that can support these distinct modes of retrieval remains unclear. We used fMRI to examine whether activation within subsystems of DMN differed as a function of retrieval demands, or the type of association to be retrieved, or both. In a picture association task, participants retrieved semantic associations that were either contextual or emotional in nature. Participants were asked to avoid generating episodic associations. In the generate phase, these associations were retrieved from a novel picture, while in the switch phase, participants retrieved a new association for the same image. Semantic context and emotion trials were associated with dissociable DMN subnetworks, indicating that a key dimension of DMN organisation relates to the type of association being accessed. The frontotemporal and medial temporal DMN showed a preference for emotional and semantic contextual associations, respectively. Relative to the generate phase, the switch phase recruited clusters closer to the heteromodal apex of the principal gradient-a cortical hierarchy separating unimodal and heteromodal regions. There were no differences in this effect between association types. Instead, memory switching was associated with a distinct subnetwork associated with controlled internal cognition. These findings delineate distinct patterns of DMN recruitment for different kinds of associations yet common responses across tasks that reflect retrieval demands.

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE), one of the most common pharmaco-resistant epilepsies, is associated with pathology of paralimbic brain regions, particularly in the mesiotemporal lobe. Cognitive dysfunction in TLE is frequent, and particularly affects episodic memory. Crucially, these difficulties challenge the quality of life of patients, sometimes more than seizures, underscoring the need to assess neural processes of cognitive dysfunction in TLE to improve patient management. Our work harnessed a novel conceptual and analytical approach to assess spatial gradients of microstructural differentiation between cortical areas based on high-resolution MRI analysis. Gradients track region-to-region variations in intracortical lamination and myeloarchitecture, serving as a system-level measure of structural and functional reorganization. Comparing cortex-wide microstructural gradients between 21 patients and 35 healthy controls, we observed a reorganization of this gradient in TLE driven by reduced microstructural differentiation between paralimbic cortices and the remaining cortex with marked abnormalities in ipsilateral temporopolar and dorsolateral prefrontal regions. Findings were replicated in an independent cohort. Using an independent post-mortem dataset, we observed that in vivo findings reflected topographical variations in cortical cytoarchitecture. We indeed found that macroscale changes in microstructural differentiation in TLE reflected increased similarity of paralimbic and primary sensory/motor regions. Disease-related transcriptomics could furthermore show specificity of our findings to TLE over other common epilepsy syndromes. Finally, microstructural dedifferentiation was associated with cognitive network reorganization seen during an episodic memory functional MRI paradigm and correlated with interindividual differences in task accuracy. Collectively, our findings showing a pattern of reduced microarchitectural differentiation between paralimbic regions and the remaining cortex provide a structurally-grounded explanation for large-scale functional network reorganization and cognitive dysfunction characteristic of TLE.

Differential relational memory impairment in temporal lobe epilepsy.

OBJECTIVE: Temporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory, including episodic, semantic, and spatial memory processes. While it is widely accepted that TLE-associated hippocampal alterations underlie memory deficits, it remains unclear whether impairments relate to a specific cognitive domain or multiple ones. METHODS: We administered a recently validated task paradigm to evaluate episodic, semantic, and spatial memory in 24 pharmacoresistant TLE patients and 50 age- and sex-matched healthy controls. We carried out two-way analyses of variance to identify memory deficits in individuals with TLE relative to controls across different relational memory domains, and used partial least squares correlation to identify factors contributing to variations in relational memory performance across both cohorts. RESULTS: Compared to controls, TLE patients showed marked impairments in episodic and spatial memory, with mixed findings in semantic memory. Even when additionally controlling for age, sex, and overall cognitive function, between-group differences persisted along episodic and spatial domains. Moreover, age, diagnostic group, and hippocampal volume were all associated with relational memory behavioral phenotypes. SIGNIFICANCE: Our behavioral findings show graded deficits across relational memory domains in people with TLE, which provides further insights into the complex pattern of cognitive impairment in the condition.

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.

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.

Creativity in verbal associations is linked to semantic control.

Although memory is known to play a key role in creativity, previous studies have not isolated the critical component processes and networks. We asked participants to generate links between words that ranged from strongly related to completely unrelated in long-term memory, delineating the neurocognitive processes that underpin more unusual versus stereotypical patterns of retrieval. More creative responses to strongly associated word-pairs were associated with greater engagement of episodic memory: in highly familiar situations, semantic, and episodic stores converge on the same information enabling participants to form a personal link between items. This pattern of retrieval was associated with greater engagement of core default mode network (DMN). In contrast, more creative responses to weakly associated word-pairs were associated with the controlled retrieval of less dominant semantic information and greater recruitment of the semantic control network, which overlaps with the dorsomedial subsystem of DMN. Although both controlled semantic and episodic patterns of retrieval are associated with activation within DMN, these processes show little overlap in activation. These findings demonstrate that controlled aspects of semantic cognition play an important role in verbal creativity.

Physical distance to sensory-motor landmarks predicts language function.

Auditory language comprehension recruits cortical regions that are both close to sensory-motor landmarks (supporting auditory and motor features) and far from these landmarks (supporting word meaning). We investigated whether the responsiveness of these regions in task-based functional MRI is related to individual differences in their physical distance to primary sensorimotor landmarks. Parcels in the auditory network, that were equally responsive across story and math tasks, showed stronger activation in individuals who had less distance between these parcels and transverse temporal sulcus, in line with the predictions of the "tethering hypothesis," which suggests that greater proximity to input regions might increase the fidelity of sensory processing. Conversely, language and default mode parcels, which were more active for the story task, showed positive correlations between individual differences in activation and sensory-motor distance from primary sensory-motor landmarks, consistent with the view that physical separation from sensory-motor inputs supports aspects of cognition that draw on semantic memory. These results demonstrate that distance from sensorimotor regions provides an organizing principle of functional differentiation within the cortex. The relationship between activation and geodesic distance to sensory-motor landmarks is in opposite directions for cortical regions that are proximal to the heteromodal (DMN and language network) and unimodal ends of the principal gradient of intrinsic connectivity.

The impact of social isolation and changes in work patterns on ongoing thought during the first COVID-19 lockdown in the United Kingdom.

The COVID-19 pandemic led to lockdowns in countries across the world, changing the lives of billions of people. The United Kingdom's first national lockdown, for example, restricted people's ability to socialize and work. The current study examined how changes to socializing and working during this lockdown impacted ongoing thought patterns in daily life. We compared the prevalence of thought patterns between two independent real-world, experience-sampling cohorts, collected before and during lockdown. In both samples, young (18 to 35 y) and older (55+ y) participants completed experience-sampling measures five times daily for 7 d. Dimension reduction was applied to these data to identify common "patterns of thought." Linear mixed modeling compared the prevalence of each thought pattern 1) before and during lockdown, 2) in different age groups, and 3) across different social and activity contexts. During lockdown, when people were alone, social thinking was reduced, but on the rare occasions when social interactions were possible, we observed a greater increase in social thinking than prelockdown. Furthermore, lockdown was associated with a reduction in future-directed problem solving, but this thought pattern was reinstated when individuals engaged in work. Therefore, our study suggests that the lockdown led to significant changes in ongoing thought patterns in daily life and that these changes were associated with changes to our daily routine that occurred during lockdown.

Dissecting the neuroanatomy of creativity and curiosity: The subdivisions within networks matter.

Ivancovsky et al. argue that the neurocognitive mechanisms of creativity and curiosity both rely on the interplay among brain networks. Research to date demonstrates that such inter-network dynamics are further complicated by functional fractionation within networks. Investigating how networks subdivide and reconfigure in service of a task offers insights about the precise anatomy that underpins creative and curious behaviour.

Perceptual coupling and decoupling are associated with individual differences in working memory encoding and maintenance.

Working memory (WM) allows goal-relevant information to be encoded and maintained in mind, even when the contents of WM are incongruent with the immediate environment. While regions of heteromodal cortex are important for WM, the neural mechanisms that relate to individual differences in the encoding and maintenance of goal-relevant information remain unclear. Here, we used behavioral correlates of two large-scale heteromodal networks at rest, the default mode (DMN) and frontoparietal (FPN) networks, to understand their contributions to distinct features of WM. We assessed each individual's ability to resist distracting information during the encoding and maintenance phases of a visuospatial WM task. Individuals with stronger connectivity of DMN with medial visual and retrosplenial cortex were less affected by encoding distraction. Conversely, weaker connectivity of both DMN and FPN with visual regions was associated with better WM performance when target information was no longer in the environment and distractors were presented in the maintenance phase. Our study suggests that stronger coupling between heteromodal cortex and visual-spatial regions supports WM encoding by reducing the influence of concurrently presented distractors, while weaker visual coupling is associated with better maintenance of goal-relevant information because it relates to the capacity to ignore task-irrelevant changes in the environment.

Context free and context-dependent conceptual representation in the brain.

How concepts are coded in the brain is a core issue in cognitive neuroscience. Studies have focused on how individual concepts are processed, but the way in which conceptual representation changes to suit the context is unclear. We parametrically manipulated the association strength between words, presented in pairs one word at a time using a slow event-related fMRI design. We combined representational similarity analysis and computational linguistics to probe the neurocomputational content of these trials. Individual word meaning was maintained in supramarginal gyrus (associated with verbal short-term memory) when items were judged to be unrelated, but not when a linking context was retrieved. Context-dependent meaning was instead represented in left lateral prefrontal gyrus (associated with controlled retrieval), angular gyrus, and ventral temporal lobe (regions associated with integrative aspects of memory). Analyses of informational connectivity, examining the similarity of activation patterns across trials between sites, showed that control network regions had more similar multivariate responses across trials when association strength was weak, reflecting a common controlled retrieval state when the task required more unusual associations. These findings indicate that semantic control and representational sites amplify contextually relevant meanings in trials judged to be related.

Patterns of ongoing thought in the real world.

Health and well-being are impacted by our thoughts and the things we do. In the laboratory, studies suggest specific task contexts impact thought processes. More broadly, this suggests the people we are with, the places we are in, and the activities we perform may influence our thought patterns. In our study, participants completed experience sampling surveys for five days in daily life. Principal component analysis decomposed this data to identify common "patterns of thought," and linear mixed modelling related these patterns to the participants' activities. Our study replicated the influence of socializing on patterns of thought and established that this is part of a broader set of relationships linking activities to how thoughts are organized in daily life. Our study suggests sampling thinking in the real world may help map thoughts to activities, and these "thought-activity" mappings could be useful to researchers and health care professionals interested in health and well-being.

Both Default and Multiple-Demand Regions Represent Semantic Goal Information.

We used a semantic feature-matching task combined with multivoxel pattern decoding to test contrasting accounts of the role of the default mode network (DMN) in cognitive flexibility. By one view, DMN and multiple-demand cortex have opposing roles in cognition, with DMN and multiple-demand regions within the dorsal attention network (DAN) supporting internal and external cognition, respectively. Consequently, while multiple-demand regions can decode current goal information, semantically relevant DMN regions might decode conceptual similarity regardless of task demands. Alternatively, DMN regions, like multiple-demand cortex, might show sensitivity to changing task demands, since both networks dynamically alter their patterns of connectivity depending on the context. Our task required human participants (any sex) to integrate conceptual knowledge with changing task goals, such that successive decisions were based on different features of the items (color, shape, and size). This allowed us to simultaneously decode semantic category and current goal information using whole-brain searchlight decoding. As expected, multiple-demand cortex, including DAN and frontoparietal control network, represented information about currently relevant conceptual features. Similar decoding results were found in DMN, including in angular gyrus and posterior cingulate cortex, indicating that DMN and multiple-demand regions can support the same function rather than being strictly competitive. Semantic category could be decoded in lateral occipital cortex independently of task demands, but not in most regions of DMN. Conceptual information related to the current goal dominates the multivariate response within DMN, which supports flexible retrieval by modulating its response to suit the task demands, alongside regions of multiple-demand cortex.SIGNIFICANCE STATEMENT We tested contrasting accounts of default mode network (DMN) function using multivoxel pattern analysis. By one view, semantically relevant parts of DMN represent conceptual similarity, regardless of task context. By an alternative view, DMN tracks changing task demands. Our semantic feature-matching task required participants to integrate conceptual knowledge with task goals, such that successive decisions were based on different features of the items. We demonstrate that DMN regions can decode the current goal, as it is applied, alongside multiple-demand regions traditionally associated with cognitive control, speaking to how DMN supports flexible cognition.

Intrinsic connectivity of left ventrolateral prefrontal cortex predicts individual differences in controlled semantic retrieval.

Control processes allow us to constrain the retrieval of semantic information from long-term memory so that it is appropriate for the task or context. Control demands are influenced by the strength of the target information itself and by the circumstances in which it is retrieved, with more control needed when relatively weak aspects of knowledge are required and after the sustained retrieval of related concepts. To investigate the neurocognitive basis of individual differences in these aspects of semantic control, we used resting-state fMRI to characterise the intrinsic connectivity of left ventrolateral prefrontal cortex (VLPFC), implicated in controlled retrieval, and examined associations on a paced serial semantic task, in which participants were asked to detect category members amongst distractors. This task manipulated both the strength of target associations and the requirement to sustain retrieval within a narrow semantic category over time. We found that individuals with stronger connectivity between VLPFC and medial prefrontal cortex within the default mode network (DMN) showed better retrieval of strong associations (which are thought to be recalled more automatically). Stronger connectivity between the same VLPFC seed and another DMN region in medial parietal cortex was associated with larger declines in retrieval over the course of the category. In contrast, participants with stronger connectivity between VLPFC and cognitive control regions within the ventral attention network (VAN) had better controlled retrieval of weak associations and were better able to sustain their comprehension throughout the category. These effects overlapped in left insular cortex within the VAN, indicating that a common pattern of connectivity is associated with different aspects of controlled semantic retrieval induced by both the structure of long-term knowledge and the sustained retrieval of related information.

The neural and computational bases of semantic cognition.

Semantic cognition refers to our ability to use, manipulate and generalize knowledge that is acquired over the lifespan to support innumerable verbal and non-verbal behaviours. This Review summarizes key findings and issues arising from a decade of research into the neurocognitive and neurocomputational underpinnings of this ability, leading to a new framework that we term controlled semantic cognition (CSC). CSC offers solutions to long-standing queries in philosophy and cognitive science, and yields a convergent framework for understanding the neural and computational bases of healthy semantic cognition and its dysfunction in brain disorders.

A Structure-Function Substrate of Memory for Spatial Configurations in Medial and Lateral Temporal Cortices.

Prior research has shown a role of the medial temporal lobe, particularly the hippocampal-parahippocampal complex, in spatial cognition. Here, we developed a new paradigm, the conformational shift spatial task (CSST), which examines the ability to encode and retrieve spatial relations between unrelated items. This task is short, uses symbolic cues, incorporates two difficulty levels, and can be administered inside the scanner. A cohort of 48 healthy young adults underwent the CSST, together with a set of behavioral measures and multimodal magnetic resonance imaging (MRI). Inter-individual differences in CSST performance correlated with scores on an established spatial memory paradigm, but neither with episodic memory nor mnemonic discrimination, supporting specificity. Analyzing high-resolution structural MRI data, individuals with better spatial memory showed thicker medial and lateral temporal cortices. Functional relevance of these findings was supported by task-based functional MRI analysis in the same participants and ad hoc meta-analysis. Exploratory resting-state functional MRI analyses centered on clusters of morphological effects revealed additional modulation of intrinsic network integration, particularly between lateral and medial temporal structures. Our work presents a novel spatial memory paradigm and supports an integrated structure-function substrate in the human temporal lobe. Task paradigms are programmed in python and made open access.

Training flexible conceptual retrieval in post-stroke aphasia.

Semantic therapy in post-stroke aphasia typically focusses on strengthening links between conceptual representations and their lexical-articulatory forms to aid word retrieval. However, research has shown that semantic deficits in this group can affect both verbal and non-verbal tasks, particularly in patients with deregulated retrieval as opposed to degraded knowledge. This study, therefore, aimed to facilitate semantic cognition in a sample of such patients with post-stroke semantic aphasia (SA) by training the identification of both strong and weak semantic associations and providing explicit pictorial feedback that demonstrated both common and more unusual ways of linking concepts together. We assessed the effects of this training on (i) trained and untrained items; and (ii) trained and untrained tasks in eleven individuals with SA. In the training task, the SA group showed improvement with practice, particularly for trained items. A similar untrained task using pictorial stimuli (Camel and Cactus Test) also improved. Together, these results suggest that semantic training can be beneficial in patients with SA and may show some degree of generalization to untrained situations. Future research should seek to understand which patients are most likely to benefit from this type of training.