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.

Unveiling the core functional networks of cognition: An ontology-guided machine learning approach.

Deciphering the functional architecture that underpins diverse cognitive functions is fundamental quest in neuroscience. In this study, we employed an innovative machine learning framework that integrated cognitive ontology with functional connectivity analysis to identify brain networks essential for cognition. We identified a core assembly of functional connectomes, primarily located within the association cortex, which showed superior predictive performance compared to two conventional methods widely employed in previous research across various cognitive domains. Our approach achieved a mean prediction accuracy of 0.13 across 16 cognitive tasks, including working memory, reading comprehension, and sustained attention, outperforming the traditional methods' accuracy of 0.08. In contrast, our method showed limited predictive power for sensory, motor, and emotional functions, with a mean prediction accuracy of 0.03 across 9 relevant tasks, slightly lower than the traditional methods' accuracy of 0.04. These cognitive connectomes were further characterized by distinctive patterns of resting-state functional connectivity, structural connectivity via white matter tracts, and gene expression, highlighting their neurogenetic underpinnings. Our findings reveal a domain-general functional network fingerprint that pivotal to cognition, offering a novel computational approach to explore the neural foundations of cognitive abilities.

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 Nature of Interfacial Catalysis over Pt/NiAl2O4 for Hydrogen Production from Methanol Reforming Reaction.

Reforming of methanol is one of the most favorable chemical processes for on-board H2 production, which alleviates the limitation of H2 storage and transportation. The most important catalytic systems for methanol reacting with water are interfacial catalysts including metal/metal oxide and metal/carbide. Nevertheless, the assessment on the reaction mechanism and active sites of these interfacial catalysts are still controversial. In this work, by spectroscopic, kinetic, and isotopic investigations, we established a compact cascade reaction model (ca. the Langmuir-Hinshelwood model) to describe the methanol and water activation over Pt/NiAl2O4. We show here that reforming of methanol experiences methanol dehydrogenation followed by water-gas shift reaction (WGS), in which two separated kinetically relevant steps have been identified, that is, C-H bond rupture within methoxyl adsorbed on interface sites and O-H bond rupture within OlH (Ol: oxygen-filled surface vacancy), respectively. In addition, these two reactions were primarily determined by the most abundant surface intermediates, which were methoxyl and CO species adsorbed on NiAl2O4 and Pt, respectively. More importantly, the excellent reaction performance benefits from the following bidirectional spillover of methoxyl and CO species since the interface and the vacancies on the support were considered as the real active component in methanol dehydrogenation and the WGS reaction, respectively. These findings provide deep insight into the reaction process as well as the active component during catalysis, which may guide the design of new catalytic systems.

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.

Discovering the Mechanisms of Oleodaphnone as a Potential HIV Latency-Reversing Agent by Transcriptome Profiling.

Latent HIV is a key factor that makes AIDS difficult to cure. Highly effective and specific latent HIV activators can effectively activate latent HIV, and then combined with antiretroviral therapy to achieve a functional cure of AIDS. Here, four sesquiterpenes (1-4) including a new one (1), five flavonoids (5-9) including three biflavonoid structures, and two lignans (10 and 11) were obtained from the roots of Wikstroemia chamaedaphne. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configuration of 1 was determined by experimental electronic circular dichroism. NH2 cell model was used to test the activity of these 11 compounds in activating latent HIV. Oleodaphnone (2) showed the latent HIV activation effect as well as the positive drug prostratin, and the activation effect was time- and concentration-dependent. Based on transcriptome analysis, the underlying mechanism was that oleodaphnone regulated the TNF, C-type lectin receptor, NF-κB, IL-17, MAPK, NOD-like receptor, JAK-Stat, FoxO, and Toll-like receptor signaling pathways. This study provides the basis for the potential development of oleodaphnone as an effective HIV latency-reversing agent.

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.

Knowing what you need to know in advance: The neural processes underpinning flexible semantic retrieval of thematic and taxonomic relations.

Semantic retrieval is flexible, allowing us to focus on subsets of features and associations that are relevant to the current task or context: for example, we use taxonomic relations to locate items in the supermarket (carrots are a vegetable), but thematic associations to decide which tools we need when cooking (carrot goes with peeler). We used fMRI to investigate the neural basis of this form of semantic flexibility; in particular, we asked how retrieval unfolds differently when participants have advanced knowledge of the type of link to retrieve between concepts (taxonomic or thematic). Participants performed a semantic relatedness judgement task: on half the trials, they were cued to search for a taxonomic or thematic link, while on the remaining trials, they judged relatedness without knowing which type of semantic relationship would be relevant. Left inferior frontal gyrus showed greater activation when participants knew the trial type in advance. An overlapping region showed a stronger response when the semantic relationship between the items was weaker, suggesting this structure supports both top-down and bottom-up forms of semantic control. Multivariate pattern analysis further revealed that the neural response in left inferior frontal gyrus reflects goal information related to different conceptual relationships. Top-down control specifically modulated the response in visual cortex: when the goal was unknown, there was greater deactivation to the first word, and greater activation to the second word. We conclude that top-down control of semantic retrieval is primarily achieved through the gating of task-relevant 'spoke' regions.

Distinct and common neural coding of semantic and non-semantic control demands.

The flexible retrieval of knowledge is critical in everyday situations involving problem solving, reasoning and social interaction. Current theories emphasise the importance of a left-lateralised semantic control network (SCN) in supporting flexible semantic behaviour, while a bilateral multiple-demand network (MDN) is implicated in executive functions across domains. No study, however, has examined whether semantic and non-semantic demands are reflected in a common neural code within regions specifically implicated in semantic control. Using functional MRI and univariate parametric modulation analysis as well as multivariate pattern analysis, we found that semantic and non-semantic demands gave rise to both similar and distinct neural responses across control-related networks. Though activity patterns in SCN and MDN could decode the difficulty of both semantic and verbal working memory decisions, there was no shared common neural coding of cognitive demands in SCN regions. In contrast, regions in MDN showed common patterns across manipulations of semantic and working memory control demands, with successful cross-classification of difficulty across tasks. Therefore, SCN and MDN can be dissociated according to the information they maintain about cognitive demands.

A gradient from long-term memory to novel cognition: Transitions through default mode and executive cortex.

Human cognition flexibly guides decision-making in familiar and novel situations. Although these decisions are often treated as dichotomous, in reality, situations are neither completely familiar, nor entirely new. Contemporary accounts of brain organization suggest that neural function is organized along a connectivity gradient from unimodal regions of sensorimotor cortex, through executive regions to transmodal default mode network. We examined whether this graded view of neural organization helps to explain how decision-making changes across situations that vary in their alignment with long-term knowledge. We used a semantic judgment task, which parametrically varied the global semantic similarity of items within a feature matching task to create a 'task gradient', from conceptual combinations that were highly overlapping in long-term memory to trials that only shared the goal-relevant feature. We found the brain's response to the task gradient varied systematically along the connectivity gradient, with the strongest response in default mode network when the probe and target items were highly overlapping conceptually. This graded functional change was seen in multiple brain regions and within individual brains, and was not readily explained by task difficulty. Moreover, the gradient captured the spatial layout of networks involved in semantic processing, providing an organizational principle for controlled semantic cognition across the cortex. In this way, the cortex is organized to support semantic decision-making in both highly familiar and less familiar situations.

Individual variation in patterns of task focused, and detailed, thought are uniquely associated within the architecture of the medial temporal lobe.

Understanding the neural processes that support different patterns of ongoing thought is an important goal of contemporary cognitive neuroscience. Early accounts assumed the default mode network (DMN) was especially important for conscious attention to task-irrelevant/personally relevant materials. However, simple task-negative accounts of the DMN are incompatible with more recent evidence that neural patterns within the system can be related to ongoing processing during active task states. To better characterise the contribution of the DMN to ongoing thought, we conducted a cross-sectional analysis of the relationship between the structural organisation of the brain, as indexed by cortical thickness, and patterns of experience, identified using experience sampling in the cognitive laboratory. In a sample of 181 healthy individuals (mean age 20 years, 117 females) we identified an association between cortical thickness in the anterior parahippocampus and patterns of task focused thought, as well as an adjacent posterior region in which cortical thickness was associated with experiences with higher levels of subjective detail. Both regions fell within regions of medial temporal lobe associated with the DMN, yet varied in their functional connectivity: the time series of signals in the 'on-task' region were more correlated with systems important for external task-relevant processing (as determined by meta-analysis) including the dorsal and ventral attention, and fronto-parietal networks. In contrast, connectivity within the region linked to subjective 'detail' was more correlated with the medial core of the DMN (posterior cingulate and the medial pre-frontal cortex) and regions of primary visual cortex. These results provide cross-sectional evidence that confirms a role of the DMN in how detailed experiences are and so provide further evidence that the role of this system in experience is not simply task-irrelevant. Our results also highlight processes within the medial temporal lobe, and their interactions with other regions of cortex, as important in determining multiple aspects of how human cognition unfolds.

The structural basis of semantic control: Evidence from individual differences in cortical thickness.

Semantic control allows us to shape our conceptual retrieval to suit the circumstances in a flexible way. Tasks requiring semantic control activate a large-scale network including left inferior prefrontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) - this network responds when retrieval is focussed on weak as opposed to dominant associations. However, little is known about the biological basis of individual differences in this cognitive capacity: regions that are commonly activated in task-based fMRI may not relate to variation in controlled retrieval. The current study combined analyses of MRI-based cortical thickness with resting-state fMRI connectivity to identify structural markers of individual differences in semantic control. We found that participants who performed relatively well on tests of controlled semantic retrieval showed increased structural covariance between left pMTG and left anterior middle frontal gyrus (aMFG). This pattern of structural covariance was specific to semantic control and did not predict performance when harder non-semantic judgements were contrasted with easier semantic judgements. The intrinsic functional connectivity of these two regions forming a structural covariance network overlapped with previously-described semantic control regions, including bilateral IFG and intraparietal sulcus, and left posterior temporal cortex. These results add to our knowledge of the neural basis of semantic control in three ways: (i) Semantic control performance was predicted by the structural covariance network of left pMTG, a site that is less consistently activated than left IFG across studies. (ii) Our results provide further evidence that semantic control is at least partially separable from domain-general executive control. (iii) More flexible patterns of memory retrieval occurred when pMTG co-varied with distant regions in aMFG, as opposed to nearby visual, temporal or parietal lobe regions, providing further evidence that left prefrontal and posterior temporal areas form a distributed network for semantic control.

The organization of the semantic network as reflected by the neural correlates of six semantic dimensions.

Multiple sensory-motor and non-sensory-motor dimensions have been proposed for semantic representation, but it remains unclear how the semantic system is organized along them in the human brain. Using naturalistic fMRI data and large-scale semantic ratings, we investigated the overlaps and dissociations between the neural correlates of six semantic dimensions: vision, motor, socialness, emotion, space, and time. Our findings revealed a more complex semantic atlas than what is predicted by current neurobiological models of semantic representation. Brain regions that are selectively sensitive to specific semantic dimensions were found both within and outside the brain networks assumed to represent multimodal general and/or abstract semantics. Overlaps between the neural correlates of different semantic dimensions were mainly found inside the default mode network, concentrated in the left anterior superior temporal gyrus and angular gyrus, which have been proposed as two connector hubs that bridge the multimodal experiential semantic system and the language-supported semantic system.

Unveiling the Core Functional Networks of Cognition: An Ontology-Guided Machine Learning Approach.

Deciphering the functional architecture that underpins diverse cognitive functions is fundamental quest in neuroscience. In this study, we employed an innovative machine learning framework that integrated cognitive ontology with functional connectivity analysis to identify brain networks essential for cognition. We identified a core assembly of functional connectomes, primarily located within the association cortex, which showed superior predictive performance compared to two conventional methods widely employed in previous research across various cognitive domains. Our approach achieved a mean prediction accuracy of 0.13 across 16 cognitive tasks, including working memory, reading comprehension, and sustained attention, outperforming the traditional methods' accuracy of 0.08. In contrast, our method showed limited predictive power for sensory, motor, and emotional functions, with a mean prediction accuracy of 0.03 across 9 relevant tasks, slightly lower than the traditional methods' accuracy of 0.04. These cognitive connectomes were further characterized by distinctive patterns of resting-state functional connectivity, structural connectivity via white matter tracts, and gene expression, highlighting their neurogenetic underpinnings. Our findings reveal a domain-general functional network fingerprint that pivotal to cognition, offering a novel computational approach to explore the neural foundations of cognitive abilities.

Compensation or Preservation? Different Roles of Functional Lateralization in Speech Perception of Older Non-musicians and Musicians.

Musical training can counteract age-related decline in speech perception in noisy environments. However, it remains unclear whether older non-musicians and musicians rely on functional compensation or functional preservation to counteract the adverse effects of aging. This study utilized resting-state functional connectivity (FC) to investigate functional lateralization, a fundamental organization feature, in older musicians (OM), older non-musicians (ONM), and young non-musicians (YNM). Results showed that OM outperformed ONM and achieved comparable performance to YNM in speech-in-noise and speech-in-speech tasks. ONM exhibited reduced lateralization than YNM in lateralization index (LI) of intrahemispheric FC (LI_intra) in the cingulo-opercular network (CON) and LI of interhemispheric heterotopic FC (LI_he) in the language network (LAN). Conversely, OM showed higher neural alignment to YNM (i.e., a more similar lateralization pattern) compared to ONM in CON, LAN, frontoparietal network (FPN), dorsal attention network (DAN), and default mode network (DMN), indicating preservation of youth-like lateralization patterns due to musical experience. Furthermore, in ONM, stronger left-lateralized and lower alignment-to-young of LI_intra in the somatomotor network (SMN) and DAN and LI_he in DMN correlated with better speech performance, indicating a functional compensation mechanism. In contrast, stronger right-lateralized LI_intra in FPN and DAN and higher alignment-to-young of LI_he in LAN correlated with better performance in OM, suggesting a functional preservation mechanism. These findings highlight the differential roles of functional preservation and compensation of lateralization in speech perception in noise among elderly individuals with and without musical expertise, offering insights into successful aging theories from the lens of functional lateralization and speech perception.

Macroscale brain states support the control of semantic cognition.

A crucial aim in neuroscience is to understand how the human brain adapts to varying cognitive demands. This study investigates network reconfiguration during controlled semantic retrieval in differing contexts. We analyze brain responses to two semantic tasks of varying difficulty - global association and feature matching judgments - which are contrasted with non-semantic tasks on the cortical surface and within a whole-brain state space. Demanding semantic association tasks elicit activation in anterior prefrontal and temporal regions, while challenging semantic feature matching and non-semantic tasks predominantly activate posterior regions. Task difficulty also modulates activation along different dimensions of functional organization, suggesting different mechanisms of cognitive control. More demanding semantic association judgments engage cognitive control and default mode networks together, while feature matching and non-semantic tasks are skewed towards cognitive control networks. These findings highlight the brain's dynamic ability to tailor its networks to support diverse neurocognitive states, enriching our understanding of controlled cognition.

Graded and sharp transitions in semantic function in left temporal lobe.

Recent work has focussed on how patterns of functional change within the temporal lobe relate to whole-brain dimensions of intrinsic connectivity variation (Margulies et al., 2016). We examined two such 'connectivity gradients' reflecting the separation of (i) unimodal versus heteromodal and (ii) visual versus auditory-motor cortex, examining visually presented verbal associative and feature judgments, plus picture-based context and emotion generation. Functional responses along the first dimension sometimes showed graded change between modality-tuned and heteromodal cortex (in the verbal matching task), and other times showed sharp functional transitions, with deactivation at the extremes and activation in the middle of this gradient (internal generation). The second gradient revealed more visual than auditory-motor activation, regardless of content (associative, feature, context, emotion) or task process (matching/generation). We also uncovered subtle differences across each gradient for content type, which predominantly manifested as differences in relative magnitude of activation or deactivation.

Successful aging of musicians: Preservation of sensorimotor regions aids audiovisual speech-in-noise perception.

Musicianship can mitigate age-related declines in audiovisual speech-in-noise perception. We tested whether this benefit originates from functional preservation or functional compensation by comparing fMRI responses of older musicians, older nonmusicians, and young nonmusicians identifying noise-masked audiovisual syllables. Older musicians outperformed older nonmusicians and showed comparable performance to young nonmusicians. Notably, older musicians retained similar neural specificity of speech representations in sensorimotor areas to young nonmusicians, while older nonmusicians showed degraded neural representations. In the same region, older musicians showed higher neural alignment to young nonmusicians than older nonmusicians, which was associated with their training intensity. In older nonmusicians, the degree of neural alignment predicted better performance. In addition, older musicians showed greater activation in frontal-parietal, speech motor, and visual motion regions and greater deactivation in the angular gyrus than older nonmusicians, which predicted higher neural alignment in sensorimotor areas. Together, these findings suggest that musicianship-related benefit in audiovisual speech-in-noise processing is rooted in preserving youth-like representations in sensorimotor regions.

A social-semantic working-memory account for two canonical language areas.

Language and social cognition are traditionally studied as separate cognitive domains, yet accumulative studies reveal overlapping neural correlates at the left ventral temporoparietal junction (vTPJ) and the left lateral anterior temporal lobe (lATL), which have been attributed to sentence processing and social concept activation. We propose a common cognitive component underlying both effects: social-semantic working memory. We confirmed two key predictions of our hypothesis using functional MRI. First, the left vTPJ and lATL showed sensitivity to sentences only when the sentences conveyed social meaning; second, these regions showed persistent social-semantic-selective activity after the linguistic stimuli disappeared. We additionally found that both regions were sensitive to the socialness of non-linguistic stimuli and were more tightly connected with the social-semantic-processing areas than with the sentence-processing areas. The converging evidence indicates the social-semantic working-memory function of the left vTPJ and lATL and challenges the general-semantic and/or syntactic accounts for the neural activity of these regions.