A network-level test of the role of the co-activated default mode network in episodic recall and social cognition.

Resting-state network research is extremely influential, yet the functions of many networks remain unknown. In part, this is due to typical (e.g., univariate) analyses independently testing the function of individual regions and not examining the full set of regions that form a network whilst co-activated. Connectivity is dynamic and the function of a region may change based on its current connections. Therefore, determining the function of a network requires assessment at this network-level. Yet popular theories implicating the default mode network (DMN) in episodic memory and social cognition, rest principally upon analyses performed at the level of individual brain regions. Here we use independent component analysis to formally test the role of the DMN in episodic and social processing at the network level. As well as an episodic retrieval task, two independent datasets were employed to assess DMN function across the breadth of social cognition; a person knowledge judgement and a theory of mind task. Each task dataset was separated into networks of co-activated regions. In each, the co-activated DMN, was identified through comparison to an a priori template and its relation to the task model assessed. This co-activated DMN did not show greater activity in episodic or social tasks than high-level baseline conditions. Thus, no evidence was found to support hypotheses that the co-activated DMN is involved in explicit episodic or social tasks at a network-level. The networks associated with these processes are described. Implications for prior univariate findings and the functional significance of the co-activated DMN are considered.

Dual-axes of functional organisation across lateral parietal cortex: the angular gyrus forms part of a multi-modal buffering system.

Decades of neuropsychological and neuroimaging evidence have implicated the lateral parietal cortex (LPC) in a myriad of cognitive domains, generating numerous influential theoretical models. However, these theories fail to explain why distinct cognitive activities appear to implicate common neural regions. Here we discuss a unifying model in which the angular gyrus forms part of a wider LPC system with a core underlying neurocomputational function; the multi-sensory buffering of spatio-temporally extended representations. We review the principles derived from computational modelling with neuroimaging task data and functional and structural connectivity measures that underpin the unified neurocomputational framework. We propose that although a variety of cognitive activities might draw on shared underlying machinery, variations in task preference across angular gyrus, and wider LPC, arise from graded changes in the underlying structural connectivity of the region to different input/output information sources. More specifically, we propose two primary axes of organisation: a dorsal-ventral axis and an anterior-posterior axis, with variations in task preference arising from underlying connectivity to different core cognitive networks (e.g. the executive, language, visual, or episodic memory networks).

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.

The convergence and divergence of episodic and semantic functions across lateral parietal cortex.

Decades of research have highlighted the importance of lateral parietal cortex (LPC) across a myriad of cognitive domains. Yet, the underlying function of LPC remains unclear. Two domains that have emphasized LPC involvement are semantic memory and episodic memory retrieval. From each domain, sophisticated functional models have been proposed, as well as the more domain-general assumption that LPC is engaged by any form of internally directed cognition (episodic/semantic retrieval being examples). Here we used a combination of functional magnetic resonance imaging, functional connectivity, and diffusion tensor imaging white-matter connectivity to show that (i) ventral LPC (angular gyrus [AG]) was positively engaged during episodic retrieval but disengaged during semantic memory retrieval and (ii) activity negatively varied with task difficulty in the semantic task whereas episodic activation was independent of difficulty. In contrast, dorsal LPC (intraparietal sulcus) showed domain general activation that was positively correlated with task difficulty. Finally, (iii) a dorsal-ventral and anterior-posterior gradient of functional and structural connectivity was found across the AG (e.g. mid-AG connected with episodic retrieval). We propose a unifying model in which LPC as a whole might share a common underlying neurocomputation (multimodal buffering) with variations in the emergent cognitive functions across subregions arising from differences in the underlying connectivity.

A Unifying Account of Angular Gyrus Contributions to Episodic and Semantic Cognition.

The angular gyrus (AG) region of lateral parietal cortex has been implicated in a wide variety of tasks and functions, generating numerous influential theories. However, these theories largely fail to explain why so many apparently distinct cognitive activities implicate common parietal structures. We propose a unifying model, based on a set of central principles, to account for coalescences of cognitive task activations across AG. To illustrate the proposed framework, we show how these principles account for findings from studies of episodic and semantic memory that have independently implicated the same AG regions but thus far been considered from largely domain-specific perspectives. We conclude that AG computations, as part of a wider lateral parietal system, enable the online dynamic buffering of multisensory spatiotemporally extended representations.

Overarching Principles and Dimensions of the Functional Organization in the Inferior Parietal Cortex.

The parietal cortex (PC) is implicated in a confusing myriad of different cognitive processes/tasks. Consequently, understanding the nature and organization of the core underlying neurocomputations is challenging. According to the Parietal Unified Connectivity-biased Computation model, two properties underpin PC function and organization. Firstly, PC is a multidomain, context-dependent buffer of time- and space-varying input, the function of which, over time, becomes sensitive to the statistical temporal/spatial structure of events. Secondly, over and above this core buffering computation, differences in long-range connectivity will generate graded variations in task engagement across subregions. The current study tested these hypotheses using a group independent component analysis technique with two independent functional magnetic resonance imaging datasets (task and resting state data). Three functional organizational principles were revealed: Factor 1, inferior PC was sensitive to the statistical structure of sequences for all stimulus types (pictures, sentences, numbers); Factor 2, a dorsal-ventral variation in generally task-positive versus task-negative (variable) engagement; and Factor 3, an anterior-posterior dimension in inferior PC reflecting different engagement in verbal versus visual tasks, respectively. Together, the data suggest that the core neurocomputation implemented by PC is common across domains, with graded task engagement across regions reflecting variations in the connectivity of task-specific networks that interact with PC.

Bipartite Functional Fractionation within the Default Network Supports Disparate Forms of Internally Oriented Cognition.

Our understanding about the functionality of the brain's default network (DN) has significantly evolved over the past decade. Whereas traditional views define this network based on its suspension/disengagement during task-oriented behavior, contemporary accounts have characterized various situations wherein the DN actively contributes to task performance. However, it is unclear how different task-contexts drive componential regions of the DN to coalesce into a unitary network and fractionate into different subnetworks. Here we report a compendium of evidence that provides answers to these questions. Across multiple analyses, we found a striking dyadic structure within the DN in terms of the profiles of task-triggered fMRI response and effective connectivity, significantly extending beyond previous inferences based on meta-analysis and resting-state activities. In this dichotomy, one subset of DN regions prefers mental activities "interfacing with" perceptible events, while the other subset prefers activities "detached from" perceptible events. While both show a common "aversion" to sensory-motoric activities, their differential preferences manifest a subdivision that sheds light upon the taxonomy of the brain's memory systems. This dichotomy is consistent with proposals of a macroscale gradational structure spanning across the cerebrum. This gradient increases its representational complexity, from primitive sensory-motoric processing, through lexical-semantic representations, to elaborated self-generated thoughts.

Revealing the neural networks that extract conceptual gestalts from continuously evolving or changing semantic contexts.

Reading a book, understanding the news reports or any other behaviour involving the processing of meaningful stimuli requires the semantic system to have two main features: being active during an extended period of time and flexibly adapting the internal representation according to the changing environment. Despite being key features of many everyday tasks, formation and updating of the semantic "gestalt" are still poorly understood. In this fMRI study we used naturalistic stimuli and task manipulations to identify the neural network that forms and updates conceptual gestalts during time-extended integration of meaningful stimuli. Univariate and multivariate techniques allowed us to draw a distinction between networks that are crucial for the formation of a semantic gestalt (meaning integration) and those that instead are important for linking incoming cues about the current context (e.g., time and space cues) into a schema representation. Specifically, we revealed that time-extended formation of the conceptual gestalt was reflected in the neuro-computations of the anterior temporal lobe accompanied by multi-demand areas and hippocampus, with a key role of brain structures in the right hemisphere. This "semantic gestalt network" was strongly recruited when an update of the current semantic representation was required during narrative processing. A distinct fronto-parietal network, instead, was recruited for context integration, independently from the meaning associations between words (semantic coherence). Finally, in contrast with accounts positing that the default mode network (DMN) may have a crucial role in semantic cognition, our findings revealed that DMN activity was sensitive to task difficulty, but not to semantic integration. The implications of these findings for neurocognitive models of semantic cognition and the literature on narrative processing are discussed.

Time for a quick word? The striking benefits of training speed and accuracy of word retrieval in post-stroke aphasia.

One-third of stroke survivors experience deficits in word retrieval as a core characteristic of their aphasia, which is frustrating, socially limiting and disabling for their professional and everyday lives. The, as yet, undiscovered 'holy grail' of clinical practice is to establish a treatment that not only improves item naming, but also generalizes to patients' connected speech. Speech production in healthy participants is a remarkable feat of cognitive processing being both rapid (at least 120 words per minute) and accurate (∼one error per 1000 words). Accordingly, we tested the hypothesis that word-finding treatment will only be successful and generalize to connected speech if word retrieval is both accurate and quick. This study compared a novel combined speed- and accuracy-focused intervention-'repeated, increasingly-speeded production'-to standard accuracy-focused treatment. Both treatments were evaluated for naming, connected speech outcomes, and related to participants' neuropsychological and lesion profiles. Twenty participants with post-stroke chronic aphasia of varying severity and subtype took part in 12 computer-based treatment sessions over 6 weeks. Four carefully matched word sets were randomly allocated either to the speed- and accuracy-focused treatment, standard accuracy-only treatment, or untreated (two control sets). In the standard treatment, sound-based naming cues facilitated naming accuracy. The speed- and accuracy-focused treatment encouraged naming to become gradually quicker, aiming towards the naming time of age-matched controls. The novel treatment was significantly more effective in improving and maintaining picture naming accuracy and speed (reduced latencies). Generalization of treated vocabulary to connected speech was significantly increased for all items relative to the baseline. The speed- and accuracy-focused treatment generated substantial and significantly greater deployment of targeted items in connected speech. These gains were maintained at 1-month post-intervention. There was a significant negative correlation for the speed- and accuracy-focused treatment between the patients' phonological scores and the magnitude of the therapy effect, which may have reflected the fact that the substantial beneficial effect of the novel treatment generated a ceiling effect in the milder patients. Maintenance of the speed- and accuracy-treatment effect correlated positively with executive skills. The neural correlate analyses revealed that participants with the greatest damage to the posterior superior temporal gyrus extending into the white matter of the inferior longitudinal fasciculus, showed the greatest speed- and accuracy treatment benefit. The novel treatment was well tolerated by participants across the range of severity and aphasia subtype, indicating that this type of intervention has considerable clinical utility and broad applicability.

Controlled semantic cognition relies upon dynamic and flexible interactions between the executive 'semantic control' and hub-and-spoke 'semantic representation' systems.

Built upon a wealth of neuroimaging, neurostimulation, and neuropsychology data, a recent proposal set forth a framework termed controlled semantic cognition (CSC) to account for how the brain underpins the ability to flexibly use semantic knowledge (Lambon Ralph et al., 2017; Nature Reviews Neuroscience). In CSC, the 'semantic control' system, underpinned predominantly by the prefrontal cortex, dynamically monitors and modulates the 'semantic representation' system that consists of a 'hub' (anterior temporal lobe, ATL) and multiple 'spokes' (modality-specific areas). CSC predicts that unfamiliar and exacting semantic tasks should intensify communication between the 'control' and 'representation' systems, relative to familiar and less taxing tasks. In the present study, we used functional magnetic resonance imaging (fMRI) to test this hypothesis. Participants paired unrelated concepts by canonical colours (a less accustomed task - e.g., pairing ketchup with fire-extinguishers due to both being red) or paired well-related concepts by semantic relationship (a typical task - e.g., ketchup is related to mustard). We found the 'control' system was more engaged by atypical than typical pairing. While both tasks activated the ATL 'hub', colour pairing additionally involved occipitotemporal 'spoke' regions abutting areas of hue perception. Furthermore, we uncovered a gradient along the ventral temporal cortex, transitioning from the caudal 'spoke' zones preferring canonical colour processing to the rostral 'hub' zones preferring semantic relationship. Functional connectivity also differed between the tasks: Compared with semantic pairing, colour pairing relied more upon the inferior frontal gyrus, a key node of the control system, driving enhanced connectivity with occipitotemporal 'spoke'. Together, our findings characterise the interaction within the neural architecture of semantic cognition - the control system dynamically heightens its connectivity with relevant components of the representation system, in response to different semantic contents and difficulty levels.

Mapping Domain-Selective and Counterpointed Domain-General Higher Cognitive Functions in the Lateral Parietal Cortex: Evidence from fMRI Comparisons of Difficulty-Varying Semantic Versus Visuo-Spatial Tasks, and Functional Connectivity Analyses.

Numerous cognitive domains have been associated with the lateral parietal cortex, yet how these disparate functions are packed into this region remains unclear. Whilst areas within the dorsal and the ventral parietal cortex (DPC and VPC) show differential function, there is considerable disagreement as to what these functions might be. Studies focussed on individual domains have plotted out variations of function across the region. Direct cross-domain comparisons are rare yet, when they have been undertaken, at least some regions (particularly the intraparietal sulcus [IPS] and core angular gyrus [AG]) appear to have contrastive domain-general qualities. In order to pursue this parietal puzzle, this study utilized both functional and resting-state magnetic resonance imaging to investigate a potential unifying neurocomputational framework-in which both domain general as well as domain-selective regions arise from differential patterns of connectivity into subregions of the lateral parietal cortex. Specifically we found that, consistent with their contrastive patterns of functional connectivity, subregions of DPC (anterior IPS) and VPC (AG) exhibit counterpointed functions sensitive to task/item-difficulty irrespective of cognitive domain. We propose that these regions serve as top-down executively penetrated and automatic bottom-up domain-general buffers of active information, respectively. In contrast, other parietal and nonparietal regions are tuned toward specific domains.

Establishing task- and modality-dependent dissociations between the semantic and default mode networks.

The default mode network (DMN) and semantic network (SN) are two of the most extensively studied systems, and both are increasingly used as clinical biomarkers in neurological studies. There are strong theoretical reasons to assume a relationship between the networks, as well as anatomical evidence that they might rely on overlapping cortical regions, such as the anterior temporal lobe (ATL) or angular gyrus (AG). Despite these strong motivations, the relationship between the two systems has received minimal attention. We directly compared the SN and DMN using a large (n = 69) distortion-corrected functional MRI (fMRI) dataset, spanning a range of semantic and nonsemantic tasks that varied input modality. The results showed that both networks fractionate depending on the semantic nature of the task, stimulus type, modality, and task difficulty. Furthermore, despite recent claims that both AG and ATL are semantic hubs, the two areas responded very differently, with results supporting the role of ATL, but not AG, in semantic representation. Specifically, the left ATL was positively activated for all semantic tasks, but deactivated during nonsemantic task performance. In contrast, the left AG was deactivated for all tasks, with the level of deactivation related to task difficulty. Thus, ATL and AG do not share a common interest in semantic tasks, but, rather, a common "disinterest" in nonsemantic tasks. The implications for the variability in the DMN, its cognitive coherence, and interpretation of resting-state fMRI data are discussed.

Fusion and Fission of Cognitive Functions in the Human Parietal Cortex.

How is higher cognitive function organized in the human parietal cortex? A century of neuropsychology and 30 years of functional neuroimaging has implicated the parietal lobe in many different verbal and nonverbal cognitive domains. There is little clarity, however, on how these functions are organized, that is, where do these functions coalesce (implying a shared, underpinning neurocomputation) and where do they divide (indicating different underlying neural functions). Until now, there has been no multi-domain synthesis in order to reveal where there is fusion or fission of functions in the parietal cortex. This aim was achieved through a large-scale activation likelihood estimation (ALE) analysis of 386 studies (3952 activation peaks) covering 8 cognitive domains. A tripartite, domain-general neuroanatomical division and 5 principles of cognitive organization were established, and these are discussed with respect to a unified theory of parietal functional organization.

Hand specific representations in language comprehension.

Theories of embodied cognition argue that language comprehension involves sensory-motor re-enactments of the actions described. However, the degree of specificity of these re-enactments as well as the relationship between action and language remains a matter of debate. Here we investigate these issues by examining how hand-specific information (left or right hand) is recruited in language comprehension and action execution. An fMRI study tested self-reported right-handed participants in two separate tasks that were designed to be as similar as possible to increase sensitivity of the comparison across task: an action execution go/no-go task where participants performed right or left hand actions, and a language task where participants read sentences describing the same left or right handed actions as in the execution task. We found that language-induced activity did not match the hand-specific patterns of activity found for action execution in primary somatosensory and motor cortex, but it overlapped with pre-motor and parietal regions associated with action planning. Within these pre-motor regions, both right hand actions and sentences elicited stronger activity than left hand actions and sentences-a dominant hand effect. Importantly, both dorsal and ventral sections of the left pre-central gyrus were recruited by both tasks, suggesting different action features being recruited. These results suggest that (a) language comprehension elicits motor representations that are hand-specific and akin to multimodal action plans, rather than full action re-enactments; and (b) language comprehension and action execution share schematic hand-specific representations that are richer for the dominant hand, and thus linked to previous motor experience.

Competitive mechanisms in sentence processing: common and distinct production and reading comprehension networks linked to the prefrontal cortex.

Despite much interest in language production and comprehension mechanisms, little is known about the relationship between the two. Previous research suggests that linguistic knowledge is shared across these tasks and that the left inferior frontal gyrus (LIFG) may be commonly recruited. However, it remains unclear the extent to which production and comprehension share competition mechanisms. Here we investigate this issue and specifically examine competition in determining the event roles in a sentence (agent or affected participant). We used both behavioral and fMRI methods and compared the reading and production of high- and low-competition sentences, specifically targeting LIFG. We found that activity in pars opercularis (PO), independently identified by a competition-driven localizer, was modulated by competition in both tasks. Psychophysiological interaction analyses seeded in PO revealed task-specific networks: In comprehension, PO only interacted with the posterior temporal lobe, whereas in production, it interacted with a large network including hippocampal, posterior temporal, medial frontal and subcortical structures. Production and comprehension therefore recruit partially distinct functional networks but share competitive processes within fronto-temporal regions. We argue that these common regions store long-term linguistic associations and compute their higher-order contingencies, but competition in production ignites a larger neural network implementing planning, as required by task demands.

Motion and actions in language: semantic representations in occipito-temporal cortex.

Understanding verbs typically activates posterior temporal regions and, in some circumstances, motion perception area V5. However, the nature and role of this activation remains unclear: does language alone indeed activate V5? And are posterior temporal representations modality-specific motion representations, or supra-modal motion-independent event representations? Here, we address these issues by investigating human and object motion sentences compared to corresponding state descriptions. We adopted the blank screen paradigm, which is known to encourage visual imagery, and used a localizer to identify V5 and temporal structures responding to motion. Analyses in each individual brain suggested that language modulated activity in the posterior temporal lobe but not within V5 in most participants. Moreover, posterior temporal structures strongly responded to both motion sentences and human static sentences. These results suggest that descriptive language alone need not recruit V5 and instead engages more schematic event representations in temporal cortex encoding animacy and motion.