Functional integration and segregation during semantic cognition: Evidence across age groups.

Semantic cognition is underpinned by ventral anterior temporal lobe (vATL) which encodes knowledge representations and inferior frontal gyrus (IFG), which controls activation of knowledge based on the needs of the current context. This core semantic network has been validated in substantial empirical findings in the past. However, it remains unclear how these core semantic areas dynamically communicate with each other, and with other neural networks, to achieve successful semantic processing. Here, we investigated this question by testing functional connectivity in the core semantic network during semantic tasks and whether these connections were affected by cognitive ageing. Compared to a non-semantic task, semantic tasks increased the connectivity between left and right IFGs, indicating a bilateral semantic control system. Strengthened connectivity was also found between left IFG and left vATL, and this effect was stronger in the young group. At a whole-brain scale, IFG and vATL increased their coupling with multiple-demand regions during semantic tasks, even though these areas were deactivated relative to non-semantic tasks. This suggests that the domain-general executive network contributes to semantic processing. In contrast, IFG and vATL decreased their interaction with default mode network (DMN) areas during semantic tasks, even though these areas were positively activated by the task. This suggests that DMN areas do not contribute to all semantic tasks: their activation may sometimes reflect automatic retrieval of task-irrelevant memories and associations. Taken together, our study characterizes a dynamic connectivity mechanism supporting semantic cognition within and beyond core semantic regions.

Verbal semantic expertise is associated with reduced functional connectivity between left and right anterior temporal lobes.

The left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialization in function, with the left ATL contributing preferentially to verbal semantic processing. We investigated the cognitive correlates of this organization, using resting-state functional connectivity as a measure of functional segregation between ATLs. We analyzed two independent resting-state fMRI datasets (n = 86 and n = 642) in which participants' verbal semantic expertise was measured using vocabulary tests. In both datasets, people with more advanced verbal semantic knowledge showed weaker functional connectivity between left and right ventral ATLs. This effect was highly specific. It was not observed for within-hemisphere connections between semantic regions (ventral ATL and inferior frontal gyrus (IFG), though it was found for left-right IFG connectivity in one dataset). Effects were not found for tasks probing semantic control, nonsemantic cognition, or face recognition. Our results suggest that hemispheric specialization in the ATLs is not an innate property but rather emerges as people develop highly detailed verbal semantic representations. We speculate that this effect is a consequence of the left ATL's greater connectivity with left-lateralized written word recognition regions, which causes it to preferentially represent meaning for advanced vocabulary acquired primarily through reading.

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 neural basis of naturalistic semantic and social cognition.

Decoding social environments and engaging meaningfully with other people are critical aspects of human cognition. Multiple cognitive systems, including social and semantic cognition, work alongside each other to support these processes. This study investigated shared processing between social and semantic systems using neuroimaging data collected during movie-viewing, which captures the multimodal environment in which social knowledge is exchanged. Semantic and social content from movie events (event-level) and movie transcripts (word-level) were used in parametric modulation analyses to test (1) the degree to which semantic and social information is processed within each respective network and (2) engagement of the same cross-network regions or the same domain-general hub located within the semantic network during semantic and social processing. Semantic word and event-level content engaged the same fronto-temporo-parietal network and a portion of the semantic hub in the anterior temporal lobe (ATL). Social word and event-level content engaged the supplementary motor area and right angular gyrus within the social network, but only social words engaged the domain-general semantic hub in left ATL. There was evidence of shared processing between the social and semantic systems in the dorsolateral portion of right ATL which was engaged by word and event-level semantic and social content. Overlap between the semantic and social word and event results was highly variable within and across participants, with the most consistent loci of overlap occurring in left inferior frontal, bilateral precentral and supramarginal gyri for social and semantic words and in bilateral superior temporal gyrus extending from ATL posteriorly into supramarginal gyri for social and semantic events. These results indicate a complex pattern of shared and distinct regions for social and semantic cognition during naturalistic processing. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on October 11, 2022. The protocol, as accepted by the journal, can be found at: https://doi.org/10.17605/OSF.IO/ACWQY .

Representation of event and object concepts in ventral anterior temporal lobe and angular gyrus.

Semantic knowledge includes understanding of objects and their features and also understanding of the characteristics of events. The hub-and-spoke theory holds that these conceptual representations rely on multiple information sources that are integrated in a central hub in the ventral anterior temporal lobes. The dual-hub theory expands this framework with the claim that the ventral anterior temporal lobe hub is specialized for object representation, while a second hub in angular gyrus is specialized for event representation. To test these ideas, we used representational similarity analysis, univariate and psychophysiological interaction analyses of fMRI data collected while participants processed object and event concepts (e.g. "an apple," "a wedding") presented as images and written words. Representational similarity analysis showed that angular gyrus encoded event concept similarity more than object similarity, although the left angular gyrus also encoded object similarity. Bilateral ventral anterior temporal lobes encoded both object and event concept structure, and left ventral anterior temporal lobe exhibited stronger coding for events. Psychophysiological interaction analysis revealed greater connectivity between left ventral anterior temporal lobe and right pMTG, and between right angular gyrus and bilateral ITG and middle occipital gyrus, for event concepts compared to object concepts. These findings support the specialization of angular gyrus for event semantics, though with some involvement in object coding, but do not support ventral anterior temporal lobe specialization for object concepts.

Dictionary learning for integrative, multimodal and scalable single-cell analysis.

Mapping single-cell sequencing profiles to comprehensive reference datasets provides a powerful alternative to unsupervised analysis. However, most reference datasets are constructed from single-cell RNA-sequencing data and cannot be used to annotate datasets that do not measure gene expression. Here we introduce 'bridge integration', a method to integrate single-cell datasets across modalities using a multiomic dataset as a molecular bridge. Each cell in the multiomic dataset constitutes an element in a 'dictionary', which is used to reconstruct unimodal datasets and transform them into a shared space. Our procedure accurately integrates transcriptomic data with independent single-cell measurements of chromatin accessibility, histone modifications, DNA methylation and protein levels. Moreover, we demonstrate how dictionary learning can be combined with sketching techniques to improve computational scalability and harmonize 8.6 million human immune cell profiles from sequencing and mass cytometry experiments. Our approach, implemented in version 5 of our Seurat toolkit ( http://www.satijalab.org/seurat ), broadens the utility of single-cell reference datasets and facilitates comparisons across diverse molecular modalities.

The Year in Thoracic Anesthesia: Selected Highlights from 2022.

This article reviews research highlights in the field of thoracic anesthesia. The highlights of this year included new developments in the preoperative assessment and prehabilitation of patients requiring thoracic surgery, updates on the use of devices for one-lung ventilation (OLV) in adults and children, updates on the anesthetic and postoperative management of these patients, including protective OLV ventilation, the use of opioid-sparing techniques and regional anesthesia, and outcomes using enhanced recovery after surgery, as well as the use of expanding indications for extracorporeal membrane oxygenation, specialized anesthetic techniques for airway surgery, and nonintubated video-assisted thoracic surgery.

Discourse coherence modulates use of predictive processing during sentence comprehension.

Context has been shown to be vitally important for comprehension. Lexical processing is facilitated when words are highly predictable given their local sentence context, suggesting that people pre-activate likely upcoming words to aid comprehension. However, this facilitation is affected by knowledge about the global context in which comprehension takes place: people predict less when in an environment where expectations are frequently violated. The current study investigated whether discourse coherence is an additional cue that comprehenders use to modulate lexical prediction. In a series of online, self-paced reading experiments, participants read target sentences preceded by short contextual preambles. Local facilitation effects were manipulated through the cloze probability of a critical word within the target sentence and discourse coherence was manipulated by varying the degree to which the target sentence was consistent with the information presented in the preamble. In the first two experiments, target sentences were read more slowly when they occurred in less coherent discourses, but no local facilitation effects were observed. In the third experiment, we strengthened the predictability manipulation by using semantically anomalous critical words. In this experiment, predictable words were processed more quickly and anomalous words more slowly when they occurred in highly coherent discourse. Our results suggest that comprehenders are sensitive to shifts in the topic of discourse and that they downregulate predictive processing when they encounter incoherence in the discourse. This is consistent with recent theoretical accounts suggesting that comprehenders flexibly engage in predictive processing, pre-activating semantic and lexical information less when their expectations are less likely to be reliable.

Collaborative learning of new information in older age: a systematic review.

Ageing is accompanied by a multitude of changes in cognitive abilities, which in turn affect learning. Learning collaboratively may benefit older adults by negating some of these age-related changes. However, studies on collaborative learning in older age differ in their methodology and findings. This systematic review provides an overview of the current research on collaborative learning in older age, exploring what factors influence collaborative learning in this age group. The titles and abstracts of imported 6629 works were screened, as well as four works added manually, which resulted in 29 studies. These studies were conducted across five countries (Canada, United States, United Kingdom, Switzerland and Belgium) between 1993 and 2023. Most studies were quantitative with a non-randomized (n = 16) design. Of the 29 studies, almost all studied collaboration in pairs (n = 28). The results suggest that the benefits of collaborating in older age may depend on the type of learning material, that familiarity between partners does not affect learning, and that age differences appear to decrease or disappear when older adults are provided with adequate time or trials. In addition, this systematic review identifies several gaps in the literature that future research should investigate further. This study was preregistered prior to its commencement on 21 January 2022. The accepted Stage 1 manuscript, unchanged from the point of in-principle acceptance, may be viewed at https://osf.io/tj4w7/. The data and materials of this study can be found at https://osf.io/8xvqf/.

Healthy ageing has divergent effects on verbal and non-verbal semantic cognition.

Semantic cognition refers to the storage and appropriate use of knowledge acquired over the lifespan and underpins our everyday verbal and non-verbal behaviours. Successful semantic cognition requires representation of knowledge and control processes which ensure that currently relevant aspects of knowledge are retrieved and selected. Although these abilities have been widely studied in healthy young populations and semantically impaired patients, it is unclear how they change as a function of healthy ageing, especially for non-verbal semantic processing. Here, we addressed this issue by comparing the performance profiles of young and older people on a semantic knowledge task and a semantic control task, across verbal (word) and non-verbal (picture) versions. The results revealed distinct patterns of change during adulthood for semantic knowledge and semantic control. Older people performed better in both verbal and non-verbal knowledge tasks than young people. However, although the older group showed preserved controlled retrieval for verbal semantics, they demonstrated a specific impairment for non-verbal semantic control. These findings indicate that the effects of ageing on semantic cognition are more complex than previously assumed, and that input modality plays an important role in the shifting cognitive architecture of semantics in later life.

Age differences in the neural processing of semantics, within and beyond the core semantic network.

Aging is associated with functional activation changes in domain-specific regions and large-scale brain networks. This preregistered Functional magnetic resonance imaging (fMRI) study investigated these effects within the domain of semantic cognition. Participants completed 1 nonsemantic and 2 semantic tasks. We found no age differences in semantic activation in core semantic regions. However, the right inferior frontal gyrus showed difficulty-related increases in both age groups. This suggests that age-related upregulation of this area may be a compensatory response to increased processing demands. At a network level, older people showed more engagement in the default mode network and less in the executive multiple-demand network, aligning with older people's greater knowledge reserves and executive declines. In contrast, activation was age-invariant in semantic control regions. Finally, older adults showed reduced demand-related modulation of multiple-demand network activation in the nonsemantic task but not the semantic tasks. These findings provide a new perspective on the neural basis of semantic cognition in aging, suggesting that preserved function in specialized semantic networks may help to maintain semantic cognition in later life.

A common neural code for meaning in discourse production and comprehension.

How does the brain code the meanings conveyed by language? Neuroimaging studies have investigated this by linking neural activity patterns during discourse comprehension to semantic models of language content. Here, we applied this approach to the production of discourse for the first time. Participants underwent fMRI while producing and listening to discourse on a range of topics. We used a distributional semantic model to quantify the similarity between different speech passages and identified where similarity in neural activity was predicted by semantic similarity. When people produced discourse, speech on similar topics elicited similar activation patterns in a widely distributed and bilateral brain network. This network was overlapping with, but more extensive than, the regions that showed similarity effects during comprehension. Critically, cross-task neural similarities between comprehension and production were also predicted by similarities in semantic content. This result suggests that discourse semantics engages a common neural code that is shared between comprehension and production. Effects of semantic similarity were bilateral in all three RSA analyses, even while univariate activation contrasts in the same data indicated left-lateralised BOLD responses. This indicates that right-hemisphere regions encode semantic properties even when they are not activated above baseline. We suggest that right-hemisphere regions play a supporting role in processing the meaning of discourse during both comprehension and production.

Taxonomic and thematic relations rely on different types of semantic features: Evidence from an fMRI meta-analysis and a semantic priming study.

Taxonomic and thematic relations are major components of semantic representation but their neurocognitive underpinnings are still debated. We hypothesised that taxonomic relations preferentially activate parts of anterior temporal lobe (ATL) because they rely more on colour and shape features, while thematic relations preferentially activate temporoparietal cortex (TPC) because they rely more on action and location knowledge. We first conducted activation likelihood estimation (ALE) meta-analysis to assess evidence for neural specialisation in the existing fMRI literature (Study 1), then used a primed semantic judgement task to examine if the two relations are primed by different feature types (Study 2). We find that taxonomic relations show minimal feature-based specialisation but preferentially activate the lingual gyrus. Thematic relations are more dependent on action and location features and preferentially engage TPC. The meta-analysis also showed that lateral ATL is preferentially engaged by Thematic relations, which may reflect their greater reliance on verbal associations.

The words that little by little revealed everything: Neural response to lexical-semantic content during narrative comprehension.

The ease with which narratives are understood belies the complexity of the information being conveyed and the cognitive processes that support comprehension. The meanings of the words must be rapidly accessed and integrated with the reader's mental representation of the overarching, unfolding scenario. A broad, bilateral brain network is engaged by this process, but it is not clear how words that vary on specific semantic dimensions, such as ambiguity, emotion, or socialness, engage the semantic, semantic control, or social cognition systems. In the present study, data from 48 participants who listened to The Little Prince audiobook during MRI scanning were selected from the Le Petit Prince dataset. The lexical and semantic content within the narrative was quantified from the transcript words with factor scores capturing Word Length, Semantic Flexibility, Emotional Strength, and Social Impact. These scores, along with word quantity variables, were used to investigate where these predictors co-vary with activation across the brain. In contrast to studies of isolated word processing, large networks were found to co-vary with the lexical and semantic content within the narrative. An increase in semantic content engaged the ventral portion of ventrolateral ATL, consistent with its role as a semantic hub. Decreased semantic content engaged temporal pole and inferior parietal lobule, which may reflect semantic integration. The semantic control network was engaged by words with low Semantic Flexibility, perhaps due to the demand required to process infrequent, less semantically diverse language. Activation in ATL co-varied with an increase in Social Impact, which is consistent with the claim that social knowledge is housed within the neural architecture of the semantic system. These results suggest that current models of language processing may present an impoverished estimate of the neural systems that coordinate to support narrative comprehension, and, by extension, real-world language processing.

Emplacement of the Franklin large igneous province and initiation of the Sturtian Snowball Earth.

During the Cryogenian (720 to 635 Ma ago) Snowball Earth glaciations, ice extended to sea level near the equator. The cause of this catastrophic failure of Earth's thermostat has been unclear, but previous geochronology has suggested a rough coincidence of glacial onset with one of the largest magmatic episodes in the geological record, the Franklin large igneous province. U-Pb geochronology on zircon and baddeleyite from sills associated with the paleo-equatorial Franklin large igneous province in Arctic Canada record rapid emplacement between 719.86 ± 0.21 and 718.61 ± 0.30 Ma ago, 0.9 to 1.6 Ma before the onset of widespread glaciation. Geologic observations and (U-Th)/He dates on Franklin sills are compatible with major post-Franklin exhumation, possibly due to development of mafic volcanic highlands on windward equatorial Laurentia and increased global weatherability. After a transient magmatic CO2 flux, long-term carbon sequestration associated with increased weatherability could have nudged Earth over the threshold for runaway ice-albedo feedback.

Damage to temporoparietal cortex is sufficient for impaired semantic control.

Semantic control allows us to focus semantic activation on currently relevant aspects of knowledge, even in the face of competition or when the required information is weakly encoded. Diverse cortical regions, including left prefrontal and posterior temporal cortex, are implicated in semantic control, however; the relative contribution of these regions is unclear. For the first time, we compared semantic aphasia (SA) patients with damage restricted to temporoparietal cortex (TPC; N = 8) to patients with infarcts encompassing prefrontal cortex (PF+; N = 22), to determine if prefrontal lesions are necessary for semantic control deficits. These SA groups were also compared with semantic dementia (SD; N = 10), characterised by degraded semantic representations. We asked whether TPC cases with semantic impairment show controlled retrieval deficits equivalent to PF+ cases or conceptual degradation similar to patients with SD. Independent of lesion location, the SA subgroups showed similarities, whereas SD patients showed a qualitatively distinct semantic impairment. Relative to SD, both TPC and PF+ SA subgroups: (1) showed few correlations in performance across tasks with differing control demands, but a strong relationship between tasks of similar difficulty; (2) exhibited attenuated effects of lexical frequency and concept familiarity, (3) showed evidence of poor semantic regulation in their verbal output - performance on picture naming was substantially improved when provided with a phonological cue, and (4) showed effects of control demands, such as retrieval difficulty, which were equivalent in severity across TPC and PF+ groups. These findings show that semantic impairment in SA is underpinned by damage to a distributed semantic control network, instantiated across anterior and posterior cortical areas.

Modulation of brain activity by psycholinguistic information during naturalistic speech comprehension and production.

Language processing requires the integration of diverse sources of information across multiple levels of processing. A range of psycholinguistic properties have been documented in previous studies as having influence on brain activation during language processing. However, most of those studies have used factorial designs to probe the effect of one or two individual properties using highly controlled stimuli and experimental paradigms. Little is known about the neural correlates of psycholinguistic properties in more naturalistic discourse, especially during language production. The aim of our study is to explore the above issues in a rich fMRI dataset in which participants both listened to recorded passages of discourse and produced their own narrative discourse in response to prompts. Specifically, we measured 13 psycholinguistic properties of the discourse comprehended or produced by the participants, and we used principal components analysis (PCA) to address covariation in these properties and extract a smaller set of latent language characteristics. These latent components indexed vocabulary complexity, sensory-motor and emotional language content, discourse coherence and speech quantity. A parametric approach was adopted to study the effects of these psycholinguistic variables on brain activation during comprehension and production. We found that the pattern of effects across the cortex was somewhat convergent across comprehension and production. However, the degree of convergence varied across language properties, being strongest for the component indexing sensory-motor language content. We report the full, unthresholded effect maps for each psycholinguistic variable, as well as mapping how these effects change along a large-scale cortical gradient of brain function. We believe that our findings provide a valuable starting point for future, confirmatory studies of discourse processing.

Transcriptome variation in human tissues revealed by long-read sequencing.

Regulation of transcript structure generates transcript diversity and plays an important role in human disease1-7. The advent of long-read sequencing technologies offers the opportunity to study the role of genetic variation in transcript structure8-16. In this Article, we present a large human long-read RNA-seq dataset using the Oxford Nanopore Technologies platform from 88 samples from Genotype-Tissue Expression (GTEx) tissues and cell lines, complementing the GTEx resource. We identified just over 70,000 novel transcripts for annotated genes, and validated the protein expression of 10% of novel transcripts. We developed a new computational package, LORALS, to analyse the genetic effects of rare and common variants on the transcriptome by allele-specific analysis of long reads. We characterized allele-specific expression and transcript structure events, providing new insights into the specific transcript alterations caused by common and rare genetic variants and highlighting the resolution gained from long-read data. We were able to perturb the transcript structure upon knockdown of PTBP1, an RNA binding protein that mediates splicing, thereby finding genetic regulatory effects that are modified by the cellular environment. Finally, we used this dataset to enhance variant interpretation and study rare variants leading to aberrant splicing patterns.

Representation of motion concepts in occipitotemporal cortex: fMRI activation, decoding and connectivity analyses.

Embodied theories of semantic cognition predict that brain regions involved in motion perception are engaged when people comprehend motion concepts expressed in language. Left lateral occipitotemporal cortex (LOTC) is implicated in both motion perception and motion concept processing but prior studies have produced mixed findings on which parts of this region are engaged by motion language. We scanned participants performing semantic judgements about sentences describing motion events and static events. We performed univariate analyses, multivariate pattern analyses (MVPA) and psychophysiological interaction (PPI) analyses to investigate the effect of motion on activity and connectivity in different parts of LOTC. In multivariate analyses that decoded whether a sentence described motion or not, the middle and posterior parts of LOTC showed above-chance level performance, with performance exceeding that of other brain regions. Univariate ROI analyses found the middle part of LOTC was more active for motion events than static ones. Finally, PPI analyses found that when processing motion events, the middle and posterior parts of LOTC (overlapping with motion perception regions), increased their connectivity with cognitive control regions. Taken together, these results indicate that the more posterior parts of LOTC, including motion perception cortex, respond differently to motion vs. static events. These findings are consistent with embodiment accounts of semantic processing, and suggest that understanding verbal descriptions of motion engages areas of the occipitotemporal cortex involved in perceiving motion.

The cognitive and neural underpinnings of discourse coherence in post-stroke aphasia.

Although impaired discourse production is one of the prominent features of aphasia, only a handful of investigations have addressed the cognitive, linguistic and neural processes that support the production of coherent discourse. In this study, we investigated the cognitive and neural correlates of discourse coherence in a large mixed cohort of patients with post-stroke aphasia, including the first voxel-based lesion-symptom mapping of coherence deficits. Discourse responses using different tasks were collected from 46 patients with post-stroke aphasia, including a wide range of classifications and severity levels, and 20 matched neuro-typical controls. Global coherence, defined as the degree to which utterances related to the expected topic of discourse, was estimated using a previously validated computational linguistic approach. Coherence was then related to fundamental language and cognitive components in aphasia identified using an extensive neuropsychological battery. Relative to neuro-typical controls, patients with aphasia exhibited impaired coherence, and their ability to maintain coherent discourse was related to their performance on other language components: phonological production, fluency and semantic processing, rather than executive functions or motor speech. These results suggest that impairments in core language components play a role in reducing discourse coherence in post-stroke aphasia. Whole-brain voxel-wise lesion-symptom mapping using univariate and multivariate approaches identified the contribution of the left prefrontal cortex, and particularly the inferior frontal gyrus (pars triangularis), to discourse coherence. These findings provide convergent evidence for the role of the inferior frontal gyrus in maintaining discourse coherence, which is consistent with the established role of this region in producing connected speech and semantic control (organizing and selecting appropriate context-relevant concepts). These results make an important contribution to understanding the root causes of disrupted discourse production in post-stroke aphasia.