Biology subjects

Jefferies, E.

Publications and source records attributed to Jefferies, E..

At least 55 records · Page 3Linked to original sources

bioRxiv2022

DIFFERENTIAL MEMORY IMPAIRMENT ACROSS RELATIONAL DOMAINS IN TEMPORAL LOBE EPILEPSY

BO_SCPLOWACKGROUNDC_SCPLOWTemporal lobe epilepsy (TLE) is typically associated with pathology of the hippocampus, a key structure involved in relational memory processes, including episodic, semantic, and spatial memory. While it is widely accepted that TLE-associated hippocampal alterations may underlie global deficits in memory, it remains poorly understood whether TLE may present with shared or unique impairment across distinct relational memory domains. MO_SCPLOWETHODSC_SCPLOWWe administered a recently validated behavioral paradigm to evaluate episodic, semantic, and spatial memory in 20 pharmacoresistant TLE patients and 53 age- and sex-matched healthy controls. We implemented linear mixed effects models to identify memory deficits in individuals with TLE relative to controls, and used partial least squares analysis to identify factors contributing to overall variations in relational memory performance across both cohorts. RO_SCPLOWESULTSC_SCPLOWTLE patients showed marked impairment in episodic memory compared to controls, while spatial and semantic memory remained relatively intact. Findings were robust, with slight decreases in effect sizes after controlling for performance on executive function tests. Via partial least squares analysis, we identified group, age, and bilateral hippocampal volumes as important variables relating to relational memory impairment. CO_SCPLOWONCLUSIONC_SCPLOWOur behavioral framework provides a granular approach for assessing relational memory deficits in people with TLE and may inform future prognostic strategies in patients with hippocampal pathology. Our work warrants further investigations into the underlying neural substrates of relational memory.

neuroscience↗

bioRxiv2022

Cortical microstructural gradients capture memory network reorganization in temporal lobe epilepsy

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

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bioRxiv2022

Patterns of Ongoing Thought in the Real-World

Previous research has indicated that health and well-being are impacted on by both the way we think, and the things we do. In the laboratory, studies suggest that specific task contexts affect this process because the people we are with, the places we are in, and the activities we perform may influence our thought patterns. In our study participants completed multi-dimensional experience-sampling surveys eight times per day for 5 days to generate thought data across a variety of dimensions in daily life. Principal component analysis was used to decompose the experience sampling data, and linear mixed modelling related these patterns to the activity in daily life in which they emerged. Our study replicated the influence of socializing on patterns of ongoing thought observed in our prior study and established that this is part of a broader set of relationship that links our current activities to how our thoughts are organised in daily life. We also found that factors such as time of day and the physical location are associated with reported patterns of thought, factors that are important for future studies to explore. Our study suggests that sampling thinking in the real world may be able to provide a set of comprehensive thinking-activity mappings that will be useful to researchers and health care professionals interested in health and well-being.

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bioRxiv2022

Flexing the principal gradient of the cerebral cortex to suit changing semantic task demands

Understanding how thought emerges from the topographical structure of the cerebral cortex is a primary goal of cognitive neuroscience. Recent work has revealed a principal gradient of intrinsic connectivity capturing the separation of sensory-motor cortex from transmodal regions of the default mode network (DMN); this is thought to facilitate memory-guided cognition. However, studies have not explored how this dimension of connectivity changes when conceptual retrieval is controlled to suit the context. We used gradient decomposition of informational connectivity in a semantic association task to establish how the similarity in connectivity across brain regions changes during familiar and more original patterns of retrieval. Multivoxel activation patterns at opposite ends of the principal gradient were more divergent when participants retrieved stronger associations; therefore, when long-term semantic information is sufficient for ongoing cognition, regions supporting heteromodal memory are functionally separated from sensory-motor experience. In contrast, when less related concepts were linked, this dimension of connectivity was reduced in strength as semantic control regions separated from the DMN to generate more flexible and original responses. We also observed fewer dimensions within the neural response towards the apex of the principal gradient when strong associations were retrieved, reflecting less complex or varied neural coding across trials and participants. In this way, the principal gradient explains how semantic cognition is organised in the human cerebral cortex: the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared. Significance statementA central task in neuroscience is to understand how cognition emerges from the topographical structure of cerebral cortex. We used fMRI during a semantic task to assess informational connectivity as participants retrieved stereotypical or more unusual associations. The principal gradient of variation in informational connectivity captured the separation of heteromodal memory regions from unimodal cortex. This separation was reduced when weaker associations were retrieved; these trials also produced higher-dimensional neural responses in heteromodal regions. We conclude that the separation of DMN from sensory-motor systems is a hallmark of the retrieval of strong conceptual links that are culturally shared, while more complex and diverse cognition can be generated as this separation in connectivity is reduced.

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bioRxiv2022

Creativity in Verbal Associations is Linked to Semantic Control

While 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 unique versus stereotypical patterns of retrieval. Less 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. This pattern of retrieval was associated with greater engagement of core default mode network. 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 default mode network. Consequently, although both creative/controlled and stereotypical/more automatic patterns of retrieval are associated with activation within default mode network, these processes show little overlap in activation. These findings show that creativity emerges from controlled aspects of semantic cognition.

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bioRxiv2021

Mapping lesion, structural disconnection, and functional disconnection to symptoms in semantic aphasia

Patients with semantic aphasia have impaired control of semantic retrieval, often accompanied by executive dysfunction following left hemisphere stroke. Many but not all of these patients have damage to the left inferior frontal gyrus, important for semantic and cognitive control. Yet semantic and cognitive control networks are highly distributed, including posterior as well as anterior components. Accordingly, semantic aphasia might not only reflect local damage but also white matter structural and functional disconnection. Here we characterise the lesions and predicted patterns of structural and functional disconnection in individuals with semantic aphasia and relate these effects to semantic and executive impairment. Impaired semantic cognition was associated with infarction in distributed left- hemisphere regions, including in the left anterior inferior frontal and posterior temporal cortex. Lesions were associated with executive dysfunction within a set of adjacent but distinct left frontoparietal clusters. Performance on executive tasks was also associated with interhemispheric structural disconnection across the corpus callosum. In contrast, poor semantic cognition was associated with small left-lateralized structurally disconnected clusters, including in the left posterior temporal cortex. Little insight was gained from functional disconnection symptom mapping. These results demonstrate that while left- lateralized semantic and executive control regions are often damaged together in stroke aphasia, these deficits are associated with distinct patterns of structural disconnection, consistent with the bilateral nature of executive control and the left-lateralized yet distributed semantic control network.

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bioRxiv2021

Couching the brain's multiple-demand and language-specific systems within a macroscale gradient of cortical connectivity

Semantic control is the capability to operate on meaningful representations, selectively focusing on certain aspects of meaning while purposefully ignoring other aspects based on ones behavioural aim. This ability is especially vital for comprehending figurative/ambiguous language. It remains unclear, at the topographical level, why/how regions involved in semantic control seem reliably juxtaposed alongside other functionally specialised regions in the association cortex. We investigated this issue by characterising 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 confirmed 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 a preference for cognitively demanding processing (multiple-demand) and a preference for meaningful representations (default-mode) into a domain-specific preference for difficult operations 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.

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bioRxiv2021

The Unique Cytoarchitecture and Wiring of the Human Default Mode Network

The default mode network (DMN) is implicated in many aspects of complex thought and behavior. Here, we leverage post-mortem histology and in vivo neuroimaging to characterise the anatomy of the DMN to better understand its role in information processing and cortical communication. Our results show that the DMN is cytoarchitecturally heterogenous, containing cytoarchitectural types that are variably specialised for unimodal, heteromodal, and memory-related processing. Studying diffusion-based structural connectivity in combination with cytoarchitecture, we found the DMN contains regions receptive to input from sensory cortex and a core that is relatively insulated from environmental input. Finally, analysis of signal flow with effective connectivity models showed that the DMN is unique amongst cortical networks in balancing its output across the levels of sensory hierarchies. Together, our study establishes an anatomical foundation from which mechanistic accounts of the broad role the DMN plays in human brain function and cognition can be developed.

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bioRxiv2021

Motivated semantic control: Exploring the effects of extrinsic reward and self-reference on semantic retrieval in semantic aphasia

Recent insights show increased motivation can benefit executive control, but this effect has not been explored in relation to semantic cognition. Patients with deficits of controlled semantic retrieval in the context of semantic aphasia (SA) after stroke may benefit from this approach since semantic control is considered an executive process. Deficits in this domain are partially distinct from domain-general deficits of cognitive control. We assessed the effect of both extrinsic and intrinsic motivation in healthy controls and semantic aphasia patients. Experiment 1 manipulated extrinsic reward using high or low levels of points for correct responses during a semantic association task. Experiment 2 manipulated the intrinsic value of items using self-reference; allocating pictures of items to the participant ( self) or researcher ( other) in a shopping game before people retrieved their semantic associations. These experiments revealed that patients, but not controls, showed better performance when given an extrinsic reward, consistent with the view that increased external motivation may help to ameliorate patients semantic control deficits. However, while self-reference was associated with better episodic memory, there was no effect on semantic retrieval. We conclude that semantic control deficits can be reduced when extrinsic rewards are anticipated; this enhanced motivational state is expected to support proactive control, for example, through the maintenance of task representations. It may be possible to harness this modulatory impact of reward to combat the control demands of semantic tasks in SA patients.

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bioRxiv2021

Context Free and Context-Dependent Conceptual Representation in the Temporal Lobes

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.

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bioRxiv2021

A tale of two gradients: Differences between the left and right hemispheres predict semantic cognition and visual reasoning

Decomposition of whole-brain functional connectivity patterns reveals a principal gradient that captures the separation of sensorimotor cortex from heteromodal regions in the default mode network (DMN); this gradient captures the systematic order of networks on the cortical surface. Functional homotopy is strongest in sensorimotor areas, and weakest in heteromodal cortices, suggesting there may be differences between the left and right hemispheres (LH/RH) in the principal gradient, especially towards its apex. This study characterised hemispheric differences in the position of large-scale cortical networks along the principal gradient, and their functional significance. We collected resting-state fMRI and semantic and non-verbal reasoning task performance in 175+ healthy volunteers. We then extracted the principal gradient of connectivity for each participant and tested which networks showed significant hemispheric differences in gradient value. We investigated the functional associations of these differences by regressing participants behavioural efficiency in tasks outside the scanner against their interhemispheric gradient difference for each network. LH showed a higher overall principal gradient value, consistent with its role in heteromodal semantic cognition. One frontotemporal control subnetwork was linked to individual differences in semantic cognition: when it was nearer heteromodal DMN on the principal gradient in LH, participants showed more efficient semantic retrieval. In contrast, when a dorsal attention subnetwork was closer to the heteromodal end of the principal gradient in RH, participants showed better visual reasoning. Lateralization of function may reflect differences in connectivity between control and heteromodal regions in LH, and attention and visual regions in RH.

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bioRxiv2020

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.

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bioRxiv2020

A structure-function substrate of memory for spatial configurations in medial and lateral temporal cortices

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

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bioRxiv2020

Distinct default mode network subsystems show similarities and differences in the effect of task focus across reading and autobiographical memory

While reading, the mind can wander to unrelated autobiographical information, creating a perceptually-decoupled state detrimental to narrative comprehension. To understand how this mind-wandering state emerges, we asked whether retrieving autobiographical content necessitates functional disengagement from visual input. In Experiment 1, brain activity was recorded using functional magnetic resonance imaging (fMRI) in an experimental situation mimicking naturally occurring mind-wandering, allowing us to precisely delineate neural regions involved in memory and reading. Individuals read expository texts and ignored personally relevant autobiographical memories, as well as the opposite situation. Medial regions of the default mode network (DMN) were recruited during memory retrieval. In contrast, left temporal and lateral prefrontal regions of the DMN, as well as ventral visual cortex, were recruited when reading for comprehension. Experiment 2 used functional connectivity at rest to establish that (i) DMN regions linked to memory are more functionally decoupled from regions of ventral visual cortex than regions in the same network engaged when reading, and (ii) individuals reporting more mind-wandering and worse comprehension, while reading in the lab, showed increased functional decoupling between visually-connected DMN sites important for reading and a region of dorsal occipital cortex linked to autobiographical memory in Experiment 1. These data suggest we lose track of the narrative when our mind wanders because the generation of autobiographical mental content relies on cortical regions within the DMN which are functionally decoupled from ventral visual regions engaged during reading. Significance statementWhen the mind wanders during reading, we lose track of information from the narrative. We hypothesised that poor comprehension occurs because retrieving autobiographical memories reduces the perceptual coupling necessary to understand written words. We show that default mode network (DMN) areas involved in reading are functionally more connected to ventral visual regions than DMN regions important for autobiographical memory. Furthermore, individuals who mind-wander more, and comprehend less, have weaker connectivity between visually-coupled DMN regions linked to reading and dorsal occipital areas linked to autobiographical memory. These data suggest that when our minds wander during reading, retrieval of personally-relevant information activates DMN regions that are functionally disconnected from visual input, creating a perceptually decoupled state detrimental to comprehension.

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bioRxiv2020

Exploring patterns of ongoing thought under naturalistic and task-based conditions

Previous research suggests that patterns of ongoing thought are heterogeneous, varying across situations and individuals. The current study investigated the influence of a wide range of tasks and individual affective style on ongoing patterns of thought. In total, we used 9 different tasks and measured ongoing thought using multidimensional experience sampling. A Principle Component Analysis of the experience sampling data revealed four patterns of ongoing thought. Linear Mixed Modelling was used to examine the contextual distribution of the thought patterns. Different thought patterns were found to relate to different types of conditions. Intrusive and negative thought pattern expression was found to be influenced by individual affective style (depression level). Overall, these data show that patterns of thought are subject to both contextual and intrinsic variation, suggesting that understanding these important features of experience across a broad range of situations will be useful in understanding their role in human experience. HighlightsO_LIPatterns of thought vary across different task contexts C_LIO_LIThought pattern expression is influenced by individual affective style C_LIO_LIThere is a need to broaden the tasks used to study ongoing thought C_LI

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bioRxiv2020

Individual Differences in the Connectivity of Left and Right Anterior Temporal Lobes Relate to Modality and Category Effects in Semantic Categorisation

Contemporary neuroscientific accounts suggest that ventral anterior temporal lobe (ATL) regions act as a bilateral heteromodal semantic hub. However, research also shows graded functional differences between the hemispheres relating to linguistic versus non-linguistic semantic tasks and to knowledge of objects versus people. Individual differences in connectivity from bilateral ATL and between left and right ATL might therefore give rise to differences in function within this system. We investigated whether the relative strength of intrinsic connectivity from left and right ATL would relate to differences in performance on semantic tasks. We examined resting-state fMRI in 74 individuals and, in a separate session, examined semantic categorisation, manipulating stimulus type (famous faces versus landmarks) and modality of presentation (visual versus verbal). We found that people with greater connectivity between left and right ATL were more efficient at categorising landmarks, especially when these were presented visually. In addition, participants who showed stronger connectivity from right than left ATL to medial occipital cortex showed more efficient semantic categorisation of landmarks regardless of modality of presentation. These findings show that individual differences in the intrinsic connectivity of left and right ATL are associated with effects of category and modality in semantic categorisation. The results can be interpreted in terms of graded differences in the strengths of inputs from spoke regions, such as regions of visual cortex, to a bilateral yet partially segregated semantic hub, encompassing left and right ATL.

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bioRxiv2020

A gradient from long-term memory to novel cognition: graded 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 gradient from unimodal regions of sensorimotor cortex, through executive regions to transmodal default 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. Functional magnetic resonance imaging found that as decisions are made in an increasingly familiar context, the BOLD signal follows this neural gradient, with stronger responses in default regions when items are linked in long-term memory. In this way, neural organization is optimized to support decision-making in both highly familiar and less familiar situations.

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bioRxiv2020

Missing the forest because of the trees: Slower alternations during binocular rivalry are associated with lower levels of visual detail

Conscious awareness of the world fluctuates, either through variation in the quality with which we perceive the environment, or, when attention switches to information generated using imagination rather than the external environment. Our study combined individual differences in experience sampling, psychophysical reports of perception, and neuroimaging descriptions of structural connectivity, to better understand these changes in conscious awareness. In particular, we (a) examined if aspects of ongoing thought, as measured by multi-dimensional experience sampling during a sustained attention task, are associated with the white matter fibre organization of the cortex as reflected by their relative degree of anisotropic diffusion, and (b) whether these neuro-cognitive descriptions of ongoing experience are related to a more constrained measure of visual consciousness provided by the analysis of bistable perception during binocular rivalry. Individuals with greater fractional anisotropy (FA) in right hemisphere white matter regions involving the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus and the cortico-spinal tract, described their ongoing thoughts as lacking external details. Subsequent analysis indicated that the combination of low FA in these right hemisphere regions, with reports of high level external details, was associated with the shortest periods of dominance during binocular rivalry. Since variation in binocular rivalry reflects differences between bottom-up and top-down influences on vision, our study suggests that reports of ongoing thoughts with vivid external details may occur when conscious precedence is given to bottom-up representation of perceptual information and that this may partly be rooted in the white matter fibre organization of the cortex.

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