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.

Systematic evaluation of high-level visual deficits and lesions in posterior cerebral artery stroke.

Knowledge about the consequences of stroke on high-level vision comes primarily from single case studies of patients selected based on their behavioural profiles, typically patients with specific stroke syndromes like pure alexia or prosopagnosia. There are, however, no systematic, detailed, large-scale evaluations of the more typical clinical behavioural and lesion profiles of impairments in high-level vision after posterior cerebral artery stroke. We present behavioural and lesion data from the Back of the Brain project, to date the largest (N = 64) and most detailed examination of patients with cortical posterior cerebral artery strokes selected based on lesion location. The aim of the current study was to relate behavioural performance with faces, objects and written words to lesion data through two complementary analyses: (i) a multivariate multiple regression analysis to establish the relationships between lesion volume, lesion laterality and the presence of a bilateral lesion with performance and (ii) a voxel-based correlational methodology analysis to establish whether there are distinct or separate regions within the posterior cerebral artery territory that underpin the visual processing of words, faces and objects. Behaviourally, most patients showed more general deficits in high-level vision (n = 22) or no deficits at all (n = 21). Category-selective deficits were rare (n = 6) and were only found for words. Overall, total lesion volume was most strongly related to performance across all three domains. While behavioural impairments in all domains were observed following unilateral left and right as well as bilateral lesions, the regions most strongly related to performance mainly confirmed the pattern reported in more selective cases. For words, these included a left hemisphere cluster extending from the occipital pole along the fusiform and lingual gyri; for objects, bilateral clusters which overlapped with the word cluster in the left occipital lobe. Face performance mainly correlated with a right hemisphere cluster within the white matter, partly overlapping with the object cluster. While the findings provide partial support for the relative laterality of posterior brain regions supporting reading and face processing, the results also suggest that both hemispheres are involved in the visual processing of faces, words and objects.

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.

Implicit, automatic semantic word categorisation in the left occipito-temporal cortex as revealed by fast periodic visual stimulation.

Conceptual knowledge allows the categorisation of items according to their meaning beyond their physical similarities. This ability to respond to different stimuli (e.g., a leek, a cabbage, etc.) based on similar semantic representations (e.g., belonging to the vegetable category) is particularly important for language processing, because word meaning and the stimulus form are unrelated. The neural basis of this core human ability is debated and is complicated by the strong reliance of most neural measures on explicit tasks, involving many non-semantic processes. Here we establish an implicit method, i.e., fast periodic visual stimulation (FPVS) coupled with electroencephalography (EEG), to study neural conceptual categorisation processes with written word stimuli. Fourteen neurotypical participants were presented with different written words belonging to the same semantic category (e.g., different animals) alternating at 4 Hz rate. Words from a different semantic category (e.g., different cities) appeared every 4 stimuli (i.e., at 1 Hz). Following a few minutes of recording, objective electrophysiological responses at 1 Hz, highlighting the human brain's ability to implicitly categorize stimuli belonging to distinct conceptual categories, were found over the left occipito-temporal region. Topographic differences were observed depending on whether the periodic change involved living items, associated with relatively more ventro-temporal activity as compared to non-living items associated with relatively more dorsal posterior activity. Overall, this study demonstrates the validity and high sensitivity of an implicit frequency-tagged marker of word-based semantic memory abilities.

The neural bases of resilient semantic system: evidence of variable neuro-displacement in cognitive systems.

The purpose of this study was to explore an important research goal in cognitive and clinical neuroscience: What are the neurocomputational mechanisms that make cognitive systems "well engineered" and thus resilient across a range of performance demands and to mild levels of perturbation or even damage? A new hypothesis called 'variable neuro-displacement' suggests that cognitive systems are formed with dynamic, spare processing capacity, which balances energy consumption against performance requirements and can be resilient to changes in performance demands. Here, we tested this hypothesis by investigating the neural dynamics of the semantic system by manipulating performance demand. The performance demand was manipulated with two levels of task difficulty (easy vs. hard) in two different ways (stimulus type and response timing). We found that the demanding semantic processing increased regional activity in both the domain-specific semantic representational system (anterior temporal lobe) and the parallel executive control networks (prefrontal, posterior temporal, and parietal regions). Functional connectivity between these regions was also increased during demanding semantic processing and these increases were related to better semantic task performance. Our results suggest that semantic cognition is made resilient by flexible, dynamic changes including increased regional activity and functional connectivity across both domain-specific and domain-general systems. It reveals the intrinsic resilience-related mechanisms of semantic cognition, mimicking alterations caused by perturbation or brain damage. Our findings provide a strong implication that the intrinsic mechanisms of a well-engineered semantic system might be attributed to the compensatory functional alterations in the impaired brain.

Category-selective deficits are the exception and not the rule: Evidence from a case-series of 64 patients with ventral occipito-temporal cortex damage.

The organisational principles of the visual ventral stream are still highly debated, particularly the relative association/dissociation between word and face recognition and the degree of lateralisation of the underlying processes. Reports of dissociations between word and face recognition stem from single case-studies of category selective impairments, and neuroimaging investigations of healthy participants. Despite the historical reliance on single case-studies, more recent group studies have highlighted a greater commonality between word and face recognition. Studying individual patients with rare selective deficits misses (a) important variability between patients, (b) systematic associations between task performance, and (c) patients with mild, severe and/or non-selective impairments; meaning that the full spectrum of deficits is unknown. The Back of the Brain project assessed the range and specificity of visual perceptual impairment in 64 patients with posterior cerebral artery stroke recruited based on lesion localization and not behavioural performance. Word, object, and face processing were measured with comparable tests across different levels of processing to investigate associations and dissociations across domains. We present two complementary analyses of the extensive behavioural battery: (1) a data-driven analysis of the whole patient group, and (2) a single-subject case-series analysis testing for deficits and dissociations in each individual patient. In both analyses, the general organisational principle was of associations between words, objects, and faces even following unilateral lesions. The majority of patients either showed deficits across all domains or in no domain, suggesting a spectrum of visuo-perceptual deficits post stroke. Dissociations were observed, but they were the exception and not the rule: Category-selective impairments were found in only a minority of patients, all of whom showed disproportionate deficits for words. Interestingly, such selective word impairments were found following both left and right hemisphere lesions. This large-scale investigation of posterior cerebral artery stroke patients highlights the bilateral representation of visual perceptual function.

Intrinsic connectivity of anterior temporal lobe relates to individual differences in semantic retrieval for landmarks.

Contemporary neuroscientific accounts suggest that ventral anterior temporal lobe (ATL) acts as a bilateral heteromodal semantic hub, which is particularly critical for the specific-level knowledge needed to recognise unique entities, such as familiar landmarks and faces. There may also be graded functional differences between left and right ATL, relating to effects of modality (linguistic versus non-linguistic) and category (e.g., knowledge of people and places). Individual differences in intrinsic connectivity from left and right ATL might be associated with variation in semantic categorisation performance across these categories and modalities. We recorded resting-state fMRI in 74 individuals and, in a separate session, examined semantic categorisation. People with greater connectivity between left and right ATL were more efficient at categorising landmarks (e.g., Eiffel Tower), 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 results can be interpreted in terms of graded differences in the patterns of connectivity across left and right ATL, which give rise to a bilateral yet partially segregated semantic 'hub'. More specifically, right ATL connectivity supports the efficient semantic categorisation of landmarks.

The Architect Who Lost the Ability to Imagine: The Cerebral Basis of Visual Imagery.

While the loss of mental imagery following brain lesions was first described more than a century ago, the key cerebral areas involved remain elusive. Here we report neuropsychological data from an architect (PL518) who lost his ability for visual imagery following a bilateral posterior cerebral artery (PCA) stroke. We compare his profile to three other patients with bilateral PCA stroke and another architect with a large PCA lesion confined to the right hemisphere. We also compare structural images of their lesions, aiming to delineate cerebral areas selectively lesioned in acquired aphantasia. When comparing the neuropsychological profile and structural magnetic resonance imaging (MRI) for the aphantasic architect PL518 to patients with either a comparable background (an architect) or bilateral PCA lesions, we find: (1) there is a large overlap of cognitive deficits between patients, with the very notable exception of aphantasia which only occurs in PL518, and (2) there is large overlap of the patients' lesions. The only areas of selective lesion in PL518 is a small patch in the left fusiform gyrus as well as part of the right lingual gyrus. We suggest that these areas, and perhaps in particular the region in the left fusiform gyrus, play an important role in the cerebral network involved in visual imagery.

Revealing the Dynamic Modulations That Underpin a Resilient Neural Network for Semantic Cognition: An fMRI Investigation in Patients With Anterior Temporal Lobe Resection.

One critical feature of any well-engineered system is its resilience to perturbation and minor damage. The purpose of the current study was to investigate how resilience is achieved in higher cognitive systems, which we explored through the domain of semantic cognition. Convergent evidence implicates the bilateral anterior temporal lobes (ATLs) as a conceptual knowledge hub. While bilateral damage to this region produces profound semantic impairment, unilateral atrophy/resection or transient perturbation has a limited effect. Two neural mechanisms might underpin this resilience to unilateral ATL damage: 1) the undamaged ATL upregulates its activation in order to compensate; and/or 2) prefrontal regions involved in control of semantic retrieval upregulate to compensate for the impoverished semantic representations that follow from ATL damage. To test these possibilities, 34 postsurgical temporal lobe epilepsy patients and 20 age-matched controls were scanned whilst completing semantic tasks. Pictorial tasks, which produced bilateral frontal and temporal activation, showed few activation differences between patients and control participants. Written word tasks, however, produced a left-lateralized activation pattern and greater differences between the groups. Patients with right ATL resection increased activation in left inferior frontal gyrus (IFG). Patients with left ATL resection upregulated both the right ATL and right IFG. Consistent with recent computational models, these results indicate that 1) written word semantic processing in patients with ATL resection is supported by upregulation of semantic knowledge and control regions, principally in the undamaged hemisphere, and 2) pictorial semantic processing is less affected, presumably because it draws on a more bilateral network.

Concrete versus abstract forms of social concept: an fMRI comparison of knowledge about people versus social terms.

The anterior temporal lobes (ATLs) play a key role in conceptual knowledge representation. The hub-and-spoke theory suggests that the contribution of the ATLs to semantic representation is (a) transmodal, i.e. integrating information from multiple sensorimotor and verbal modalities, and (b) pan-categorical, representing concepts from all categories. Another literature, however, suggests that this region's responses are modality- and category-selective; prominent examples include category selectivity for socially relevant concepts and face recognition. The predictions of each approach have never been directly compared. We used data from three studies to compare category-selective responses within the ATLs. Study 1 compared ATL responses to famous people versus another conceptual category (landmarks) from visual versus auditory inputs. Study 2 compared ATL responses to famous people from pictorial and written word inputs. Study 3 compared ATL responses to a different kind of socially relevant stimuli, namely abstract non-person-related words, in order to ascertain whether ATL subregions are engaged for social concepts more generally or only for person-related knowledge. Across all three studies a dominant bilateral ventral ATL cluster responded to all categories in all modalities. Anterior to this 'pan-category' transmodal region, a second cluster responded more weakly overall yet selectively for people, but did so equally for spoken names and faces (Study 1). A third region in the anterior superior temporal gyrus responded selectively to abstract socially relevant words (Study 3), but did not respond to concrete socially relevant words (i.e. written names; Study 2). These findings can be accommodated by the graded hub-and-spoke model of concept representation. On this view, the ventral ATL is the centre point of a bilateral ATL hub, which contributes to conceptual representation through transmodal distillation of information arising from multiple modality-specific association cortices. Partial specialization occurs across the graded ATL hub as a consequence of gradedly differential connectivity across the region.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.

The Roles of Left Versus Right Anterior Temporal Lobes in Semantic Memory: A Neuropsychological Comparison of Postsurgical Temporal Lobe Epilepsy Patients.

The presence and degree of specialization between the anterior temporal lobes (ATLs) is a key issue in debates about the neural architecture of semantic memory. Here, we comprehensively assessed multiple aspects of semantic cognition in a large group of postsurgical temporal lobe epilepsy (TLE) patients with left versus right anterior temporal lobectomy (n = 40). Both subgroups showed deficits in expressive and receptive verbal semantic tasks, word and object recognition, naming and recognition of famous faces and perception of faces and emotions. Graded differences in performance between the left and right groups were secondary to the overall mild semantic impairment; primarily, left resected TLE patients showed weaker performance on tasks that required naming or accessing semantic information from a written word. Right resected TLE patients were relatively more impaired at recognizing famous faces as familiar, although this effect was observed less consistently. These findings unify previous partial, inconsistent results and also align directly with fMRI and transcranial magnetic stimulation results in neurologically intact participants. Taken together, these data support a model in which the 2 ATLs act as a coupled bilateral system for the representation of semantic knowledge, and in which graded hemispheric specializations emerge as a consequence of differential connectivity to lateralized speech production and face perception regions.

An emergent functional parcellation of the temporal cortex.

The temporal lobe has been associated with various cognitive functions which include memory, auditory cognition and semantics. However, at a higher level of conceptualisation, all of the functions associated with the temporal lobe can be considered as lying along one major axis; from modality-specific to modality-general processing. This paper used a spectral reordering technique on resting-state and task-based functional data to extract the major organisational axis of the temporal lobe in a bottom-up, data-driven fashion. Independent parcellations were performed on resting-state scans from 71 participants and active semantic task scans from 23 participants acquired using dual echo gradient echo planar imaging in order to preserve signal in inferior temporal cortex. The resulting organisational axis was consistent (over dataset and hemisphere) and progressed from superior temporal gyrus and posterior inferior temporal cortex to ventrolateral anterior temporal cortex. A hard parcellation separated a posterior (superior temporal and posterior fusiform and inferior temporal gyri) and an anterior cluster (ventrolateral anterior temporal lobe). The functional connectivity of the hard clusters supported the hypothesis that the connectivity gradient separated modality-specific and modality-general regions. This hypothesis was then directly tested by performing a VOI analysis upon an independent semantic task-based data set including auditory and visually presented stimuli. This confirmed that the ventrolateral anterior aspects of the temporal lobe are associated with modality-general processes whilst posterior and superior aspects are specific to certain modalities, with the posterior inferior subregions involved in visual processes and superior regions involved in audition.

Distinct but Overlapping Patterns of Response to Words and Faces in the Fusiform Gyrus.

Converging evidence suggests that the fusiform gyrus is involved in the processing of both faces and words. We used fMRI to investigate the extent to which the representation of words and faces in this region of the brain is based on a common neural representation. In Experiment 1, a univariate analysis revealed regions in the fusiform gyrus that were only selective for faces and other regions that were only selective for words. However, we also found regions that showed both word-selective and face-selective responses, particularly in the left hemisphere. We then used a multivariate analysis to measure the pattern of response to faces and words. Despite the overlap in regional responses, we found distinct patterns of response to both faces and words in the left and right fusiform gyrus. In Experiment 2, fMR adaptation was used to determine whether information about familiar faces and names is integrated in the fusiform gyrus. Distinct regions of the fusiform gyrus showed adaptation to either familiar faces or familiar names. However, there was no adaptation to sequences of faces and names with the same identity. Taken together, these results provide evidence for distinct, but overlapping, neural representations for words and faces in the fusiform gyrus.

Graded specialization within and between the anterior temporal lobes.

Considerable evidence from different methodologies has identified the anterior temporal lobes (ATLs) as key regions for the representation of semantic knowledge. Research interest is now shifting to investigate the roles of different ATL subregions in semantic representation, with particular emphasis on the functions of the left versus right ATLs. In this review, we provide evidence for graded specializations both between and within the ATLs. We argue (1) that multimodal, pan-category semantic representations are supported jointly by both left and right ATLs, yet (2) that the ATLs are not homogeneous in their function. Instead, subtle functional gradations both between and within the ATLs emerge as a consequence of differential connectivity with primary sensory/motor/limbic regions. This graded specialization account of semantic representation provides a compromise between theories that posit no differences between the functions of the left and right ATLs and those that posit that the left and right ATLs are entirely segregated in function. Evidence for this graded account comes from converging sources, and its benefits have been exemplified in formal computational models. We propose that this graded principle is not only a defining feature of the ATLs but is also a more general neurocomputational principle found throughout the temporal lobes.

Low-level properties of natural images predict topographic patterns of neural response in the ventral visual pathway.

Neuroimaging research over the past 20 years has begun to reveal a picture of how the human visual system is organized. A key distinction that has arisen from these studies is the difference in the organization of low-level and high-level visual regions. Low-level regions contain topographic maps that are tightly linked to properties of the image. In contrast, high-level visual areas are thought to be arranged in modules that are tightly linked to categorical or semantic information in the image. To date, an unresolved question has been how the strong functional selectivity for object categories in high-level visual regions might arise from the image-based representations found in low-level visual regions. Here, we review recent evidence suggesting that patterns of response in high-level visual areas may be better explained by response to image properties that are characteristic of different object categories.

The Roles of Left Versus Right Anterior Temporal Lobes in Conceptual Knowledge: An ALE Meta-analysis of 97 Functional Neuroimaging Studies.

The roles of the right and left anterior temporal lobes (ATLs) in conceptual knowledge are a source of debate between 4 conflicting accounts. Possible ATL specializations include: (1) Processing of verbal versus non-verbal inputs; (2) the involvement of word retrieval; and (3) the social content of the stimuli. Conversely, the "hub-and-spoke" account holds that both ATLs form a bilateral functionally unified system. Using activation likelihood estimation (ALE) to compare the probability of left and right ATL activation, we analyzed 97 functional neuroimaging studies of conceptual knowledge, organized according to the predictions of the three specialized hypotheses. The primary result was that ATL activation was predominately bilateral and highly overlapping for all stimulus types. Secondary to this bilateral representation, there were subtle gradations both between and within the ATLs. Activations were more likely to be left lateralized when the input was a written word or when word retrieval was required. These data are best accommodated by a graded version of the hub-and-spoke account, whereby representation of conceptual knowledge is supported through bilateral yet graded connectivity between the ATLs and various modality-specific sensory, motor, and limbic cortices.

Low-level image properties of visual objects predict patterns of neural response across category-selective regions of the ventral visual pathway.

Neuroimaging studies have revealed strong selectivity for object categories in high-level regions of the human visual system. However, it is unknown whether this selectivity is truly based on object category, or whether it reflects tuning for low-level features that are common to images from a particular category. To address this issue, we measured the neural response to different object categories across the ventral visual pathway. Each object category elicited a distinct neural pattern of response. Next, we compared the patterns of neural response between object categories. We found a strong positive correlation between the neural patterns and the underlying low-level image properties. Importantly, this correlation was still evident when the within-category correlations were removed from the analysis. Next, we asked whether basic image properties could also explain variation in the pattern of response to different exemplars from one object category (faces). A significant correlation was also evident between the similarity of neural patterns of response and the low-level properties of different faces, particularly in regions associated with face processing. These results suggest that the appearance of category-selective regions at this coarse scale of representation may be explained by the systematic convergence of responses to low-level features that are characteristic of each category.