A neuroanatomical and cognitive model of impaired social behaviour in frontotemporal dementia.

Impaired social cognition is a core deficit in frontotemporal dementia (FTD). It is most commonly associated with the behavioural-variant of FTD, with atrophy of the orbitofrontal and ventromedial prefrontal cortex. Social cognitive changes are also common in semantic dementia, with atrophy centred on the anterior temporal lobes. The impairment of social behaviour in FTD has typically been attributed to damage to the orbitofrontal cortex and/or temporal poles and/or the uncinate fasciculus that connects them. However, the relative contributions of each region are unresolved. In this Review, we present a unified neurocognitive model of controlled social behaviour that not only explains the observed impairment of social behaviours in FTD, but also assimilates both consistent and potentially contradictory findings from other patient groups, comparative neurology and normative cognitive neuroscience. We propose that impaired social behaviour results from damage to two cognitively- and anatomically-distinct components. The first component is social-semantic knowledge, a part of the general semantic-conceptual system supported by the anterior temporal lobes bilaterally. The second component is social control, supported by the orbitofrontal cortex, medial frontal cortex and ventrolateral frontal cortex, which interacts with social-semantic knowledge to guide and shape social behaviour.

Semantic-specific and domain-general mechanisms for integration and update of contextual information.

Recent research has highlighted the importance of domain-general processes and brain regions for language and semantic cognition. Yet, this has been mainly observed in executively demanding tasks, leaving open the question of the contribution of domain-general processes to natural language and semantic cognition. Using fMRI, we investigated whether neural processes reflecting context integration and context update-two key aspects of naturalistic language and semantic processing-are domain-specific versus domain-general. Thus, we compared neural responses during the integration of contextual information across semantic and non-semantic tasks. Whole-brain results revealed both shared (left posterior-dorsal inferior frontal gyrus, left posterior inferior temporal gyrus, and left dorsal angular gyrus/intraparietal sulcus) and distinct (left anterior-ventral inferior frontal gyrus, left anterior ventral angular gyrus, left posterior middle temporal gyrus for semantic control only) regions involved in context integration and update. Furthermore, data-driven functional connectivity analysis clustered domain-specific versus domain-general brain regions into distinct but interacting functional neural networks. These results provide a first characterisation of the neural processes required for context-dependent integration during language processing along the domain-specificity dimension, and at the same time, they bring new insights into the role of left posterior lateral temporal cortex and left angular gyrus for semantic cognition.

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.

Distance-dependent distribution thresholding in probabilistic tractography.

Tractography is widely used in human studies of connectivity with respect to every brain region, function, and is explored developmentally, in adulthood, ageing, and in disease. However, the core issue of how to systematically threshold, taking into account the inherent differences in connectivity values for different track lengths, and to do this in a comparable way across studies has not been solved. By utilising 54 healthy individuals' diffusion-weighted image data taken from HCP, this study adopted Monte Carlo derived distance-dependent distributions (DDDs) to generate distance-dependent thresholds with various levels of alpha for connections of varying lengths. As a test case, we applied the DDD approach to generate a language connectome. The resulting connectome showed both short- and long-distance structural connectivity in the close and distant regions as expected for the dorsal and ventral language pathways, consistent with the literature. The finding demonstrates that the DDD approach is feasible to generate data-driven DDDs for common thresholding and can be used for both individual and group thresholding. Critically, it offers a standard method that can be applied to various probabilistic tracking datasets.

Verbal fluency tests assess global cognitive status but have limited diagnostic differentiation: evidence from a large-scale examination of six neurodegenerative diseases.

Verbal fluency is widely used as a clinical test, but its utility in differentiating between neurodegenerative dementias and progressive aphasias, and from healthy controls, remains unclear. We assessed whether various measures of fluency performance could differentiate between Alzheimer's disease, behavioural variant of frontotemporal dementia, non-fluent and semantic variants of primary progressive aphasia, progressive supranuclear palsy, corticobasal syndrome and healthy controls. Category and letter fluency tasks were administered to 33 controls and 139 patients at their baseline clinical visit. We assessed group differences for total number of words produced, psycholinguistic word properties and associations between production order and exemplar psycholinguistic properties. Receiver operating characteristic curves determined which measure could best discriminate patient groups and controls. The total word count distinguished controls from all patient groups, but neither this measure nor the word properties differentiated the patient groups. Receiver operating characteristic curves revealed that, when comparing controls to patients, the strongest discriminators were total word count followed by word frequency. Word frequency was the strongest discriminator for semantic variant of primary progressive aphasia versus other groups. Fluency word counts were associated with global severity as measured by Addenbrooke's Cognitive Examination Revised. Verbal fluency is an efficient test for assessing global brain-cognitive health but has limited utility in differentiating between cognitively and anatomically disparate patient groups. This outcome is consistent with the fact that verbal fluency requires many different aspects of higher cognition and language.

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.

Mapping behavioural, cognitive and affective transdiagnostic dimensions in frontotemporal dementia.

Two common clinical variants of frontotemporal dementia are the behavioural variant frontotemporal dementia, presenting with behavioural and personality changes attributable to prefrontal atrophy, and semantic dementia, displaying early semantic dysfunction primarily due to anterior temporal degeneration. Despite representing independent diagnostic entities, mounting evidence indicates overlapping cognitive-behavioural profiles in these syndromes, particularly with disease progression. Why such overlap occurs remains unclear. Understanding the nature of this overlap, however, is essential to improve early diagnosis, characterization and management of those affected. Here, we explored common cognitive-behavioural and neural mechanisms contributing to heterogeneous frontotemporal dementia presentations, irrespective of clinical diagnosis. This transdiagnostic approach allowed us to ascertain whether symptoms not currently considered core to these two syndromes are present in a significant proportion of cases and to explore the neural basis of clinical heterogeneity. Sixty-two frontotemporal dementia patients (31 behavioural variant frontotemporal dementia and 31 semantic dementia) underwent comprehensive neuropsychological, behavioural and structural neuroimaging assessments. Orthogonally rotated principal component analysis of neuropsychological and behavioural data uncovered eight statistically independent factors explaining the majority of cognitive-behavioural performance variation in behavioural variant frontotemporal dementia and semantic dementia. These factors included Behavioural changes, Semantic dysfunction, General Cognition, Executive function, Initiation, Disinhibition, Visuospatial function and Affective changes. Marked individual-level overlap between behavioural variant frontotemporal dementia and semantic dementia was evident on the Behavioural changes, General Cognition, Initiation, Disinhibition and Affective changes factors. Compared to behavioural variant frontotemporal dementia, semantic dementia patients displayed disproportionate impairment on the Semantic dysfunction factor, whereas greater impairment on Executive and Visuospatial function factors was noted in behavioural variant frontotemporal dementia. Both patient groups showed comparable magnitude of atrophy to frontal regions, whereas severe temporal lobe atrophy was characteristic of semantic dementia. Whole-brain voxel-based morphometry correlations with emergent factors revealed associations between fronto-insular and striatal grey matter changes with Behavioural, Executive and Initiation factor performance, bilateral temporal atrophy with Semantic dysfunction factor scores, parietal-subcortical regions with General Cognitive performance and ventral temporal atrophy associated with Visuospatial factor scores. Together, these findings indicate that cognitive-behavioural overlap (i) occurs systematically in frontotemporal dementia; (ii) varies in a graded manner between individuals and (iii) is associated with degeneration of different neural systems. Our findings suggest that phenotypic heterogeneity in frontotemporal dementia syndromes can be captured along continuous, multidimensional spectra of cognitive-behavioural changes. This has implications for the diagnosis of both syndromes amidst overlapping features as well as the design of symptomatic treatments applicable to multiple syndromes.

Decoding semantic representations in mind and brain.

A key goal for cognitive neuroscience is to understand the neurocognitive systems that support semantic memory. Recent multivariate analyses of neuroimaging data have contributed greatly to this effort, but the rapid development of these novel approaches has made it difficult to track the diversity of findings and to understand how and why they sometimes lead to contradictory conclusions. We address this challenge by reviewing cognitive theories of semantic representation and their neural instantiation. We then consider contemporary approaches to neural decoding and assess which types of representation each can possibly detect. The analysis suggests why the results are heterogeneous and identifies crucial links between cognitive theory, data collection, and analysis that can help to better connect neuroimaging to mechanistic theories of semantic cognition.

Colour perception deficits after posterior stroke: Not so rare after all?

Cerebral achromatopsia is an acquired colour perception impairment caused by brain injury, and is generally considered to be rare. Both hemispheres are thought to contribute to colour perception, but most published cases have had bilateral or right hemisphere lesions. In contrast to congenital colour blindness that affects the discrimination between specific hues, cerebral achromatopsia is often described as affecting perception across all colours. Most studies of cerebral achromatopsia have been single cases or case series of patients with colour perception deficits. Here, we explore colour perception deficits in an unbiased sample of patients with stroke affecting the posterior cerebral artery (N = 63) from the Back of the Brain project. Patients were selected based on lesion location only, and not on the presence of a given symptom. All patients were tested with the Farnsworth D-15 Dichotomous Colour Blindness Test and performance compared to matched controls (N = 45) using single case statistics. In patients with abnormal performance, the patterns of colour difficulties were qualitatively analysed. 22% of the patients showed significant problems with colour discrimination (44% of patients with bilateral lesions, 28% with left hemisphere lesions and 5% with right hemisphere lesions). Lesion analyses identified two regions in ventral occipital temporal areas in the left hemisphere as particularly strongly related to impaired performance in colour perception, but also indicated that bilateral lesions are more strongly associated with impaired performance that unilateral lesions. While some patients only had mild deficits, colour perception impairments were in many cases severe. Many patients had selective deficits only affecting the perception of some hues. The results suggest that colour perception difficulties following PCA stroke are common, and that they vary in severity and expression. In addition, the results point towards bilateral processing of colour perception with a left hemispheric domination, contradicting previous reports.

The cross-domain functional organization of posterior lateral temporal cortex: insights from ALE meta-analyses of 7 cognitive domains spanning 12,000 participants.

The posterior lateral temporal cortex is implicated in many verbal, nonverbal, and social cognitive domains and processes. Yet without directly comparing these disparate domains, the region's organization remains unclear; do distinct processes engage discrete subregions, or could different domains engage shared neural correlates and processes? Here, using activation likelihood estimation meta-analyses, the bilateral posterior lateral temporal cortex subregions engaged in 7 domains were directly compared. These domains comprised semantics, semantic control, phonology, biological motion, face processing, theory of mind, and representation of tools. Although phonology and biological motion were predominantly associated with distinct regions, other domains implicated overlapping areas, perhaps due to shared underlying processes. Theory of mind recruited regions implicated in semantic representation, tools engaged semantic control areas, and faces engaged subregions for biological motion and theory of mind. This cross-domain approach provides insight into how posterior lateral temporal cortex is organized and why.

Using in vivo functional and structural connectivity to predict chronic stroke aphasia deficits.

Focal brain damage caused by stroke can result in aphasia and advances in cognitive neuroscience suggest that impairment may be associated with network-level disorder rather than just circumscribed cortical damage. Several studies have shown meaningful relationships between brain-behaviour using lesions; however, only a handful of studies have incorporated in vivo structural and functional connectivity. Patients with chronic post-stroke aphasia were assessed with structural (n = 68) and functional (n = 39) MRI to assess whether predicting performance can be improved with multiple modalities and if additional variance can be explained compared to lesion models alone. These neural measurements were used to construct models to predict four key language-cognitive factors: (i) phonology; (ii) semantics; (iii) executive function; and (iv) fluency. Our results showed that each factor (except executive ability) could be significantly related to each neural measurement alone; however, structural and functional connectivity models did not explain additional variance above the lesion models. We did find evidence that the structural and functional predictors may be linked to the core lesion sites. First, the predictive functional connectivity features were found to be located within functional resting-state networks identified in healthy controls, suggesting that the result might reflect functionally specific reorganization (damage to a node within a network can result in disruption to the entire network). Second, predictive structural connectivity features were located within core lesion sites, suggesting that multimodal information may be redundant in prediction modelling. In addition, we observed that the optimum sparsity within the regularized regression models differed for each behavioural component and across different imaging features, suggesting that future studies should consider optimizing hyperparameters related to sparsity per target. Together, the results indicate that the observed network-level disruption was predicted by the lesion alone and does not significantly improve model performance in predicting the profile of language impairment.

Bipartite functional fractionation within the neural system for social cognition supports the psychological continuity of self versus other.

Research of social neuroscience establishes that regions in the brain's default-mode network (DN) and semantic network (SN) are engaged by socio-cognitive tasks. Research of the human connectome shows that DN and SN regions are both situated at the transmodal end of a cortical gradient but differ in their loci along this gradient. Here we integrated these 2 bodies of research, used the psychological continuity of self versus other as a "test-case," and used functional magnetic resonance imaging to investigate whether these 2 networks would encode social concepts differently. We found a robust dissociation between the DN and SN-while both networks contained sufficient information for decoding broad-stroke distinction of social categories, the DN carried more generalizable information for cross-classifying across social distance and emotive valence than did the SN. We also found that the overarching distinction of self versus other was a principal divider of the representational space while social distance was an auxiliary factor (subdivision, nested within the principal dimension), and this representational landscape was more manifested in the DN than in the SN. Taken together, our findings demonstrate how insights from connectome research can benefit social neuroscience and have implications for clarifying the 2 networks' differential contributions to social cognition.

Distinct but cooperating brain networks supporting semantic cognition.

Semantic cognition is a complex multifaceted brain function involving multiple processes including sensory, semantic, and domain-general cognitive systems. However, it remains unclear how these systems cooperate with each other to achieve effective semantic cognition. Here, we used independent component analysis (ICA) to investigate the functional brain networks that support semantic cognition. We used a semantic judgment task and a pattern-matching control task, each with 2 levels of difficulty, to disentangle task-specific networks from domain-general networks. ICA revealed 2 task-specific networks (the left-lateralized semantic network [SN] and a bilateral, extended semantic network [ESN]) and domain-general networks including the frontoparietal network (FPN) and default mode network (DMN). SN was coupled with the ESN and FPN but decoupled from the DMN, whereas the ESN was synchronized with the FPN alone and did not show a decoupling with the DMN. The degree of decoupling between the SN and DMN was associated with semantic task performance, with the strongest decoupling for the poorest performing participants. Our findings suggest that human higher cognition is achieved by the multiple brain networks, serving distinct and shared cognitive functions depending on task demands, and that the neural dynamics between these networks may be crucial for efficient semantic cognition.

A middle ground where executive control meets semantics: the neural substrates of semantic control are topographically sandwiched between the multiple-demand and default-mode systems.

Semantic control is the capability to operate on meaningful representations, selectively focusing on certain aspects of meaning while purposefully ignoring other aspects based on one's behavioral aim. This ability is especially vital for comprehending figurative/ambiguous language. It remains unclear why and how regions involved in semantic control seem reliably juxtaposed alongside other functionally specialized regions in the association cortex, prompting speculation about the relationship between topography and function. We investigated this issue by characterizing how semantic control regions topographically relate to the default-mode network (associated with memory and abstract cognition) and multiple-demand network (associated with executive control). Topographically, we established that semantic control areas were sandwiched by the default-mode and multi-demand networks, forming an orderly arrangement observed both at the individual and group level. Functionally, semantic control regions exhibited "hybrid" responses, fusing generic preferences for cognitively demanding operation (multiple-demand) and for meaningful representations (default-mode) into a domain-specific preference for difficult operation on meaningful representations. When projected onto the principal gradient of human connectome, the neural activity of semantic control showed a robustly dissociable trajectory from visuospatial control, implying different roles in the functional transition from sensation to cognition. We discuss why the hybrid functional profile of semantic control regions might result from their intermediate topographical positions on the cortex.

Attention to attention in aphasia - elucidating impairment patterns, modality differences and neural correlates.

It is increasingly acknowledged that patients with aphasia following a left-hemisphere stroke often have difficulties in other cognitive domains. One of these domains is attention, the very fundamental ability to detect, select, and react to the abundance of stimuli present in the environment. Basic and more complex attentional functions are usually distinguished, and a variety of tests has been developed to assess attentional performance at a behavioural level. Attentional performance in aphasia has been investigated previously, but often only one specific task, stimulus modality, or type of measure was considered and usually only group-level analyses or data based on experimental tasks were presented. Also, information on brain-behaviour relationships for this cognitive domain and patient group is scarce. We report detailed analyses on a comprehensive dataset including patients' performance on various subtests of two well-known, standardised neuropsychological test batteries assessing attention. These tasks allowed us to explore: 1) how many patients show impaired performance in comparison to normative data, in which tasks and on what measure; 2) how the different tasks and measures relate to each other and to patients' language abilities; 3) the neural correlates associated with attentional performance. Up to 32 patients with varying aphasia severity were assessed with subtests from the Test of Attentional Performance (TAP) as well as the Test of Everyday Attention (TEA). Performance was compared to normative data, relationships between attention measures and other background data were explored with principal component analyses and correlations, and brain-behaviour relationships were assessed by means of voxel-based correlational methodology. Depending on the task and measure, between 3 and 53 percent of the patients showed impaired performance compared to normative data. The highest proportion of impaired performance was noted for complex attention tasks involving auditory stimuli. Patients differed in their patterns of performance and only the performance in the divided attention tests was (weakly) associated with their overall language impairment. Principal components analyses yielded four underlying factors, each being associated with distinct neural correlates. We thus extend previous research in characterizing different aspects of attentional performance within one sample of patients with chronic post stroke aphasia. Performance on a broad range of attention tasks and measures was variable and largely independent of patients' language abilities, which underlines the importance of assessing this cognitive domain in aphasic patients. Notably, a considerable proportion of patients showed difficulties with attention allocation to auditory stimuli. The reasons for these potentially modality-specific difficulties are currently not well understood and warrant additional investigations.

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.

Efficient and effective assessment of deficits and their neural bases in stroke aphasia.

OBJECTIVE: Multi-assessment batteries are necessary for diagnosing and quantifying the multifaceted deficits observed post-stroke. Extensive batteries are thorough but impractically long for clinical settings or large-scale research studies. Clinically-targeted "shallow" batteries superficially cover a wide range of language skills relatively quickly but can struggle to identify mild deficits or quantify the impairment level. Our aim was to compare these batteries across a large group of chronic stroke aphasia and to test a novel data-driven reduced version of an extensive battery that maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure. METHODS: We tested 75 chronic left-sided stroke participants, spanning global to mild aphasia. The underlying structure of these three batteries was analysed using cross-validation and principal component analysis, in addition to univariate and multivariate lesion-symptom mapping. RESULTS: This revealed a four-factor solution for the extensive and data-reduced batteries, identifying phonology, semantic skills, fluency and executive function in contrast to a two-factor solution using the shallow battery (language severity and cognitive severity). Lesion symptom mapping using participants' factor scores identified convergent neural structures for phonology (superior temporal gyrus), semantics (inferior temporal gyrus), speech fluency (precentral gyrus) and executive function (lateral occipitotemporal cortex). The two shallow battery components converged with the phonology and executive function clusters. In addition, we show that multivariate models could predict the component scores using neural data, however not for every component. CONCLUSIONS: Overall, the data-driven battery appears to be an effective way to save time yet retain maintained sensitivity to mild impairment, ability to grade deficits and the underlying component structure observed in post-stroke aphasia.

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.

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.