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Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion-symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia.

Objectives: The few voxel-wise lesion-symptom mapping (VLSM) studies aimed at identifying the anatomy of executive function are limited by the absence of a model and by small populations. Using Trail Making Test (TMT) and verbal fluency and a model of their architectures, our objective was to identify the key structures underlying two major executive processes, set-shifting and strategic word search. Methods: We applied a validated VLSM analysis to harmonized cognitive and imaging data from 2009 ischemic stroke patients as a part of the Meta VCI Map consortium. All contrast analyses used an adjusted threshold with 2000 Freedman–Lane permutations (p ≤ 0.05). Results: The TMT parts A and B were associated with structures involved in visual-spatial processing, the motor system, the frontal lobes, and their subcortical connections. Set-shifting depended on the left dorsomedial frontal region. Both semantic and phonemic fluency tests depended on verbal output abilities and processing speed with similar slopes in different languages. The strategic search process depended on Broca's area, F2 and related tracts, temporal and deep regions. Lastly, the lesion map of set-shifting did not overlap with those of strategic word search processes. Interpretation: Our results identify the anatomical substrates of two main executive processes, revealing that they represent only a specific subpart of previously reported structures. Finally, our results indicate that executive functions depend on several specific, anatomically separable executive processes mainly operating in various parts of the frontal lobes. [ABSTRACT FROM AUTHOR]

Focal structural damage to white matter tracts can result in functional deficits in stroke patients. Traditional voxel‐based lesion‐symptom mapping is commonly used to localize brain structures linked to neurological deficits. Emerging evidence suggests that the impact of structural focal damage may extend beyond immediate lesion sites. In this study, we present a disconnectome mapping approach based on support vector regression (SVR) to identify brain structures and white matter pathways associated with functional deficits in stroke patients. For clinical validation, we utilized imaging data from 340 stroke patients exhibiting motor deficits. A disconnectome map was initially derived from lesions for each patient. Bootstrap sampling was then employed to balance the sample size between a minority group of patients exhibiting right or left motor deficits and those without deficits. Subsequently, SVR analysis was used to identify voxels associated with motor deficits (p <.005). Our disconnectome‐based analysis significantly outperformed alternative lesion‐symptom approaches in identifying major white matter pathways within the corticospinal tracts associated with upper–lower limb motor deficits. Bootstrapping significantly increased the sensitivity (80%–87%) for identifying patients with motor deficits, with a minimum lesion size of 32 and 235 mm3 for the right and left motor deficit, respectively. Overall, the lesion‐based methods achieved lower sensitivities compared with those based on disconnection maps. The primary contribution of our approach lies in introducing a bootstrapped disconnectome‐based mapping approach to identify lesion‐derived white matter disconnections associated with functional deficits, particularly efficient in handling imbalanced data. [ABSTRACT FROM AUTHOR]

An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention.

Ideomotor apraxia is a cognitive disorder most often resulting from acquired brain lesions (i.e., strokes or tumors). Neuroimaging and lesion studies have implicated several brain regions in praxis and apraxia, but most studies have described (sub)acute patients. This study aimed to extend previous research by analyzing data from 115 left hemisphere chronic stroke patients using the praxis subtest of the Western Aphasia Battery, which is divided into four action types: facial, upper limb, complex, and instrumental. Lesion–symptom mapping was used to identify brain regions most critically associated with difficulties in each of the four subtests. Complex and instrumental action deficits were associated with left precentral, postcentral, and superior parietal gyri (Brodmann areas 2, 3, 4, 5, and 6), while the facial and upper limb action deficits maps were restricted to left inferior, middle, and medial temporal gyri (Brodmann areas 20, 21, 22, and 48). We discuss ideas about neuroplasticity and cortical reorganization in chronic stroke and how different methodologies can reveal different aspects of lesion and recovery networks in apraxia.

IntroductionThe Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.MethodsCohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage.ResultsForty-seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population-based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage.DiscussionMeta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join.

Objective: Lexical retrieval deficits are characteristic of a variety of different neurological disorders. However, the exact substrates responsible for this are not known. We studied a large cohort of patients undergoing surgery in the dominant temporal lobe for medically intractable epilepsy (n = 95) to localize brain regions that were associated with anomia. Methods: We performed a multivariate voxel‐based lesion–symptom mapping analysis to correlate surgical lesions within the temporal lobe with changes in naming ability. Additionally, we used a surface‐based mixed‐effects multilevel analysis to estimate group‐level broadband gamma activity during naming across a subset of patients with electrocorticographic recordings and integrated these results with lesion–deficit findings. Results: We observed that ventral temporal regions, centered around the middle fusiform gyrus, were significantly associated with a decline in naming. Furthermore, we found that the ventral aspect of temporal lobectomies was linearly correlated to a decline in naming, with a clinically significant decline occurring once the resection extended 6 cm from the anterior tip of the temporal lobe on the ventral surface. On electrocorticography, the majority of these cortical regions were functionally active following visual processing. These loci coincide with the sites of susceptibility artifacts during echoplanar imaging, which may explain why this region has been previously underappreciated as the locus responsible for postoperative naming deficits. Significance: Taken together, these data highlight the crucial contribution of the ventral temporal cortex in naming and its important role in the pathophysiology of anomia following temporal lobe resections. As such, surgical strategies should attempt to preserve this region to mitigate postoperative language deficits. [ABSTRACT FROM AUTHOR]

One of the widely used metrics in lesion-symptom mapping is lesion load that codes the amount of damage to a given brain region of interest. Lesion load aims to reduce the complex 3D lesion information into a feature that can reflect both site of damage, defined by the location of the region of interest, and size of damage within that region of interest. Basically, the process of estimation of lesion load converts a voxel-based lesion map into a region-based lesion map, with regions defined as atlas-based or data-driven spatial patterns. Here, after examining current definitions of lesion load, four methodological issues are discussed: (1) lesion load is agnostic to the location of damage within the region of interest, and it disregards damage outside the region of interest, (2) lesion load estimates are prone to errors introduced by the uncertainty in lesion delineation, spatial warping of the lesion/region, and binarization of the lesion/region, (3) lesion load calculation depends on brain parcellation selection, and (4) lesion load does not necessarily reflect a white matter disconnection. Overall, lesion load, when calculated in a robust way, can serve as a clinically-useful feature for explaining and predicting post-stroke outcome and recovery. [ABSTRACT FROM AUTHOR]

Studies in patients with brain lesions play a fundamental role in unraveling the brain's functional anatomy. Lesion‐symptom mapping (LSM) techniques can relate lesion location to cognitive performance. However, a limitation of current LSM approaches is that they can only evaluate one cognitive outcome at a time, without considering interdependencies between different cognitive tests. To overcome this challenge, we implemented canonical correlation analysis (CCA) as combined multivariable and multioutcome LSM approach. We performed a proof‐of‐concept study on 1075 patients with acute ischemic stroke to explore whether addition of CCA to a multivariable single‐outcome LSM approach (support vector regression) could identify infarct locations associated with deficits in three well‐defined verbal memory functions (encoding, consolidation, retrieval) based on four verbal memory subscores derived from the Seoul Verbal Learning Test (immediate recall, delayed recall, recognition, learning ability). We evaluated whether CCA could extract cognitive score patterns that matched prior knowledge of these verbal memory functions, and if these patterns could be linked to more specific infarct locations than through single‐outcome LSM alone. Two of the canonical modes identified with CCA showed distinct cognitive patterns that matched prior knowledge on encoding and consolidation. In addition, CCA revealed that each canonical mode was linked to a distinct infarct pattern, while with multivariable single‐outcome LSM individual verbal memory subscores were associated with largely overlapping patterns. In conclusion, our findings demonstrate that CCA can complement single‐outcome LSM techniques to help disentangle cognitive functions and their neuroanatomical correlates. [ABSTRACT FROM AUTHOR]

Understanding neural circuits that support mood is a central goal of affective neuroscience, and improved understanding of the anatomy could inform more targeted interventions in mood disorders. Lesion studies provide a method of inferring the anatomical sites causally related to specific functions, including mood. Here, we performed a large-scale study evaluating the location of acquired, focal brain lesions in relation to symptoms of depression. Five hundred and twenty-six individuals participated in the study across two sites (356 male, average age 52.4 ± 14.5 years). Each subject had a focal brain lesion identified on structural imaging and an assessment of depression using the Beck Depression Inventory-II, both obtained in the chronic period post-lesion (>3 months). Multivariate lesion–symptom mapping was performed to identify lesion sites associated with higher or lower depression symptom burden, which we refer to as 'risk' versus 'resilience' regions. The brain networks and white matter tracts associated with peak regional findings were identified using functional and structural lesion network mapping, respectively. Lesion–symptom mapping identified brain regions significantly associated with both higher and lower depression severity (r = 0.11; P = 0.01). Peak 'risk' regions include the bilateral anterior insula, bilateral dorsolateral prefrontal cortex and left dorsomedial prefrontal cortex. Functional lesion network mapping demonstrated that these 'risk' regions localized to nodes of the salience network. Peak 'resilience' regions include the right orbitofrontal cortex, right medial prefrontal cortex and right inferolateral temporal cortex, nodes of the default mode network. Structural lesion network mapping implicated dorsal prefrontal white matter tracts as 'risk' tracts and ventral prefrontal white matter tracts as 'resilience' tracts, although the structural lesion network mapping findings did not survive correction for multiple comparisons. Taken together, these results demonstrate that lesions to specific nodes of the salience network and default mode network are associated with greater risk versus resiliency for depression symptoms in the setting of focal brain lesions. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the influence of stroke lesions in predefined highly interconnected (rich‐club) brain regions on functional outcome post‐stroke, determine their spatial specificity and explore the effects of biological sex on their relevance. We analyzed MRI data recorded at index stroke and ~3‐months modified Rankin Scale (mRS) data from patients with acute ischemic stroke enrolled in the multisite MRI‐GENIE study. Spatially normalized structural stroke lesions were parcellated into 108 atlas‐defined bilateral (sub)cortical brain regions. Unfavorable outcome (mRS > 2) was modeled in a Bayesian logistic regression framework. Effects of individual brain regions were captured as two compound effects for (i) six bilateral rich club and (ii) all further non‐rich club regions. In spatial specificity analyses, we randomized the split into "rich club" and "non‐rich club" regions and compared the effect of the actual rich club regions to the distribution of effects from 1000 combinations of six random regions. In sex‐specific analyses, we introduced an additional hierarchical level in our model structure to compare male and female‐specific rich club effects. A total of 822 patients (age: 64.7[15.0], 39% women) were analyzed. Rich club regions had substantial relevance in explaining unfavorable functional outcome (mean of posterior distribution: 0.08, area under the curve: 0.8). In particular, the rich club‐combination had a higher relevance than 98.4% of random constellations. Rich club regions were substantially more important in explaining long‐term outcome in women than in men. All in all, lesions in rich club regions were associated with increased odds of unfavorable outcome. These effects were spatially specific and more pronounced in women. [ABSTRACT FROM AUTHOR]

Understanding the impact of variation in lesion topography on the expression of functional impairments following stroke is important, as it may pave the way to modeling structure–function relations in statistical terms while pointing to constraints for adaptive remapping and functional recovery. Multi‐perturbation Shapley‐value analysis (MSA) is a relatively novel game‐theoretical approach for multivariate lesion‐symptom mapping. In this methodological paper, we provide a comprehensive explanation of MSA. We use synthetic data to assess the method's accuracy and perform parameter optimization. We then demonstrate its application using a cohort of 107 first‐event subacute stroke patients, assessed for upper limb (UL) motor impairment (Fugl‐Meyer Assessment scale). Under the conditions tested, MSA could correctly detect simulated ground‐truth lesion‐symptom relationships with a sensitivity of 75% and specificity of ~90%. For real behavioral data, MSA disclosed a strong hemispheric effect in the relative contribution of specific regions‐of‐interest (ROIs): poststroke UL motor function was mostly contributed by damage to ROIs associated with movement planning (supplementary motor cortex and superior frontal gyrus) following left‐hemispheric damage (LHD) and by ROIs associated with movement execution (primary motor and somatosensory cortices and the ventral brainstem) following right‐hemispheric damage (RHD). Residual UL motor ability following LHD was found to depend on a wider array of brain structures compared to the residual motor ability of RHD patients. The results demonstrate that MSA can provide a unique insight into the relative importance of different hubs in neural networks, which is difficult to obtain using standard univariate methods. [ABSTRACT FROM AUTHOR]

Statistical lesion-symptom mapping is largely dominated by frequentist approaches with null hypothesis significance testing. They are popular for mapping functional brain anatomy but are accompanied by some challenges and limitations. The typical analysis design and the structure of clinical lesion data are linked to the multiple comparison problem, an association problem, limitations to statistical power, and a lack of insights into evidence for the null hypothesis. Bayesian lesion deficit inference (BLDI) could be an improvement as it collects evidence for the null hypothesis, i.e. the absence of effects, and does not accumulate α-errors with repeated testing. We implemented BLDI by Bayes factor mapping with Bayesian t-tests and general linear models and evaluated its performance in comparison to frequentist lesion-symptom mapping with a permutation-based family-wise error correction. We mapped the voxel-wise neural correlates of simulated deficits in an in-silico-study with 300 stroke patients, and the voxel-wise and disconnection-wise neural correlates of phonemic verbal fluency and constructive ability in 137 stroke patients. Both the performance of frequentist and Bayesian lesion-deficit inference varied largely across analyses. In general, BLDI could find areas with evidence for the null hypothesis and was statistically more liberal in providing evidence for the alternative hypothesis, i.e. the identification of lesion-deficit associations. BLDI performed better in situations in which the frequentist method is typically strongly limited, for example with on average small lesions and in situations with low power, where BLDI also provided unprecedented transparency in terms of the informative value of the data. On the other hand, BLDI suffered more from the association problem, which led to a pronounced overshoot of lesion-deficit associations in analyses with high statistical power. We further implemented a new approach to lesion size control, adaptive lesion size control, that, in many situations, was able to counter the limitations imposed by the association problem, and increased true evidence both for the null and the alternative hypothesis. In summary, our results suggest that BLDI is a valuable addition to the method portfolio of lesion-deficit inference with some specific and exclusive advantages: it deals better with smaller lesions and low statistical power (i.e. small samples and effect sizes) and identifies regions with absent lesion-deficit associations. However, it is not superior to established frequentist approaches in all respects and therefore not to be seen as a general replacement. To make Bayesian lesion-deficit inference widely accessible, we published an R toolkit for the analysis of voxel-wise and disconnection-wise data.

Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated 'multiple demand' frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it. We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven's Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects. Impaired performance was confined to patients with frontal lesions [ F (2,387) = 18.491; P < 0.001; frontal worse than non-frontal and healthy participants P < 0.01, P <0.001], more marked on the right than left [ F (4,385) = 12.237; P < 0.001; right worse than left and healthy participants P < 0.01, P < 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses. Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven's Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction. [ABSTRACT FROM AUTHOR]

In vivo tracking of white matter fibres catalysed a modern perspective on the pivotal role of brain connectome disruption in neuropsychological deficits. However, the examination of white matter integrity in neurological patients by diffusion-weighted magnetic resonance imaging bears conceptual limitations and is not widely applicable, as it requires imaging-compatible patients and resources beyond the capabilities of many researchers. The indirect estimation of structural disconnection offers an elegant and economical alternative. For this approach, a patient's structural lesion information and normative connectome data are combined to estimate different measures of lesion-induced structural disconnection. Using one of several toolboxes, this method is relatively easy to implement and is even available to scientists without expertise in fibre tracking analyses. Nevertheless, the anatomo-behavioural statistical mapping of structural brain disconnection requires analysis steps that are not covered by these toolboxes. In this paper, we first review the current state of indirect lesion disconnection estimation, the different existing measures, and the available software. Second, we aim to fill the remaining methodological gap in statistical disconnection-symptom mapping by providing an overview and guide to disconnection data and the statistical mapping of their relationship to behavioural measurements using either univariate or multivariate statistical modelling. To assist in the practical implementation of statistical analyses, we have included software tutorials and analysis scripts. [ABSTRACT FROM AUTHOR]

Understanding the relationships between brain organization and behavior is a central goal of neuroscience. Traditional teaching emphasizes that the human cerebrum includes many distinct areas for which damage or dysfunction would lead to a unique and specific behavioral syndrome. This teaching implies that brain areas correspond to encapsulated modules that are specialized for specific cognitive operations. However, empirically, local damage from stroke more often produces one of a small number of clusters of deficits and disrupts brain-wide connectivity in a small number of predictable ways (relative to the vast complexity of behavior and brain connectivity). Behaviors that involve shared operations show correlated deficits following a stroke, consistent with a low-dimensional behavioral space. Because of the networked organization of the brain, local damage from a stroke can result in widespread functional abnormalities, matching the low dimensionality of behavioral deficit. In alignment with this, neurological disease, psychiatric disease, and altered brain states produce behavioral changes that are highly correlated across a range of behaviors. We discuss how known structural and functional network priors in addition to graph theoretical concepts such as modularity and entropy have provided inroads to understanding this more complex relationship between brain and behavior. This model for brain disease has important implications for normal brain-behavior relationships and the treatment of neurological and psychiatric diseases. [ABSTRACT FROM AUTHOR]

Objective: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments. Methods: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume). Potential effects of histological and molecular subtype and corresponding WHO grades on the risk of cognitive impairment were investigated using Chi square tests. P-values were adjusted for multiple comparisons (p <.001 and p <.05 for voxel- and cluster-level, resp.). Results: A cohort of 179 intracranial tumor patients was included [aged 19–85 years, median age (SD) = 58.46 (14.62), 50% females]. In this cohort, test-specific impairment was detected in 20–30% of patients. Higher WHO grade was associated with lower processing speed, cognitive flexibility and delayed memory in gliomas, while no acute surgery-effects were found. No grading, nor surgery effects were found in meningiomas. The voxel-wise analyses showed that tumor locations in left temporal areas and right temporo-parietal areas were related to verbal memory and processing speed, respectively. Interpretation: Patients with intracranial tumors affecting the left temporal areas and right temporo-parietal areas might specifically be vulnerable for lower verbal memory and processing speed. These specific patients at-risk might benefit from early-stage interventions. Furthermore, based on future validation studies, imaging-informed surgical and radiotherapy planning could further be improved. [ABSTRACT FROM AUTHOR]

Aphasia is an acquired disorder caused by damage, most commonly due to stroke, to brain regions involved in speech and language. While language impairment is the defining symptom of aphasia, the co-occurrence of non-language cognitive deficits and their importance in predicting rehabilitation and recovery outcomes is well documented. However, people with aphasia (PWA) are rarely tested on higher-order cognitive functions, making it difficult for studies to associate these functions with a consistent lesion correlate. Broca’s area is a particular brain region of interest that has long been implicated in speech and language production. Contrary to classic models of speech and language, cumulative evidence shows that Broca’s area and surrounding regions in the left inferior frontal cortex (LIFC) are involved in, but not specific to, speech production. In this study we aimed to explore the brain-behaviour relationships between tests of cognitive skill and language abilities in thirty-six adults with long-term speech production deficits caused by post-stroke aphasia.Our findings suggest that non-linguistic cognitive functions, namely executive functions and verbal working memory, explain more of the behavioural variance in PWA than classical language models imply. Additionally, lesions to the LIFC, including Broca’s area, were associated with non-linguistic executive (dys)function, suggesting that lesions to this area are associated with non-language-specific higher-order cognitive deficits in aphasia. Whether executive (dys)function – and its neural correlate in Broca’s area – contributes directly to PWA’s language production deficits or simply co-occurs with it, adding to communication difficulties, remains unclear. These findings support contemporary models of speech production that place language processing within the context of domain-general perception, action and conceptual knowledge. An understanding of the covariance between language and non-language deficits and their underlying neural correlates will inform better targeted aphasia treatment and outcomes.

Introduction: Lesion-symptom mapping is a key tool in understanding the relationship between brain structures and behavior. However, the behavioral consequences of lesions from different etiologies may vary because of how they affect brain tissue and how they are distributed. The inclusion of different etiologies would increase the statistical power but has been critically debated. Meanwhile, findings from lesion studies are a valuable resource for clinicians and used across different etiologies. Therefore, the main objective of the present study was to directly compare lesion-symptom maps for memory and language functions from two populations, a tumor versus a stroke population. Methods: Data from two different studies were combined. Both the brain tumor (N = 196) and stroke (N = 147) patient populations underwent neuropsychological testing and an MRI, pre-operatively for the tumor population and within three months after stroke. For this study, we selected two internationally widely used standardized cognitive tasks, the Rey Auditory Verbal Learning Test and the Verbal Fluency Test. We used a state-of-the-art machine learning-based, multivariate voxel-wise approach to produce lesion-symptom maps for these cognitive tasks for both populations separately and combined. Results: Our lesion-symptom mapping results for the separate patient populations largely followed the expected neuroanatomical pattern based on previous literature. Substantial differences in lesion distribution hindered direct comparison. Still, in brain areas with adequate coverage in both groups, considerable LSM differences between the two populations were present for both memory and fluency tasks. Post-hoc analyses of these locations confirmed that the cognitive consequences of focal brain damage varied between etiologies. Conclusion: The differences in the lesion-symptom maps between the stroke and tumor population could partly be explained by differences in lesion volume and topography. Despite these methodological limitations, both the lesion-symptom mapping results and the post-hoc analyses confirmed that etiology matters when investigating the cognitive consequences of lesions with lesion-symptom mapping. Therefore, caution is advised with generalizing lesion-symptom results across etiologies.

Background: This study aimed to investigate cerebellar mutism syndrome (CMS)-related voxels and build a voxel-wise predictive model for CMS. Methods: From July 2013 to January 2022, 188 pediatric patients diagnosed with posterior fossa tumor were included in this study, including 38 from a prospective cohort recruited between 2020 and January 2022, and the remaining from a retrospective cohort recruited in July 2013-Aug 2020. The retrospective cohort was divided into the training and validation sets; the prospective cohort served as a prospective validation set. Voxel-based lesion symptoms were assessed to identify voxels related to CMS, and a predictive model was constructed and tested in the validation and prospective validation sets. Results: No significant differences were detected among these three data sets in CMS rate, gender, age, tumor size, tumor consistency, presence of hydrocephalus and paraventricular edema. Voxels related to CMS were mainly located in bilateral superior and inferior cerebellar peduncles and the superior part of the cerebellum. The areas under the curves for the model in the training, validation and prospective validation sets were 0.889, 0.784 and 0.791, respectively. Conclusions: Superior and inferior cerebellar peduncles and the superior part of the cerebellum were related to CMS, especially the right side, and voxel-based lesion-symptom analysis could provide valuable predictive information before surgery.

Wernicke's area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, in 2015 and 2019, Mesulam and colleagues raised what they termed the 'Wernicke conundrum', noting widespread variability in the anatomical definition of this area and presenting data from primary progressive aphasia that challenged this classical assumption. To resolve the conundrum, they posited a 'double disconnection' hypothesis: that word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernicke's area itself. To test this hypothesis, we performed lesion-deficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex non-canonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and non-canonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for non-canonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and non-canonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. Our results largely agree with the classical notion that Wernicke's area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernicke's aphasia result from double disconnection. [ABSTRACT FROM AUTHOR]

Semantic processing is a central component of language and cognition. The anterior temporal lobe is postulated to be a key hub for semantic processing, but the posterior temporoparietal cortex is also involved in thematic associations during language. It is possible that these regions act in concert and depend on an anteroposterior network linking the temporal pole with posterior structures to support thematic semantic processing during language production. We employed connectome-based lesion-symptom mapping to examine the causal relationship between lesioned white matter pathways and thematic processing language deficits among individuals with post-stroke aphasia. Seventy-nine adults with chronic aphasia completed the Philadelphia Naming Test, and semantic errors were coded as either thematic or taxonomic to control for taxonomic errors. Controlling for nonverbal conceptual-semantic knowledge as measured by the Pyramids and Palm Trees Test, lesion size, and the taxonomic error rate, thematic error rate was associated with loss of white matter connections from the temporal pole traversing in peri-Sylvian regions to the posterior cingulate and the insula. These findings support the existence of a distributed network underlying thematic relationship processing in language as opposed to discrete cortical areas. [ABSTRACT FROM AUTHOR]

Connectome-based lesion-symptom mapping relates behavioural impairments to disruption of structural brain connectivity. Connectome-based lesion-symptom mapping can be based on different approaches (diffusion MRI versus lesion mask), network scales (whole brain versus regions of interest) and measure types (tract-based, parcel-based, or network-based metrics). We evaluated the similarity of different connectome-based lesion-symptom mapping processing choices and identified factors that influence the results using multiverse analysis-the strategy of conducting and displaying the results of all reasonable processing choices. Metrics derived from lesion masks and diffusion-weighted images were tested for association with Boston Naming Test and Token Test performance in a sample of 50 participants with aphasia following left hemispheric stroke. 'Direct' measures were derived from diffusion-weighted images. 'Indirect' measures were derived by overlaying lesion masks on a white matter atlas. Parcel-based connectomes were constructed for the whole brain and regions of interest (14 language-relevant parcels). Numerous tract-based and network-based metrics were calculated. There was a high discrepancy across processing approaches (diffusion-weighted images versus lesion masks), network scales (whole brain versus regions of interest) and metric types. Results indicate weak correlations and different connectome-based lesion-symptom mapping results across the processing choices. Substantial methodological work is needed to validate the various decision points that arise when conducting connectome-based lesion-symptom mapping analyses. Multiverse analysis is a useful strategy for evaluating the similarity across different processing choices in connectome-based lesion-symptom mapping., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Memory disorders are a common consequence of cerebrovascular accident (CVA). However, uncertainties remain about the exact anatomical correlates of memory impairment and the material-specific lateralization of memory function in the brain. We used lesion-symptom mapping (LSM) in patients with first-time CVA to identify which brain structures are pivotal for verbal and nonverbal memory and to re-examine whether verbal and nonverbal memory functions are lateralized processes in the brain. The cognitive performance of a relatively large cohort of 114 patients in five classic episodic memory tests was analysed with factor analysis. Two factors were extracted that distinguished the verbal and nonverbal components of these memory tests, and their scores were subsequently tested for anatomical correlates by combining univariate and multivariate LSM. LSM analysis revealed for the verbal factor exclusively left-hemispheric insular, subcortical and adjacent white matter regions and for the nonverbal factor exclusively right-hemispheric temporal, occipital, insular, subcortical and adjacent white matter structures. These results corroborate the long-standing hypothesis of a material-specific lateralization of memory function in the brain and confirm a robust association between right temporal lobe lesions and nonverbal memory dysfunction. The right-hemispheric correlates for the nonverbal aspects of episodic memory include not only classic memory structures in the medial temporal lobe but also a more distributed network that includes cortical and subcortical structures also known for implicit memory processes. [ABSTRACT FROM AUTHOR]

An influential model of spatial attention postulates three main attention-orienting mechanisms: disengagement, shifting, and engagement. Early research linked disengagement deficits with superior parietal damage, regardless of hemisphere or presence of spatial neglect. Subsequent studies supported the involvement of more ventral parietal regions, especially in the right hemisphere, and linked spatial neglect to deficient disengagement from ipsilateral cues. However, previous lesion studies faced serious limitations, such as small sample sizes and the lack of brain-injured controls without neglect. Additionally, some studies employed symbolic cues or used long cue-target intervals, which may fail to reveal impaired disengagement. We here used a machine-learning approach to conduct lesion-symptom mapping (LSM) on 89 patients with focal cerebral lesions to the left (LH) or right (RH) cerebral hemisphere. A group of 54 healthy participants served as controls. The paradigm used to uncover disengagement deficits employed non-predictive cues presented in the visual periphery and at short cue-target intervals, targeting exogenous attention. The main factors of interest were group (healthy participants, LH, RH), target position (left, right hemifield) and cue validity (valid, invalid). LSM-analyses were performed on two indices: the validity effect, computed as the absolute difference between reaction times (RTs) following invalid compared to valid cues, and the disengagement deficit, determined by the difference between contralesional and ipsilesional validity effects. While LH patients showed general slowing of RTs to contralesional targets, only RH patients exhibited a disengagement deficit from ipsilesional cues. LSM associated the validity effect with a right lateral frontal cluster, which additionally affected subcortical white matter of the right arcuate fasciculus, the corticothalamic pathway, and the superior longitudinal fasciculus. In contrast, the disengagement deficit was related to damage involving the right temporoparietal junction. Thus, our results support the crucial role of right inferior parietal and posterior temporal regions for attentional disengagement, but also emphasize the importance of lateral frontal regions, for the reorienting of attention. • Early research associated disengagement deficits with parietal damage. • Methodological issues with previous studies challenge this conclusion. • Damage to right lateral frontal cortex associated with validity effect. • Right temporoparietal junction associated with disengagement deficit. • Reorienting of attention reflects frontoparietal interactions. [ABSTRACT FROM AUTHOR]

The cerebellar cognitive affective syndrome (CCAS) has been consistently described in patients with acute/subacute cerebellar injuries. However, studies with chronic patients have had controversial findings that have not been explored with new cerebellar-target tests, such as the CCAS scale (CCAS-S). The objective of this research is to prove and contrast the usefulness of the CCAS-S and the Montreal Cognitive Assessment (MoCA) test to evaluate cognitive/affective impairments in patients with chronic acquired cerebellar lesions, and to map the cerebellar areas whose lesions correlated with dysfunctions in these tests. CCAS-S and MoCA were administrated to 22 patients with isolated chronic cerebellar strokes and a matched comparison group. The neural bases underpinning both tests were explored with multivariate lesion-symptom mapping (LSM) methods. MoCA and CCAS-S had an adequate test performance with efficient discrimination between patients and healthy volunteers. However, only impairments determined by the CCAS-S resulted in significant regional localization within the cerebellum. Specifically, patients with chronic cerebellar lesions in right-lateralized posterolateral regions manifested cognitive impairments inherent to CCAS. These findings concurred with the anterior-sensorimotor/posterior-cognitive dichotomy in the human cerebellum and revealed clinically intra- and cross-lobular significant regions (portions of right lobule VI, VII, Crus I-II) for verbal tasks that overlap with the "language" functional boundaries in the cerebellum. Our findings prove the usefulness of MoCA and CCAS-S to reveal cognitive impairments in patients with chronic acquired cerebellar lesions. This study extends the understanding of long-term CCAS and introduces multivariate LSM methods to identify clinically intra- and cross-lobular significant regions underpinning chronic CCAS. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to determine and compare lesion patterns and structural dysconnectivity underlying poststroke aprosodia and amusia, using a data‐driven multimodal neuroimaging approach. Methods: Thirty‐nine patients with right or left hemisphere stroke were enrolled in a cohort study and tested for linguistic and affective prosody perception and musical pitch and rhythm perception at subacute and 3‐month poststroke stages. Participants listened to words spoken with different prosodic stress that changed their meaning, and to words spoken with six different emotions, and chose which meaning or emotion was expressed. In the music tasks, participants judged pairs of short melodies as the same or different in terms of pitch or rhythm. Structural magnetic resonance imaging data were acquired at both stages, and machine learning‐based lesion–symptom mapping and deterministic tractography were used to identify lesion patterns and damaged white matter pathways giving rise to aprosodia and amusia. Results: Both aprosodia and amusia were behaviorally strongly correlated and associated with similar lesion patterns in right frontoinsular and striatal areas. In multiple regression models, reduced fractional anisotropy and lower tract volume of the right inferior fronto‐occipital fasciculus were the strongest predictors for both disorders, over time. Conclusions: These results highlight a common origin of aprosodia and amusia, both arising from damage and disconnection of the right ventral auditory stream integrating rhythmic–melodic acoustic information in prosody and music. Comorbidity of these disabilities may worsen the prognosis and affect rehabilitation success. [ABSTRACT FROM AUTHOR]

Auditory sentence comprehension requires coordination of multiple levels of processing: auditory-phonological perception, lexical-semantic comprehension, syntactic parsing and discourse construction, as well as executive functions such as verbal working memory (WM) and cognitive control. This study examined the lesion correlates of sentence comprehension deficits in post-stroke aphasia, building on prior work on this topic by using a different and clinically-relevant measure of sentence comprehension (the Token Test) and multivariate (SCCAN) and connectome-based lesion-symptom mapping methods. The key findings were that lesions in the posterior superior temporal lobe and inferior frontal gyrus (pars triangularis) were associated with sentence comprehension deficits, which was observed in both mass univariate and multivariate lesion-symptom mapping. Graph theoretic measures of connectome disruption were not statistically significantly associated with sentence comprehension deficits after accounting for overall lesion size.

Theories of language organization in the brain commonly posit that different regions underlie distinct linguistic mechanisms. However, such theories have been criticized on the grounds that many neuroimaging studies of language processing find similar effects across regions. Moreover, condition by region interaction effects, which provide the strongest evidence of functional differentiation between regions, have rarely been offered in support of these theories. Here we address this by using lesion-symptom mapping in three large, partially-overlapping groups of aphasia patients with left hemisphere brain damage due to stroke (N = 121, N = 92, N = 218). We identified multiple measure by region interaction effects, associating damage to the posterior middle temporal gyrus with syntactic comprehension deficits, damage to posterior inferior frontal gyrus with expressive agrammatism, and damage to inferior angular gyrus with semantic category word fluency deficits. Our results are inconsistent with recent hypotheses that regions of the language network are undifferentiated with respect to high-level linguistic processing.

Background: Post-stroke cognitive impairment can occur after damage to various brain regions, and cognitive deficits depend on infarct location. The Mini-Mental State Examination (MMSE) is still widely used to assess post-stroke cognition, but it has been criticized for capturing only certain cognitive deficits. Along these lines, it might be hypothesized that cognitive deficits as measured with the MMSE primarily involve certain infarct locations. Aims: This comprehensive lesion-symptom mapping study aimed to determine which acute infarct locations are associated with post-stroke cognitive impairment on the MMSE. Methods: We examined associations between impairment on the MMSE (<5th percentile; normative data) and infarct location in 1198 patients (age 67-12 years, 43% female) with acute ischemic stroke using voxel-based lesion-symptom mapping. As a frame of reference, infarct patterns associated with impairments in individual cognitive domains were determined, based on a more detailed neuropsychological assessment. Results: Impairment on the MMSE was present in 420 patients (35%). Large voxel clusters in the left middle cerebral artery territory and thalamus were significantly (p<0.01) associated with cognitive impairment on the MMSE, with highest odds ratios (>15) in the thalamus and superior temporal gyrus. In comparison, domain-specific impairments were related to various infarct patterns across both hemispheres including the left medial temporal lobe (verbal memory) and right parietal lobe (visuospatial functioning). Conclusions: Our findings indicate that post-stroke cognitive impairment on the MMSE primarily relates to infarct locations in the left middle cerebral artery territory. The MMSE is apparently less sensitive to cognitive deficits that specifically relate to other locations. [ABSTRACT FROM AUTHOR]

BackgroundManagement of language difficulties is an important aspect of clinical care for glioma patients, and accurately identifying the possible language deficits in patients based on lesion location would be beneficial to clinicians. To that end, we examined the relationship between lesion presence and language performance on tests of receptive language and expressive language using a highly specific voxel-based lesion-symptom mapping (VLSM) approach in glioma patients.Methods98 adults with primary glioma, who were pre-surgical candidates, were administered seven neurocognitive tests within the domains of receptive language and expressive language. The association between language performance and lesion presence was examined using VLSM. Statistical parametric maps were created for each test, and composite maps for both receptive language and expressive language were created to display the significant voxels common to all tests within these language domains.ResultsWe identified clusters of voxels with a significant relationship between lesion presence and language performance. All tasks were associated with several white matter pathways. The receptive language tasks were additionally all associated with regions primarily within the lateral temporal lobe and medial temporal lobe. In contrast, the expressive language tasks shared little overlap, despite each task being independently associated with large anatomic areas.ConclusionsOur findings identify the key anatomic structures involved in language functioning in adult glioma patients using an innovative lesion analysis technique and suggest that expressive language abilities may be more task-dependent and distributed than receptive language abilities.

Working memory and episodic memory are two different processes, although the nature of their interrelationship is debated. As these processes are predominantly studied in isolation, it is unclear whether they crucially rely on different neural substrates. To obtain more insight in this, 81 adults with sub-acute ischemic stroke and 29 elderly controls were assessed on a visual working memory task, followed by a surprise subsequent memory test for the same stimuli. Multivariate, atlas- and track-based lesion-symptom mapping (LSM) analyses were performed to identify anatomical correlates of visual memory. Behavioral results gave moderate evidence for independence between discriminability in working memory and subsequent memory, and strong evidence for a correlation in response bias on the two tasks in stroke patients. LSM analyses suggested there might be independent regions associated with working memory and episodic memory. Lesions in the right arcuate fasciculus were more strongly associated with discriminability in working memory than in subsequent memory, while lesions in the frontal operculum in the right hemisphere were more strongly associated with criterion setting in subsequent memory. These findings support the view that some processes involved in working memory and episodic memory rely on separate mechanisms, while acknowledging that there might also be shared processes. [ABSTRACT FROM AUTHOR]

Several diffusion tensor imaging studies reveal that white matter (WM) lesions are common in children suffering from benign cerebellar tumours who are treated with surgery only. The clinical implications of WM alterations that occur as a direct consequence of cerebellar disease have not been thoroughly studied. Here, we analysed structural and diffusion imaging data from cerebellar patients with chronic surgical lesions after resection for benign cerebellar tumours. We aimed to elucidate the impact of focal lesions of the cerebellum on WM integrity across the entire brain, and to investigate whether WM deficits were associated with behavioural impairment in three different motor tasks. Lesion symptom mapping analysis suggested that lesions in critical cerebellar regions were related to deficits in savings during an eyeblink conditioning task, as well as to deficits in motor action timing. Diffusion imaging analysis of cerebellar WM indicated that better behavioural performance was associated with higher fractional anisotropy (FA) in the superior cerebellar peduncle, cerebellum's main outflow path. Moreover, voxel‐wise analysis revealed a global pattern of WM deficits in patients within many cerebral WM tracts critical for motor and non‐motor function. Finally, we observed a positive correlation between FA and savings within cerebello‐thalamo‐cortical pathways in patients but not in controls, showing that saving effects partly depend on extracerebellar areas, and may be recruited for compensation. These results confirm that the cerebellum has extended connections with many cerebral areas involved in motor/cognitive functions, and the observed WM changes likely contribute to long‐term clinical deficits of posterior fossa tumour survivors. [ABSTRACT FROM AUTHOR]

Lesion–symptom mapping studies have reported a temporal versus frontal dissociation between semantic and letter fluency, and mixed evidence regarding the role of white matter. Mass‐univariate and multivariate lesion–symptom mapping was used to identify regions associated with semantic and letter fluency deficits in post‐stroke aphasia. Multivariate LSM revealed broad networks including underlying white matter, and substantial overlap between both types of fluency, suggesting that semantic fluency and letter fluency largely rely on the same neural system. All data are available on OSF. [ABSTRACT FROM AUTHOR]

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia Battery-Revised from 70 participants with aphasia after a left-hemisphere stroke were utilized to evaluate both reading and auditory comprehension of linguistically equivalent stimuli. Repeated-measures and univariate ANOVA were used to assess the relationship between auditory comprehension and aphasia types and correlations were employed to test the relationship between reading and auditory comprehension deficits. Lesion-symptom mapping was used to determine the dissociation of crucial brain structures supporting reading comprehension deficits controlling for auditory deficits and vice versa. Participants with Broca's or global aphasia had the worst performance on reading comprehension. Auditory comprehension explained 26% of the variance in reading comprehension for sentence completion and 44% for following sequential commands. Controlling for auditory comprehension, worse reading comprehension performance was independently associated with damage to the inferior temporal gyrus, fusiform gyrus, posterior inferior temporal gyrus, inferior occipital gyrus, lingual gyrus and posterior thalamic radiation. Auditory and reading comprehension are only partly correlated in aphasia. Reading is an integral part of daily life and directly associated with quality of life and functional outcomes. This study demonstrated that reading performance is directly related to lesioned areas in the boundaries between visual association regions and ventral stream language areas. This behavioural and neuroanatomical dissociation provides information about the neurobiology of language and mechanisms for potential future treatment interventions., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The clinical profiles of individuals with post-stroke aphasia demonstrate considerable variation in the presentation of symptoms. Recent aphasiological studies have attempted to account for this individual variability using a multivariate data-driven approach (principal component analysis) on an extensive neuropsychological and aphasiological battery, to identify fundamental domains of post-stroke aphasia. These domains mainly reflect phonology, semantics and fluency; however, these studies did not account for variability in response to different forms of connected speech, i.e. discourse genres. In the current study, we initially examined differences in the quantity, diversity and informativeness between three different discourse genres, including a simple descriptive genre and two naturalistic forms of connected speech (storytelling narrative, and procedural discourse). Subsequently, we provided the first quantitative investigation on the multidimensionality of connected speech production at both behavioural and neural levels. Connected speech samples across descriptive, narrative, and procedural discourse genres were collected from 46 patients with chronic post-stroke aphasia and 20 neurotypical adults. Content analyses conducted on all connected speech samples indicated that performance differed across discourse genres and between groups. Specifically, storytelling narratives provided higher quantities of content words and lexical diversity compared to composite picture description and procedural discourse. The analyses further revealed that, relative to neurotypical adults, patients with aphasia, both fluent and non-fluent, showed reduction in the quantity of verbal production, lexical diversity, and informativeness across all discourses. Given the differences across the discourses, we submitted the connected speech metrics to principal component analysis alongside an extensive neuropsychological/aphasiological battery that assesses a wide range of language and cognitive skills. In contrast to previous research, three unique orthogonal connected speech components were extracted in a unified model, reflecting verbal quantity, verbal quality, and motor speech, alongside four core language and cognitive components: phonological production, semantic processing, phonological recognition, and executive functions. Voxel-wise lesion-symptom mapping using these components provided evidence on the involvement of widespread cortical regions and their white matter connections. Specifically, left frontal regions and their underlying white matter tracts corresponding to the frontal aslant tract and the anterior segment of the arcuate fasciculus were particularly engaged with the quantity and quality of fluent connected speech production while controlling for other co-factors. The neural correlates associated with the other language domains align with existing models on the ventral and dorsal pathways for language processing. [ABSTRACT FROM AUTHOR]

Mental rotation (MR) is widely regarded as a quintessential example of an embodied cognitive process. This viewpoint stems from the functional parallels between MR and the physical rotation of tangible objects, as well as participants' inclination to employ motor-based strategies when tackling MR tasks involving bodily stimuli. These commonalities imply that MR may depend on brain regions crucial for the planning and execution of motor programs. However, there is disagreement regarding the anatomy of MR between findings from functional imaging and lesion studies involving brain-injured patients. The former indicate the involvement of the right-hemispheric parietal cortex, while the latter underscore the significance of posterior areas in the left hemisphere. In this study, we aimed to discern the neural underpinnings of MR using lesion-symptom mapping (LSM) for both bodily (hands) and non-bodily (letters) stimuli. Behavioral results from the two MR tasks revealed impaired MR of bodily stimuli in patients with left hemisphere damage. LSM results pinpointed the left primary motor and somatosensory cortices, along with the superior parietal lobule, as the anatomical substrates of MR for both bodily and non-bodily stimuli. Furthermore, damage to the left angular gyrus, supramarginal gyrus, supplementary motor area, and retrosplenial cortex was associated with MR of non-bodily stimuli. These findings support the causal involvement of the left hemisphere in MR and underscore the existence of a common anatomical substrate in brain regions pertinent to motor planning and execution. • Mental rotation is widely regarded as an embodied cognitive process. • Lesion-symptom mapping reveals causal involvement of the left hemisphere. • Mental rotation of bodily and non-bodily stimuli shares common neural substrate. • Mental rotation recruits brain regions relevant for motor planning and execution. [ABSTRACT FROM AUTHOR]

Fluent speech production is a critical aspect of language processing and is central to aphasia diagnosis and treatment. Multiple cognitive processes and neural subsystems must be coordinated to produce fluent narrative speech. To refine the understanding of these systems, measures that minimize the influence of other cognitive processes were defined for articulatory deficits and grammatical deficits. Articulatory deficits were measured by the proportion of phonetic errors (articulatory and prosodic) in a word repetition task in 115 participants with aphasia following left hemisphere stroke. Grammatical deficits were assessed in 46 participants based on two measures—proportion of closed class words and proportion of words in sentences—generated during semistructured narrative speech production (telling the Cinderella story). These measures were used to identify brain regions critical for articulatory and grammatical aspects of speech production using a multivariate lesion-symptom mapping approach based on support vector regression. Phonetic error proportion was associated with damage to the postcentral gyrus and the inferior parietal lobule (particularly the supramarginal gyrus). Proportion of closed class words in narrative speech did not have consistent lesion correlates. Proportion of words in sentences was strongly associated with frontal lobe damage, particularly the inferior and middle frontal gyri. Grammatical sentence structuring relies on frontal regions, particularly the inferior and middle frontal gyri, whereas phonetic-articulatory planning and execution relies on parietal regions, particularly the postcentral and supramarginal gyri. These results clarify and extend current understanding of the functional components of the frontoparietal speech production system. [ABSTRACT FROM AUTHOR]