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Development of brain functions and the structural-functional correlates of brain injury remain difficult to evaluate in the young infant. Thus, new noninvasive methods capable of early functional diagnosis are needed. This review describes the use of functional magnetic resonance imaging (fMRI) for studying localization of brain function in the developing brain when standard clinical investigations are not available or conclusive. This promising neuroimaging technique has been successfully used in healthy newborns and in newborns with brain injury using different paradigms, including passive visual, somato-sensorial, and auditory stimulation. We summarize the major findings of previous fMRI studies in young infants, describe ongoing methodological challenges, and propose exciting future developments in using resting-state protocols and functional connectivity techniques to assist in evaluating early life brain function and its recovery from injury. © Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

A clinically useful characterization of the cognitive aging process requires the development of valid and robust behavioral tests, with an emphasis on explaining and understanding typical inter-individual variability in cognition. Here, using a dataset that includes behavioral scores collected with the National Institute of Health Toolbox Cognition Battery (NIHTB-CB) and other auxiliary tests, we examined (1) the differences between young and old adults across different cognitive domains, (2) the strength of across-subject correlations in behavioral test scores, (3) the consistency of low-dimensional behavioral representations across age using factor analysis, and (4) the accuracy of behavioral scores in predicting participants' age. Our results revealed that (1) elderly females had better verbal episodic memory scores than elderly males, (2) across-subject correlations between behavioral tests varied with age group, (3) although a three-factor model explained the behavioral data in both age groups, some tasks loaded to different factors between the two groups, and (4) age-performance relationship (i.e. a regression model linking age to cognitive scores) in one group cannot be extrapolated to predict age in the other group, indicating an inconsistency in age-performance relationships across groups. These findings suggest that executive function tests might tap into different cognitive processes in different age groups, which might ultimately suggest that a statistically significant between-group difference in test performance might not always reflect differences in the same underlying cognitive processes. Overall, this study calls for more caution when interpreting age-related differences and similarities between age groups with different cognitive abilities even when the same tests are used., (© 2024. The Author(s).)

Brain-behavior relationships are complex. For instance, one might know a brain region's function(s) but still be unable to accurately predict deficit type or severity after damage to that region. Here, I discuss the case of damage to the angular gyrus (AG) that can cause left-right confusion, finger agnosia, attention deficit, and lexical agraphia, as well as impairment in sentence processing, episodic memory, number processing, and gesture imitation. Some of these symptoms are grouped under AG syndrome or Gerstmann's syndrome, though its exact underlying neuronal systems remain elusive. This review applies recent frameworks of brain-behavior modes and principles from modern lesion-symptom mapping to explain symptomatology after AG damage. It highlights four major issues for future studies: (1) functionally heterogeneous symptoms after AG damage need to be considered in terms of the degree of damage to (i) different subdivisions of the AG, (ii) different AG connectivity profiles that disconnect AG from distant regions, and (iii) lesion extent into neighboring regions damaged by the same infarct. (2) To explain why similar symptoms can also be observed after damage to other regions, AG damage needs to be studied in terms of the networks of regions that AG functions with, and other independent networks that might subsume the same functions. (3) To explain inter-patient variability on AG symptomatology, the degree of recovery-related brain reorganisation needs to account for time post-stroke, demographics, therapy input, and pre-stroke differences in functional anatomy. (4) A better integration of the results from lesion and functional neuroimaging investigations of AG function is required, with only the latter so far considering AG function in terms of a hub within the default mode network. Overall, this review discusses why it is so difficult to fully characterize the AG syndrome from lesion data, and how this might be addressed with modern lesion-symptom mapping., Competing Interests: Declaration of competing interest The author declares that he has no conflict of interest., (Copyright © 2024 The Author. Published by Elsevier Ltd.. All rights reserved.)

We investigated which parts of the cerebellum are involved in formulating and articulating sentences using (i) a sentence production task that involved describing simple events in pictures; (ii) an auditory sentence repetition task involving the same sentence articulation but not sentence formulation; and (iii) an auditory sentence-to-picture matching task that involved the same pictorial events and no overt articulation. Activation for each of these tasks was compared to the equivalent word processing tasks: noun production, verb production, auditory noun repetition, and auditory noun-to-picture matching. We associate activation in bilateral cerebellum lobule VIIb with sequencing words into sentences because it increased for sentence production compared to all other conditions and was also activated by word production compared to word matching. We associate a paravermal part of right cerebellar lobule VIIIb with overt motor execution of speech, because activation was higher during (i) production and repetition of sentences compared to the corresponding noun conditions and (ii) noun and verb production compared to all matching tasks, with no activation relative to fixation during any silent (nonspeaking) matching task. We associate activation within right cerebellar Crus II with covert articulatory activity because it activated for (i) all speech production more than matching tasks and (ii) sentences compared to nouns during silent (nonspeaking) matching as well as sentence production and sentence repetition. Our study serendipitously segregated, for the first time, three distinct functional roles for the cerebellum in generic speech production, and it demonstrated how sentence production enhanced the demands on these cerebellar regions., Competing Interests: Competing Interests: The authors have declared that no competing interests exist., (© 2024 Massachusetts Institute of Technology.)

Accurate segmentation of chronic stroke lesions from mono-spectral magnetic resonance imaging scans (e.g., T1-weighted images) is a difficult task due to the arbitrary shape, complex texture, variable size and intensities, and varied locations of the lesions. Due to this inherent spatial heterogeneity, existing machine learning methods have shown moderate performance for chronic lesion delineation. In this study, we introduced: (1) a method that integrates transformers' deformable feature attention mechanism with convolutional deep learning architecture to improve the accuracy and generalizability of stroke lesion segmentation, and (2) an ecological data augmentation technique based on inserting real lesions into intact brain regions. Our combination of these two approaches resulted in a significant increase in segmentation performance, with a Dice index of 0.82 (±0.39), outperforming the existing methods trained and tested on the same Anatomical Tracings of Lesions After Stroke (ATLAS) 2022 dataset. Our method performed relatively well even for cases with small stroke lesions. We validated the robustness of our method through an ablation study and by testing it on new unseen brain scans from the Ischemic Stroke Lesion Segmentation (ISLES) 2015 dataset. Overall, our proposed approach of transformers with ecological data augmentation offers a robust way to delineate chronic stroke lesions with clinically relevant accuracy. Our method can be extended to other challenging tasks that require automated detection and segmentation of diverse brain abnormalities from clinical scans., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

There is a growing interest in imaging understudied orthographies to unravel their neuronal correlates and their implications for existing computational and neuroanatomical models. Here, we review current brain mapping literature about Arabic words. We first offer a succinct description of some unique linguistic features of Arabic that challenge current cognitive models of reading. We then appraise the existing functional neuroimaging studies that investigated written Arabic word processing. Our review revealed that (1) Arabic is still understudied, (2) the most investigated features concerned the effects of vowelling and diglossia in Arabic reading, (3) findings were not always discussed in the light of existing reading models such as the dual route cascaded, the triangle, and the connectionist dual process models, and (4) current evidence is unreliable when it comes to the exact neuronal pathways that sustain Arabic word processing. Overall, despite the fact that Arabic has some unique linguistic features that challenge and ultimately enrich current reading models, the existing functional neuroimaging literature falls short of offering a reliable evidence about brain networks of Arabic reading. We conclude by highlighting the need for more systematic studies of the linguistic features of Arabic to build theoretical and neuroanatomical models that are concurrently specific and general., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Presurgical evaluation with functional magnetic resonance imaging (fMRI) can reduce postsurgical morbidity. Here, we discuss presurgical fMRI mapping at ultra-high magnetic fields (UHF), i.e., ≥ 7 T, in the light of the current growing interest in artificial intelligence (AI) and robot-assisted neurosurgery. The potential of submillimetre fMRI mapping can help better appreciate uncertainty on resection margins, though geometric distortions at UHF might lessen the accuracy of fMRI maps. A useful trade-off for UHF fMRI is to collect data with 1-mm isotropic resolution to ensure high sensitivity and subsequently a low risk of false negatives. Scanning at UHF might yield a revival interest in slow event-related fMRI, thereby offering a richer depiction of the dynamics of fMRI responses. The potential applications of AI concern denoising and artefact removal, generation of super-resolution fMRI maps, and accurate fusion or coregistration between anatomical and fMRI maps. The latter can benefit from the use of T1-weighted echo-planar imaging for better visualization of brain activations. Such AI-augmented fMRI maps would provide high-quality input data to robotic surgery systems, thereby improving the accuracy and reliability of robot-assisted neurosurgery. Ultimately, the advancement in fMRI at UHF would promote clinically useful synergies between fMRI, AI, and robotic neurosurgery.Relevance statement This review highlights the potential synergies between fMRI at UHF, AI, and robotic neurosurgery in improving the accuracy and reliability of fMRI-based presurgical mapping.Key points• Presurgical fMRI mapping at UHF improves spatial resolution and sensitivity.• Slow event-related designs offer a richer depiction of fMRI responses dynamics.• AI can support denoising, artefact removal, and generation of super-resolution fMRI maps.• AI-augmented fMRI maps can provide high-quality input data to robotic surgery systems., (© 2024. The Author(s).)

Projected trends in population aging have forecasted a massive increase in the number of people with dementia, in particular in sub-Saharan Africa and the Middle East and North Africa (MENA) region. Cognitive decline is a significant marker for dementia, typically assessed with standardized neuropsychological tools that have been validated in some well-researched languages such as English. However, with the existing language diversity, current tools cannot cater to speakers of understudied languages, putting these populations at a disadvantage when it comes to access to early and accurate diagnosis of dementia. Here, we shed light on the detrimental impact of this language gap in the context of the MENA region, highlighting inadequate tools and an unacceptable lack of expertise for a MENA population of a half billion people. Our perspective calls for more research to unravel the exact impact of the language gap on the quality of cognitive decline assessment in speakers of understudied languages., Highlights: Cognitive decline is a marker for dementia, assessed with neuropsychological tests.There is a lack of culturally valid tests for speakers of understudied languages.For example, suboptimal cognitive tests are used in the Middle East and North Africa region.Linguistic diversity should be considered in the development of cognitive tests., Competing Interests: The authors declare no conflicts of interest. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Early identification of mental disorders, based on subjective interviews, is extremely challenging in the clinical setting. There is a growing interest in developing automated screening tools for potential mental health problems based on biological markers. Here, we demonstrate the feasibility of an AI-powered diagnosis of different mental disorders using EEG data. Specifically, this work aims to classify different mental disorders in the following ecological context accurately: (1) using raw EEG data, (2) collected during rest, (3) during both eye open, and eye closed conditions, (4) at short 2-min duration, (5) on participants with different psychiatric conditions, (6) with some overlapping symptoms, and (7) with strongly imbalanced classes. To tackle this challenge, we designed and optimized a transformer-based architecture, where class imbalance is addressed through focal loss and class weight balancing. Using the recently released TDBRAIN dataset (n= 1274 participants), our method classifies each participant as either a neurotypical or suffering from major depressive disorder (MDD), attention deficit hyperactivity disorder (ADHD), subjective memory complaints (SMC), or obsessive-compulsive disorder (OCD). We evaluate the performance of the proposed architecture on both the window-level and the patient-level. The classification of the 2-min raw EEG data into five classes achieved a window-level accuracy of 63.2% and 65.8% for open and closed eye conditions, respectively. When the classification is limited to three main classes (MDD, ADHD, SMC), window level accuracy improved to 75.1% and 69.9% for eye open and eye closed conditions, respectively. Our work paves the way for developing novel AI-based methods for accurately diagnosing mental disorders using raw resting-state EEG data., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Automated demarcation of stoke lesions from monospectral magnetic resonance imaging scans is extremely useful for diverse research and clinical applications, including lesion-symptom mapping to explain deficits and predict recovery. There is a significant surge of interest in the development of supervised artificial intelligence (AI) methods for that purpose, including deep learning, with a performance comparable to trained experts. Such AI-based methods, however, require copious amounts of data. Thanks to the availability of large datasets, the development of AI-based methods for lesion segmentation has immensely accelerated in the last decade. One of these datasets is the Anatomical Tracings of Lesions After Stroke (ATLAS) dataset which includes T1-weighted images from hundreds of chronic stroke survivors with their manually traced lesions. This systematic review offers an appraisal of the impact of the ATLAS dataset in promoting the development of AI-based segmentation of stroke lesions. An examination of all published studies, that used the ATLAS dataset to both train and test their methods, highlighted an overall moderate performance (median Dice index = 59.40%) and a huge variability across studies in terms of data preprocessing, data augmentation, AI architecture, and the mode of operation (two-dimensional versus three-dimensional methods). Perhaps most importantly, almost all AI tools were borrowed from existing AI architectures in computer vision, as 90% of all selected studies relied on conventional convolutional neural network-based architectures. Overall, current research has not led to the development of robust AI architectures than can handle spatially heterogenous lesion patterns. This review also highlights the difficulty of gauging the performance of AI tools in the presence of uncertainties in the definition of the ground truth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Alzheimer's Disease (AD) is the most common form of dementia, specifically a progressive degenerative disorder affecting 47 million people worldwide and is only expected to grow in the elderly population. The detection of AD in its early stages is crucial to allow early intervention aiding in the prevention or slowing down of the disease. The effect of using comorbidity features in machine learning models to predict the time until a patient develops a prodrome was observed. In this study, we used Alzheimer's Disease Neuroimaging Initiative (ADNI) high-dimensional clinical data to compare the performance of six machine learning algorithms for survival analysis, combined with six feature selection methods trained on two settings: with and without comorbidities features. Our ridge model combined with permutation feature selection achieves maximum performance of 0.90 when using comorbidity features with the concordance index as a performance indicator. This demonstrated that incorporating comorbidities into the feature set enhances the performance of survival analysis for Alzheimer's disease. There is potential to identify risk factors (coronary artery disease) from comorbidities which could guide preventative care based on medical history.

This paper considers the steps needed to generate pragmatic and interpretable lesion-symptom mappings that can be used for clinically reliable prognoses. The novel contributions are 3-fold. We first define and inter-relate five neurobiological and five methodological constraints that need to be accounted for when interpreting lesion-symptom associations and generating synthetic lesion data. The first implication is that, because of these constraints, lesion-symptom mapping needs to focus on probabilistic relationships between Lesion and Symptom, with Lesion as a multivariate spatial pattern, Symptom as a time-dependent behavioural profile and evidence that Lesion raises the probability of Symptom. The second implication is that in order to assess the strength of probabilistic causality, we need to distinguish between causal lesion sites, incidental lesion sites, spared but dysfunctional sites and intact sites, all of which might affect the accuracy of the predictions and prognoses generated. We then formulate lesion-symptom mappings in logical notations, including combinatorial rules, that are then used to evaluate and better understand complex brain-behaviour relationships. The logical and theoretical framework presented applies to any type of neurological disorder but is primarily discussed in relationship to stroke damage. Accommodating the identified constraints, we discuss how the 1965 Bradford Hill criteria for inferring probabilistic causality, post hoc , from observed correlations in epidemiology-can be applied to lesion-symptom mapping in stroke survivors. Finally, we propose that rather than rely on post hoc evaluation of how well the causality criteria have been met, the neurobiological and methodological constraints should be addressed, a priori , by changing the experimental design of lesion-symptom mappings and setting up an open platform to share and validate the discovery of reliable and accurate lesion rules that are clinically useful., Competing Interests: The authors report no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Here, the functions of the angular gyrus (AG) are evaluated in the light of current evidence from transcranial magnetic/electric stimulation (TMS/TES) and EEG/MEG studies. 65 TMS/TES and 52 EEG/MEG studies were examined in this review. TMS/TES literature points to a causal role in semantic processing, word and number processing, attention and visual search, self-guided movement, memory, and self-processing. EEG/MEG studies reported AG effects at latencies varying between 32 and 800 ms in a wide range of domains, with a high probability to detect an effect at 300-350 ms post-stimulus onset. A three-phase unifying model revolving around the process of sensemaking is then suggested: (1) early AG involvement in defining the current context, within the first 200 ms, with a bias toward the right hemisphere; (2) attention re-orientation and retrieval of relevant information within 200-500 ms; and (3) cross-modal integration at late latencies with a bias toward the left hemisphere. This sensemaking process can favour accuracy (e.g. for word and number processing) or plausibility (e.g. for comprehension and social cognition). Such functions of the AG depend on the status of other connected regions. The much-debated semantic role is also discussed as follows: (1) there is a strong TMS/TES evidence for a causal semantic role, (2) current EEG/MEG evidence is however weak, but (3) the existing arguments against a semantic role for the AG are not strong. Some outstanding questions for future research are proposed. This review recognizes that cracking the role(s) of the AG in cognition is possible only when its exact contributions within the default mode network are teased apart., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Pre- and intra-operative language mapping in neurosurgery patients frequently involves an object naming task. The choice of the optimal object naming paradigm remains challenging due to lack of normative data and standardization in mapping practices. The aim of this study was to identify object naming paradigms that robustly and consistently activate classical language regions and could therefore be used to improve the sensitivity of language mapping in brain tumor and epilepsy patients. Methods: Functional magnetic resonance imaging (fMRI) data from two independent groups of healthy controls (total = 79) were used to generate threshold-weighted voxel-based consistency maps. This novel approach allowed us to compare inter-subject consistency of activation for naming single objects in the visual and auditory modality and naming two objects in a phrase or a sentence. Results: We found that the consistency of activation in language regions was greater for naming two objects per picture than one object per picture, even when controlling for the number of names produced in 5 s. Conclusion: More consistent activation in language areas for naming two objects compared to one object suggests that two-object naming tasks may be more suitable for delimiting language eloquent regions with pre- and intra-operative language testing. More broadly, we propose that the functional specificity of brain mapping paradigms for a whole range of different linguistic and non-linguistic functions could be enhanced by referring to databased models of inter-subject consistency and variability in typical and atypical brain responses., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ekert, Kirkman, Seghier, Green and Price.)

Big data is transforming many sectors, with far-reaching consequences to how decisions are made and how knowledge is produced and shared. In the current move toward more data-led decisions and data-intensive science, we aim here to examine three issues that are changing the way data are read and used. First, there is a shift toward paradigms that involve a large amount of data. In such paradigms, the creation of complex data-led models becomes tractable and appealing to generate predictions and explanations. This necessitates for instance a rethinking of Occam's razor principle in the context of knowledge discovery. Second, there is a growing erosion of the human role in decision making and knowledge discovery processes. Human users' involvement is decreasing at an alarming rate, with no say on how to read, process, and summarize data. This makes legal responsibility and accountability hard to define. Third, thanks to its increasing popularity, big data is gaining a seductive allure, where volume and complexity of big data can de facto confer more persuasion and significance to knowledge or decisions that result from big-data-based processes. These issues call for an active human role by creating opportunities to incorporate, in the most unbiased way, human expertise and prior knowledge in decision making and knowledge production. This also requires putting in place robust monitoring and appraisal mechanisms to ensure that relevant data is answering the right questions. As the proliferation of data continues to grow, we need to rethink the way we interact with data to serve human needs., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Seghier ML.)

Broca's area in the posterior half of the left inferior frontal gyrus has long been thought to be critical for speech production. The current view is that long-term speech production outcome in patients with Broca's area damage is best explained by the combination of damage to Broca's area and neighbouring regions including the underlying white matter, which was also damaged in Paul Broca's two historic cases. Here, we dissociate the effect of damage to Broca's area from the effect of damage to surrounding areas by studying long-term speech production outcome in 134 stroke survivors with relatively circumscribed left frontal lobe lesions that spared posterior speech production areas in lateral inferior parietal and superior temporal association cortices. Collectively, these patients had varying degrees of damage to one or more of nine atlas-based grey or white matter regions: Brodmann areas 44 and 45 (together known as Broca's area), ventral premotor cortex, primary motor cortex, insula, putamen, the anterior segment of the arcuate fasciculus, uncinate fasciculus and frontal aslant tract. Spoken picture description scores from the Comprehensive Aphasia Test were used as the outcome measure. Multiple regression analyses allowed us to tease apart the contribution of other variables influencing speech production abilities such as total lesion volume and time post-stroke. We found that, in our sample of patients with left frontal damage, long-term speech production impairments (lasting beyond 3 months post-stroke) were solely predicted by the degree of damage to white matter, directly above the insula, in the vicinity of the anterior part of the arcuate fasciculus, with no contribution from the degree of damage to Broca's area (as confirmed with Bayesian statistics). The effect of white matter damage cannot be explained by a disconnection of Broca's area, because speech production scores were worse after damage to the anterior arcuate fasciculus with relative sparing of Broca's area than after damage to Broca's area with relative sparing of the anterior arcuate fasciculus. Our findings provide evidence for three novel conclusions: (i) Broca's area damage does not contribute to long-term speech production outcome after left frontal lobe strokes; (ii) persistent speech production impairments after damage to the anterior arcuate fasciculus cannot be explained by a disconnection of Broca's area; and (iii) the prior association between persistent speech production impairments and Broca's area damage can be explained by co-occurring white matter damage, above the insula, in the vicinity of the anterior part of the arcuate fasciculus., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Prior studies have reported inconsistency in the lesion sites associated with verbal short-term memory impairments. Here we asked: How many different lesion sites can account for selective impairments in verbal short-term memory that persist over time, and how consistently do these lesion sites impair verbal short-term memory? We assessed verbal short-term memory impairments using a forward digit span task from the Comprehensive Aphasia Test. First, we identified the incidence of digit span impairments in a sample of 816 stroke survivors (541 males/275 females; age at stroke onset 56 ± 13 years; time post-stroke 4.4 ± 5.2 years). Second, we studied the lesion sites in a subgroup of these patients ( n  = 39) with left hemisphere damage and selective digit span impairment-defined as impaired digit span with unimpaired spoken picture naming and spoken word comprehension (tests of speech production and speech perception, respectively). Third, we examined how often these lesion sites were observed in patients who either had no digit span impairments or digit span impairments that co-occurred with difficulties in speech perception and/or production tasks. Digit span impairments were observed in 222/816 patients. Almost all (199/222 = 90%) had left hemisphere damage to five small regions in basal ganglia and/or temporo-parietal areas. Even complete damage to one or more of these five regions was not consistently associated with persistent digit span impairment. However, when the same regions were spared, only 5% (23/455) presented with digit span impairments. These data suggest that verbal short-term memory impairments are most consistently associated with damage to left temporo-parietal and basal ganglia structures. Sparing of these regions very rarely results in persistently poor verbal short-term memory. These findings have clinical implications for predicting recovery of verbal short-term memory after stroke., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Functional MRI (fMRI) findings hold many potential applications for education, and yet, the translation of fMRI findings to education has not flowed. Here, we address the types of fMRI that could better support applications of neuroscience to the classroom. This 'educational fMRI' comprises eight main challenges: (1) collecting artifact-free fMRI data in school-aged participants and in vulnerable young populations, (2) investigating heterogenous cohorts with wide variability in learning abilities and disabilities, (3) studying the brain under natural and ecological conditions, given that many practical topics of interest for education can be addressed only in ecological contexts, (4) depicting complex age-dependent associations of brain and behaviour with multi-modal imaging, (5) assessing changes in brain function related to developmental trajectories and instructional intervention with longitudinal designs, (6) providing system-level mechanistic explanations of brain function, so that useful individualized predictions about learning can be generated, (7) reporting negative findings, so that resources are not wasted on developing ineffective interventions, and (8) sharing data and creating large-scale longitudinal data repositories to ensure transparency and reproducibility of fMRI findings for education. These issues are of paramount importance to the development of optimal fMRI practices for educational applications., (Copyright © 2019 Seghier, Fahim and Habak.)

This paper provides a worked example of using Dynamic Causal Modelling (DCM) and Parametric Empirical Bayes (PEB) to characterise inter-subject variability in neural circuitry (effective connectivity). It steps through an analysis in detail and provides a tutorial style explanation of the underlying theory and assumptions (i.e, priors). The analysis procedure involves specifying a hierarchical model with two or more levels. At the first level, state space models (DCMs) are used to infer the effective connectivity that best explains a subject's neuroimaging timeseries (e.g. fMRI, MEG, EEG). Subject-specific connectivity parameters are then taken to the group level, where they are modelled using a General Linear Model (GLM) that partitions between-subject variability into designed effects and additive random effects. The ensuing (Bayesian) hierarchical model conveys both the estimated connection strengths and their uncertainty (i.e., posterior covariance) from the subject to the group level; enabling hypotheses to be tested about the commonalities and differences across subjects. This approach can also finesse parameter estimation at the subject level, by using the group-level parameters as empirical priors. The preliminary first level (subject specific) DCM for fMRI analysis is covered in a companion paper. Here, we detail group-level analysis procedures that are suitable for use with data from any neuroimaging modality. This paper is accompanied by an example dataset, together with step-by-step instructions demonstrating how to reproduce the analyses., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Dynamic Causal Modelling (DCM) is the predominant method for inferring effective connectivity from neuroimaging data. In the 15 years since its introduction, the neural models and statistical routines in DCM have developed in parallel, driven by the needs of researchers in cognitive and clinical neuroscience. In this guide, we step through an exemplar fMRI analysis in detail, reviewing the current implementation of DCM and demonstrating recent developments in group-level connectivity analysis. In the appendices, we detail the theory underlying DCM and the assumptions (i.e., priors) in the models. In the first part of the guide (current paper), we focus on issues specific to DCM for fMRI. This is accompanied by all the necessary data and instructions to reproduce the analyses using the SPM software. In the second part (in a companion paper), we move from subject-level to group-level modelling using the Parametric Empirical Bayes framework, and illustrate how to test for commonalities and differences in effective connectivity across subjects, based on imaging data from any modality., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

During word and object recognition, extensive activation has consistently been observed in the left ventral occipito-temporal cortex (vOT), focused around the occipito-temporal sulcus (OTs). Previous studies have shown that there is a hierarchy of responses from posterior to anterior vOT regions (along the y-axis) that corresponds with increasing levels of recognition - from perceptual to semantic processing, respectively. In contrast, the functional differences between superior and inferior vOT responses (i.e. along the z-axis) have not yet been elucidated. To investigate, we conducted an extensive review of the literature and found that peak activation for reading varies by more than 1 cm in the z-axis. In addition, we investigated functional differences between superior and inferior parts of left vOT by analysing functional MRI data from 58 neurologically normal skilled readers performing 8 different visual processing tasks. We found that group activation in superior vOT was significantly more sensitive than inferior vOT to the type of task, with more superior vOT activation when participants were matching visual stimuli for their semantic or perceptual content than producing speech to the same stimuli. This functional difference along the z-axis was compared to existing boundaries between cytoarchitectonic areas around the OTs. In addition, using dynamic causal modelling, we show that connectivity from superior vOT to anterior vOT increased with semantic content during matching tasks but not during speaking tasks whereas connectivity from inferior vOT to anterior vOT was sensitive to semantic content for matching and speaking tasks. The finding of a functional dissociation between superior and inferior parts of vOT has implications for predicting deficits and response to rehabilitation for patients with partial damage to vOT following stroke or neurosurgery., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

FMRI-based laterality index (LI) is widely used to assess relative left-right differences in brain function. Here we investigated objective ways to generate categorical LI. By defining left and right hemisphere contributions as discrete random variables, it was possible to depict the probability mass function of LI. Its distribution has a shape of a symmetrical truncated exponential function. We demonstrate that LI = ± 0.2 is an objective cut-off to categorize classification of hemispheric dominance. We then searched for parallels between LI and classic similarity or association indices. A parallel between LI and Sorensen-Dice index can be established under maximal voxel-wise overlap between left and right hemispheres. To redefine LI as a proper distance metric, we suggest instead to relate LI to Jaccard-Tanimoto similarity index. Accordingly, a new LI formula can be derived: LI new  = LH-RH/max(LH,RH). Using this new formula, all LI new values follow a uniform-like distribution, and optimal categorization of hemispheric dominance can be achieved at cut-off LI new  = ± 1/3. Overall, this study investigated some statistical properties of LI and revealed interesting parallels with classic similarity indices in taxonomy. The theoretical distribution of LI should be taken into account when quantifying any existing bias in empirical distributions of lateralization in healthy or clinical populations.

Decisions differ in difficulty and rely on perceptual information that varies in richness (complexity); aging affects cognitive function including decision-making, and yet, the interaction between difficulty and perceptual complexity have rarely been addressed in aging. Using a parametric fMRI modulation analysis and psychophysics, we address how task difficulty affects decision-making when controlling for the complexity of the perceptual context in which decisions are made. Perceptual complexity was varied in a factorial design while participants made perceptual judgments on the spatial frequency of two patches that either shared the same orientation (simple condition) or were orthogonal in orientation (complex condition). Psychophysical thresholds were measured for each participant in each condition and served to set individualized levels of difficulty during scanning. Findings indicate that discriminability interacts with complexity, to influence decisional difficulty. Modulation as a function of difficulty is maintained with age, as indicated by coupling between increased activation in fronto-parietal regions and suppression in the lateral hubs, however, age has a specific effect in the ventral anterior cingulate cortex (ACC), driven by performance at near-threshold (difficult) levels for the simpler stimulus combination condition, but not the more complex one. Taken together, our findings suggest that the context of difficulty, or what is perceived as important, changes with age, and that decisions that would seem neutral to younger participants, may carry more emphasis with age.

Acquired language disorders after stroke are strongly associated with left hemisphere damage. When language difficulties are observed in the context of right hemisphere strokes, patients are usually considered to have atypical functional anatomy. By systematically integrating behavioural and lesion data from brain damaged patients with functional MRI data from neurologically normal participants, we investigated when and why right hemisphere strokes cause language disorders. Experiment 1 studied right-handed patients with unilateral strokes that damaged the right (n = 109) or left (n = 369) hemispheres. The most frequently impaired language task was: auditory sentence-to-picture matching after right hemisphere strokes; and spoken picture description after left hemisphere strokes. For those with auditory sentence-to-picture matching impairments after right hemisphere strokes, the majority (n = 9) had normal performance on tests of perceptual (visual or auditory) and linguistic (semantic, phonological or syntactic) processing. Experiment 2 found that these nine patients had significantly more damage to dorsal parts of the superior longitudinal fasciculus and the right inferior frontal sulcus compared to 75 other patients who also had right hemisphere strokes but were not impaired on the auditory sentence-to-picture matching task. Damage to these right hemisphere regions caused long-term speech comprehension difficulties in 67% of patients. Experiments 3 and 4 used functional MRI in two groups of 25 neurologically normal individuals to show that within the regions identified by Experiment 2, the right inferior frontal sulcus was normally activated by (i) auditory sentence-to-picture matching; and (ii) one-back matching when the demands on linguistic and non-linguistic working memory were high. Together, these experiments demonstrate that the right inferior frontal cortex contributes to linguistic and non-linguistic working memory capacity (executive function) that is needed for normal speech comprehension. Our results link previously unrelated literatures on the role of the right inferior frontal cortex in executive processing and the role of executive processing in sentence comprehension; which in turn helps to explain why right inferior frontal activity has previously been reported to increase during recovery of language function after left hemisphere stroke. The clinical relevance of our findings is that the detrimental effect of right hemisphere strokes on language is (i) much greater than expected; (ii) frequently observed after damage to the right inferior frontal sulcus; (iii) task dependent; (iv) different to the type of impairments observed after left hemisphere strokes; and (v) can result in long-lasting deficits that are (vi) not the consequence of atypical language lateralization.

Model-free methods are widely used for the processing of brain fMRI data collected under natural stimulations, sleep, or rest. Among them is the popular fuzzy c -mean algorithm, commonly combined with cluster validity (CV) indices to identify the 'true' number of clusters (components), in an unsupervised way. CV indices may however reveal different optimal c -partitions for the same fMRI data, and their effectiveness can be hindered by the high data dimensionality, the limited signal-to-noise ratio, the small proportion of relevant voxels, and the presence of artefacts or outliers. Here, the author investigated the behaviour of seven robust CV indices. A new CV index that incorporates both compactness and separation measures is also introduced. Using both artificial and real fMRI data, the findings highlight the importance of looking at the behavior of different compactness and separation measures, defined here as building blocks of CV indices, to depict a full description of the data structure, in particular when no agreement is found between CV indices. Overall, for fMRI, it makes sense to relax the assumption that only one unique c -partition exists, and appreciate that different c -partitions (with different optimal numbers of clusters) can be useful explanations of the data, given the hierarchical organization of many brain networks., Competing Interests: The authors declare there are no competing interests.

This study investigated how sample size affects the reproducibility of findings from univariate voxel-based lesion-deficit analyses (e.g., voxel-based lesion-symptom mapping and voxel-based morphometry). Our effect of interest was the strength of the mapping between brain damage and speech articulation difficulties, as measured in terms of the proportion of variance explained. First, we identified a region of interest by searching on a voxel-by-voxel basis for brain areas where greater lesion load was associated with poorer speech articulation using a large sample of 360 right-handed English-speaking stroke survivors. We then randomly drew thousands of bootstrap samples from this data set that included either 30, 60, 90, 120, 180, or 360 patients. For each resample, we recorded effect size estimates and p values after conducting exactly the same lesion-deficit analysis within the previously identified region of interest and holding all procedures constant. The results show (1) how often small effect sizes in a heterogeneous population fail to be detected; (2) how effect size and its statistical significance varies with sample size; (3) how low-powered studies (due to small sample sizes) can greatly over-estimate as well as under-estimate effect sizes; and (4) how large sample sizes (N ≥ 90) can yield highly significant p values even when effect sizes are so small that they become trivial in practical terms. The implications of these findings for interpreting the results from univariate voxel-based lesion-deficit analyses are discussed., (Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In this study, we hypothesized that if the same deficit can be caused by damage to one or another part of a distributed neural system, then voxel-based analyses might miss critical lesion sites because preservation of each site will not be consistently associated with preserved function. The first part of our investigation used voxel-based multiple regression analyses of data from 359 right-handed stroke survivors to identify brain regions where lesion load is associated with picture naming abilities after factoring out variance related to object recognition, semantics and speech articulation so as to focus on deficits arising at the word retrieval level. A highly significant lesion-deficit relationship was identified in left temporal and frontal/premotor regions. Post-hoc analyses showed that damage to either of these sites caused the deficit of interest in less than half the affected patients (76/162 = 47%). After excluding all patients with damage to one or both of the identified regions, our second analysis revealed a new region, in the anterior part of the left putamen, which had not been previously detected because many patients had the deficit of interest after temporal or frontal damage that preserved the left putamen. The results illustrate how (i) false negative results arise when the same deficit can be caused by different lesion sites; (ii) some of the missed effects can be unveiled by adopting an iterative approach that systematically excludes patients with lesions to the areas identified in previous analyses, (iii) statistically significant voxel-based lesion-deficit mappings can be driven by a subset of patients; (iv) focal lesions to the identified regions are needed to determine whether the deficit of interest is the consequence of focal damage or much more extensive damage that includes the identified region; and, finally, (v) univariate voxel-based lesion-deficit mappings cannot, in isolation, be used to predict outcome in other patients., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We consider between-subject variance in brain function as data rather than noise. We describe variability as a natural output of a noisy plastic system (the brain) where each subject embodies a particular parameterisation of that system. In this context, variability becomes an opportunity to: (i) better characterise typical versus atypical brain functions; (ii) reveal the different cognitive strategies and processing networks that can sustain similar tasks; and (iii) predict recovery capacity after brain damage by taking into account both damaged and spared processing pathways. This has many ramifications for understanding individual learning preferences and explaining the wide differences in human abilities and disabilities. Understanding variability boosts the translational potential of neuroimaging findings, in particular in clinical and educational neuroscience., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Stroke survivors with acquired language deficits are commonly thought to reach a 'plateau' within a year of stroke onset, after which their residual language skills will remain stable. Nevertheless, there have been reports of patients who appear to recover over years. Here, we analysed longitudinal change in 28 left-hemisphere stroke patients, each more than a year post-stroke when first assessed-testing each patient's spoken object naming skills and acquiring structural brain scans twice. Some of the patients appeared to improve over time while others declined; both directions of change were associated with, and predictable given, structural adaptation in the intact right hemisphere of the brain. Contrary to the prevailing view that these patients' language skills are stable, these results imply that real change continues over years. The strongest brain-behaviour associations (the 'peak clusters') were in the anterior temporal lobe and the precentral gyrus. Using functional magnetic resonance imaging, we confirmed that both regions are actively involved when neurologically normal control subjects name visually presented objects, but neither appeared to be involved when the same participants used a finger press to make semantic association decisions on the same stimuli. This suggests that these regions serve word-retrieval or articulatory functions in the undamaged brain. We teased these interpretations apart by reference to change in other tasks. Consistent with the claim that the real change is occurring here, change in spoken object naming was correlated with change in two other similar tasks, spoken action naming and written object naming, each of which was independently associated with structural adaptation in similar (overlapping) right hemisphere regions. Change in written object naming, which requires word-retrieval but not articulation, was also significantly more correlated with both (i) change in spoken object naming; and (ii) structural adaptation in the two peak clusters, than was change in another task-auditory word repetition-which requires articulation but not word retrieval. This suggests that the changes in spoken object naming reflected variation at the level of word-retrieval processes. Surprisingly, given their qualitatively similar activation profiles, hypertrophy in the anterior temporal region was associated with improving behaviour, while hypertrophy in the precentral gyrus was associated with declining behaviour. We predict that either or both of these regions might be fruitful targets for neural stimulation studies (suppressing the precentral region and/or enhancing the anterior temporal region), aiming to encourage recovery or arrest decline even years after stroke occurs., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Transcranial magnetic stimulation focused on either the left anterior supramarginal gyrus or opercular part of the left inferior frontal gyrus has been reported to transiently impair the ability to perform phonological more than semantic tasks. Here we tested whether phonological processing abilities were also impaired following lesions to these regions in right-handed, English speaking adults, who were investigated at least 1 year after a left-hemisphere stroke. When our regions of interest were limited to 0.5 cm3 of grey matter centred around sites that had been identified with transcranial magnetic stimulation-based functional localization, phonological impairments were observed in 74% (40/54) of patients with damage to the regions and 21% (21/100) of patients sparing these regions. This classification accuracy was better than that observed when using regions of interest centred on activation sites in previous functional magnetic resonance imaging studies of phonological processing, or transcranial magnetic stimulation sites that did not use functional localization. New regions of interest were generated by redefining the borders of each of the transcranial magnetic stimulation sites to include areas that were consistently damaged in the patients with phonological impairments. This increased the incidence of phonological impairments in the presence of damage to 85% (46/54) and also reduced the incidence of phonological impairments in the absence of damage to 15% (15/100). The difference in phonological processing abilities between those with and without damage to these 'transcranial magnetic stimulation-guided' regions remained highly significant even after controlling for the effect of lesion size. The classification accuracy of the transcranial magnetic stimulation-guided regions was validated in a second sample of 108 patients and found to be better than that for (i) functional magnetic resonance imaging-guided regions; (ii) a region identified from an unguided lesion overlap map; and (iii) a region identified from voxel-based lesion-symptom mapping. Finally, consistent with prior findings from functional imaging and transcranial magnetic stimulation in healthy participants, we show how damage to our transcranial magnetic stimulation-guided regions affected performance on phonologically more than semantically demanding tasks. The observation that phonological processing abilities were impaired years after the stroke, suggests that other brain regions were not able to fully compensate for the contribution that the transcranial magnetic stimulation-guided regions make to language tasks. More generally, our novel transcranial magnetic stimulation-guided lesion-deficit mapping approach shows how non-invasive stimulation of the healthy brain can be used to guide the identification of regions where brain damage is likely to cause persistent behavioural effects., (© The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.)

In this paper, we consider solutions to ten of the challenges faced when trying to predict an individual's functional outcome after stroke on the basis of lesion site. A primary goal is to find lesion-outcome associations that are consistently observed in large populations of stroke patients because consistent associations maximise confidence in future individualised predictions. To understand and control multiple sources of inter-patient variability, we need to systematically investigate each contributing factor and how each factor depends on other factors. This requires very large cohorts of patients, who differ from one another in typical and measurable ways, including lesion site, lesion size, functional outcome and time post stroke (weeks to decades). These multivariate investigations are complex, particularly when the contributions of different variables interact with one another. Machine learning algorithms can help to identify the most influential variables and indicate dependencies between different factors. Multivariate lesion analyses are needed to understand how the effect of damage to one brain region depends on damage or preservation in other brain regions. Such data-led investigations can reveal predictive relationships between lesion site and outcome. However, to understand and improve the predictions we need explanatory models of the neural networks and degenerate pathways that support functions of interest. This will entail integrating the results of lesion analyses with those from functional imaging (fMRI, MEG), transcranial magnetic stimulation (TMS) and diffusor tensor imaging (DTI) studies of healthy participants and patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

This paper considers the identification of large directed graphs for resting-state brain networks based on biophysical models of distributed neuronal activity, that is, effective connectivity . This identification can be contrasted with functional connectivity methods based on symmetric correlations that are ubiquitous in resting-state functional MRI (fMRI). We use spectral dynamic causal modeling (DCM) to invert large graphs comprising dozens of nodes or regions. The ensuing graphs are directed and weighted, hence providing a neurobiologically plausible characterization of connectivity in terms of excitatory and inhibitory coupling. Furthermore, we show that the use of to discover the most likely sparse graph (or model) from a parent (e.g., fully connected) graph eschews the arbitrary thresholding often applied to large symmetric (functional connectivity) graphs. Using empirical fMRI data, we show that spectral DCM furnishes connectivity estimates on large graphs that correlate strongly with the estimates provided by stochastic DCM. Furthermore, we increase the efficiency of model inversion using functional connectivity modes to place prior constraints on effective connectivity. In other words, we use a small number of modes to finesse the potentially redundant parameterization of large DCMs. We show that spectral DCM-with functional connectivity priors-is ideally suited for directed graph theoretic analyses of resting-state fMRI. We envision that directed graphs will prove useful in understanding the psychopathology and pathophysiology of neurodegenerative and neurodevelopmental disorders. We will demonstrate the utility of large directed graphs in clinical populations in subsequent reports, using the procedures described in this paper., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

We used fMRI in 85 healthy participants to investigate whether different parts of the left supramarginal gyrus (SMG) are involved in processing phonological inputs and outputs. The experiment involved 2 tasks (speech production (SP) and one-back (OB) matching) on 8 different types of stimuli that systematically varied the demands on sensory processing (visual vs. auditory), sublexical phonological input (words and pseudowords vs. nonverbal stimuli), and semantic content (words and objects vs. pseudowords and meaningless baseline stimuli). In ventral SMG, we found an anterior subregion associated with articulatory sequencing (for SP > OB matching) and a posterior subregion associated with auditory short-term memory (for all auditory > visual stimuli and written words and pseudowords > objects). In dorsal SMG, a posterior subregion was most highly activated by words, indicating a role in the integration of sublexical and lexical cues. In anterior dorsal SMG, activation was higher for both pseudoword reading and object naming compared with word reading, which is more consistent with executive demands than phonological processing. The dissociation of these four "functionally-distinct" regions, all within left SMG, has implications for differentiating between different types of phonological processing, understanding the functional anatomy of language and predicting the effect of brain damage., (© The Author 2016. Published by Oxford University Press.)

Functional neuroimaging studies are revealing the neural systems sustaining many sensory, motor and cognitive abilities. A proper understanding of these systems requires an appreciation of the degree to which they vary across subjects. Some sources of inter-subject variability might be easy to measure (demographics, behavioural scores, or experimental factors), while others are more difficult (cognitive strategies, learning effects, and other hidden sources). Here, we introduce a simple way of visualising whole-brain consistency and variability in brain responses across subjects using threshold-weighted voxel-based overlap maps. The output quantifies the proportion of subjects activating a particular voxel or region over a wide range of statistical thresholds. The sensitivity of our approach was assessed in 30 healthy adults performing a matching task with their dominant hand. We show how overlap maps revealed many effects that were only present in a subsample of our group; we discuss how overlap maps can provide information that may be missed or misrepresented by standard group analysis, and how this information can help users to understand their data. In particular, we emphasize that functional overlap maps can be particularly useful when it comes to explaining typical (or atypical) compensatory mechanisms used by patients following brain damage.

Brain imaging studies of functional outcomes after white matter damage have quantified the severity of white matter damage in different ways. Here we compared how the outcome of such studies depends on two different types of measurements: the proportion of the target tract that has been destroyed ('lesion load') and tract disconnection. We demonstrate that conclusions from analyses based on two examples of these measures diverge and that conclusions based solely on lesion load may be misleading. First, we reproduce a recent lesion-load-only analysis which suggests that damage to the arcuate fasciculus, and not to the uncinate fasciculus, is significantly associated with deficits in fluency and naming skills. Next, we repeat the analysis after replacing the measures of lesion load with measures of tract disconnection for both tracts, and observe significant associations between both tracts and both language skills: i.e. the change increases the apparent relevance of the uncinate fasciculus to fluency and naming skills. Finally we show that, in this dataset, disconnection data explains significant variance in both language skills that is not accounted for by lesion load or volume, but lesion load data explains no unique variance in those skills, once disconnection and lesion volume are taken into account., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The PLORAS Database is a relational repository of anatomical and functional imaging data that has primarily been acquired from stroke survivors, along with standardized scores on a wide range of sensory, motor and cognitive abilities, demographic details and medical history. As of January 2015, we have data from 750 patients with an expected accrual rate of 200 patients per year. Expansion will accelerate as we extend our collaborations. The main aim of the database is to Predict Language Outcome and Recovery After Stroke (PLORAS) on the basis of a single structural (anatomical) brain scan that indexes the stereotactic location and extent of brain damage. Predictions are made for individual patients by indicating how other patients with the most similar brain damage, cognitive abilities and demographic details recovered their language skills over time. Predictions are validated by longitudinal follow-ups of patients who initially presented with speech and language difficulties. The PLORAS Database can also be used to predict recovery of other cognitive abilities on the basis of anatomical brain scans. The functional imaging data can be used to understand the neural mechanisms that support recovery from brain damage; and all the data can be used to understand the main sources of inter-subject variability in structure-function mappings in the human brain. Data will be made available for sharing, subject to: funding, ethical approval and patient consent., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

We used fMRI in 35 healthy participants to investigate how two neighbouring subregions in the lateral anterior temporal lobe (LATL) contribute to semantic matching and object naming. Four different levels of processing were considered: (A) recognition of the object concepts; (B) search for semantic associations related to object stimuli; (C) retrieval of semantic concepts of interest; and (D) retrieval of stimulus specific concepts as required for naming. During semantic association matching on picture stimuli or heard object names, we found that activation in both subregions was higher when the objects were semantically related (mug-kettle) than unrelated (car-teapot). This is consistent with both LATL subregions playing a role in (C), the successful retrieval of amodal semantic concepts. In addition, one subregion was more activated for object naming than matching semantically related objects, consistent with (D), the retrieval of a specific concept for naming. We discuss the implications of these novel findings for cognitive models of semantic processing and left anterior temporal lobe function., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Post-stroke prognoses are usually inductive, generalizing trends learned from one group of patients, whose outcomes are known, to make predictions for new patients. Research into the recovery of language function is almost exclusively focused on monolingual stroke patients, but bilingualism is the norm in many parts of the world. If bilingual language recruits qualitatively different networks in the brain, prognostic models developed for monolinguals might not generalize well to bilingual stroke patients. Here, we sought to establish how applicable post-stroke prognostic models, trained with monolingual patient data, are to bilingual stroke patients who had been ordinarily resident in the UK for many years. We used an algorithm to extract binary lesion images for each stroke patient, and assessed their language with a standard tool. We used feature selection and cross-validation to find 'good' prognostic models for each of 22 different language skills, using monolingual data only (174 patients; 112 males and 62 females; age at stroke: mean = 53.0 years, standard deviation = 12.2 years, range = 17.2-80.1 years; time post-stroke: mean = 55.6 months, standard deviation = 62.6 months, range = 3.1-431.9 months), then made predictions for both monolinguals and bilinguals (33 patients; 18 males and 15 females; age at stroke: mean = 49.0 years, standard deviation = 13.2 years, range = 23.1-77.0 years; time post-stroke: mean = 49.2 months, standard deviation = 55.8 months, range = 3.9-219.9 months) separately, after training with monolingual data only. We measured group differences by comparing prediction error distributions, and used a Bayesian test to search for group differences in terms of lesion-deficit associations in the brain. Our models distinguish better outcomes from worse outcomes equally well within each group, but tended to be over-optimistic when predicting bilingual language outcomes: our bilingual patients tended to have poorer language skills than expected, based on trends learned from monolingual data alone, and this was significant (P < 0.05, corrected for multiple comparisons) in 13/22 language tasks. Both patient groups appeared to be sensitive to damage in the same sets of regions, though the bilinguals were more sensitive than the monolinguals. media-1vid1 10.1093/brain/awv020&#95;video&#95;abstract awv020&#95;video&#95;abstract., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.)

The parietal operculum, particularly the cytoarchitectonic area OP1 of the secondary somatosensory area (SII), is involved in somatosensory feedback. Using fMRI with 58 human subjects, we investigated task-dependent differences in SII/OP1 activity during three familiar speech production tasks: object naming, reading and repeatedly saying "1-2-3." Bilateral SII/OP1 was significantly suppressed (relative to rest) during object naming, to a lesser extent when repeatedly saying "1-2-3" and not at all during reading. These results cannot be explained by task difficulty but the contrasting difference between naming and reading illustrates how the demands on somatosensory activity change with task, even when motor output (i.e., production of object names) is matched. To investigate what determined SII/OP1 deactivation during object naming, we searched the whole brain for areas where activity increased as that in SII/OP1 decreased. This across subject covariance analysis revealed a region in the right superior temporal sulcus (STS) that lies within the auditory cortex, and is activated by auditory feedback during speech production. The tradeoff between activity in SII/OP1 and STS was not observed during reading, which showed significantly more activation than naming in both SII/OP1 and STS bilaterally. These findings suggest that, although object naming is more error prone than reading, subjects can afford to rely more or less on somatosensory or auditory feedback during naming. In contrast, fast and efficient error-free reading places more consistent demands on both types of feedback, perhaps because of the potential for increased competition between lexical and sublexical codes at the articulatory level., (Copyright © 2015 Seghier et al.)

The left putamen is known to be important for speech production, but some patients with left putamen damage can produce speech remarkably well. We investigated the neural mechanisms that support this recovery by using a combination of techniques to identify the neural regions and pathways that compensate for loss of the left putamen during speech production. First, we used fMRI to identify the brain regions that were activated during reading aloud and picture naming in a patient with left putamen damage. This revealed that the patient had abnormally high activity in the left premotor cortex. Second, we used dynamic causal modeling of the patient's fMRI data to understand how this premotor activity influenced other speech production regions and whether the same neural pathway was used by our 24 neurologically normal control subjects. Third, we validated the compensatory relationship between putamen and premotor cortex by showing, in the control subjects, that lower connectivity through the putamen increased connectivity through premotor cortex. Finally, in a lesion-deficit analysis, we demonstrate the explanatory power of our fMRI results in new patients who had damage to the left putamen, left premotor cortex, or both. Those with damage to both had worse reading and naming scores. The results of our four-pronged approach therefore have clinical implications for predicting which patients are more or less likely to recover their speech after left putaminal damage., (Copyright © 2014 Seghier et al.)