Cognitive decline assessment in speakers of understudied languages.

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.

Transformers for autonomous recognition of psychiatric dysfunction via raw and imbalanced EEG signals.

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.

An appraisal of the performance of AI tools for chronic stroke lesion segmentation.

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.

Interpreting and validating complexity and causality in lesion-symptom prognoses.

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.

The elusive metric of lesion load.

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.

Multiple functions of the angular gyrus at high temporal resolution.

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.

A Data-Based Approach for Selecting Pre- and Intra-Operative Language Mapping Tasks.

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.

Lesions that do or do not impair digit span: a study of 816 stroke survivors.

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.

Damage to Broca's area does not contribute to long-term speech production outcome after stroke.

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.

An active human role is essential in big data-led decisions and data-intensive science.

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.

Educational fMRI: From the Lab to the Classroom.

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.

Dissociating the functions of superior and inferior parts of the left ventral occipito-temporal cortex during visual word and object processing.

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.

A guide to group effective connectivity analysis, part 2: Second level analysis with PEB.

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.

A guide to group effective connectivity analysis, part 1: First level analysis with DCM for fMRI.

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.

Age Affects How Task Difficulty and Complexity Modulate Perceptual Decision-Making.

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.

Categorical laterality indices in fMRI: a parallel with classic similarity indices.

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: LInew = LH-RH/max(LH,RH). Using this new formula, all LInew values follow a uniform-like distribution, and optimal categorization of hemispheric dominance can be achieved at cut-off LInew = ± 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.

How right hemisphere damage after stroke can impair speech comprehension.

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.