Design of a video game for assessment of executive functions in deaf and hearing children.

This study investigates the effectiveness of a computerized cognitive test battery embedded within a video game to assess executive functions (EF) in deaf and hearing children. We evaluated a diverse cohort of 290 elementary school students aged 5 to 13 years (mean age = 8.86, SD = 1.96), comprising 74 sign language users, 14 Spanish-speaking deaf participants, 23 children with mixed communication methods, and 179 typically hearing individuals. Our statistical analysis focused on item discrimination, reliability, and criterion validation of the game-based assessments. The results indicated high reliability and effective discrimination of EF across the game's three primary stages. External validation was conducted using the Matrices Test, educational attainment, and age as variables. A significant positive correlation (r = 0.377, p < 0.001) was observed between the Matrices Test scores and game-based achievement scores. Furthermore, linear regression analysis revealed education (Standardized Beta = 0.339) and age (Standardized Beta = 0.179) as significant predictors of performance in these scores. This study underscores the value of integrating computerized cognitive assessments within a video game environment for comprehensive neuropsychological evaluations, highlighting its potential in diverse child populations.

Classification of Alzheimer's disease and frontotemporal dementia using routine clinical and cognitive measures across multicentric underrepresented samples: A cross sectional observational study.

Background: Global brain health initiatives call for improving methods for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD) in underrepresented populations. However, diagnostic procedures in upper-middle-income countries (UMICs) and lower-middle income countries (LMICs), such as Latin American countries (LAC), face multiple challenges. These include the heterogeneity in diagnostic methods, lack of clinical harmonisation, and limited access to biomarkers. Methods: This cross-sectional observational study aimed to identify the best combination of predictors to discriminate between AD and FTD using demographic, clinical and cognitive data among 1794 participants [904 diagnosed with AD, 282 diagnosed with FTD, and 606 healthy controls (HCs)] collected in 11 clinical centres across five LAC (ReDLat cohort). Findings: A fully automated computational approach included classical statistical methods, support vector machine procedures, and machine learning techniques (random forest and sequential feature selection procedures). Results demonstrated an accurate classification of patients with AD and FTD and HCs. A machine learning model produced the best values to differentiate AD from FTD patients with an accuracy = 0.91. The top features included social cognition, neuropsychiatric symptoms, executive functioning performance, and cognitive screening; with secondary contributions from age, educational attainment, and sex. Interpretation: Results demonstrate that data-driven techniques applied in archival clinical datasets could enhance diagnostic procedures in regions with limited resources. These results also suggest specific fine-grained cognitive and behavioural measures may aid in the diagnosis of AD and FTD in LAC. Moreover, our results highlight an opportunity for harmonisation of clinical tools for dementia diagnosis in the region. Funding: This work was supported by the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat), funded by NIA/NIH (R01AG057234), Alzheimer's Association (SG-20-725707-ReDLat), Rainwater Foundation, Takeda (CW2680521), Global Brain Health Institute; as well as CONICET; FONCYT-PICT (2017-1818, 2017-1820); PIIECC, Facultad de Humanidades, Usach; Sistema General de Regalías de Colombia (BPIN2018000100059), Universidad del Valle (CI 5316); ANID/FONDECYT Regular (1210195, 1210176, 1210176); ANID/FONDAP (15150012); ANID/PIA/ANILLOS ACT210096; and Alzheimer's Association GBHI ALZ UK-22-865742.

Semantic Memory and Lexical Availability in Parkinson's Disease: A Statistical Learning Study.

Parkinson's disease (PD) is a neurodegenerative disorder that causes a progressive impairment in motor and cognitive functions. Although semantic fluency deficits have been described in PD, more specific semantic memory (SM) and lexical availability (LA) domains have not been previously addressed. Here, we aimed to characterize the cognitive performance of PD patients in a set of SM and LA measures and determine the smallest set of neuropsychological (lexical, semantic, or executive) variables that most accurately classify groups. Thirty early-stage non-demented PD patients (age 35-75, 10 females) and thirty healthy controls (age 36-76, 12 females) were assessed via general cognitive, SM [three subtests of the CaGi battery including living (i.e., elephant) and non-living things (i.e., fork)], and LA (eliciting words from 10 semantic categories related to everyday life) measures. Results showed that PD patients performed lower than controls in two SM global scores (picture naming and naming in response to an oral description). This impairment was particularly pronounced in the non-living things subscale. Also, the number of words in the LA measure was inferior in PD patients than controls, in both larger and smaller semantic fields, showing a more inadequate recall strategy. Notably, the classification algorithms indicated that the SM task had high classification accuracy. In particular, the denomination of non-living things had a classification accuracy of ∼80%. These results suggest that frontostriatal deterioration in PD leads to search strategy deficits in SF and the potential disruption in semantic categorization. These findings are consistent with the embodied view of cognition.

Predicting and Characterizing Neurodegenerative Subtypes with Multimodal Neurocognitive Signatures of Social and Cognitive Processes.

BACKGROUND: Social cognition is critically compromised across neurodegenerative diseases, including the behavioral variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD). However, no previous study has used social cognition and other cognitive tasks to predict diagnoses of these conditions, let alone reporting the brain correlates of prediction outcomes. OBJECTIVE: We performed a diagnostic classification analysis using social cognition, cognitive screening (CS), and executive function (EF) measures, and explored which anatomical and functional networks were associated with main predictors. METHODS: Multiple group discriminant function analyses (MDAs) and ROC analyses of social cognition (facial emotional recognition, theory of mind), CS, and EF were implemented in 223 participants (bvFTD, AD, PD, controls). Gray matter volume and functional connectivity correlates of top discriminant scores were investigated. RESULTS: Although all patient groups revealed deficits in social cognition, CS, and EF, our classification approach provided robust discriminatory characterizations. Regarding controls, probabilistic social cognition outcomes provided the best characterization for bvFTD (together with CS) and PD, but not AD (for which CS alone was the best predictor). Within patient groups, the best MDA probabilities scores yielded high classification rates for bvFTD versus PD (98.3%, social cognition), AD versus PD (98.6%, social cognition + CS), and bvFTD versus AD (71.7%, social cognition + CS). Top MDA scores were associated with specific patterns of atrophy and functional networks across neurodegenerative conditions. CONCLUSION: Standardized validated measures of social cognition, in combination with CS, can provide a dimensional classification with specific pathophysiological markers of neurodegeneration diagnoses.

Short-Term Memory Binding Distinguishing Amnestic Mild Cognitive Impairment from Healthy Aging: A Machine Learning Study.

BACKGROUND: Amnestic mild cognitive impairment (aMCI) is the most common preclinical stage of Alzheimer's disease (AD). A strategy to reduce the impact of AD is the early aMCI diagnosis and clinical intervention. Neuroimaging, neurobiological, and genetic markers have proved to be sensitive and specific for the early diagnosis of AD. However, the high cost of these procedures is prohibitive in low-income and middle-income countries (LIMCs). The neuropsychological assessments currently aim to identify cognitive markers that could contribute to the early diagnosis of dementia. OBJECTIVE: Compare machine learning (ML) architectures classifying and predicting aMCI and asset the contribution of cognitive measures including binding function in distinction and prediction of aMCI. METHODS: We conducted a two-year follow-up assessment of a sample of 154 subjects with a comprehensive multidomain neuropsychological battery. Statistical analysis was proposed using complete ML architectures to compare subjects' performance to classify and predict aMCI. Additionally, permutation importance and Shapley additive explanations (SHAP) routines were implemented for feature importance selection. RESULTS: AdaBoost, gradient boosting, and XGBoost had the highest performance with over 80%success classifying aMCI, and decision tree and random forest had the highest performance with over 70%success predictive routines. Feature importance points, the auditory verbal learning test, short-term memory binding tasks, and verbal and category fluency tasks were used as variables with the first grade of importance to distinguish healthy cognition and aMCI. CONCLUSION: Although neuropsychological measures do not replace biomarkers' utility, it is a relatively sensitive and specific diagnostic tool for aMCI. Further studies with ML must identify cognitive performance that differentiates conversion from average MCI to the pathological MCI observed in AD.

Classifying Parkinson's Disease Patients With Syntactic and Socio-emotional Verbal Measures.

Frontostriatal disorders, such as Parkinson's disease (PD), are characterized by progressive disruption of cortico-subcortical dopaminergic loops involved in diverse higher-order domains, including language. Indeed, syntactic and emotional language tasks have emerged as potential biomarkers of frontostriatal disturbances. However, relevant studies and models have typically considered these linguistic dimensions in isolation, overlooking the potential advantages of targeting multidimensional markers. Here, we examined whether patient classification can be improved through the joint assessment of both dimensions using sentential stimuli. We evaluated 31 early PD patients and 24 healthy controls via two syntactic measures (functional-role assignment, parsing of long-distance dependencies) and a verbal task tapping social emotions (envy, Schadenfreude) and compared their classification accuracy when analyzed in isolation and in combination. Complementarily, we replicated our approach to discriminate between patients on and off medication. Results showed that specific measures of each dimension were selectively impaired in PD. In particular, joint analysis of outcomes in functional-role assignment and Schadenfreude improved the classification accuracy of patients and controls, irrespective of their overall cognitive and affective state. These results suggest that multidimensional linguistic assessments may better capture the complexity and multi-functional impact of frontostriatal disruptions, highlighting their potential contributions in the ongoing quest for sensitive markers of PD.

Transcranial Direct Current Stimulation to Enhance Cognitive Impairment in Parkinson's Disease: A Systematic Review and Meta-Analysis.

Cognitive deficits are increasingly being recognized as a common trait in Parkinson's disease (PD). Recently, transcranial direct current stimulation (tDCS) has been shown to exert positive effects as an adjunctive therapy on motor and non-motor symptoms in PD. This systematic review and meta-analysis aims to provide an overview of reported evidence on the efficacy of tDCS interventions in the treatment of cognitive impairments in PD. A systematic literature review was conducted to examine articles that were published in the past 10 years and that study the effects of tDCS on cognitive deficits in PD patients. The PubMed, Scopus and Scielo databases were searched. Eight tDCS studies involving 168 participants were included for the analysis. Our meta-analysis results showed that anodal tDCS (atDCS) had various levels or no evidence of effectiveness. In the pre-post stimulation analysis, a strong effect was reported for executive functions (pre-post: g = 1.51, Z = 2.41, p = 0.016); non-significant effects were reported for visuospatial skills (pre-post: g = 0.27, Z = 0.69, p = 0.490); attention (pre-post: g = 0.02, Z = 0.08, p = 0.934), memory (pre-post: g = 0.01, Z = 0.03, p = 0.972) and language (pre-post: g = 0.07, Z = 0.21, p = 0.832). However, in the pre-follow-up stimulation analysis, the duration of the effect was not clear. This study highlights the potential effectiveness of atDCS to improve cognitive performance in PD patients but failed to establish a cause-effect relationship between tDCS intervention and cognitive improvement in PD. Future directions and recommendations for methodological improvements are outlined.

From discourse to pathology: Automatic identification of Parkinson's disease patients via morphological measures across three languages.

Embodied cognition research on Parkinson's disease (PD) points to disruptions of frontostriatal language functions as sensitive targets for clinical assessment. However, no existing approach has been tested for crosslinguistic validity, let alone by combining naturalistic tasks with machine-learning tools. To address these issues, we conducted the first classifier-based examination of morphological processing (a core frontostriatal function) in spontaneous monologues from PD patients across three typologically different languages. The study comprised 330 participants, encompassing speakers of Spanish (61 patients, 57 matched controls), German (88 patients, 88 matched controls), and Czech (20 patients, 16 matched controls). All subjects described the activities they perform during a regular day, and their monologues were automatically coded via morphological tagging, a computerized method that labels each word with a part-of-speech tag (e.g., noun, verb) and specific morphological tags (e.g., person, gender, number, tense). The ensuing data were subjected to machine-learning analyses to assess whether differential morphological patterns could classify between patients and controls and reflect the former's degree of motor impairment. Results showed robust classification rates, with over 80% of patients being discriminated from controls in each language separately. Moreover, the most discriminative morphological features were associated with the patients' motor compromise (as indicated by Pearson r correlations between predicted and collected motor impairment scores that ranged from moderate to moderate-to-strong across languages). Taken together, our results suggest that morphological patterning, an embodied frontostriatal domain, may be distinctively affected in PD across languages and even under ecological testing conditions.

Assessment of Conjunctive Binding in Aging: A Promising Approach for Alzheimer's Disease Detection.

The visual experience of objects lies in the ability to perceive and integrate their constitutive features. Conjunctive binding (CB) is the cognitive function that integrates the features of objects as wholes. This review covers the main findings (over the last 10 years) concerning the role of CB in visual working memory (VWM) and cognitive theory, its neural correlates, as well as perspectives for future work. First, we discuss the theoretical cognitive models of CB and how these relate to other cognitive functions. We then integrate neuroimaging evidence with cognitive theory to identify the neural functional network of CB for encoding and maintenance. Also, we describe the field's transition from experimental to clinical research, which paves the way for work in the area of VWM binding and aging. Finally, we expose the challenges faced by this field of research and analyze its role in the study of dementia and the construction of neuro-cognitive models of conjunctive binding.

Early bilateral and massive compromise of the frontal lobes.

The frontal lobes are one of the most complex brain structures involved in both domain-general and specific functions. The goal of this work was to assess the anatomical and cognitive affectations from a unique case with massive bilateral frontal affectation. We report the case of GC, an eight-year old child with nearly complete affectation of bilateral frontal structures and spared temporal, parietal, occipital, and cerebellar regions. We performed behavioral, neuropsychological, and imaging (MRI, DTI, fMRI) evaluations. Neurological and neuropsychological examinations revealed a mixed pattern of affected (executive control/abstraction capacity) and considerably preserved (consciousness, language, memory, spatial orientation, and socio-emotional) functions. Both structural (DTI) and functional (fMRI) connectivity evidenced abnormal anterior connections of the amygdala and parietal networks. In addition, brain structural connectivity analysis revealed almost complete loss of frontal connections, with atypical temporo-posterior pathways. Similarly, functional connectivity showed an aberrant frontoparietal network and relative preservation of the posterior part of the default mode network and the visual network. We discuss this multilevel pattern of behavioral, structural, and functional connectivity results. With its unique pattern of compromised and preserved structures and functions, this exceptional case offers new constraints and challenges for neurocognitive theories.

Syntax, action verbs, action semantics, and object semantics in Parkinson's disease: Dissociability, progression, and executive influences.

Several studies have recently shown that basal ganglia (BG) deterioration leads to distinctive impairments in the domains of syntax, action verbs, and action semantics. In particular, such disruptions have been repeatedly observed in Parkinson's disease (PD) patients. However, it remains unclear whether these deficits are language-specific and whether they are equally dissociable from other reported disturbances -viz., processing of object semantics. To address these issues, we administered linguistic, semantic, and executive function (EFs) tasks to two groups of non-demented PD patients, with and without mild cognitive impairment (PD-MCI and PD-nMCI, respectively). We compared these two groups with each other and with matched samples of healthy controls. Our results showed that PD patients exhibited linguistic and semantic deficits even in the absence of MCI. However, not all domains were equally related to EFs and MCI across samples. Whereas EFs predicted disturbances of syntax and object semantics in both PD-nMCI and PD-MCI, they had no impact on action-verb and action-semantic impairments in either group. Critically, patients showed disruptions of action-verb production and action semantics in the absence of MCI and without any executive influence, suggesting a sui generis deficit present since early stages of the disease. These findings indicate that varied language domains are differentially related to the BG, contradicting popular approaches to neurolinguistics.

The impact of neuromyelitis optica on the recognition of emotional facial expressions: a preliminary report.

Although neuromyelitis optica (NMO) is classically recognized as an affectation of optic nerves and spinal cord, recent reports have shown brain atrophy and cognitive dysfunction in this condition. Importantly, emotion-related brain regions appear to be impaired in NMO. However, no studies of NMO' emotional processing have been published. The goal of the current study was to investigate facial emotion recognition in 10 patients with NMO and 10 healthy controls by controlling for relevant cognitive factors. Consistent with previous reports, NMO patients performed poorly across cognitive domains (divided attention, working memory, and information-processing speed). Our findings further evidence the relative inability of NMO patients to recognize negative emotions (disgust, anger, and fear), in comparison to controls, with these deficits not explained by other cognitive impairments. Results provide the first evidence that NMO may impair the ability to recognize negative emotions. These impairments appear to be related to possible damage in brain regions underling emotional networks, including the anterior cingulate cortex, amygdala, and medial prefrontal cortex. Findings increased both our understanding of NMO's cognitive impairment, and the neural networks underlying negative emotions.

How embodied is action language? Neurological evidence from motor diseases.

Although motor-language coupling is now being extensively studied, its underlying mechanisms are not fully understood. In this sense, a crucial opposition has emerged between the non-representational and the representational views of embodiment. The former posits that action language is grounded on the non-brain motor system directly engaged by musculoskeletal activity - i.e., peripheral involvement of ongoing actions. Conversely, the latter proposes that such grounding is afforded by the brain's motor system - i.e., activation of neural areas representing motor action. We addressed this controversy through the action-sentence compatibility effect (ACE) paradigm, which induces a contextual coupling of motor actions and verbal processing. ACEs were measured in three patient groups - early Parkinson's disease (EPD), neuromyelitis optica (NMO), and acute transverse myelitis (ATM) patients - as well as their respective healthy controls. NMO and ATM constitute models of injury to non-brain motor areas and the peripheral motor system, whereas EPD provides a model of brain motor system impairment. In our study, EPD patients exhibited impaired ACE and verbal processing relative to healthy participants, NMO, and ATM patients. These results indicate that the processing of action-related words is mainly subserved by a cortico-subcortical motor network system, thus supporting a brain-based embodied view on action language. More generally, our findings are consistent with contemporary perspectives for which action/verb processing depends on distributed brain networks supporting context-sensitive motor-language coupling.

N400 ERPs for actions: building meaning in context.

Converging neuroscientific evidence suggests the existence of close links between language and sensorimotor cognition. Accordingly, during the comprehension of meaningful actions, our brain would recruit semantic-related operations similar to those associated with the processing of language information. Consistent with this view, electrophysiological findings show that the N400 component, traditionally linked to the semantic processing of linguistic material, can also be elicited by action-related material. This review outlines recent data from N400 studies that examine the understanding of action events. We focus on three specific domains, including everyday action comprehension, co-speech gesture integration, and the semantics involved in motor planning and execution. Based on the reviewed findings, we suggest that both negativities (the N400 and the action-N400) reflect a common neurocognitive mechanism involved in the construction of meaning through the expectancies created by previous experiences and current contextual information. To shed light on how this process is instantiated in the brain, a testable contextual fronto-temporo-parietal model is proposed.

Motor-language coupling: direct evidence from early Parkinson's disease and intracranial cortical recordings.

Language and action systems are functionally coupled in the brain as demonstrated by converging evidence using Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), transcranial magnetic stimulation (TMS), and lesion studies. In particular, this coupling has been demonstrated using the action-sentence compatibility effect (ACE) in which motor activity and language interact. The ACE task requires participants to listen to sentences that described actions typically performed with an open hand (e.g., clapping), a closed hand (e.g., hammering), or without any hand action (neutral); and to press a large button with either an open hand position or closed hand position immediately upon comprehending each sentence. The ACE is defined as a longer reaction time (RT) in the action-sentence incompatible conditions than in the compatible conditions. Here we investigated direct motor-language coupling in two novel and uniquely informative ways. First, we measured the behavioural ACE in patients with motor impairment (early Parkinson's disease - EPD), and second, in epileptic patients with direct electrocorticography (ECoG) recordings. In experiment 1, EPD participants with preserved general cognitive repertoire, showed a much diminished ACE relative to non-EPD volunteers. Moreover, a correlation between ACE performance and action-verb processing (kissing and dancing test - KDT) was observed. Direct cortical recordings (ECoG) in motor and language areas (experiment 2) demonstrated simultaneous bidirectional effects: motor preparation affected language processing (N400 at left inferior frontal gyrus and middle/superior temporal gyrus), and language processing affected activity in movement-related areas (motor potential at premotor and M1). Our findings show that the ACE paradigm requires ongoing integration of preserved motor and language coupling (abolished in EPD) and engages motor-temporal cortices in a bidirectional way. In addition, both experiments suggest the presence of a motor-language network which is not restricted to somatotopically defined brain areas. These results open new pathways in the fields of motor diseases, theoretical approaches to language understanding, and models of action-perception coupling.

Potential consequences of abandonment in preschool-age: neuropsychological findings in institutionalized children.

OBJECTIVE: Several longitudinal studies had shown that early deprivation and institutionalization during the first six months of life affects the emotional, cognitive, social and neurophysiologic development. Nevertheless, our understanding of possible similar effects of delayed institutionalization, in preschool-age remains unclear to this day. The goal of this study is to evaluate the cognitive performance of institutionalized children with history of preschool-age physical abandonment. METHOD: 18 male institutionalized children with history of abandonment during the preschool-age (2-5 years old) and comparison group matched by age, handedness, gender, educational and socioeconomic level were tested on multiple tasks of attention, memory and executive functions. RESULTS: We found a cognitive impairment in the institutionalized children in several measures of attention, memory and executive functions. This is the first report of cognitive impairment related to late abandonment and institutionalization effects (after 2 years old), extending the already known effects on early institutionalization. CONCLUSIONS: This preliminary study suggests that environmental factors including abandonment and institutional care, can affect not only the infancy period, but also the preschool period providing new insights into our understanding of neurocognitive development.

Facial and semantic emotional interference: a pilot study on the behavioral and cortical responses to the Dual Valence Association Task.

BACKGROUND: Integration of compatible or incompatible emotional valence and semantic information is an essential aspect of complex social interactions. A modified version of the Implicit Association Test (IAT) called Dual Valence Association Task (DVAT) was designed in order to measure conflict resolution processing from compatibility/incompatibly of semantic and facial valence. The DVAT involves two emotional valence evaluative tasks which elicits two forms of emotional compatible/incompatible associations (facial and semantic). METHODS: Behavioural measures and Event Related Potentials were recorded while participants performed the DVAT. RESULTS: Behavioural data showed a robust effect that distinguished compatible/incompatible tasks. The effects of valence and contextual association (between facial and semantic stimuli) showed early discrimination in N170 of faces. The LPP component was modulated by the compatibility of the DVAT. CONCLUSIONS: Results suggest that DVAT is a robust paradigm for studying the emotional interference effect in the processing of simultaneous information from semantic and facial stimuli.