Brain health in diverse settings: How age, demographics and cognition shape brain function.

Diversity in brain health is influenced by individual differences in demographics and cognition. However, most studies on brain health and diseases have typically controlled for these factors rather than explored their potential to predict brain signals. Here, we assessed the role of individual differences in demographics (age, sex, and education; n = 1298) and cognition (n = 725) as predictors of different metrics usually used in case-control studies. These included power spectrum and aperiodic (1/f slope, knee, offset) metrics, as well as complexity (fractal dimension estimation, permutation entropy, Wiener entropy, spectral structure variability) and connectivity (graph-theoretic mutual information, conditional mutual information, organizational information) from the source space resting-state EEG activity in a diverse sample from the global south and north populations. Brain-phenotype models were computed using EEG metrics reflecting local activity (power spectrum and aperiodic components) and brain dynamics and interactions (complexity and graph-theoretic measures). Electrophysiological brain dynamics were modulated by individual differences despite the varied methods of data acquisition and assessments across multiple centers, indicating that results were unlikely to be accounted for by methodological discrepancies. Variations in brain signals were mainly influenced by age and cognition, while education and sex exhibited less importance. Power spectrum activity and graph-theoretic measures were the most sensitive in capturing individual differences. Older age, poorer cognition, and being male were associated with reduced alpha power, whereas older age and less education were associated with reduced network integration and segregation. Findings suggest that basic individual differences impact core metrics of brain function that are used in standard case-control studies. Considering individual variability and diversity in global settings would contribute to a more tailored understanding of brain function.

Structural inequality and temporal brain dynamics across diverse samples.

BACKGROUND: Structural income inequality - the uneven income distribution across regions or countries - could affect brain structure and function, beyond individual differences. However, the impact of structural income inequality on the brain dynamics and the roles of demographics and cognition in these associations remains unexplored. METHODS: Here, we assessed the impact of structural income inequality, as measured by the Gini coefficient on multiple EEG metrics, while considering the subject-level effects of demographic (age, sex, education) and cognitive factors. Resting-state EEG signals were collected from a diverse sample (countries = 10; healthy individuals = 1394 from Argentina, Brazil, Colombia, Chile, Cuba, Greece, Ireland, Italy, Turkey and United Kingdom). Complexity (fractal dimension, permutation entropy, Wiener entropy, spectral structure variability), power spectral and aperiodic components (1/f slope, knee, offset), as well as graph-theoretic measures were analysed. FINDINGS: Despite variability in samples, data collection methods, and EEG acquisition parameters, structural inequality systematically predicted electrophysiological brain dynamics, proving to be a more crucial determinant of brain dynamics than individual-level factors. Complexity and aperiodic activity metrics captured better the effects of structural inequality on brain function. Following inequality, age and cognition emerged as the most influential predictors. The overall results provided convergent multimodal metrics of biologic embedding of structural income inequality characterised by less complex signals, increased random asynchronous neural activity, and reduced alpha and beta power, particularly over temporoposterior regions. CONCLUSION: These findings might challenge conventional neuroscience approaches that tend to overemphasise the influence of individual-level factors, while neglecting structural factors. Results pave the way for neuroscience-informed public policies aimed at tackling structural inequalities in diverse populations.

Brain clocks capture diversity and disparity in aging and dementia.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of multimodal diversity (geographical, socioeconomic, sociodemographic, sex, neurodegeneration) on the brain age gap (BAG) is unknown. Here, we analyzed datasets from 5,306 participants across 15 countries (7 Latin American countries -LAC, 8 non-LAC). Based on higher-order interactions in brain signals, we developed a BAG deep learning architecture for functional magnetic resonance imaging (fMRI=2,953) and electroencephalography (EEG=2,353). The datasets comprised healthy controls, and individuals with mild cognitive impairment, Alzheimer's disease, and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (fMRI: MDE=5.60, RMSE=11.91; EEG: MDE=5.34, RMSE=9.82) compared to non-LAC, associated with frontoposterior networks. Structural socioeconomic inequality and other disparity-related factors (pollution, health disparities) were influential predictors of increased brain age gaps, especially in LAC (R2=0.37, F2=0.59, RMSE=6.9). A gradient of increasing BAG from controls to mild cognitive impairment to Alzheimer's disease was found. In LAC, we observed larger BAGs in females in control and Alzheimer's disease groups compared to respective males. Results were not explained by variations in signal quality, demographics, or acquisition methods. Findings provide a quantitative framework capturing the multimodal diversity of accelerated brain aging.

Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations.

Brain clocks, which quantify discrepancies between brain age and chronological age, hold promise for understanding brain health and disease. However, the impact of diversity (including geographical, socioeconomic, sociodemographic, sex and neurodegeneration) on the brain-age gap is unknown. We analyzed datasets from 5,306 participants across 15 countries (7 Latin American and Caribbean countries (LAC) and 8 non-LAC countries). Based on higher-order interactions, we developed a brain-age gap deep learning architecture for functional magnetic resonance imaging (2,953) and electroencephalography (2,353). The datasets comprised healthy controls and individuals with mild cognitive impairment, Alzheimer disease and behavioral variant frontotemporal dementia. LAC models evidenced older brain ages (functional magnetic resonance imaging: mean directional error = 5.60, root mean square error (r.m.s.e.) = 11.91; electroencephalography: mean directional error = 5.34, r.m.s.e. = 9.82) associated with frontoposterior networks compared with non-LAC models. Structural socioeconomic inequality, pollution and health disparities were influential predictors of increased brain-age gaps, especially in LAC (R² = 0.37, F² = 0.59, r.m.s.e. = 6.9). An ascending brain-age gap from healthy controls to mild cognitive impairment to Alzheimer disease was found. In LAC, we observed larger brain-age gaps in females in control and Alzheimer disease groups compared with the respective males. The results were not explained by variations in signal quality, demographics or acquisition methods. These findings provide a quantitative framework capturing the diversity of accelerated brain aging.

DIVA Meets EEG: Model Validation Using Formant-Shift Reflex.

The neurocomputational model 'Directions into Velocities of Articulators' (DIVA) was developed to account for various aspects of normal and disordered speech production and acquisition. The neural substrates of DIVA were established through functional magnetic resonance imaging (fMRI), providing physiological validation of the model. This study introduces DIVA_EEG an extension of DIVA that utilizes electroencephalography (EEG) to leverage the high temporal resolution and broad availability of EEG over fMRI. For the development of DIVA_EEG, EEG-like signals were derived from original equations describing the activity of the different DIVA maps. Synthetic EEG associated with the utterance of syllables was generated when both unperturbed and perturbed auditory feedback (first formant perturbations) were simulated. The cortical activation maps derived from synthetic EEG closely resembled those of the original DIVA model. To validate DIVA_EEG, the EEG of individuals with typical voices (N = 30) was acquired during an altered auditory feedback paradigm. The resulting empirical brain activity maps significantly overlapped with those predicted by DIVA_EEG. In conjunction with other recent model extensions, DIVA_EEG lays the foundations for constructing a complete neurocomputational framework to tackle vocal and speech disorders, which can guide model-driven personalized interventions.

Harmonized multi-metric and multi-centric assessment of EEG source space connectivity for dementia characterization.

Introduction: Harmonization protocols that address batch effects and cross-site methodological differences in multi-center studies are critical for strengthening electroencephalography (EEG) signatures of functional connectivity (FC) as potential dementia biomarkers. Methods: We implemented an automatic processing pipeline incorporating electrode layout integrations, patient-control normalizations, and multi-metric EEG source space connectomics analyses. Results: Spline interpolations of EEG signals onto a head mesh model with 6067 virtual electrodes resulted in an effective method for integrating electrode layouts. Z-score transformations of EEG time series resulted in source space connectivity matrices with high bilateral symmetry, reinforced long-range connections, and diminished short-range functional interactions. A composite FC metric allowed for accurate multicentric classifications of Alzheimer's disease and behavioral variant frontotemporal dementia. Discussion: Harmonized multi-metric analysis of EEG source space connectivity can address data heterogeneities in multi-centric studies, representing a powerful tool for accurately characterizing dementia.

ECG Multilead QT Interval Estimation Using Support Vector Machines.

This work reports a multilead QT interval measurement algorithm for a high-resolution digital electrocardiograph. The software enables off-line ECG processing including QRS detection as well as an accurate multilead QT interval detection algorithm using support vector machines (SVMs). Two fiducial points (Q ini and T end) are estimated using the SVM algorithm on each incoming beat. This enables segmentation of the current beat for obtaining the P, QRS, and T waves. The QT interval is estimated by updating the QT interval on each lead, considering shifting techniques with respect to a valid beat template. The validation of the QT interval measurement algorithm is attained using the Physionet PTB diagnostic ECG database showing a percent error of 2.60 ± 2.25 msec with respect to the database annotations. The usefulness of this software tool is also tested by considering the analysis of the ECG signals for a group of 60 patients acquired using our digital electrocardiograph. In this case, the validation is performed by comparing the estimated QT interval with respect to the estimation obtained using the Cardiosoft software providing a percent error of 2.49 ± 1.99 msec.