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Browsing by Author "Cruzat, Josefina"

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    Allostatic-Interoceptive Overload in Frontotemporal Dementia
    (2022) Birba, Agustina; Santamaría-García, Hernando; Prado, Pavel; Cruzat, Josefina; Sainz Ballesteros , Agustín; Legaz , Agustina; Fittipaldi, Sol; Duran-Aniotz , Claudia; Slachevsky Chonchol, Andrea; Santibañez , Rodrigo; Sigman , Mariano; M. García , Adolfo; Whelan , Robert; Moguilner , Sebastián; Ibáñez , Agustín
    Background : The predictive coding theory of allostatic-interoceptive load states that brain networks mediating autonomic regulation and interoceptive-exteroceptive balance regulate the internal milieu to anticipate future needs and environmental demands. These functions seem to be distinctly compromised in behavioral variant frontotemporal dementia (bvFTD), including alterations of the allostatic-interoceptive network (AIN). Here, we hypothesize that bvFTD is typified by an allostatic-interoceptive overload. Methods : We assessed resting-state heartbeat evoked potential (rsHEP) modulation as well as its behavioral and multimodal neuroimaging correlates in patients with bvFTD relative to healthy control subjects and patients with Alzheimer’s disease (N = 94). We measured 1) resting-state electroencephalography (to assess the rsHEP, prompted by visceral inputs and modulated by internal body sensing), 2) associations between rsHEP and its neural generators (source location), 3) cognitive disturbances (cognitive state, executive functions, facial emotion recognition), 4) brain atrophy, and 5) resting-state functional magnetic resonance imaging functional connectivity (AIN vs. control networks). Results : Relative to healthy control subjects and patients with Alzheimer’s disease, patients with bvFTD presented more negative rsHEP amplitudes with sources in critical hubs of the AIN (insula, amygdala, somatosensory cortex, hippocampus, anterior cingulate cortex). This exacerbated rsHEP modulation selectively predicted the patients’ cognitive profile (including cognitive decline, executive dysfunction, and emotional impairments). In addition, increased rsHEP modulation in bvFTD was associated with decreased brain volume and connectivity of the AIN. Machine learning results confirmed AIN specificity in predicting the bvFTD group. Conclusions : Altogether, these results suggest that bvFTD may be characterized by an allostatic-interoceptive overload manifested in ongoing electrophysiological markers, brain atrophy, functional networks, and cognition.
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    Author Correction: Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations
    (2024) Moguilner, Sebastian; Baez, Sandra; Hernandez, Hernan; Migeot, Joaquín; Legaz, Agustina; Gonzalez, Raul; Farina, Francesca; Prado, Pavel; Cuadros, Jhosmary; Tagliazucchi, Enzo; Altschuler, Florencia; Maito, Marcelo; Godoy, María; Cruzat, Josefina; Valdes, Pedro; Lopera, Francisco; Ochoa, John; Gonzalez, Alfredis; Bonilla, Jasmin; Gonzalez, Rodrigo; Anghinah, Renato; d'Almeida, Luís; Fittipaldi, Sol; Medel, Vicente; Olivares, Daniela; Yener, Görsev; Escudero, Javier; Babiloni, Claudio; Whelan, Robert; Güntekin, Bahar; Yırıkoğulları, Harun; Santamaria, Hernando; Fernández, Alberto; Huepe, David; Di Caterina, Gaetano; Soto, Marcio; Birba, Agustina; Sainz, Agustin; Coronel, Carlos; Yigezu, Amanuel; Behrens, Maria Isabel
    Los relojes cerebrales capturan la diversidad y las disparidades en el envejecimiento y la demencia en poblaciones geográficamente diversas. 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.
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    Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations
    (2024) Moguilner, Sebastian; Baez, Sandra; Hernandez, Hernan; Migeot, Joaquín; Legaz, Agustina; Gonzalez, Raul; Farina, Francesca; Prado, Pavel; Cuadros, Jhosmary; Tagliazucchi, Enzo; Altschuler, Florencia; Maito, Marcelo; Godoy, María; Cruzat, Josefina; Valdes, Pedro; Lopera, Francisco; Ochoa, John; González, Alfredis; Bonilla, Jazmín; Gonzalez, Rodrigo; Anghinah, Renato; d'Almeida, Luis; Fittipaldi, Sol; Medel, Vicente; Olivares, Daniela; Yener, Görsev; Escudero, Javier; Babiloni, Claudio; Whelan, Robert; Guntekin, Bahar; Yırıkoğulları, Harun; Santamaria, Hernando; Fernández, Alberto; Huepe, David; Di Caterina, Gaetano; Soto, Marcio; Birba, Agustina; Sainz, Agustin; Coronel, Carlos; Yigezu, Amanuel; Behrens, Maria Isabel
    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. Los relojes cerebrales, que cuantifican las discrepancias entre la edad cerebral y la edad cronológica, son prometedores para comprender la salud y la enfermedad cerebral. Sin embargo, se desconoce el impacto de la diversidad (incluida la geográfica, socioeconómica, sociodemográfica, sexual y neurodegenerativa) en la brecha de edad cerebral. Analizamos conjuntos de datos de 5306 participantes en 15 países (7 países de América Latina y el Caribe (ALC) y 8 países no pertenecientes a ALC). Con base en interacciones de orden superior, desarrollamos una arquitectura de aprendizaje profundo de brecha de edad cerebral para imágenes de resonancia magnética funcional (2953) y electroencefalografía (2353). Los conjuntos de datos comprendían controles sanos e individuos con deterioro cognitivo leve, enfermedad de Alzheimer y demencia frontotemporal variante conductual. Los modelos LAC evidenciaron edades cerebrales más avanzadas (imágenes por resonancia magnética funcional: error direccional medio = 5,60, error cuadrático medio (rmse) = 11,91; electroencefalografía: error direccional medio = 5,34, rmse = 9,82) asociadas con redes frontoposteriores en comparación con los modelos no LAC. La desigualdad socioeconómica estructural, la contaminación y las disparidades en la salud fueron predictores influyentes de mayores brechas de edad cerebral, especialmente en LAC (R² = 0,37, F² = 0,59, rmse = 6,9). Se encontró una brecha ascendente de edad cerebral desde controles sanos hasta deterioro cognitivo leve y enfermedad de Alzheimer. En LAC, observamos brechas de edad cerebral más grandes en mujeres en los grupos de control y enfermedad de Alzheimer en comparación con los respectivos hombres. Los resultados no se explicaron por variaciones en la calidad de la señal, la demografía o los métodos de adquisición. Estos hallazgos proporcionan un marco cuantitativo que captura la diversidad del envejecimiento cerebral acelerado.
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    Multi-feature computational framework for combined signatures of dementia in underrepresented settings
    (2022) Moguilner, Sebastián; Birba, Agustina; Fittipaldi, Sol; Gonzalez, Cecilia; Tagliazucchi, Enzo; Reyes, Pablo; Matallana, Diana; Parra, Mario; Slachevsky Chonchol, Andrea; Farías, Gonzalo; Cruzat, Josefina; García, Adolfo; Eyre, Harris; La Joie, Renaud; Rabinovici, Gil; Whelan, Robert; Ibáñez, Agustín
    Objective.The differential diagnosis of behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD) remains challenging in underrepresented, underdiagnosed groups, including Latinos, as advanced biomarkers are rarely available. Recent guidelines for the study of dementia highlight the critical role of biomarkers. Thus, novel cost-effective complementary approaches are required in clinical settings.Approach. We developed a novel framework based on a gradient boosting machine learning classifier, tuned by Bayesian optimization, on a multi-feature multimodal approach (combining demographic, neuropsychological, magnetic resonance imaging (MRI), and electroencephalography/functional MRI connectivity data) to characterize neurodegeneration using site harmonization and sequential feature selection. We assessed 54 bvFTD and 76 AD patients and 152 healthy controls (HCs) from a Latin American consortium (ReDLat).Main results. The multimodal model yielded high area under the curve classification values (bvFTD patients vs HCs: 0.93 (±0.01); AD patients vs HCs: 0.95 (±0.01); bvFTD vs AD patients: 0.92 (±0.01)). The feature selection approach successfully filtered non-informative multimodal markers (from thousands to dozens).Results. Proved robust against multimodal heterogeneity, sociodemographic variability, and missing data.Significance. The model accurately identified dementia subtypes using measures readily available in underrepresented settings, with a similar performance than advanced biomarkers. This approach, if confirmed and replicated, may potentially complement clinical assessments in developing countries

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