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BACKGROUND: Education influences brain health and dementia. However, its impact across regions, specifically Latin America (LA) and the United States (US), is unknown. METHODS: A total of 1412 participants comprising controls, patients with Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD) from LA and the US were included. We studied the association of education with brain volume and functional connectivity while controlling for imaging quality and variability, age, sex, total intracranial volume (TIV), and recording type. RESULTS: Education influenced brain measures, explaining 24%-98% of the geographical differences. The educational disparities between LA and the US were associated with gray matter volume and connectivity variations, especially in LA and AD patients. Education emerged as a critical factor in classifying aging and dementia across regions. DISCUSSION: The results underscore the impact of education on brain structure and function in LA, highlighting the importance of incorporating educational factors into diagnosing, care, and prevention, and emphasizing the need for global diversity in research. HIGHLIGHTS: Lower education was linked to reduced brain volume and connectivity in healthy controls (HCs), Alzheimer's disease (AD), and frontotemporal lobar degeneration (FTLD). Latin American cohorts have lower educational levels compared to the those in the United States. Educational disparities majorly drive brain health differences between regions. Educational differences were significant in both conditions, but more in AD than FTLD. Education stands as a critical factor in classifying aging and dementia across regions.
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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, 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.
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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.
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Encéfalo , Cognición , Electroencefalografía , Humanos , Masculino , Femenino , Adulto , Cognición/fisiología , Persona de Mediana Edad , Encéfalo/fisiología , Anciano , Adulto Joven , Individualidad , Adolescente , Factores de Edad , Envejecimiento/fisiologíaRESUMEN
INTRODUCTION: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) lack mechanistic biophysical modeling in diverse, underrepresented populations. Electroencephalography (EEG) is a high temporal resolution, cost-effective technique for studying dementia globally, but lacks mechanistic models and produces non-replicable results. METHODS: We developed a generative whole-brain model that combines EEG source-level metaconnectivity, anatomical priors, and a perturbational approach. This model was applied to Global South participants (AD, bvFTD, and healthy controls). RESULTS: Metaconnectivity outperformed pairwise connectivity and revealed more viscous dynamics in patients, with altered metaconnectivity patterns associated with multimodal disease presentation. The biophysical model showed that connectome disintegration and hypoexcitability triggered altered metaconnectivity dynamics and identified critical regions for brain stimulation. We replicated the main results in a second subset of participants for validation with unharmonized, heterogeneous recording settings. DISCUSSION: The results provide a novel agenda for developing mechanistic model-inspired characterization and therapies in clinical, translational, and computational neuroscience settings.
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Enfermedad de Alzheimer , Encéfalo , Electroencefalografía , Demencia Frontotemporal , Humanos , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/patología , Encéfalo/fisiopatología , Encéfalo/patología , Femenino , Enfermedad de Alzheimer/fisiopatología , Masculino , Anciano , Conectoma , Persona de Mediana Edad , Modelos NeurológicosRESUMEN
The Latin American Brain Health Institute (BrainLat) has released a unique multimodal neuroimaging dataset of 780 participants from Latin American. The dataset includes 530 patients with neurodegenerative diseases such as Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), multiple sclerosis (MS), Parkinson's disease (PD), and 250 healthy controls (HCs). This dataset (62.7 ± 9.5 years, age range 21-89 years) was collected through a multicentric effort across five Latin American countries to address the need for affordable, scalable, and available biomarkers in regions with larger inequities. The BrainLat is the first regional collection of clinical and cognitive assessments, anatomical magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), diffusion-weighted MRI (DWI), and high density resting-state electroencephalography (EEG) in dementia patients. In addition, it includes demographic information about harmonized recruitment and assessment protocols. The dataset is publicly available to encourage further research and development of tools and health applications for neurodegeneration based on multimodal neuroimaging, promoting the assessment of regional variability and inclusion of underrepresented participants in research.
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Enfermedad de Alzheimer , Encéfalo , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Persona de Mediana Edad , Adulto Joven , Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/métodos , NeuroimagenRESUMEN
Aging may diminish social cognition, which is crucial for interaction with others, and significant changes in this capacity can indicate pathological processes like dementia. However, the extent to which non-specific factors explain variability in social cognition performance, especially among older adults and in global settings, remains unknown. A computational approach assessed combined heterogeneous contributors to social cognition in a diverse sample of 1063 older adults from 9 countries. Support vector regressions predicted the performance in emotion recognition, mentalizing, and a total social cognition score from a combination of disparate factors, including clinical diagnosis (healthy controls, subjective cognitive complaints, mild cognitive impairment, Alzheimer's disease, behavioral variant frontotemporal dementia), demographics (sex, age, education, and country income as a proxy of socioeconomic status), cognition (cognitive and executive functions), structural brain reserve, and in-scanner motion artifacts. Cognitive and executive functions and educational level consistently emerged among the top predictors of social cognition across models. Such non-specific factors showed more substantial influence than diagnosis (dementia or cognitive decline) and brain reserve. Notably, age did not make a significant contribution when considering all predictors. While fMRI brain networks did not show predictive value, head movements significantly contributed to emotion recognition. Models explained between 28-44% of the variance in social cognition performance. Results challenge traditional interpretations of age-related decline, patient-control differences, and brain signatures of social cognition, emphasizing the role of heterogeneous factors. Findings advance our understanding of social cognition in brain health and disease, with implications for predictive models, assessments, and interventions.
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Although social functioning relies on working memory, whether a social-specific mechanism exists remains unclear. This undermines the characterization of neurodegenerative conditions with both working memory and social deficits. We assessed working memory domain-specificity across behavioral, electrophysiological, and neuroimaging dimensions in 245 participants. A novel working memory task involving social and non-social stimuli with three load levels was assessed across controls and different neurodegenerative conditions with recognized impairments in: working memory and social cognition (behavioral-variant frontotemporal dementia); general cognition (Alzheimer's disease); and unspecific patterns (Parkinson's disease). We also examined resting-state theta oscillations and functional connectivity correlates of working memory domain-specificity. Results in controls and all groups together evidenced increased working memory demands for social stimuli associated with frontocinguloparietal theta oscillations and salience network connectivity. Canonical frontal theta oscillations and executive-default mode network anticorrelation indexed non-social stimuli. Behavioral-variant frontotemporal dementia presented generalized working memory deficits related to posterior theta oscillations, with social stimuli linked to salience network connectivity. In Alzheimer's disease, generalized working memory impairments were related to temporoparietal theta oscillations, with non-social stimuli linked to the executive network. Parkinson's disease showed spared working memory performance and canonical brain correlates. Findings support a social-specific working memory and related disease-selective pathophysiological mechanisms.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad de Parkinson , Humanos , Memoria a Corto Plazo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Pruebas NeuropsicológicasRESUMEN
Disease-specific mechanisms underlying emotion recognition difficulties in behavioural-variant frontotemporal dementia (bvFTD), Alzheimer's disease (AD), and Parkinson's disease (PD) are unknown. Interoceptive accuracy, accurately detecting internal cues (e.g., one's heart beating), and cognitive abilities are candidate mechanisms underlying emotion recognition. One hundred and sixty-eight participants (52 bvFTD; 41 AD; 24 PD; 51 controls) were recruited. Emotion recognition was measured via the Facial Affect Selection Task or the Mini-Social and Emotional Assessment Emotion Recognition Task. Interoception was assessed with a heartbeat detection task. Participants pressed a button each time they: 1) felt their heartbeat (Interoception); or 2) heard a recorded heartbeat (Exteroception-control). Cognition was measured via the Addenbrooke's Cognitive Examination-III or the Montreal Cognitive Assessment. Voxel-based morphometry analyses identified neural correlates associated with emotion recognition and interoceptive accuracy. All patient groups showed worse emotion recognition and cognition than controls (all P's ≤ .008). Only the bvFTD showed worse interoceptive accuracy than controls (P < .001). Regression analyses revealed that in bvFTD worse interoceptive accuracy predicted worse emotion recognition (P = .008). Whereas worse cognition predicted worse emotion recognition overall (P < .001). Neuroimaging analyses revealed that the insula, orbitofrontal cortex, and amygdala were involved in emotion recognition and interoceptive accuracy in bvFTD. Here, we provide evidence for disease-specific mechanisms for emotion recognition difficulties. In bvFTD, emotion recognition impairment is driven by inaccurate perception of the internal milieu. Whereas, in AD and PD, cognitive impairment likely underlies emotion recognition deficits. The current study furthers our theoretical understanding of emotion and highlights the need for targeted interventions.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Interocepción , Enfermedad de Parkinson , Humanos , Enfermedad de Alzheimer/psicología , Demencia Frontotemporal/psicología , Imagen por Resonancia Magnética/métodos , Emociones , Cognición , Pruebas NeuropsicológicasRESUMEN
Brain functional connectivity in dementia has been assessed with dissimilar EEG connectivity metrics and estimation procedures, thereby increasing results' heterogeneity. In this scenario, joint analyses integrating information from different metrics may allow for a more comprehensive characterization of brain functional interactions in different dementia subtypes. To test this hypothesis, resting-state electroencephalogram (rsEEG) was recorded in individuals with Alzheimer's Disease (AD), behavioral variant frontotemporal dementia (bvFTD), and healthy controls (HCs). Whole-brain functional connectivity was estimated in the EEG source space using 101 different types of functional connectivity, capturing linear and nonlinear interactions in both time and frequency-domains. Multivariate machine learning and progressive feature elimination was run to discriminate AD from HCs, and bvFTD from HCs, based on joint analyses of i) EEG frequency bands, ii) complementary frequency-domain metrics (e.g., instantaneous, lagged, and total connectivity), and iii) time-domain metrics with different linearity assumption (e.g., Pearson correlation coefficient and mutual information). <10% of all possible connections were responsible for the differences between patients and controls, and atypical connectivity was never captured by >1/4 of all possible connectivity measures. Joint analyses revealed patterns of hypoconnectivity (patients
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Enfermedad de Alzheimer , Encéfalo , Conectoma , Demencia Frontotemporal , Vías Nerviosas , Anciano , Femenino , Humanos , Masculino , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/fisiopatología , Electroencefalografía , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/metabolismo , Demencia Frontotemporal/fisiopatología , Imagen por Resonancia Magnética , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Reproducibilidad de los Resultados , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiopatologíaRESUMEN
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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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedad de Alzheimer/patología , Atrofia/patología , Encéfalo , Mapeo Encefálico , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/patología , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Hypertensive disease (HTD), a prominent risk factor for cardiovascular and cerebrovascular diseases, is characterized by elevated stress-proneness. Since stress levels are underpinned by both cardiac and neural factors, multidimensional insights are required to robustly understand their disruption in HTD. Yet, despite their crucial relevance, heart rate variability (HRV) and multimodal neurocognitive markers of stress in HTD remain controversial and unexplored respectively. To bridge this gap, we studied cardiodynamic as well as electrophysiological and neuroanatomical measures of stress in HTD patients and healthy controls. Both groups performed the Trier Social Stress Test (TSST), a validated stress-inducing task comprising a baseline and a mental stress period. During both stages, we assessed a sensitive HRV parameter (the low frequency/high frequency [LF/HF ratio]) and an online neurophysiological measure (the heartbeat-evoked potential [HEP]). Also, we obtained neuroanatomical data via voxel-based morphometry (VBM) for correlation with online markers. Relative to controls, HTD patients exhibited increased LF/HF ratio and greater HEP modulations during baseline, reduced changes between baseline and stress periods, and lack of significant stress-related HRV modulations associated with the grey matter volume of putative frontrostriatal regions. Briefly, HTD patients presented signs of stress-related autonomic imbalance, reflected in a potential basal stress overload and a lack of responsiveness to acute psychosocial stress, accompanied by neurophysiological and neuroanatomical alterations. These multimodal insights underscore the relevance of neurocognitive data for developing innovations in the characterization, prognosis and treatment of HTD and other conditions with autonomic imbalance. More generally, these findings may offer new insights into heart-brain interactions.
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Sistema Nervioso Autónomo , Hipertensión , Sistema Nervioso Autónomo/fisiología , Encéfalo , Cognición , Frecuencia Cardíaca/fisiología , HumanosRESUMEN
Social feedback can selectively enhance learning in diverse domains. Relevant neurocognitive mechanisms have been studied mainly in healthy persons, yielding correlational findings. Neurodegenerative lesion models, coupled with multimodal brain measures, can complement standard approaches by revealing direct multidimensional correlates of the phenomenon. To this end, we assessed socially reinforced and non-socially reinforced learning in 40 healthy participants as well as persons with behavioural variant frontotemporal dementia (n = 21), Parkinson's disease (n = 31) and Alzheimer's disease (n = 20). These conditions are typified by predominant deficits in social cognition, feedback-based learning and associative learning, respectively, although all three domains may be partly compromised in the other conditions. We combined a validated behavioural task with ongoing EEG signatures of implicit learning (medial frontal negativity) and offline MRI measures (voxel-based morphometry). In healthy participants, learning was facilitated by social feedback relative to non-social feedback. In comparison with controls, this effect was specifically impaired in behavioural variant frontotemporal dementia and Parkinson's disease, while unspecific learning deficits (across social and non-social conditions) were observed in Alzheimer's disease. EEG results showed increased medial frontal negativity in healthy controls during social feedback and learning. Such a modulation was selectively disrupted in behavioural variant frontotemporal dementia. Neuroanatomical results revealed extended temporo-parietal and fronto-limbic correlates of socially reinforced learning, with specific temporo-parietal associations in behavioural variant frontotemporal dementia and predominantly fronto-limbic regions in Alzheimer's disease. In contrast, non-socially reinforced learning was consistently linked to medial temporal/hippocampal regions. No associations with cortical volume were found in Parkinson's disease. Results are consistent with core social deficits in behavioural variant frontotemporal dementia, subtle disruptions in ongoing feedback-mechanisms and social processes in Parkinson's disease and generalized learning alterations in Alzheimer's disease. This multimodal approach highlights the impact of different neurodegenerative profiles on learning and social feedback. Our findings inform a promising theoretical and clinical agenda in the fields of social learning, socially reinforced learning and neurodegeneration.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Enfermedad de Alzheimer/patología , Encéfalo/patología , Demencia Frontotemporal/patología , Humanos , Enfermedades Neurodegenerativas/patología , Enfermedad de Parkinson/patologíaRESUMEN
Neurodegeneration has multiscalar impacts, including behavioral, neuroanatomical, and neurofunctional disruptions. Can disease-differential alterations be captured across such dimensions using naturalistic stimuli? To address this question, we assessed comprehension of four naturalistic stories, highlighting action, nonaction, social, and nonsocial events, in Parkinson's disease (PD) and behavioral variant frontotemporal dementia (bvFTD) relative to Alzheimer's disease patients and healthy controls. Text-specific correlates were evaluated via voxel-based morphometry, spatial (fMRI), and temporal (hd-EEG) functional connectivity. PD patients presented action-text deficits related to the volume of action-observation regions, connectivity across motor-related and multimodal-semantic hubs, and frontal hd-EEG hypoconnectivity. BvFTD patients exhibited social-text deficits, associated with atrophy and spatial connectivity patterns along social-network hubs, alongside right frontotemporal hd-EEG hypoconnectivity. Alzheimer's disease patients showed impairments in all stories, widespread atrophy and spatial connectivity patterns, and heightened occipitotemporal hd-EEG connectivity. Our framework revealed disease-specific signatures across behavioral, neuroanatomical, and neurofunctional dimensions, highlighting the sensitivity and specificity of a single naturalistic task. This investigation opens a translational agenda combining ecological approaches and multimodal cognitive neuroscience for the study of neurodegeneration.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Enfermedades Neurodegenerativas , Enfermedad de Alzheimer/patología , Atrofia/patología , Biomarcadores , Encéfalo , Demencia Frontotemporal/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Enfermedades Neurodegenerativas/diagnóstico por imagen , Pruebas NeuropsicológicasRESUMEN
Recent frameworks in cognitive neuroscience and behavioral neurology underscore interoceptive priors as core modulators of negative emotions. However, the field lacks experimental designs manipulating the priming of emotions via interoception and exploring their multimodal signatures in neurodegenerative models. Here, we designed a novel task that involves interoceptive and control-exteroceptive priming conditions followed by post-interoception and post-exteroception facial emotion recognition (FER). We recruited 114 participants, including healthy controls (HCs) as well as patients with behavioral variant frontotemporal dementia (bvFTD), Parkinson's disease (PD), and Alzheimer's disease (AD). We measured online EEG modulations of the heart-evoked potential (HEP), and associations with both brain structural and resting-state functional connectivity patterns. Behaviorally, post-interoception negative FER was enhanced in HCs but selectively disrupted in bvFTD and PD, with AD presenting generalized disruptions across emotion types. Only bvFTD presented impaired interoceptive accuracy. Increased HEP modulations during post-interoception negative FER was observed in HCs and AD, but not in bvFTD or PD patients. Across all groups, post-interoception negative FER correlated with the volume of the insula and the ACC. Also, negative FER was associated with functional connectivity along the (a) salience network in the post-interoception condition, and along the (b) executive network in the post-exteroception condition. These patterns were selectively disrupted in bvFTD (a) and PD (b), respectively. Our approach underscores the multidimensional impact of interoception on emotion, while revealing a specific pathophysiological marker of bvFTD. These findings inform a promising theoretical and clinical agenda in the fields of nteroception, emotion, allostasis, and neurodegeneration.SIGNIFICANCE STATEMENT We examined whether and how emotions are primed by interoceptive states combining multimodal measures in healthy controls and neurodegenerative models. In controls, negative emotion recognition and ongoing HEP modulations were increased after interoception. These patterns were selectively disrupted in patients with atrophy across key interoceptive-emotional regions (e.g., the insula and the cingulate in frontotemporal dementia, frontostriatal networks in Parkinson's disease), whereas persons with Alzheimer's disease presented generalized emotional processing abnormalities with preserved interoceptive mechanisms. The integration of both domains was associated with the volume and connectivity (salience network) of canonical interoceptive-emotional hubs, critically involving the insula and the anterior cingulate. Our study reveals multimodal markers of interoceptive-emotional priming, laying the groundwork for new agendas in cognitive neuroscience and behavioral neurology.
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Emociones/fisiología , Reconocimiento Facial , Interocepción/fisiología , Degeneración Nerviosa/fisiopatología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/psicología , Mapeo Encefálico , Electroencefalografía , Potenciales Evocados/fisiología , Femenino , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/psicología , Humanos , Masculino , Persona de Mediana Edad , Vías Nerviosas/fisiología , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Desempeño Psicomotor/fisiologíaRESUMEN
Heart-brain integration dynamics are critical for interoception (i.e. the sensing of body signals). In this unprecedented longitudinal study, we assessed neurocognitive markers of interoception in patients who underwent orthotopic heart transplants and matched healthy controls. Patients were assessed longitudinally before surgery (T1), a few months later (T2) and a year after (T3). We assessed behavioural (heartbeat detection) and electrophysiological (heartbeat evoked potential) markers of interoception. Heartbeat detection task revealed that pre-surgery (T1) interoception was similar between patients and controls. However, patients were outperformed by controls after heart transplant (T2), but no such differences were observed in the follow-up analysis (T3). Neurophysiologically, although heartbeat evoked potential analyses revealed no differences between groups before the surgery (T1), reduced amplitudes of this event-related potential were found for the patients in the two post-transplant stages (T2, T3). All these significant effects persisted after covariation with different cardiological measures. In sum, this study brings new insights into the adaptive properties of brain-heart pathways.
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The mechanisms underlying emotional alterations constitute a key research target in neuroscience. Emerging evidence indicates that these disruptions can be related to abnormal interoception (i.e., the sensing of visceral feelings), as observed in patients with cardiodynamic deficits. To directly assess these links, we performed the first multicenter study on emotion recognition and interoception in patients with hypertensive heart disease (HHD). Participants from two countries completed a facial emotion recognition test, and a subsample additionally underwent an interoception protocol based on a validated heartbeat detection task. HHD patients from both countries presented deficits in the recognition of overall and negative emotions. Moreover, interoceptive performance was impaired in the HHD group. In addition, a significant association between interoceptive performance and emotion recognition was observed in the control group, but this relation was abolished in the HHD group. All results survived after covariance with cognitive status measures, suggesting they were not biased by general cognitive deficits in the patients. Taken together, these findings suggest that emotional recognition alterations could represent a sui generis deficit in HHD, and that it may be partially explained by the disruption of mechanisms subserving the integration of neuro-visceral signals.
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Emociones/fisiología , Cardiopatías/psicología , Hipertensión/psicología , Interocepción/fisiología , Regulación Emocional/fisiología , Expresión Facial , Femenino , Cardiopatías/patología , Humanos , Hipertensión/patología , Masculino , Persona de Mediana EdadRESUMEN
Multiple sclerosis (MS) patients present several alterations related to sensing of bodily signals. However, no specific neurocognitive impairment has yet been proposed as a core deficit underlying such symptoms. We aimed to determine whether MS patients present changes in interoception-that is, the monitoring of autonomic bodily information-a process that might be related to various bodily dysfunctions. We performed two studies in 34 relapsing-remitting, early-stage MS patients and 46 controls matched for gender, age, and education. In Study 1, we evaluated the heartbeat-evoked potential (HEP), a cortical signature of interoception, via a 128-channel EEG system during a heartbeat detection task including an exteroceptive and an interoceptive condition. Then, we obtained whole-brain MRI recordings. In Study 2, participants underwent fMRI recordings during two resting-state conditions: mind wandering and interoception. In Study 1, controls exhibited greater HEP modulation during the interoceptive condition than the exteroceptive one, but no systematic differences between conditions emerged in MS patients. Patients presented atrophy in the left insula, the posterior part of the right insula, and the right anterior cingulate cortex, with abnormal associations between neurophysiological and neuroanatomical patterns. In Study 2, controls showed higher functional connectivity and degree for the interoceptive state compared with mind wandering; however, this pattern was absent in patients, who nonetheless presented greater connectivity and degree than controls during mind wandering. MS patients were characterized by atypical multimodal brain signatures of interoception. This finding opens a new agenda to examine the role of inner-signal monitoring in the body symptomatology of MS.
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Corteza Cerebral/fisiopatología , Conectoma/métodos , Electroencefalografía/métodos , Potenciales Evocados/fisiología , Frecuencia Cardíaca/fisiología , Interocepción/fisiología , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Adulto , Atrofia/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/patologíaRESUMEN
The linguistic profile of Parkinson's disease (PD) is characterized by difficulties in processing units which denote bodily movements. However, the available evidence has low ecological validity, as it stems from atomistic tasks which are never encountered in real life. Here, we assessed whether such deficits also occur for meanings evoked by context-rich narratives, considering patients with and without mild cognitive impairment (PD-MCI and PD-nMCI, respectively) and matched controls for each group. Participants read two naturalistic stories (an action text and a neutral text) and responded to questions tapping the appraisal of verb-related and circumstantial information. In PD-MCI, impairments in the appraisal of action meanings emerged alongside difficulties in other categories, but they were unique in their independence from general cognitive dysfunction. However, in PD-nMCI, deficits were observed only for action meanings, irrespective of the patients' domain-general skills (executive functions and general cognitive state). Also, using multiple group discriminant function analyses, we found that appraisal of action meanings was the only discourse-level variable that robustly contributed to classifying PD-MCI patients from controls (with an accuracy of 88% for all participants and for each sample separately). Moreover, this variable actually superseded a sensitive executive battery in discriminating between PD-nMCI and controls (with a combined accuracy of 83% for all participants, correctly classifying 79.2% of patients and 87.5% of controls). In sum, action appraisal deficits seem to constitute both a hallmark of naturalistic discourse processing in PD and a sensitive subject-level marker for patients with and without MCI. Such findings highlight the relevance of ecological measures of embodied cognitive functions in the assessment of this population.