Allostatic interoceptive overload across psychiatric and neurological conditions.

Emerging theories emphasize the crucial role of allostasis (anticipatory and adaptive regulation of the body's biological processes) and interoception (integration, anticipation, and regulation of internal bodily states) in adjusting physiological responses to environmental and bodily demands. This review explores the disruptions in integrated allostatic interoceptive mechanisms in psychiatric and neurological disorders, including anxiety, depression, Alzheimer's disease, and frontotemporal dementia. We assess the biological mechanisms associated with allostatic interoception, including whole-body cascades, brain structure and function of the allostatic interoceptive network, heart-brain interactions, respiratory-brain interactions, the gut-brain-microbiota axis, peripheral biological processes (inflammatory, immune), and epigenetic pathways. These processes span psychiatric and neurological conditions and call for developing dimensional and trans-nosological frameworks. We synthesize new pathways to understand how allostatic interoceptive processes modulate interactions between environmental demands and biological functions in brain disorders. We discuss current limitations of the framework and future transdisciplinary developments. This review opens a new research agenda for understanding how allostatic interoception involves brain predictive coding in psychiatry and neurology, allowing for better clinical application and the development of new therapeutic interventions.

Healthy aging meta-analyses and scoping review of risk factors across Latin America reveal large heterogeneity and weak predictive models.

Models of healthy aging are typically based on the United States and Europe and may not apply to diverse and heterogeneous populations. In this study, our objectives were to conduct a meta-analysis to assess risk factors of cognition and functional ability across aging populations in Latin America and a scoping review focusing on methodological procedures. Our study design included randomized controlled trials and cohort, case-control and cross-sectional studies using multiple databases, including MEDLINE, the Virtual Health Library and Web of Science. From an initial pool of 455 studies, our meta-analysis included 38 final studies (28 assessing cognition and 10 assessing functional ability, n = 146,000 participants). Our results revealed significant but heterogeneous effects for cognition (odds ratio (OR) = 1.20, P = 0.03, confidence interval (CI) = (1.0127, 1.42); heterogeneity: I2 = 92.1%, CI = (89.8%, 94%)) and functional ability (OR = 1.20, P = 0.01, CI = (1.04, 1.39); I2 = 93.1%, CI = (89.3%, 95.5%)). Specific risk factors had limited effects, especially on functional ability, with moderate impacts for demographics and mental health and marginal effects for health status and social determinants of health. Methodological issues, such as outliers, inter-country differences and publication bias, influenced the results. Overall, we highlight the specific profile of risk factors associated with healthy aging in Latin America. The heterogeneity in results and methodological approaches in studying healthy aging call for greater harmonization and further regional research to understand healthy aging in Latin America.

Allostasis, health, and development in Latin America.

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes. We review several manifestations across cognition, behavior, and the body, observed at the psychological (e.g., cognitive, socioemotional, and behavioral dysfunctions), brain (e.g., alteration of the development, structure, and function of the brain), and physiological levels (e.g., dysregulation of the body systems and damage to organs). To address the complexity of the interactions between environmental and health-related factors, we present an allostatic framework regarding the cumulative burden of environmental stressors on physiological systems (e.g., cardiovascular, metabolic, immune, and neuroendocrine) related to health across the life course. Lastly, we explore the relevance of this allostatic integrative approach in informing regional interventions and public policy recommendations. We also propose a research agenda, potentially providing detailed profiling and personalized care by assessing the social and environmental conditions. This framework could facilitate the delivery of evidence-based interventions and informed childhood-centered policy-making.

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.

A Multidimensional, Person-Centered Framework for Functional Assessment in Dementia: Insights from the 'What', 'How', 'To Whom', and 'How Much' Questions.

Dementia is a syndrome characterized by cognitive and neuropsychiatric symptoms associated with progressive functional decline (FD). FD is a core diagnostic criterion for dementia, setting the threshold between its prodromal stages and the full-blown disease. The operationalization of FD continues to generate a great deal of controversy. For instance, the threshold of FD for the diagnosis of dementia varies across diagnostic criteria, supporting the need for standardization of this construct. Moreover, there is a need to reconsider how we are measuring FD to set boundaries between normal aging, mild cognitive impairment, and dementia. In this paper, we propose a multidimensional framework that addresses outstanding issues in the assessment of FD: i) What activities of daily living (ADLs) are necessary to sustain an independent living in aging? ii) How to assess FD in individuals with suspected neurocognitive disorders? iii) To whom is the assessment directed? and iv) How much does FD differentiate healthy aging from mild and major neurocognitive disorders? Importantly, the To Whom Question introduces a person-centered approach that regards patients and caregivers as active agents in the assessment process of FD. Thus, once impaired ADLs have been identified, patients can indicate how significant such impairments are for them in daily life. We envisage that this new framework will guide future strategies to enhance functional assessment and treatment of patients with dementia and their caregivers.

Emerging Theories of Allostatic-Interoceptive Overload in Neurodegeneration.

Recent integrative multilevel models offer novel insights into the etiology and course of neurodegenerative conditions. The predictive coding of allostatic-interoception theory posits that the brain adapts to environmental demands by modulating internal bodily signals through the allostatic-interoceptive system. Specifically, a domain-general allostatic-interoceptive network exerts adaptive physiological control by fine-tuning initial top-down predictions and bottom-up peripheral signaling. In this context, adequate adaptation implies the minimization of prediction errors thereby optimizing energy expenditure. Abnormalities in top-down interoceptive predictions or peripheral signaling can trigger allostatic overload states, ultimately leading to dysregulated interoceptive and bodily systems (endocrine, immunological, circulatory, etc.). In this context, environmental stress, social determinants of health, and harmful exposomes (i.e., the cumulative life-course exposition to different environmental stressors) may interact with physiological and genetic factors, dysregulating allostatic interoception and precipitating neurodegenerative processes. We review the allostatic-interoceptive overload framework across different neurodegenerative diseases, particularly in the behavioral variant frontotemporal dementia (bvFTD). We describe how concepts of allostasis and interoception could be integrated with principles of predictive coding to explain how the brain optimizes adaptive responses, while maintaining physiological stability through feedback loops with multiple organismic systems. Then, we introduce the model of allostatic-interoceptive overload of bvFTD and discuss its implications for the understanding of pathophysiological and neurocognitive abnormalities in multiple neurodegenerative conditions.

Insights Into Differences in Pulmonary Hemodynamics in Hispanic Patients With Pulmonary Arterial Hypertension.

Background: Emerging data suggest that Hispanic patients with pulmonary arterial hypertension (PAH) exhibit improved survival rates compared to individuals of other ethnicities with similar baseline hemodynamics. However, the underlying reasons for this survival advantage remain unclear. This study focused on comparing pulmonary hemodynamics in Hispanic and non-Hispanic PAH patients and how these differences may contribute to varied clinical outcomes. Methods: A retrospective analysis of right heart catheterization data was conducted on a treatment-naive PAH patient cohort from a single center. Results: Over a 10-year period, a total of 226 PAH patients were identified, of which 138 (61%) were Hispanic and 88 (39%) were non-Hispanic. Hispanic patients presented with lower pulmonary artery pressures, lower pulmonary vascular resistance, and exhibited significantly higher pulmonary arterial compliance (PAc). Hispanic patients had better 5-year survival rates. Conclusions: This study highlights the importance of exploring phenotypic differences in ethnically diverse PAH cohorts.

Electrophysiological biomarkers in dual pathology.

INTRODUCTION: The co-occurrence of substance use disorder with at least one other mental disorder is called dual pathology, which in turn is characterised by heterogeneous symptoms that are difficult to diagnose and have a poor response to treatment. For this reason, the identification and validation of biomarkers is necessary. Within this group, possible electroencephalographic biomarkers have been reported to be useful in diagnosis, treatment and follow-up, both in neuropsychiatric conditions and in substance use disorders. This article aims to review the existing literature on electroencephalographic biomarkers in dual pathology. METHODS: A narrative review of the literature. A bibliographic search was performed on the PubMed, Science Direct, OVID, BIREME and Scielo databases, with the keywords: electrophysiological biomarker and substance use disorder, electrophysiological biomarker and mental disorders, biomarker and dual pathology, biomarker and substance use disorder, electroencephalography, and substance use disorder or comorbid mental disorder. RESULTS: Given the greater amount of literature found in relation to electroencephalography as a biomarker of mental illness and substance use disorders, and the few articles found on dual pathology, the evidence is organised as a biomarker in psychiatry for the diagnosis and prediction of risk and as a biomarker for dual pathology. CONCLUSIONS: Although the evidence is not conclusive, it suggests the existence of a subset of sites and mechanisms where the effects of psychoactive substances and the neurobiology of some mental disorders could overlap or interact.

Viscous dynamics associated with hypoexcitation and structural disintegration in neurodegeneration via generative whole-brain modeling.

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.

The BrainLat project, a multimodal neuroimaging dataset of neurodegeneration from underrepresented backgrounds.

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.

Updates in the Pharmacotherapy of Pulmonary Hypertension in Patients with Heart Failure with Preserved Ejection Fraction.

Pulmonary hypertension (PH) associated with left heart disease (LHD) is a complex cardiopulmonary condition where a variable degree of pulmonary congestion, arterial vasoconstriction and vascular remodeling can lead to PH and right heart strain. Right heart dysfunction has a significant prognostic impact on these patients. Therefore, preserving right ventricular (RV) function is an important treatment goal. However, the treatment of PH in patients with left heart disease has produced conflicting evidence. The transition from pure LHD to LHD with PH is a continuum and clinically challenging. The heart failure with preserved ejection fraction (HFpEF) patient population is heterogeneous when it comes to PH and RV function. Appropriate clinical and hemodynamic phenotyping of patients with HFpEF and concomitant PH is paramount to making the appropriate treatment decision. This manuscript will summarize the current evidence for the use of pulmonary arterial vasodilators in patients with HFpEF.

Upscaling the effect of traits in response to drought: The relative importance of safety-efficiency and acquisitive-conservation functional axes.

We tested the idea that functional trade-offs that underlie species tolerance to drought-driven shifts in community composition via their effects on demographic processes and subsequently on shifts in species' abundance. Using data from 298 tree species from tropical dry forests during the extreme ENSO-2015, we scaled-up the effects of trait trade-offs from individuals to communities. Conservative wood and leaf traits favoured slow tree growth, increased tree survival and positively impacted species abundance and dominance at the community-level. Safe hydraulic traits, on the other hand, were related to demography but did not affect species abundance and communities. The persistent effects of the conservative-acquisitive trade-off across organizational levels is promising for generalization and predictability of tree communities. However, the safety-efficient trade-off showed more intricate effects on performance. Our results demonstrated the complex pathways in which traits scale up to communities, highlighting the importance of considering a wide range of traits and performance processes.