Country-level gender inequality is associated with structural differences in the brains of women and men.

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality.

Temporal Irreversibility of Large-Scale Brain Dynamics in Alzheimer's Disease.

Healthy brain dynamics can be understood as the emergence of a complex system far from thermodynamic equilibrium. Brain dynamics are temporally irreversible and thus establish a preferred direction in time (i.e., arrow of time). However, little is known about how the time-reversal symmetry of spontaneous brain activity is affected by Alzheimer's disease (AD). We hypothesized that the level of irreversibility would be compromised in AD, signaling a fundamental shift in the collective properties of brain activity toward equilibrium dynamics. We investigated the irreversibility from resting-state fMRI and EEG data in male and female human patients with AD and elderly healthy control subjects (HCs). We quantified the level of irreversibility and, thus, proximity to nonequilibrium dynamics by comparing forward and backward time series through time-shifted correlations. AD was associated with a breakdown of temporal irreversibility at the global, local, and network levels, and at multiple oscillatory frequency bands. At the local level, temporoparietal and frontal regions were affected by AD. The limbic, frontoparietal, default mode, and salience networks were the most compromised at the network level. The temporal reversibility was associated with cognitive decline in AD and gray matter volume in HCs. The irreversibility of brain dynamics provided higher accuracy and more distinctive information than classical neurocognitive measures when differentiating AD from control subjects. Findings were validated using an out-of-sample cohort. Present results offer new evidence regarding pathophysiological links between the entropy generation rate of brain dynamics and the clinical presentation of AD, opening new avenues for dementia characterization at different levels.SIGNIFICANCE STATEMENT By assessing the irreversibility of large-scale dynamics across multiple brain signals, we provide a precise signature capable of distinguishing Alzheimer's disease (AD) at the global, local, and network levels and different oscillatory regimes. Irreversibility of limbic, frontoparietal, default-mode, and salience networks was the most compromised by AD compared with more sensory-motor networks. Moreover, the time-irreversibility properties associated with cognitive decline and atrophy outperformed and complemented classical neurocognitive markers of AD in predictive classification performance. Findings were generalized and replicated with an out-of-sample validation procedure. We provide novel multilevel evidence of reduced irreversibility in AD brain dynamics that has the potential to open new avenues for understating neurodegeneration in terms of the temporal asymmetry of brain dynamics.

Gaming expertise induces meso­scale brain plasticity and efficiency mechanisms as revealed by whole-brain modeling.

Video games are a valuable tool for studying the effects of training and neural plasticity on the brain. However, the underlying mechanisms related to plasticity-associated brain structural changes and their impact on brain dynamics are unknown. Here, we used a semi-empirical whole-brain model to study structural neural plasticity mechanisms linked to video game expertise. We hypothesized that video game expertise is associated with neural plasticity-mediated changes in structural connectivity that manifest at the meso­scale level, resulting in a more segregated functional network topology. To test this hypothesis, we combined structural connectivity data of StarCraft II video game players (VGPs, n = 31) and non-players (NVGPs, n = 31), with generic fMRI data from the Human Connectome Project and computational models, to generate simulated fMRI recordings. Graph theory analysis on simulated data was performed during both resting-state conditions and external stimulation. VGPs' simulated functional connectivity was characterized by a meso­scale integration, with increased local connectivity in frontal, parietal, and occipital brain regions. The same analyses at the level of structural connectivity showed no differences between VGPs and NVGPs. Regions that increased their connectivity strength in VGPs are known to be involved in cognitive processes crucial for task performance such as attention, reasoning, and inference. In-silico stimulation suggested that differences in FC between VGPs and NVGPs emerge in noisy contexts, specifically when the noisy level of stimulation is increased. This indicates that the connectomes of VGPs may facilitate the filtering of noise from stimuli. These structural alterations drive the meso­scale functional changes observed in individuals with gaming expertise. Overall, our work sheds light on the mechanisms underlying structural neural plasticity triggered by video game experiences.

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.

Sleep Capital: Linking Brain Health to Wellbeing and Economic Productivity Across the Lifespan.

INTRODUCTION AND FRAMEWORK: Sleep capital contributes to individual and societal wellbeing, productivity, and economic outcomes and involves a novel aspect of brain capital. It encompasses the quality and quantity of sleep as integral components that influence cognitive abilities, mental and brain health, and physical health, affecting workplace productivity, learning, decision-making, and overall economic performance. Here, we bring a framework to understand the complex relationship between sleep quality, health, wellbeing, and economic productivity. Then we outline the multilevel impact of sleep on cognitive abilities, mental/brain health, and economic indicators, providing evidence for the substantial returns on investment in sleep health initiatives. Moreover, sleep capital is a key factor when considering brain health across the lifespan, especially for the aging population. DISCUSSION: We propose specific elements and main variables to develop specific indexes of sleep capital to address its impacts on health, wellbeing and productivity. CONCLUSION: Finally, we suggest policy recommendations, workplace interventions, and individual strategies to promote sleep health and brain capital. Investing in sleep capital is essential for fostering a healthier, happier, fairer and more productive society.

Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2.

BACKGROUND: The triggering receptor expressed on myeloid cell 2 (TREM2) is a major regulator of neuroinflammatory processes in neurodegeneration. To date, the p.H157Y variant of TREM2 has been reported only in patients with Alzheimer's disease. Here, we report three patients with frontotemporal dementia (FTD) from three unrelated families with heterozygous p.H157Y variant of TREM2: two patients from Colombian families (study 1) and a third Mexican origin case from the USA (study 2). METHODS: To determine if the p.H157Y variant might be associated with a specific FTD presentation, we compared in each study the cases with age-matched, sex-matched and education-matched groups-a healthy control group (HC) and a group with FTD with neither TREM2 mutations nor family antecedents (Ng-FTD and Ng-FTD-MND). RESULTS: The two Colombian cases presented with early behavioural changes, greater impairments in general cognition and executive function compared with both HC and Ng-FTD groups. These patients also exhibited brain atrophy in areas characteristic of FTD. Furthermore, TREM2 cases showed increased atrophy compared with Ng-FTD in frontal, temporal, parietal, precuneus, basal ganglia, parahippocampal/hippocampal and cerebellar regions. The Mexican case presented with FTD and motor neuron disease (MND), showing grey matter reduction in basal ganglia and thalamus, and extensive TDP-43 type B pathology. CONCLUSION: In all TREM2 cases, multiple atrophy peaks overlapped with the maximum peaks of TREM2 gene expression in crucial brain regions including frontal, temporal, thalamic and basal ganglia areas. These results provide the first report of an FTD presentation potentially associated with the p.H157Y variant with exacerbated neurocognitive impairments.

Associations of the 'weekend warrior' physical activity pattern with all-cause, cardiovascular disease and cancer mortality: the Mexico City Prospective Study.

OBJECTIVES: The objective was to investigate the benefits of the 'weekend warrior' physical activity pattern in Latin America, where many people take part in high levels of non-exercise physical activity. METHODS: Participants in the Mexico City Prospective Study were surveyed from 1998 to 2004 and resurveyed from 2015 to 2019. Those who exercised up to once or twice per week were termed weekend warriors. Those who exercised more often were termed regularly active. Analyses were adjusted for potential confounders. RESULTS: The main analysis included 26 006 deaths in 154 882 adults (67% female) aged 52±13 years followed for 18±4 years (mean±SD). Compared with those who reported no exercise, the HR (95% CI) was 0.88 (0.83 to 0.93) in the weekend warriors and 0.88 (0.84 to 0.91) in the regularly active. Similar results were observed for cardiovascular disease and cancer mortality, but associations were weaker. Stratified analyses showed that substantial reductions in all-cause mortality risk only occurred when the duration of exercise sessions was at least 30-60 min. The repeated-measures analysis included 843 deaths in 10 023 adults followed for 20±2 years. Compared with being inactive or becoming inactive, the HR was 0.86 (95% CI 0.65 to 1.12) when being a weekend warrior or becoming a weekend warrior and 0.85 (95% CI 0.70 to 1.03) when being regularly active or becoming regularly active. CONCLUSIONS: This is the first prospective study to investigate the benefits of the weekend warrior physical activity pattern in Latin America. The results suggest that even busy adults could benefit from taking part in one or two sessions of exercise per week.

Multivariate word properties in fluency tasks reveal markers of Alzheimer's dementia.

INTRODUCTION: Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease-specific semantic memory patterns. Here, we leveraged automated word-property analysis to capture neurocognitive markers of AD vis-à-vis behavioral variant frontotemporal dementia (bvFTD). METHODS: Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group-level discrimination, patient-level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns. RESULTS: Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group- and subject-level discrimination only in AD, also predicting executive outcomes. Disease-specific cortical thickness patterns were predicted by frequency in both disorders. Default-mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD. DISCUSSION: Word-property analysis of fluency can boost AD characterization and diagnosis. HIGHLIGHTS: We report novel word-property analyses of verbal fluency in AD and bvFTD. Standard valid response counts captured deficits and brain patterns in both groups. Specific word properties (e.g., frequency, granularity) were altered only in AD. Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD. Word-property analysis of fluency can boost AD characterization and diagnosis.

Modifiable dementia risk factors associated with objective and subjective cognition.

INTRODUCTION: Early detection of both objective and subjective cognitive impairment is important. Subjective complaints in healthy individuals can precede objective deficits. However, the differential associations of objective and subjective cognition with modifiable dementia risk factors are unclear. METHODS: We gathered a large cross-sectional sample (N = 3327, age 18 to 84) via a smartphone app and quantified the associations of 13 risk factors with subjective memory problems and three objective measures of executive function (visual working memory, cognitive flexibility, model-based planning). RESULTS: Depression, socioeconomic status, hearing handicap, loneliness, education, smoking, tinnitus, little exercise, small social network, stroke, diabetes, and hypertension were all associated with impairments in at least one cognitive measure. Subjective memory had the strongest link to most factors; these associations persisted after controlling for depression. Age mostly did not moderate these associations. DISCUSSION: Subjective cognition was more sensitive to self-report risk factors than objective cognition. Smartphones could facilitate detecting the earliest cognitive impairments. HIGHLIGHTS: Smartphone assessments of cognition were sensitive to dementia risk factors. Subjective cognition had stronger links to most factors than did objective cognition. These associations were not fully explained by depression. These associations were largely consistent across the lifespan.

Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting "brain fog" and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer's disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in Long COVID and ADRD are due to parallel neuroinflammation, astrocyte reactivity, hypoxia, and neurovascular injury. These neurophysiological abnormalities underpinning cognitive decline in COVID-19 can be detected by routine EEG exams. Future research will explore the value of EEG monitoring of COVID-19 patients for predicting long-term outcomes and monitoring efficacy of therapeutic interventions. HIGHLIGHTS: Abnormal intrinsic electrophysiological brain activity, such as slowing of EEG, reduced alpha wave, and epileptiform are characteristic findings in COVID-19 patients. EEG abnormalities have the potential as neural biomarkers to identify neurological complications at the early stage of the disease, to assist clinical assessment, and to assess cognitive decline risk in Long COVID patients. Similar slowing of intrinsic brain activity to that of COVID-19 patients is typically seen in patients with mild cognitive impairments, ADRD. Evidence presented supports the idea that cognitive deficits in Long COVID and ADRD are driven by overlapping neurophysiological abnormalities resulting, at least in part, from neuroinflammatory mechanisms and astrocyte reactivity. Identifying common biological mechanisms in Long COVID-19 and ADRD can highlight critical pathologies underlying brain disorders and cognitive decline. It elucidates research questions regarding cognitive EEG and mild cognitive impairment in Long COVID that have not yet been adequately investigated.

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 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

Educational disparities in brain health and dementia across Latin America and the United States.

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.

The Brain Economy: Advancing Brain Science to Better Understand the Modern Economy.

The coming years are likely to be turbulent due to a myriad of factors or polycrisis, including an escalation in climate extremes, emerging public health threats, weak productivity, increases in global economic instability and further weakening in the integrity of global democracy. These formidable challenges are not exogenous to the economy but are in some cases generated by the system itself. They can be overcome, but only with far-reaching changes to global economics. Our current socio-economic paradigm is insufficient for addressing these complex challenges, let alone sustaining human development, well-being and happiness. To support the flourishing of the global population in the age of polycrisis, we need a novel, person-centred and collective paradigm. The brain economy leverages insights from neuroscience to provide a novel way of centralising the human contribution to the economy, how the economy in turn shapes our lives and positive feedbacks between the two. The brain economy is primarily based on Brain Capital, an economic asset integrating brain health and brain skills, the social, emotional, and the diversity of cognitive brain resources of individuals and communities. People with healthy brains are essential to navigate increasingly complex systems. Policies and investments that improve brain health and hence citizens' cognitive functions and boost brain performance can increase productivity, stimulate greater creativity and economic dynamism, utilise often underdeveloped intellectual resources, afford social cohesion, and create a more resilient, adaptable and sustainability-engaged population.

Allostatic-interoceptive anticipation of social rejection.

Anticipating social stress evokes strong reactions in the organism, including interoceptive modulations. However, evidence for this claim comes from behavioral studies, often with inconsistent results, and relates almost solely to the reactive and recovery phase of social stress exposure. Here, we adopted an allostatic-interoceptive predictive coding framework to study interoceptive and exteroceptive anticipatory brain responses using a social rejection task. We analyzed the heart-evoked potential (HEP) and task-related oscillatory activity of 58 adolescents via scalp EEG, and 385 human intracranial recordings of three patients with intractable epilepsy. We found that anticipatory interoceptive signals increased in the face of unexpected social outcomes, reflected in larger negative HEP modulations. Such signals emerged from key brain allostatic-interoceptive network hubs, as shown by intracranial recordings. Exteroceptive signals were characterized by early activity between 1-15 Hz across conditions, and modulated by the probabilistic anticipation of reward-related outcomes, observed over distributed brain regions. Our findings suggest that the anticipation of a social outcome is characterized by allostatic-interoceptive modulations that prepare the organism for possible rejection. These results inform our understanding of interoceptive processing and constrain neurobiological models of social stress.

Social and non-social working memory in neurodegeneration.

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.

Source space connectomics of neurodegeneration: One-metric approach does not fit all.

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 (patientsHCs) in both groups was mainly identified in frontotemporal regions. These atypicalities were differently captured by frequency- and time-domain connectivity metrics, in a bandwidth-specific fashion. The multi-metric representation of source space whole-brain functional connectivity evidenced the inadequacy of single-metric approaches, and resulted in a valid alternative for the selection problem in EEG connectivity. These joint analyses reveal patterns of brain functional interdependence that are overlooked with single metrics approaches, contributing to a more reliable and interpretable description of atypical functional connectivity in neurodegeneration.

Overactivation of posterior insular, postcentral and temporal regions during preserved experience of envy in autism.

Social emotions are critical to successfully navigate in a complex social world because they promote self-regulation of behaviour. Difficulties in social behaviour are at the core of autism spectrum disorder (ASD). However, social emotions and their neural correlates have been scarcely investigated in this population. In particular, the experience of envy has not been addressed in ASD despite involving neurocognitive processes crucially compromised in this condition. Here, we used an fMRI adapted version of a well-validated task to investigate the subjective experience of envy and its neural correlates in adults with ASD (n = 30) in comparison with neurotypical controls (n = 28). Results revealed that both groups reported similarly intense experience of envy in association with canonical activation in the anterior cingulate cortex and the anterior insula, among other regions. However, in participants with ASD, the experience of envy was accompanied by overactivation of the posterior insula, the postcentral gyrus and the posterior superior temporal gyrus, regions subserving the processing of painful experiences and mentalizing. This pattern of results suggests that individuals with ASD may use compensatory strategies based on the embodied amplification of pain and additional mentalizing efforts to shape their subjective experience of envy. Results have relevant implications to better understand the heterogeneity of this condition and to develop new intervention targets.

Life-Course Brain Health as a Determinant of Late-Life Mental Health: American Association for Geriatric Psychiatry Expert Panel Recommendations.

This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years.