The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.
To investigate the clinical relationship between the interaction of iron metabolism, neuroinflammation and iron deposition in substantia nigra of Parkinson's disease (PD). 1) 30 PD patients and 30 healthy controls were recruited from the First and Second affiliated Hospitals of Xinjiang Medical University from May 2022 to October 2023. The clinical symptoms (motor symptoms and non-motor symptoms) and clinical severity of PD patients were evaluated by unified Parkinson's disease scale III (UPDRSIII), Hoehn-Yahr (H-Y) stage, Hamilton anxiety scale (HAMA), Hamilton depression scale (HAMD), mini-mental state assessment scale (MMSE) and Montreal cognitive assessment scale (MoCA). (2) A case-control study was conducted to determine the content of iron in the brain of patients with PD by magnetic sensitive quantitative imaging (QSM) to generate 3DT2, 3DT2* (SWAN), QSM and PostT1Gd, and to study the correlation between iron content and motor symptoms, non-motor symptoms (anxiety, depression, dementia), and clinical severity in PD. (3) Enzyme-linked Immunosorbent Assay (ELISA) was used to detect and compare the levels of iron, DMT1, FPN1, IL-1β, IL-6 and TNF-α in the peripheral blood of both groups, and t-test and Wilcoxon rank-sum test were used to analyze the correlation between peripheral iron metabolism and blood inflammatory factors, clinical symptoms and clinical severity in patients with PD. (4) To analyze the clinical correlation between the interaction of peripheral iron metabolism and neuroinflammation and iron deposition in substantia nigra of Parkinson's brain. 1) The quantitative susceptibility mapping (QSM) values of red nucleus, substantia nigra, putamen and caudate nucleus in PD group were higher than those in control group (P < 0.05). The QSM value of red nucleus in PD group was negatively correlated with UPDRSIII score (motor symptoms) and positively correlated with non-motor symptoms depression (P < 0.05). The QSM score of substantia nigra in midbrain was positively correlated with disease severity (H-Y stage)(P < 0.05). (2) The median levels of serum DMT1, Fe, IL-6 and TNF-α in PD group were higher than those in control group (P < 0.05). The median level of serum FPN1 in PD group was lower than that in control group (P < 0.001). There was a negative correlation between serum DMT1 and non-motor symptom intelligence (MMSE), and between peripheral blood iron content and anxiety in patients with PD (P < 0.05). There was no significant correlation between ferritin and inflammatory factors and other clinical symptoms and severity of PD (P > 0.05). (3) The quantitative value of magnetic sensitivity (QSM) of substantia nigra in PD was positively correlated with iron metabolic protein DMT1, peripheral blood inflammatory factor IL-6 and negatively correlated with peripheral blood iron ion (P < 0.05). The results of interactive analysis showed that there was interaction among magnetic sensitivity quantitative value of substantia nigra (QSM), iron metabolic protein DMT1, peripheral blood inflammatory factor IL-6 and peripheral blood iron ion. There are iron deposits in the deep nuclei and thalamus of PD patients. Iron deposition in substantia nigra is related to UPDRSIII score (motor symptoms) and disease severity (H-Y stage) in patients with PD. Iron deposition in substantia nigra may be linked to the interaction between iron metabolism and neuroinflammation.
US emerging adults under legal drinking age (underage emerging adults; U-EA; ages 18-19) are unlikely to seek or receive indicated health risk behavior interventions, thus it is imperative to find brief, effective interventions to reduce U-EA health risk behaviors, such as drinking. Developmental neuroscience reflects that peers hold higher neural salience during adolescence, as evidenced by differential neural response with real and/or simulated peers, even when those peers are not friends, and particularly in the context of alcohol. Peers also activate positive (prosocial) neural and health behavior responses among adolescents. The role of positive, prosocial peer feedback is consequential given that the most widely-used platforms for U-EA behavioral interventions are group-based platforms. We propose functional magnetic resonance imaging (fMRI) hyperscanning (tandem dyadic scanning) to evaluate U-EA brain response during group motivational interviewing (GMI) for health behavior change. This study will enroll n = 248 U-EA (ages 18-19) with ≥1 past month binge drinking event (4/3 standard drinks per occasion for males/females) via community and university campus recruitment and deliver group MI to peer dyads (no comparator; within-subjects design; ClinicalTrials.gov ID: NCT06115252). Synchronized fMRI (hyperscanning) will be used to examine brain response to positive, prosocial peer-directed health promotive language (peer-directed change talk) generated during and extracted from the GMI session. Primary outcomes include fMRI-based hyperscanning metrics (BOLD synchrony in social cognition network) and their association with behavioral measures (past-month alcohol use days measured via Timeline Followback) at 12-months (primary outcome) and 3- and 6-months (secondary outcomes) post-GMI. We hypothesize that greater neural alignment in the social cognition network during positive, prosocial peer interactions (peer-directed change talk) will be associated with greater post-intervention behavior change (lower number of past month drinking days) at each follow-up point. This translational study is crucial for making meaningful gains in improving interventions for youth health behavior. ClinicalTrials.gov NCT06115252.
Resting-state functional connectivity (RSFC) contains participant-specific patterns that can support differentiation among individuals within a cohort. This paper proposed computational approaches for determining the differential identifiability of nodes within the RSFC from the Human Connectome Project (HCP) and Leipzig Mind-Brain-Body (LEMON) datasets, and defined fingerprint-like nodes to explore individual brain functional fingerprint recognition and cognitive prediction. In addition, the predictions of fluid intelligence and working memory were explored. Experiments revealed that fingerprint-like nodes achieved higher recognition rates than whole-brain functional connectivity nodes, with individual recognition rates of at least 95.6% and 99.5% in the HCP and LEMON datasets, respectively. These nodes showed variability across brain atlases and datasets but consistent distribution within functional networks. Predictive models using these nodes also improved fluid intelligence and working memory predictions. Compared with existing methods, the proposed approaches define fingerprint-like nodes and systematically reveal their spatial distribution characteristics and contribution weights to individual functional fingerprint recognition at the node level. Although the VAN and DAN contribute less to individual identification of functional fingerprints compared to the FPN and DMN, our experiments find there are nodes within these networks that significantly impact individual identification. The fingerprint-like nodes performed well in both individual brain functional fingerprint identification and cognitive prediction. These approaches would contribute to a deeper understanding of the neural mechanisms of RSFC organization and function, as well as the mechanisms of RSFC in individual recognition and cognitive prediction.
Constipation as a public health issue impairs human health and quality of life, while current strategies against constipation often lead to adverse effects. This study evaluated the effects and underlying mechanism of 2'-fucosyllactose (2'-FL) and Bifidobacterium longum BB536 (BB536) on relieving loperamide-induced constipation and depressive-like behavior. 2'-FL + BB536 can significantly elevate fecal water content, shorten defecation time and enhance the intestinal transit rate in constipated mice. 2'-FL + BB536 increased the contents of substance P and 5-hydroxytryptamine, while reducing the contents of nitric oxide and vasoactive intestinal peptide. 2'-FL + BB536 decreased histological damage of colonic and brain tissues in constipated mice. Furthermore, 2'-FL + BB536 upregulated the mRNA and protein expression levels of AQP9 and activated the SCF/c-Kit signaling pathway in the colon. Meanwhile, 2'-FL + BB536 reduced neuroinflammation and prevented synaptic damage through suppressing the mRNA and protein expressions of TNF-α and promoting the mRNA and protein expressions of SNAP-25 and PSD-95 in the brain, thereby alleviating depressive-like behavior. Notably, 2'-FL + BB536 regulated gut microbiota diversity and enhanced the relative abundance of several bacteria, including the phylum Bacteroidetes and the genera Lactobacillus and Akkermansia. The contents of short-chain fatty acids were upregulated following 2'-FL + BB536 supplementation. Overall, 2'-FL combined with BB536 exerted alleviating effects on loperamide-induced constipation and depressive-like behavior through regulating the gut-brain axis.
Parkinson's disease (PD) is a common neurodegenerative disorder marked by progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of Lewy bodies, intracellular inclusions enriched in α-synuclein. Synphilin-1 interacts with α-synuclein, localizes to Lewy bodies, and has been implicated in inclusion formation and neuroprotection in cellular and animal models; however, its physiological function in vivo remains poorly defined. Here, we generated and characterized a synphilin-1 knockout (Sph-1 KO) mouse by targeted genetic deletion of the Sph-1 locus and performed a comprehensive phenotyping battery including behavioral testing as well as biochemical, histological, structural, and ultrastructural analyses. Sph-1 KO mice survived to nearly two years of age and showed normal body weight, lifespan, motor performance, learning and memory, anxiety-like behavior, attention, and gross brain morphology. Western blot analyses indicated that levels of α-synuclein and synaptic proteins were largely unchanged. While outer mitochondrial membrane proteins were unaffected, the mitochondrial matrix protein HSP60 was reduced, consistent with altered mitochondrial proteostasis in the absence of synphilin-1. Strikingly, histochemical analyses, magnetic resonance imaging, and electron microscopy revealed early-onset hydrocephalus in Sph-1 KO mice associated with severe loss and disorganization of motile ependymal cilia in the ventricular lining, a cell type that normally expresses high levels of synphilin-1. Ultrastructural and immunohistochemical analyses revealed disrupted ependymal architecture, mislocalization of acetylated α-tubulin to the cytoplasm, cellular swelling, and enlarged, aberrant mitochondria, whereas cortical neurons appeared largely structurally unaffected. Together, these findings identify synphilin-1 as a key regulator of microtubule organization and cytoskeletal/organelle homeostasis in ependymal cells, required to maintain motile ciliogenesis, cerebrospinal fluid flow, and ventricular integrity. This unexpected role for synphilin-1 in ciliated brain epithelia, along with a reduction in the critical mitochondrial chaperone HSP60, broadens our understanding of synphilin-1 biology and provides a new framework for its potential relevance to PD-associated pathology.
Antenatal opioid exposure is associated with adverse neurodevelopmental outcomes and smaller brain volumes, but the effects of opioids on newborn cortical folding maturation have not been defined. The Advancing Clinical Trials in Neonatal Opioid Withdrawal Outcomes of Babies With Opioid Exposure (OBOE) Study is a multisite prospective longitudinal cohort study examining the association of antenatal opioid exposure with brain maturation and outcomes in newborns. To compare cerebral cortical folding in newborns exposed to opioids vs nonexposed controls. In this cohort study, full-term newborns from the OBOE study with antenatal opioid exposure and nonexposed controls were recruited at 4 US sites, including obstetric clinics, maternal substance use treatment programs, and birth hospitals, from August 5, 2020, to December 28, 2023. Data analysis was performed from August 19, 2020, to March 25, 2026. Newborn opioid exposure, including opioid-only and polysubstance exposure as well as exposure to specific opioids. Nonsedated T2-weighted magnetic resonance imaging (MRI) data were acquired via harmonized protocols, and 3D brain images were segmented and parcellated using the Developing Brain Region Annotation With Expectation-Maximization pipeline. The inner cortical gray matter surface was used to measure cortical folding across the frontal, parietal, temporal, and occipital lobes. Group differences between opioid-exposed and nonexposed newborns were compared via analysis of covariance, adjusting for postmenstrual age at MRI, sex, birth weight, maternal age, smoking status, and education level. A total of 259 newborns (mean [SD] gestational age at birth, 39.1 [1.0] weeks; 145 [56.0%] male) were included in the analysis, of whom 164 had antenatal exposure to opioids and 95 were nonexposed controls (mean [SD] postmenstrual age at MRI, 42.8 [2.2] and 42.9 [2.0] weeks, respectively). Compared with nonexposed controls, newborns who had been exposed to opioids had significantly decreased sulcal depth in the frontal (difference, -0.11 mm [95% CI, -0.20 to -0.02 mm]), parietal (difference, -0.19 mm [95% CI, -0.31 to -0.07 mm]), and global (difference, -0.09 mm [95% CI, -0.18 to -0.01 mm]) regions, as well as decreased surface area in the frontal (difference, -1048 mm2 [95% CI, -1497 to -598 mm2]), parietal (difference, -501 mm2 [95% CI, -834 to -168 mm2]), temporal (difference, -422 mm2 [95% CI, -682 to -162 mm2]), occipital (difference, -232 mm2 [95% CI, -439 to -26 mm2]), and global (difference, -2185 mm2 [95% CI, -3327 to -1043 mm2]) surfaces. Compared with controls, newborns exposed to methadone showed larger reductions in frontal, parietal, and global surface areas than those exposed to buprenorphine, with parietal surface area significantly reduced only in the methadone-exposed group (difference, -656 mm2 [95% CI, -1111 to -202 mm2]). Newborns with polysubstance exposure had significantly reduced sulcal depth in the frontal, parietal, and global surfaces, as well as reduced surface area across all lobes compared with controls, whereas opioid-only exposed newborns showed fewer significant differences from controls, with reduced parietal sulcal depth and decreased frontal and global surface areas. In this cohort study, newborns with antenatal exposure to opioids had reduced cerebral cortical sulcal depth and surface area compared with nonexposed controls, with greater reductions among newborns exposed to methadone compared with those exposed to buprenorphine, and in newborns with polysubstance exposure compared with those with opioid exposure only. Ongoing serial MRI and long-term follow-up are under way to assess the impact of these early cortical maturational differences on later neurodevelopment and behavior.
Identifying brain phenotypes influencing social participation may help understand social deficits in psychiatric disorders. Previous research shows methodological inconsistencies, lacking consensus on which brain regions are crucial. Data-driven variable selection may overcome this, facilitating unbiased replication and discovery of social brain regions. We compare data-driven selection to literature-identification of brain regions in explaining social participation variation. In 37,576 UK Biobank participants (mean age 65 ± 8, 53% female) with structural and functional neuroimaging data, social participation (range 0-10) was derived by combining leisure activity participation and friend/family visits. First, literature review identified a subset of brain regions previously associated with social measures. Secondly, recursive feature elimination selected a subset of imaging-derived phenotypes in 25% (n = 9,394) of the sample. Hierarchical regression in the remaining 75% (n = 28,152) compared whether data-selected or literature-identified brain phenotype-sets explained more variance in social participation. Individual p-values were corrected for multiple comparisons using the false discovery rate. Recursive feature elimination selected 198 imaging-derived phenotypes. Data-selected imaging-derived-phenotypes explained more variance in social participation (1.31%) than literature-identified (0.84%, F = 3.17, p < 0.0001). Seventeen imaging-derived-phenotypes were associated with social participation including mid-posterior-cingulate, inferior-frontal/orbital and insular thickness, and functional connectivity between pericentral with medial frontoparietal and cerebellar networks. Multi-modal brain imaging-derived phenotypes can predict small but significant variation in social participation. We confirmed previously identified social brain associations of pericentral and medial frontoparietal, and orbital regions while also implicating novel relationships with the insula, acoustic radiation, and lateral frontoparietal networks. This highlights the value of data-driven approaches in solidifying social brain regional involvement, outperforming literature-based methods, and revealing previously undetected relationships.
Repetitive head impacts (RHIs) are associated with later-life neurodegeneration. Because soccer is the most widely played sport among youth worldwide, identifying early changes associated with RHI is important. To determine whether participation in 1 season of youth soccer is associated with changes in cognition, behavior, balance, brain structure or function, or blood biomarkers compared with noncontact sports. Prospective longitudinal cohort study at European centers (Munich, Germany; Leuven, Belgium; and Oslo, Norway). Male adolescent soccer players and noncontact athletes were each studied across a single competitive season with assessments at preseason, postseason, and 2 months later. Data were analyzed from January 2023 to March 2025. Soccer players were compared with noncontact athletes. In addition, self-reported heading of a soccer ball was assessed among soccer players as a measure of RHI. Cognition, behavior, balance, magnetic resonance imaging (brain structure, function, and biochemistry), and plasma biomarkers. Male adolescent soccer players (n = 82; mean [SD] age, 14.8 [0.6] years) did not differ from noncontact sport athletes (n = 47; mean [SD] age, 14.7 [0.7] years) in cognition, behavior, balance, cortical thickness, brain volumes, white-matter microstructure, or functional connectivity. At preseason, soccer players had higher total N-acetylaspartate (tNAA; β, -0.379 [95% CI, -0.627 to -0.131]; P = .003), glial fibrillary acidic protein (GFAP; β, -0.055 [95% CI, -0.103 to -0.006]; P = .03), and neurofilament light chain (NfL; β, -0.071 [95% CI, -0.122 to -0.020]; P = .01) than noncontact sport controls. Across the season, tNAA (β, 0.047 [95% CI, 0.020-0.074]; P = .001) declined in soccer players and increased in controls, converging by postseason. Group trajectories of GFAP and NfL did not differ between groups. Within soccer players, heading exposure was not significantly associated with changes in any outcome. In this cohort study of adolescent males, no statistically significant differences were detected over 1 season between soccer players and noncontact sport athletes in cognition, behavior, or brain structure and function. Group differences in GFAP and NfL may represent early signs of exposure, but lack of association with heading exposure warrants further investigation. These results highlight the need for large, multiyear studies to inform health policy.
The impact of sex hormones on the brain has been widely recognized. Polycystic ovary syndrome (PCOS) is frequently accompanied by abnormal hormone. Furthermore, psychiatric disorders are among the most common comorbidities associated with PCOS. However, whether PCOS induces alterations in brain structure remains unclear. Mendelian randomization (MR) was conducted to determine this causal association and pinpoint specific brain regions prone to PCOS. Genome wide association study (GWAS) data from the FinnGen database, for PCOS phenotypes from 39,004 PCOS patients and 731,830 controls were included. Outcomes were determined using GWAS data from the ENIGMA Consortium for brain structural traits, specifically cortical thickness and cortical surficial area, from 51,665 participants and for the volume of subcortical structures from 30,717 participants. The inverse-variance weighted (IVW) method was adopted as the primary estimate method. Additionally, several sensitivity and pleiotropy analyses were conducted to verify MR results. Genetically predicted PCOS was nominally associated with increased cortical thickness in the paracentral lobule (β = 0.0020 mm, pIVW = 0.0097) and decreased cortical thickness in the precentral gyrus (β = -0.0038 mm, pIVW = 0.0101). In addition, it was nominally associated with increased cortical surficial area in the precentral gyrus (β = 14.4026 mm2, pIVW = 0.0088), the pars opercularis (β = 5.6965 mm2, pIVW = 0.0491), and the posterior cingulate cortex (β = 3.529 mm2, pIVW = 0.0396) and reduced cortical surficial area in the inferior parietal lobule (β = -6.1279 mm2, pIVW = 0.0273) and the caudal middle frontal gyrus (β = -20.7354 mm2, pIVW = 0.0265). The results remained consistent throughout the sensitivity and pleiotropy analyses. This hypothesis-generating study provides suggestive evidence for possible associations between genetic predisposition to PCOS and alterations in cortical structure in specific brain regions. These findings highlight the need for confirmatory studies using independent datasets and alternative methodologies to validate the observed associations and elucidate underlying mechanisms. The results should be interpreted cautiously given the exploratory nature of the analyses and the limitations inherent to MR studies.
Sports/exercise engagement across the lifetime has been proposed to contribute to cognitive reserve and promote healthy brain aging. Few studies have examined whether past sports experiences are associated with current cognitive and social functions and resting-state brain activity in lifespan. The present study aimed to address that gap. Ninety healthy participants aged 20-83 years were categorized into four groups based on their self-reported sports experience: single sports (N = 25), team sports (N = 11), combined single and team sports (N = 20), and no experience (N = 34). We assessed cognitive function, social adaptation, and quality of life. Resting-state functional magnetic resonance imaging data were analyzed using amplitude of low-frequency fluctuations and seed-based functional connectivity to investigate local spontaneous activity and network-level integration. Participants with sports experience demonstrated enhanced performance in several cognitive tasks and higher social adaptation scores than those without experience. Neuroimaging analyses revealed increased amplitude of low-frequency fluctuations in the right middle frontal gyrus in the team-sport group. Furthermore, exploratory functional connectivity analysis showed reduced coupling between the right middle frontal gyrus and posterior sensory-visual regions, including the postcentral gyrus, lateral occipital cortex, and occipital fusiform gyrus. These findings suggest that lifetime sports engagement may be associated with differences in cognitive and psychosocial functioning, together with a tentative pattern of resting-state brain variation. Although the observed connectivity pattern may be broadly consistent with accounts of functional specialization or neural efficiency, the principal ALFF finding did not survive correction for multiple comparisons. Accordingly, the neuroimaging results should be regarded as preliminary and hypothesis-generating rather than confirmatory, while still providing a concrete basis for future hypothesis-driven investigation.
The properties of functional brain networks are an important determinant of cognitive function in aging and dementia. Despite this, few studies have comprehensively examined demographic and biopsychosocial predictors of functional brain networks, and none have attempted to do so across the adult lifespan while accounting for collinearity among these predictors. The current study used data from 525 individuals between the ages of 35 and 100 years from the Human Connectome Project 2.0 Lifespan Release, which includes task-based functional neuroimaging, physical and emotional health, and demographic information. Two functional brain network properties previously identified as moderators of cognitive functioning across the lifespan, entropy (regional specialization) and modularity (network segregation)-were used as outcome metrics in elastic net regression models that identified and ranked predictors of these metrics as well as their age-interaction terms. Our models ranked and established generalizability of key biopsychosocial health determinants of brain network properties across the lifespan using methodology allowing for high collinearity among predictors, differing notably from correlational findings. Derived models ranked biological sex, sleep duration, instrumental support, visual acuity, education, social isolation, diastolic blood pressure, and vigorous physical activity as the strongest generalizable factors. Biological sex exhibited a significant moderation effect such that males demonstrated greater age-related differences in entropy and modularity compared to females. Given that these brain network properties have previously been linked to cognitive functioning, understanding the complex interplay between these biopsychosocial determinants is crucial for informing intervention targets with the greatest potential for maintaining or improving cognitive functioning in aging.
We used diffusion spectrum imaging (DSI) and 3-dimensional arterial spin labeling to investigate microstructural and perfusion changes in memory-related brain regions in stroke-free patients with middle cerebral artery (MCA) occlusion. Forty-nine patients with unilateral MCA occlusion, 11 with bilateral MCA occlusion, and 30 healthy controls underwent 3.0 T MRI. Quantitative anisotropy (QA), restricted diffusion imaging (RDI), and fractional anisotropy (FA) were analyzed in memory-related gray matter regions and fiber tracts. The ratio of cerebral blood flow (CBF) and QA in the affected temporal lobe compared to the contralateral side is referred to as relative CBF (rCBF) and relative QA (rQA). Pearson correlation analysis was conducted to assess the relationship between rCBF and rQA in the temporal lobe. In unilateral MCA occlusion patients, paired t-tests revealed significantly lower QA and RDI in lesion-side regions of interest (ROIs) compared with contralateral ROIs. For healthy controls, bilateral hemispheric values were averaged, and independent t-tests were used for group comparisons. Patients with unilateral MCA occlusion showed broadly reduced QA and RDI in bilateral ROIs relative to controls, with more severe abnormalities on the lesion side. A moderate correlation between temporal lobe rCBF and rQA indicated that cerebral hypoperfusion may contribute to microstructural alterations. These findings demonstrate that stroke-free patients with unilateral MCA occlusion exhibit subclinical microstructural damage in memory-related brain regions and connected white matter tracts.
Neurofibromatosis type 1 (NF1) is a genetic disorder that affects brain development and increases the risk for neurodevelopmental conditions, including autism spectrum disorder. Given similar behavioral phenotypes and potential shared neurobiological processes in NF1 and autism spectrum disorder, this study evaluates two markers of brain maturation in youth with NF1 and typically developing youth, including auditory white matter and cortical response latency. Participants, aged 8-12 years, completed a multimodal neuroimaging protocol that included MRI with diffusion tensor imaging of the auditory radiation and magnetoencephalography. Analyses included group comparisons on fractional anisotropy measures of white matter and M50 latency responses from magnetoencephalography and the coupling between fractional anisotropy and M50. Compared to typically developing youth, youth with NF1 did not show maturation in fractional anisotropy or M50 with age and demonstrated shorter M50 auditory response latency. The association between auditory radiation fractional anisotropy and M50 was different in youth with NF1 compared to typically developing youth with youth with NF1 not showing a significant association between fractional anisotropy and M50. Maturation of auditory white matter and auditory cortical response latency is disrupted in NF1 and there is a lack of coupling between structure and function. Longitudinal imaging research is needed to further evaluate neurodevelopment and associations between these immaturities and behavior.
Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) enables non-invasive assessment of the substantia nigra pars compacta (SNpc). However, its utility in identifying dopaminergic dysfunction in idiopathic rapid eye movement sleep behavior disorder (iRBD) remains unclear. This study evaluated NM-MRI alterations in the SNpc, stratified by dopamine transporter (DaT) imaging status, to assess its performance in detecting early dopaminergic alterations. This combined retrospective and prospective study included 66 patients with iRBD (45 males, 67.0 ± 6.3 years) and 30 healthy controls (HCs) (11 males, 63.6 ± 6.5 years). Patients with iRBD were divided based on 18F-FP-CIT PET findings into those with abnormal (iRBD-CIT+) and normal (iRBD-CIT-) DaT imaging. NM metrics, including volume, signal-to-noise ratio (SNR), and contrast-to-noise ratio, were quantified using a template-based semi-automated method in the whole SNpc and its subregions (sensorimotor, associative, and limbic). Among the 66 patients with iRBD, 37 (56.1%) were classified as iRBD-CIT+. They exhibited significantly reduced NM metrics across the whole SNpc and all subregions compared to HCs. Notably, NM volume and SNR in the associative and limbic area were significantly lower in the iRBD-CIT+ group than in the iRBD-CIT- group, whereas other metrics did not differ. ROC analysis revealed fair performance for NM volume and SNR (AUC 0.73 and 0.75, respectively) in discriminating iRBD-CIT+ from iRBD-CIT-. Multivariable regression analyses confirmed these metrics as independent discriminators of DaT abnormalities. NM-MRI metrics, particularly limbic NM volume and SNR, serve as potential biomarkers for dopaminergic alterations in iRBD. These findings support NM-MRI as a strategic, radiation-free triage tool to identify high-risk patients requiring DaT imaging in iRBD.
Over the last two decades, interest in the neurobiological basis of parenthood has grown, with the primary focus being on maternal neuroplasticity. However, research on paternal brain adaptations remains limited and inconclusive. This longitudinal study investigated gray matter volume (GMV) and resting-state functional connectivity (rsFC) changes in 25 fathers immediately after childbirth and at 3, 6, 9, 12, and 24 weeks postpartum. Morphological changes were most evident as reductions in GMV within the bilateral occipital, frontal, temporal and parietal cortices, as well as the temporo-parietal junction, and the insular and hippocampal regions during the first six weeks, followed by gradual stabilization. From 12 weeks onward, local GMV increases were observed in the frontal and cerebellar regions. Connectivity analysis revealed significant reorganization within the Salience, Default Mode, and Frontoparietal Networks, with peak changes during the first 9 weeks marked by a shift from sensory processing to enhanced cognitive and affective processing. Additional rsFC analysis identified increased amygdala-cingulate and amygdala-hippocampal connectivity, indicating a significant link between the amygdala and paternal attachment during the first 12 weeks. These findings outline a clear trajectory of paternal neuroplasticity and adaptation during the early postpartum period, followed by maintenance and fine-tuning processes that likely facilitate paternal caregiving behaviors. Clinical Trial Registration: The study was registered at the German Clinical Trials register (DRKS; ID: DRKS00024875).
The aim of this study was to investigate the changes in complex networks of brain functions associated with LEV treatment and the neural mechanisms underlying the effects on executive functions. Patients with TLE, including both users and nonusers of LEV, were included in this study along with healthy controls. Rs-fMRI and an attentional network test (ANT) were performed, and 9 of the 23 patients not taking LEV were selected for LEV intervention and followed up for 18 months. Rs-fMRI and ANT were reviewed, and graph theoretic analyses were applied to investigate the changes in their topological properties. Both the LEV and HC groups showed improvements in executive function compared with the non-LEV group. At the global level, significant group differences in global efficiency and characteristic path length were observed among the three groups. At the nodal level, compared with the HC and non-LEV groups, the LEV group presented multiple differential nodes with different topological properties in the parieto-occipital lobe and frontal lobe. The TLE-LEV group had multiple differential nodes in the parieto-occipital lobe and frontal-temporal lobe compared with the TLE-N group. Notably, the LEV group's betweenness centrality of the superior frontal gyrus and dorsolateral and executive functions was significantly positively correlated with the correlation analyses. Changes in the topological properties are a key effect of LEV administration. This finding improves our understanding of the neural mechanisms by which LEV improves cognitive functioning.
This study investigated the associations of modifiable lifestyle factors with incident dementia, dementia subtypes, and structural brain changes, examined whether these associations differed across KDIGO-defined kidney function risk categories. We analyzed 304,369 participants from the UK Biobank. Kidney function was classified using the KDIGO risk framework, with participants grouped into low- and increased-risk categories. A composite lifestyle score, derived from the American Heart Association Life's Essential 8 framework, was constructed based on eight modifiable components: diet quality, physical activity, smoking status, sleep duration, body mass index, blood lipid, blood glucose, and blood pressure. Outcomes included incident dementia and total and regional brain volumes. Among participants at increased KDIGO-defined risk, those in the intermediate and highest tertiles of the lifestyle score had a lower risk of dementia compared with those in the lowest tertile (hazard ratios, 0.826 [95% CI, 0.689-0.990] and 0.749 [95% CI, 0.585-0.958], respectively). Associations differed by dementia subtype: higher lifestyle scores were consistently associated with a lower risk of vascular dementia, whereas no overall association was observed with Alzheimer's disease. Higher lifestyle scores were also associated with larger total grey matter volume and greater volumes of subcortical structures, including caudate, pallidum, putamen, and thalamus, as well as lower volumes of total, deep, and periventricular white matter hyperintensities. Similar associations were observed in the low-risk group. A healthier lifestyle was associated with a lower risk of dementia, particularly vascular dementia, and with more favorable structural brain characteristics, with similar associations across KDIGO risk groups.
Personality traits capture stable patterns of behavior and thought, and neurobiological correlates were identified in structural and functional brain networks. Here, we investigate whether the coupling between structural and functional brain networks (SC-FC coupling), during resting state and seven tasks of varying trait-relevance, is associated with individual differences in the Big Five personality traits. We used diffusion-weighted and functional magnetic resonance imaging from 764 participants of the Human Connectome Project and modelled individual differences in SC-FC coupling with similarity and communication measures. These measures approximate functional interactions unfolding on top of the structural connectome and were set in relation to individual variations in personality traits. Small but significant associations in the main analysis were only observed during trait-relevant tasks: for agreeableness during social cognition, and conscientiousness could be predicted from task-general coupling patterns. We conclude that optimizing trait-relevance of tasks during neuroscientific measurement presents a promising means to increase effect sizes in studies on brain-behavior associations. Significant relationships between the Big Five personality traits and SC‐FC coupling were absent during resting state but emerge during trait‐relevant tasks. Carefully designed tasks may amplify individual differences and thereby enhance the detectability of trait‐related neural characteristics. Our study exemplifies how established behavioral personality theories can be transferred to the neural level.
Tau PET imaging has emerged as a critical biomarker for Alzheimer's disease, informing diagnosis, staging, and therapeutic selection. We investigated whether PET tracer selection alters tau detection. We conducted a prospective, multicentre, non-randomised, within-participant comparison of [18F]flortaucipir (Tauvid), currently used in clinical settings in the USA and Europe, and [18F]MK6240, an investigational tau PET tracer. Participants were recruited from eight north American sites and underwent tau PET, amyloid-β (Aβ) PET, and detailed cognitive assessments. Tau PET with both agents was acquired within a 45-day window. Coprimary outcomes were the discriminative accuracy for Alzheimer's disease-related cognitive impairment and the frequency of tau positivity in early medial temporal lobe (MTL) and late neocortical regions. The study is registered with ClinicalTrials.gov, NCT05361382. Between March 2, 2022, and Aug 27, 2025, 775 individuals were enrolled, with 682 completing all procedures (373 [55%] female, 309 [45%] male; 38 [6%] aged 19-27 years, 214 [31%] aged 50-65 years, and 430 [63%] aged 65-89 years). 32 (5%) participants identified as Hispanic or Latino. 637 (93%) identified as White, 24 (4%) as Black or African American, 16 (2%) as Asian, and five (1%) as other. In addition, 49 (7%) individuals were identified as being from a rural area. [18F]MK6240 showed greater accuracy than [18F]flortaucipir in distinguishing Alzheimer's disease from non-Alzheimer's disease impairment (area under the curve 0·93, 95% CI 0·89-0·95 vs 0·86, 0·75-0·91; p<0·0001). Among the older adults, tau positivity status was concordant in 560 (87%) for MTL and 603 (94%) for neocortical regions. In cognitively unimpaired participants, [18F]MK6240 identified twice as many MTL-positive cases as [18F]flortaucipir (n=54 [15%] vs n=23 [6%]). Prevalence ratio in Aβ-positive was 2·43 (95% CI 1·50-3·94; p=0·0003), identifying 23 additional cases per 100. Among discordant cases, 75 (89%) were [18F]MK6240-positive only and had higher Aβ burden (p<0·0001), APOEε4 frequency (p<0·0001), and cognitive impairment (p=0·0043) than those negative on both tracers. Neocortical tau positivity was more frequent with [18F]MK6240 than with [18F]flortaucipir in cognitively impaired individuals (80 [28%] vs 46 [16%]). Prevalence ratio in Aβ-positive was 1·74 (95% CI 1·32-2·29; p<0·0001), identifying 15 additional mild cognitive impairment and 21 dementia cases per 100. Tau PET tracer selection influences the frequency of detection of tau pathology across the ageing and Alzheimer's disease spectrum. Compared with [18F]flortaucipir, [18F]MK6240 identified more individuals with tau pathology in cognitively unimpaired and cognitively impaired individuals, with direct implications for patient stratification in clinical trials and more precise guidance for therapeutic decision-making. National Institute on Aging.