Despite decades of research, the neural basis of visual distortions in amblyopia remains poorly understood. While numerous studies have reported abnormalities in both early visual cortex and extrastriate areas, these findings have rarely been integrated into a unified mechanistic framework. This review addresses that gap by proposing a dual-level model of cortical distortion in amblyopia: one level reflecting local feature encoding deficits in V1, and a second reflecting integration-level distortions in retinotopic extrastriate cortex. By synthesizing behavioral, neurophysiological, and imaging data from adult human studies as well as animal models, this review offers a coherent neurophysiological account of amblyopic visual distortions and outlines a framework for interpreting current findings and guiding future interventions.
Mouse model of Angelman syndrome exhibits reduced retinal activity during development
Angelman Syndrome (AS) is a neurodevelopmental disorder characterized by intellectual disability, seizures, and motor dysfunction caused by loss of function of the maternal UBE3A allele. A large proportion of patients exhibit visual impairments, but the underlying circuit-level mechanisms are not well understood. Spontaneous retinal waves provide essential patterned activity that guides the wiring and refinement of retinofugal projections to visual brain centers during a critical early developmental window. Here, using high-density microelectrode array recordings from postnatal day 8–11 mouse retinas, we demonstrate that Ube3a deficiency leads to reduced retinal ganglion cell (RGC) firing rates and fewer retinal waves while largely preserving retinal wave propagation properties. The reduced activity levels observed in AS retinas represent a novel finding that may help explain how Ube3a deficiency disrupts the normal activity-dependent refinement of developing neural circuits.
Biomarker value of plasma endothelial microvesicle-derived circRNA 0006222 in vascular ageing and carotid atherosclerosis
BackgroundEndothelial microvesicles (EMVs) carrying circular RNAs (circRNAs) have emerged as promising novel biomarkers of ageing-associated disorders. This study investigated the potential of plasma EMVs-circ_0006222 as vascular ageing (VA) and carotid atherosclerosis (CAS) biomarkers.MethodsA circRNA microarray was applied to screen for differentially expressed circRNAs in plasma EMVs obtained from CAS participants, VA participants and healthy controls. VA was assessed according to intima thickness, and CAS was evaluated by using computed tomography angiography. The plasma EMVs-circ_0006222 level was determined via qRT-PCR. EMVs-circ_0006222 levels in patients of different ages and with different severities of CAS were compared. The diagnostic potential of EMVs-circ_0006222 was evaluated by using multivariable logistic regression and receiver-operator characteristic (ROC) curve analyses.ResultsA total of 47 healthy controls, 81 VA participants and 216 CAS participants were included in this study. Plasma EMVs-circ_0006222 levels were observed to be negatively associated with age. The plasma level of EMVs-circ_0006222 was markedly reduced in elderly participants, as well as VA and CAS participants; moreover, the decrease was most evident in the CAS group. The plasma EMVs-circ_0006222 level was declined in the severe CAS compared with the mild and moderate CAS subjects. Plasma EMVs-circ_0006222 level was identified by multivariate logistic regression as a significant, independent risk factor for VA and CAS. The areas under the ROC curve of plasma EMVs-circ_0006222 for diagnosing VA and CAS were 0.628 and 0.773, respectively.ConclusionPlasma EMVs-circ_0006222 may serve as a promising biomarker for VA and CAS.
Verbal fluency after cochlear implantation: a longitudinal comparison with untreated hearing loss in the ELSA cohort
IntroductionHearing loss is associated with accelerated cognitive decline, and auditory rehabilitation via cochlear implantation (CI) may mitigate this trajectory. In the past, the impact of cochlear implantation on different cognitive subdomains has been described. However, verbal fluency (VF), which requires fast semantic retrieval, executive control, and processing speed, and is predictive of dementia risk and overall survival, has been rarely studied and control groups are mostly missing due to ethical reasons. The present study compares long-term VF trajectories in CI recipients and untreated hearing-impaired controls from a large population-based aging study.Materials and methodsVF was assessed in 74 CI recipients (M = 65.6 years, SD = 9.1) at pre-operative baseline and 1, 2, 4.5, and up to 9 years post-implantation, and in 383 untreated hearing-impaired participants (M = 72.6 years, SD = 10.0) from the English Longitudinal Study of Ageing (ELSA) across a comparable time frame. Scores were z-standardized within each study to enable cross-cohort comparison. Linear mixed-effects models were used to compare VF trajectories, with age, sex, and education as covariates.ResultsVF trajectories differed significantly between groups (Time × Study interaction: b = 0.562, p < 0.001). The ELSA cohort showed a steady linear decline over time (b = −0.261, p = 0.001), whereas the CI cohort exhibited an inverted-U trajectory with initial improvement followed by a plateau. After propensity score matching, results remained robust.ConclusionCochlear implantation is associated with more favorable long-term verbal fluency trajectories compared to untreated hearing loss. These findings add to the growing evidence that auditory rehabilitation may help preserve cognitive function in older adults.
Traumatic brain injury and neurological stealth syndromes
IntroductionA traumatic brain injury (TBI) of mild or more severe degree affects approximately ½ of the global population at some stage of their life. Mild TBI occurs in 70–90%, with 30 and 50% having symptoms persisting for more than 6 months. Mild TBI presentations include cognitive, elementary neurological, neuropsychiatric, endocrine, autonomic, cardiac, and general medical entities, with many behavioral neurological syndromes flying under the radar.AimsA retrospective examination of the cognitive and behavioral impairments in people with traumatic brain injury to evaluate the range of differing syndrome presentations, including hypofunction, hyperfunction and superla+ve brain function syndromes.MethodologyThe Brainbeat Cognitive Registry was a prospectively designed observational registry that collected clinical, cognitive, behavioral, neurological, neuropsychiatric, laboratory, and radiographic data from people with cognitive and behavioral disorders.ResultsIn the registry (n = 73), of predominantly men (88%), with averages for age 55.1 years, BMI 28.9, education 15.1 years, and MOCA score 21.7. Migraine, olfactory impairment, depression, anxiety, and PTSD were all relatively commonly associated conditions. Relatively common disorders with more complex syndromes, including Diogenes syndrome, IEED, ADHD, field-dependent behavior, and hyperorality, the later on presenting as a human Klüver Bucy syndrome. Less common disorders included other higher cortical function disorders (17.1%), neuropsychiatric (10.5%), cortico-ponto- cerebellar pathway syndromes (10.5%), and visual radiation disorders (6.5%). The least common were chronotaraxis, schizophrenia, bipolar disorder, content-specific delusions, tremor, ataxia, astereopsis, and prosopagnosia. The majority of TBI patients presented with an overarching frontotemporal disorder (FTD) diagnosis (n = 68, 89.4%), with abnormal FRSBE scores for one or more entities of abulia, disinhibition, and executive dysfunction. Frontal Behavioral Inventory scores were abnormal in 86%. The most common neurological sub-syndrome was Geschwind-Gastaut syndrome (n = 49, 62.8%). A category of patients demonstrating superlative abilities (n = 9), including visual art, musical, literary, architectural brilliance, and precognition, all attributed to right hemisphere hyperfunction, was also identified.ConclusionPost-TBI frontotemporal disorders are common. Deconstructing the overarching FTD diagnosis into multiple subsyndromes is clinically useful, revealing hypofunction syndromes, hyperfunction, and superlative function syndromes. The range of neurological stealth syndromes as part of the post-TBI range of maladies may facilitate a more targeted, precision management approach.
Gone fishin’… for distinct patterns of belief-updating in late-life worry and rumination
IntroductionWorry and rumination are two common forms of repetitive negative thinking encountered as core symptoms of anxiety and depression. They are difficult to treat and increase the risk of relapse for remitted depressive and anxiety disorders, especially in late-life. We propose that dysfunctional belief-updating is a fundamental cognitive mechanism underlying repetitive negative thinking and use a Bayesian model to test whether distinct components of belief updating are differentially associated with worry and rumination.MethodsWe recruited 83 older participants (age≥50) dimensionally for worry and rumination to perform a belief-updating task and undergo neuropsychological testing. We extracted three parameters from a Bayesian model of belief-updating: performance compared to the Bayesian optimal model, emphasis on initial information (prior weight), and relative weighting of new evidence compared to current beliefs (update strength). These parameters were tested for associations with worry and rumination severity, and four neuropsychological domains were tested as moderators (attention, visuospatial, working memory maintenance, and executive function).ResultsWorry severity was uniquely associated with lower prior weight, while rumination was associated with low update strength. Neither worry nor rumination were associated with performance. None of the neuropsychological domains moderated these relationships.ConclusionWorry and rumination are associated with unique alterations in belief-updating but not overall performance. Low prior weight in worry may inflate perceived uncertainty, while low update strength in rumination—specifically reflective pondering—is consistent with slower incorporation of new information. Both biases may contribute to the distinct phenomenological profiles of worry and rumination and inform specific therapeutic targets for these symptoms.
From promise to practice: artificial intelligence in mental health care in the MENA region
Mental health disorders represent a growing burden across the Middle East and North Africa (MENA) region, where depression and anxiety are highly prevalent amid conflict, displacement, and socioeconomic strain, affecting up to 40 percent of adults, yet treatment gaps remain at 80-95% due to provider shortages, financial strain, and cultural barriers. In this context, artificial intelligence (AI), in the form of large language models (LLMs) and specialized psychotherapy chatbots, may offer a scalable adjunct to help address these gaps through anonymous screening, predictive risk modeling, psychoeducation, and brief interventions. This narrative review examines current evidence of AI-driven conversational tools in mental health with a specific focus on their application, acceptance, and limitations within the MENA region. To do so, A structured search of MEDLINE and Embase (2000–2026) identified studies on conversational AI in mental health, prioritizing evidence from the MENA region and supplemented by relevant global literature. Overall, findings suggest that while these tools offer high accessibility and user engagement, particularly for low-intensity support, their effectiveness is limited by linguistic and cultural mismatches, including Arabic diglossia and poor alignment with locally grounded expressions of distress. At the same time, user acceptance reflects a paradox in which stigma and privacy concerns drive reliance on anonymous AI tools while simultaneously limiting trust in their clinical reliability, reinforcing a preference for hybrid models with human oversight. Taken together, these findings indicate that current systems remain insufficiently adapted to the MENA context, underscoring the need for culturally grounded, dialect-sensitive, and clinically supervised approaches to ensure safe and effective integration.
High perceived energy: exploring distinct patterns of energetic and cognitive functioning in older adults
BackgroundA hyperthymic temperament and high perceived energy are often framed as positive dispositional traits, particularly in later life. Indeed, these characteristics are generally associated with a greater tendency to preserve autonomy and with more favorable outcomes in terms of health, engagement, and participation in community life-key dimensions of successful aging. However, the relationship between elevated perceived energy and cognitive performance in older adults remains insufficiently explored. Therefore, this exploratory study aimed to compare cognitive performance and well-being in older adults with different self-reported levels of subjective energy, and to explore potential phenotypic heterogeneity within this population.MethodsWe conducted a cross-sectional study on older adults from the general population. Participants were classified as having higher versus lower levels of perceived energy based on item 10 of the Short Form Health Survey (SF-12) questionnaire. Cognitive performance was assessed using the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Depressive symptoms were evaluated with the Patient Health Questionnaire-9 (PHQ-9), biological and behavioral rhythm regulation with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), and quality of life with the SF-12 were also evaluated to characterize overall well-being.ResultsStatistically significant difference emerged in global cognitive performance between individuals with higher versus lower perceived energy (ES ACE-R p=0.012). Although subscale scores were within the normative range in both groups, individuals with higher perceived energy consistently showed significantly lower scores in language (p = 0.011) and attention/orientation (p = 0.049) compared to the lower perceived energy group. Interestingly, the higher perceived energy group also reported fewer depressive symptoms (p = 0.013), better social and behavioral rhythm regulation (p = 0.005), and higher quality of life (p < 0.001).Discussion/ConclusionsHyperenergy in older adults with preserved well-being is not associated with global cognitive impairment, but rather with subtle domain-specific performance variations, suggesting a heterogeneous underlying profile. These findings support a high-energy profile that does not appear to be associated with functional impairment, but is instead characterized by preserved or enhanced functioning and overall well-being, despite selective areas of lower performance. Longitudinal studies are needed to clarify its clinical and cognitive implications.
Beyond Theory of Mind: mentalization as a relational and developmental framework for autism
Autistic individuals and those around them often navigate social and emotional situations in which behaviors, intentions, and affects are difficult to interpret. Supporting mentalizing processes within child–caregiver interactions may help address these challenges; however, a broader conceptual shift is needed, moving beyond a narrow deficit-based perspective toward understanding mentalization as a multidimensional, relational, and developmental process. By shifting the focus from individual deficits to child–caregiver meaning-making processes, this framework may help clarify assessment and intervention targets and inform future research on psychopathological vulnerability in autism. This targeted narrative mini-review therefore aimed to summarize preliminary evidence suggests that other-related mentalizing may show greater difficulties than self-related mentalizing, although this hypothesis requires further replication. Findings also highlight caregiver mentalization, particularly parental reflective functioning, as a key relational process shaping how children’s behavior is interpreted, regulated, and responded to over time. In this light, preliminary intervention studies suggest that mentalization-based and mentalization-informed approaches may improve parental reflective functioning, cognitive reappraisal, self-efficacy, and inferential style, with potential indirect benefits for children’s emotional outcomes. We therefore propose a relational-developmental framework in which mentalization is conceptualized as a shared and dynamic process of meaning-making under conditions of social and emotional ambiguity. Adopting an individual, relational and developmentally informed perspective may contribute to the development of more precise assessment models, more targeted interventions, and a deeper understanding of mental health vulnerability in autism.
Construction and validation of multiple machine learning models for influencing factors of postpartum post-traumatic stress disorder in primiparas
ObjectiveTo analyze the multidimensional factors associated with postpartum post-traumatic stress disorder (PP-PTSD) in primiparas based on the Integrated Framework for Population Health Risk Management (IFPHRM), multiple machine learning-based predictive models were constructed and externally validated to identify high-risk individuals and to provide a robust evidence base for targeted preventive interventions.MethodsThis cross-sectional study consecutively enrolled 1, 135 primiparous women from the Department of Obstetrics at Hefei Maternal and Child Health Hospital between June 2024 and May 2025. Participants were divided chronologically into a training cohort and an independent temporal validation cohort. Women recruited from June 2024 to January 2025 were included in the training cohort (n = 794), whereas those recruited from February 2025 to May 2025 were included in the temporal validation cohort (n = 341). At six weeks postpartum, PP-PTSD symptoms were assessed using the Post-traumatic Stress Disorder Checklist-Civilian Version (PCL-C), with a score ≥38 indicating probable PP-PTSD. Multidimensional variables, including physiological and psychological factors, environmental and family-related factors, and social-behavioral factors, were collected. Candidate predictors were first screened using univariate analysis and then selected using least absolute shrinkage and selection operator (LASSO) regression. Multivariable logistic regression was used to identify independent associated factors. Seven machine learning models, including Logistic Regression, Naive Bayes, Support Vector Machine, Decision Tree, Gradient Boosting, AdaBoost, and Linear Discriminant Analysis, were constructed. Model performance was evaluated in the independent temporal validation cohort using receiver operating characteristic curves, calibration curves, decision curve analysis, and the DeLong test. SHAP analysis was used to interpret the optimal model.ResultsAmong the 794 participants in the training cohort, the incidence of PP-PTSD was 25.18%. Five key predictors were selected by LASSO regression: social support, depression, neonatal caregiving style, husband’s participation, and sleep quality. Multivariable logistic regression showed that depression and poor sleep quality were associated with an increased risk of PP-PTSD, whereas higher social support, greater husband’s participation, and parental assistance in neonatal care were associated with a reduced risk. Among the seven models, the Gradient Boosting model achieved the best overall performance in the temporal validation cohort, with an AUC of 0.939, F1 score of 0.700, specificity of 0.943, sensitivity of 0.651, and Youden index of 0.595. The DeLong test showed that Gradient Boosting performed significantly better than Logistic Regression. SHAP analysis further indicated that social support, husband’s participation, sleep quality, and depression were the major contributors to model prediction.ConclusionPostpartum PTSD (PP-PTSD) exhibits a higher incidence among primiparous women and exerts substantial adverse effects on maternal mental health, the mother–infant relationship, and overall family functioning. Guided by the Integrated Framework of Perinatal Health Risk Management (IFPHRM), this study elucidated the multidimensional mechanisms underlying PP-PTSD, encompassing physiological and psychological factors (e.g., sleep quality and depression), environmental and occupational factors (e.g., social support, paternal involvement, and infant caregiving practices), and social behavioral factors. The Gradient Boosting prediction model demonstrated robust performance and high predictive accuracy upon independent external validation, highlighting its potential utility for risk stratification and future clinical translation. Nevertheless, multicentre validation and the development of clinically implementable tools are warranted. Collectively, this study offers a theoretical foundation and methodological framework for the early identification, targeted intervention, and long-term health management of PP-PTSD in primiparous women.