Corticospinal tract damage is common in people with MS, but the degree of clinical symptoms varies. We hypothesize that corticospinal tract lesions are more extensive and severe in people with MS with motor impairments in both upper and lower limbs. We compared three groups of patients: isolated hyperreflexia (A), motor deficits limited to the lower limbs (B), or in both upper and lower limbs (C). We included 100 people with MS in a prospective cross-sectional study. Corticospinal tract lesions were segmented on 3D FLAIR (brain) and axial T2* and T2-weighted images (cervical and thoracic spinal cord). MP2RAGE quantitative T1 was used to assess microstructural damage severity in the brain and cervical spinal cord corticospinal tract. Ninety-two people with MS were included in the analysis (A = 38, B = 31, C = 23). Lesion volume was higher in groups B and C than in group A in the brainstem and cervical corticospinal tract (all p < 0.001), and quantitative T1 was higher only in the cervical corticospinal tract (all p < 0.05). In the multivariate analysis, age, disease duration, lesion volume in the brainstem, and quantitative T1 in the cervical spinal cord distinguished group A from groups B and C, but no differentiating factors were identified between groups B and C. Our study suggests that motor deficit in pwMS was associated with brainstem and cervical spinal cord corticospinal tract damage. Differences between pwMS with lower limb deficits and those with both lower and upper limb deficits could not be established.
Ovarian cancer, the second deadliest gynecological malignancy, necessitates the identification of novel therapeutic targets. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, has emerged as a promising target for ovarian cancer treatment owing to its diverse regulatory roles. While existing research has demonstrated FAK's role in tumor progression and angiogenesis, substantial knowledge gaps remain concerning the precise mechanisms through which FAK inhibitors hinder tumorigenesis and their specific roles in anti-angiogenic processes. This study utilized bioinformatics analysis to examine FAK expression in ovarian cancer, with validation performed using clinical samples from platinum-sensitive and platinum-resistant patients. The anti-tumor effects of FAK inhibitors were investigated through in vitro and in vivo experiments. Human induced pluripotent stem cells (hiPSCs) were differentiated into endothelial cells to facilitate vascular research. Pharmacological inhibition and genetic knockdown techniques were employed to study FAK's role in angiogenesis, followed by functional assays to analyze specific angiogenesis processes. Bioinformatics analysis identified increased FAK expression in ovarian cancer tissues, which was significantly associated with poor prognosis. Clinical specimens confirmed higher levels of total FAK and pY397 FAK in platinum-resistant cancers compared to sensitive counterparts. In vivo experiments, including laser speckle contrast imaging and CD31 immunofluorescence, demonstrated that FAK inhibitors suppress tumor angiogenesis. Both pharmacological and genetic approaches revealed a pivotal regulatory function of FAK in angiogenesis. FAK inhibition appeared particularly effective in disrupting endothelial sprouting processes across the tested models. The results provide compelling experimental evidence supporting FAK inhibitors as potential targeted therapeutic agents for ovarian cancer. Our findings suggest that the anti-tumor effects of FAK inhibitors are closely associated with the suppression of tumor angiogenesis, which may be attributed to the potent inhibitory impact of FAK blockade on endothelial sprouting. This reveals a distinct mechanism of action that differs from traditional cytotoxic agents.
Parkinson's disease (PD) remains underdiagnosed in Thailand, and its rising prevalence presents a growing challenge for the healthcare system. The previously validated CheckPD digital population screening platform has been implemented nationally in collaboration with the Thai Red Cross Society (TRCS) and the National Health Security Office (NHSO), enabling integration of digital PD risk screening into preventive health frameworks. To evaluate the early phase of a national rollout of the CheckPD platform, focusing on population reach, adoption, predictive performance, exploratory usability, and implementation factors influencing scalability across diverse real-world settings. This RE-AIM-guided implementation study in 10 Thai provinces assessed reach, adoption, completion, system performance and positive predictive value among neurologist-evaluated screen-positive participants. Preliminary usability was assessed in 30 post-screening completers using the SUS and UEQ-S. Supplementary implementation feedback was collected from Village Health Volunteers and public health officers. Between January 2024 and October 2025, 13,381 out of 18,520 users completed screening across 10 provinces (completion rate: 72.3%). The mean SUS score was 83, with a 92% first-time task completion rate. Programme reach was achieved through multiple channels, including Village Health Volunteers (6,742 participants), community field campaigns (5,207), facilitated online training initiatives (3,448), and self-initiated app downloads (3,123). When compared with neurologists' diagnoses among 730 screen-positive participants who underwent evaluation, the screening demonstrated a positive predictive value of 81.23% (593/730; 95% CI 78.39%-84.07%). Key facilitators of implementation included TRCS endorsement and network support, community volunteer engagement, and user-centred app design. Exploratory multivariable logistic regression analysis identified educational attainment and geographic context as significant predictors of screening completion, with higher educational attainment and residence outside Bangkok associated with a higher likelihood of completing the screening workflow. The CheckPD programme demonstrates that national-scale digital screening for neurological disorders is feasible in a low-to-middle-income country when embedded within trusted institutions, supported by community networks, and aligned with data protection standards. Thailand's experience provides an early, promising, and potentially scalable model for implementing population-level improvements in brain health by enabling earlier detection and assessment of individuals at risk, in alignment with the World Health Organization's Brain Health framework.
Using structural cranial magnetic resonance imaging (MRI), we constructed a structural Brain Aging Index (sBAI) and evaluated the brain aging status, expressed as Brain Predicted Age Difference (Brain-PAD), in acute ischemic stroke patients. We aim to investigate its associations with baseline clinical and imaging characteristics, small vessel disease (SVD) burden, and 12-month functional and cognitive outcomes, and explored its potential contribution to prognostic models. A retrospective cohort of 150 patients with acute ischemic stroke admitted between November 2021 and November 2023 was analyzed. Diffusion-weighted imaging (DWI) infarct volume, white matter hyperintensity (WMH) volume, lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces (EPVS), hippocampal volume, and cortical thickness were collected. Clinical and imaging differences were compared between the "age-matched group" (Brain-PAD < + 5 years) and the "accelerated brain aging group" (Brain-PAD ≥ + 5 years). Patients in the accelerated brain aging group had significantly higher admission National Institutes of Health Stroke Scale (NIHSS) scores, larger DWI infarct volumes, greater WMH burden, and higher total SVD scores. During follow-up, the accelerated brain aging group had a lower rate of favorable functional outcome at discharge and a higher incidence of poor 12-month functional outcome, together with significantly lower MoCA scores. Admission NIHSS and WMH volume (aOR = 1.10) were independent predictors of 12-month functional outcome. sBAI was significantly associated with 12-month MoCA scores. Brain aging status derived from structural MRI is closely associated with acute lesion burden, cumulative small vessel disease, and poststroke cognitive and functional outcomes.
Homelessness is a significant issue in the context of violence, particularly for Indigenous women in settler colonial countries, as are the long-lasting impacts of violence such as traumatic brain injury (TBI) including concussion. Understanding of the relationship between homelessness and healthcare access for TBI from violence among Indigenous women is critical for informing service delivery; however, research in this area remains limited. Situated within the broader experiences of accessing healthcare following violence-related TBI, this study aimed to explore the relational dynamics between violence, homelessness, healthcare access, and the implications for long term recovery and wellbeing. Using purposive and snowball sampling, semi-structured interviews and focus groups were completed with 18 Indigenous women who have experienced TBI from violence, 28 community members, and 90 community-based frontline workers to gather insights into the experiences of living with TBI family violence or supporting someone with this injury. All data were transcribed verbatim and analyzed using thematic analysis. Two themes were identified regarding how responses to family violence-related homelessness created barriers for Indigenous women to access healthcare for TBI: (1) Housing service barriers affect access to healthcare and TBI management, and (2) The (in)visibility of TBI within crisis accommodation and housing services. The dominant experience for Indigenous women who had experienced violence and homelessness was characterized by complexity, uncertainty, and distress, largely due to service delays and barriers encountered across housing pathways. Some Indigenous women were required to relocate away from their home region to secure temporary accommodation. While crisis accommodation services were widely viewed as places of safety, many did not consider TBI in environmental design or service delivery. Multi-agency case management and outreach were identified as valuable approaches for improving healthcare access. The findings illustrate the importance of TBI-informed policy and practice within housing and homelessness services, especially for Indigenous women in rural and remote regions, alongside strengthened workforce training. Stronger linkages between women's shelters, housing services, and healthcare systems - including concussion clinics - are critical for supporting both immediate and long-term care. Needs-based funding is required to ensure regional and remote housing systems can support women-led responses, including more streamlined transitions from crisis or short-term accommodation to secure housing.
Alterations in plasma sphingomyelin (SM) levels have been reported in Alzheimer's disease (AD), pointing to disturbances in lipid metabolism that may contribute to disease pathogenesis. Neuronal damage in early AD triggers tau release into central and peripheral systems. Despite influence from peripheral contributions, alterations in plasma total-tau (T-tau) remain valuable in indicating AD-related neurodegeneration. Investigating relationships between SM metabolism and tau release during preclinical AD may uncover important biochemical processes and support advancing early non-invasive detection and treatment approaches. This cross-sectional study investigated cognitively unimpaired (CU) older adults from the KARVIAH cohort, grouped by cortical amyloid-β (Aβ) status through positron emission tomography (PET) imaging (CU Aβ- and CU Aβ+) and utilised a Biocrates-targeted metabolomic platform and Single-molecule array (Simoa) technology to quantify plasma levels of SMs and T-tau, respectively. Associations between circulating SMs and T-tau were examined within each group, with T-tau-associated SMs further evaluated for their association with cognitive performance and cortical Aβ burden and their potential to discriminate CU Aβ+ from CU Aβ- individuals. Significant positive correlations were observed between SMs and T-tau levels exclusively in CU Aβ+ individuals, suggesting connections between SM-mediated biochemical pathways and tau release from early neurodegeneration in preclinical AD. Lower SM levels were associated with weaker working memory and executive function, as well as poorer global cognition, indicating their potential predictive value for weaker cognitive performance. Moreover, SMs were also inversely associated with cortical Aβ load in CU Aβ+ individuals, possibly reflecting early SM-mediated neuroprotective responses against AD pathogenesis. Receiver operating characteristic analysis further revealed the significant potential of the SM panel in distinguishing cortical PET-Aβ status and enhancing the predictive performance of plasma T-tau in CU individuals. Therefore, circulating T-tau-associated SMs may serve as promising early biomarkers of lipid-mediated processes in CU older adults with cortical amyloid pathology and tau-related neurodegeneration.
The cerebellum plays a critical role in large-scale brain functional connectivity structure and synchronizing global waves propagation. Despite extensive studies on cortical spatiotemporal architecture, particularly in zero-lag and time-lag synchrony, leaving the parsimonious cerebellar representational structure largely overlooked. Using complex principal component analysis (CPCA) on resting-state fMRI data from the Human Connectome Project, we delineate three dominant low-dimensional spatiotemporal patterns within the cerebellum, manifesting as unimodal-to-transmodal progression, functional antagonism, and hemispheric asymmetry. These patterns correlate with various empirical functional connectivity topographies, including functional connectome network structure, quasiperiodic pattern, functional connectivity gradients and brain network dynamics hierarchy. Importantly, functional connectivity reconstructed from these patterns preserves the intrinsic structural modularity, proving the robustness of the sparse cerebellar dynamics. Moreover, personalized CPCA-derived features enable accurate sex classification and prediction of cognitive, emotional, alertness and personality traits. Our findings position the cerebellum as an active, trait-sensitive integrator of brain-wide spatiotemporal organization, suggesting propagation-based motifs constitute a foundational mode of individual brain intrinsic function.
Circular RNAs (circRNAs) are a unique class of noncoding RNAs that are formed post-transcriptionally, unlike all other classes of ncRNAs that are transcribed from the genome. They are the only class of RNAs that are closed loops with no 5' and 3' ends. Recent studies showed that mammals form >100,000 unique circRNAs that contain only exons, only introns, or both exons and introns. circRNAs are formed and degraded by various mechanisms, which are specific to this class of RNAs. This review article discusses the functional significance of circRNAs in the pathophysiology of traumatic brain injury and spinal cord injury, with an emphasis on their functionality in controlling mechanisms such as inflammation, oxidative stress, apoptosis, autophagy, neuronal plasticity, neuroprotection, and functional recovery, which are all important for outcomes after an acute central nervous system injury.
Bipolar disorder (BD) exhibits significant sex differences in its frequency, symptom presentation, and treatment response, suggesting distinct underlying neurobiological mechanisms. However, transcriptomic studies investigating these sex-specific pathways have been fragmented and underpowered. We conducted the first meta-analysis of post-mortem brain RNA-seq data to delineate sex-related transcriptomic landscapes in BD. We integrated data from four public datasets (GSE80336, GSE80655, GSE202537, GSE42546) from GEO and Array Express, comprising an aggregate of 173 individuals (66 BD cases and 117 controls). After preprocessing and correcting for batch effects, sex-stratified expression analysis was performed using DESeq2. A meta-analysis was conducted with the metafor package to identify differentially expressed genes (DEGs) at an FDR < 0.05. We also performed functional enrichment, protein-protein interaction (PPI) network analysis, hub gene identification, regulatory network reconstruction, and supplementary quantitative analyses of sex-specific interaction effects. Our results reveal striking differences in transcriptomic signatures between men and women with bipolar disorder, with the most pronounced changes occurring in the brain. A meta-analysis across brain regions identified 34 significantly dysregulated genes. In females, upregulated genes were enriched for hormonal signaling (FSHR pathway, G-protein signaling) and transcriptional/epigenetic regulation (GLIS1, neural plasticity). In males, upregulated genes were involved in synaptic calcium signaling (PDLIM5, dendritic spine regulation) and DNA mismatch repair pathways (PMS1). Analysis of the striatum identified 289 differentially expressed genes. The most significantly upregulated genes in females were implicated in immunity and synaptic plasticity, while the male-specific pattern pointed to alterations in basic cellular functions like structure, internal communication, and genetic regulation. A quantitative interaction analysis revealed a negligible correlation (r = -0.122) between disease effect sizes in females and males and identified one gene with opposing, sex-dependent dysregulation (MEF2C). This study provides robust evidence that bipolar disorder engages fundamentally distinct molecular pathways in males and females, underscoring the necessity of integrating sex as a biological variable in psychiatric research and advancing toward personalized therapeutic strategies. Bipolar disorder is a mental health condition that affects mood, energy, and activity levels. It is well known that the disorder affects men and women differently. However, the biological reasons for these differences are not well understood.In this study, we investigated these differences by analyzing gene activity in brain tissue from people with and without bipolar disorder. By combining data from several existing studies, we created a large dataset to see how the disorder’s biology differs between sexes.We found that the biological basis of bipolar disorder is fundamentally different in men and women. The most striking differences were in a brain region called the striatum, which is involved in reward and motivation. In men, gene changes were related to basic cell functions like energy production. In women, the changes involved genes for brain cell communication and immune response.This means the illness process differs between males and females. These findings help explain why symptoms vary by sex. Ultimately, this research suggests that doctors should consider sex as a crucial factor. Understanding these separate biological pathways could lead to better, more personalized treatments for everyone living with bipolar disorder.
Central nervous system Burkitt lymphoma (BL) is exceptionally rare in adolescents without systemic disease. We report a 16-year-old female presenting with progressive headaches and isolated fornix lesions on MRI. Following an initial presumptive diagnosis of viral encephalitis, empiric administration of low-dose dexamethasone and antivirals induced transient symptomatic improvement. A follow-up MRI 50 days later revealed a fulminant "spark-to-wildfire" imaging progression, characterized by multifocal ventricular dissemination and obstructive hydrocephalus. Histopathology and fluorescence in situ hybridization (FISH) confirmed the BL diagnosis. This case highlights the extreme biological aggressiveness of central nervous system BL and the diagnostic challenges of atypical fornix involvement, underscoring the necessity of serial neuroimaging assessment and prompt pathological biopsy for accurate diagnosis.
Improving Thinking through Everyday Self-Assessment Training combines 16 weeks of daily mobile task-based training in IA with weekly individual coaching in applying IA to everyday behaviors. Sixty individuals with diagnoses of schizophrenia or schizoaffective disorder participated in an open trial of iTEST with assessments at baseline, 8, 12, and 16 weeks. Primary outcomes included IA on 2 trained tasks (mobile verbal learning and facial emotion recognition tests) and 3 untrained tasks (verbal memory, emotion recognition, and executive functioning). Improving Thinking through Everyday Self-Assessment Training showed strong feasibility, retaining 86.7% of participants, and strong adherence with an average daily mobile-training completion rate of 87%. In linear-mixed models with intent-to-treat data, statistically significant IA improvements were observed over time in both trained tasks and in 2 of the 3 untrained tasks (Cohen's d's = 0.5-1.28). Significant improvements were also observed in secondary outcomes of real-world function, positive symptoms, and depression. This project provides the first data, to our knowledge, to demonstrate that IA in schizophrenia can be improved. Improving Thinking through Everyday Self-Assessment Training also represents one of just a few blended digital health interventions, including remote cognitive training, and may therefore serve as a blueprint for future intervention development.
BackgroundLatino immigrants in the United States represent diverse national origins, with Mexicans comprising the largest group. Cognitive health disparities among Latino immigrants may reflect differences in migration experiences, including age at migration, socioeconomic differences, and acculturation. Whether Mexican immigrants differ from Latin American immigrants in cognitive outcomes remains unclear.ObjectiveThis study examined the independent and interactive effects of Mexican origin and age at migration on cognitive levels and decline compared to other Latin American immigrants. We also test whether socioeconomic and acculturation factors help explain differences in cognitive outcomes.MethodsData came from 2077 Latino immigrants in the Health and Retirement Study (2014-2020). Cognition was assessed using the Telephone Interview for Cognitive Status. Mixed-effects models evaluated the main and interaction effects of origins and age at migration on age-related decline, controlling for demographic, health-related, socioeconomic, and acculturation covariates.ResultsMexican immigrants had significantly lower cognitive levels than Latin American immigrants. However, after adjusting for socioeconomic indicators and language acculturation, Mexican immigrants demonstrated higher cognitive scores. Among Mexicans, late-life migration was associated with significantly poorer cognitive levels, which persisted after accounting for socioeconomic and acculturation factors. No significant differences were observed in rates of cognitive decline by origin or age at migration.ConclusionsLate-life migration is associated with poorer cognitive outcomes among Mexican immigrants. Findings indicate that socioeconomic and acculturation factors mask underlying differences in cognitive performance between Mexican and Latin American immigrants, underscoring the need to consider both migration experiences and social context when evaluating cognitive disparities.
Everyday communication is dynamic and multisensory, often involving shifting attention, overlapping speech, and visual cues. Yet, most neural attention tracking studies are still limited to highly controlled lab settings, using clean, often audio-only stimuli and requiring sustained attention to a single talker. This work addresses that gap by introducing a novel dataset from 24 normal-hearing participants. We used a wearable electroencephalography (EEG) system (44 scalp electrodes and 20 cEEGrid electrodes) in an audiovisual (AV) paradigm with three conditions: sustained attention to a single talker in a two-talker environment, attention switching between two talkers, and unscripted two-talker conversations with a competing single talker. Analysis included temporal response functions (TRFs) modeling, optimal lag analysis, selective attention classification with decision windows ranging from 1.1 to 35 s, and comparisons of TRFs for attention to AV conversations versus side audio-only talkers. Key findings show significant differences in the attention-related P2 peak between attended and ignored speech across conditions for scalp EEG. Interestingly, our results revealed strong cross-condition generalization, with models trained in one condition maintaining good performance when evaluated on the other two. No significant change in performance between switching and sustained attention suggests robustness for attention switches. Optimal lag analysis revealed a narrower peak for conversation compared to single-talker AV stimuli, reflecting the additional complexity of multi-talker processing. Classification of selective attention was consistently above chance (55%-70% accuracy) for scalp EEG, whereas cEEGrid data yielded lower correlations, highlighting the need for further methodological improvements. These results demonstrate that wearable EEG can reliably track selective attention in dynamic, multisensory listening scenarios and provide guidance for designing future AV paradigms and real-world attention tracking applications.
Accurate hospital bed occupancy forecasting is essential for effective resource planning and patient flow management. While complex machine learning models have gained popularity in healthcare forecasting, their operational utility often falls short due to high maintenance costs and limited interpretability. This study evaluates the performance and practicality of Prophet, a parsimonious time-series model, for mid-term hospital bed occupancy forecasting. We applied the Prophet model to daily bed occupancy data from the Medical Center - University of Freiburg (2010-2023), incorporating public holidays and a COVID-19 pandemic indicator as exogenous regressors. Prophet decomposes time series into trend, seasonality, and holiday effects, offering interpretable components. Forecast accuracy was assessed via rolling cross-validation over 2022-2023 for horizons of 30, 60, 90, and 180 days. A production-ready forecasting pipeline and dashboard were also implemented using cloud-native tools. Prophet achieved low MAPE values across all horizons (3.21%-3.53%) with coverage above 80%, demonstrating reliable accuracy comparable to or better than more complex models that often require higher computational resources and operational costs, such as deep neural networks. Component analysis revealed patterns aligned with hospital operations; weekly and yearly cycles, and holiday effects, highlighting the model's interpretability. This study shows that mid-term hospital bed occupancy can be accurately forecasted using a simple, interpretable model like Prophet. In contrast to more complex architectures, Prophet offers robust performance with minimal tuning, faster deployment, and clearer insights that are critical in operational settings. These findings reinforce the argument that, for structured forecasting tasks like bed occupancy, simple models can rival complex ones, not only in accuracy, but also in reproducibility, scalability, and operational value.
Fetal and neonatal connectomics, utilizing functional magnetic resonance imaging (fMRI), offers critical insights into early brain development, with transformative potential for neonatal care. This review synthesizes peer-reviewed research from 2007 to 2025, tracing the historical evolution, methodological advancements, and clinical implications of fMRI-based connectomics in fetuses and neonates. Early studies introduced resting-state fMRI, while initiatives like the Developing Human Connectome Project (dHCP) have expanded the field through large-scale datasets. Methodologies, including resting-state fMRI, independent component analysis, and network modeling, have identified small-world and modular network architectures, with predictive value for cognitive and language outcomes. Despite advantages like non-invasiveness and early disorder detection, challenges include motion artifacts in fMRI data acquisition, blood-oxygen-level-dependent (BOLD) response variability, and sometimes sedation requirements. Future directions involve refining long-term outcome predictions, integrating multimodal imaging (e.g., EEG, NIRS), and developing neonatal intensive care unit (NICU) protocols. This review, drawing on available peer-reviewed sources, highlights the field's growth and limitations, advocating for standardized protocols and interdisciplinary collaboration to bridge research and clinical practice, ultimately improving outcomes for high-risk neonates. IMPACT: This review of fetal and neonatal connectomics adds the following to existing literature. Systematic, historical review of the development of fetal and neonatal connectomics using fMRI. Detailed resources for researchers to utilize existing databases for interpretation of findings as well as describing the technical, biological, and ethical challenges limiting clinical application of these findings. Provides key research gaps in translating connectomics findings into clinical applications as well as suggestions for addressing those gaps.
Aging in the mammalian brain involves significant structural, functional, and metabolic changes, including a decrease in glutamate concentration. Glutamate-weighted chemical exchange saturation transfer (gluCEST) MRI provides a non-invasive method for mapping glutamate distribution with high spatial resolution. Collecting data from a large cohort of healthy mice aged 2 to 23 months, scanned in vivo at 17.2 T, we demonstrate that gluCEST can differentiate multiple brain regions, and introduce a gluCEST template for the mouse mid-rostrocaudal brain from Bregma -0.5 to -4 mm approximately. Our findings reveal significant age-related decreases in gluCEST values in the hippocampus, thalamus, and hypothalamus. These decreases did not correlate with volume reductions of these regions, except in the hippocampus, indicating gluCEST as a complementary neuroimaging approach to overall anatomical changes. Our study also demonstrates gluCEST's potential to monitor age-related changes in smaller brain subregions, such as cortical and hippocampal layers, providing a valuable tool for longitudinal investigations into aging and neurodegenerative diseases. The high spatial resolution and sensitivity offered by ultra-high magnetic field MR scanners enhance the precision of these measurements, paving the way for future preclinical and clinical applications.
According to predictive processing models, hallucinations can arise from over-weighting of prior expectations relative to sensory input. Individuals who hallucinate may misattribute internally-generated experiences to external sources. Combining these mechanisms, we hypothesized that hallucination-proneness in a non-clinical sample is associated with a greater reliance on internally-generated priors compared to externally-provided priors during degraded speech perception. Two online experiments were conducted with healthy adult participants. Experiment 1 (n = 92) targeted lower-level perceptual processes by assessing sensitivity and bias in distinguishing regular vocoded speech from unintelligible, spectrally-rotated vocoded stimuli at varying levels of sensory clarity. Experiment 2 (n = 100) compared the influence of internally-generated versus externally-provided priors on perception of vocoded speech content. Internal- and external-priors were matched in reliability to test if hallucination-proneness was linked to differential influences of internally-generated priors on speech perception. Experiment 1 confirmed that participants who are more hallucination-prone showed a reduced ability to distinguish potentially intelligible speech from unintelligible speech, and a higher bias toward indicating that speech was present in unintelligible stimuli. Experiment 2 confirmed differential effects of internal priors, showing that hallucination-proneness scores were linked to a greater influence on internally-generated priors on perceptual report when these were incorrect, and a lower reliance on externally-provided priors when these were correct. These findings suggest that hallucination-proneness is linked to an increased influence of internally-generated compared to externally-provided predictions on perception, suggesting an additional element of predictive processing theories of hallucinations.
Engaging in mentally and/or physically demanding activities post-injury may play a role in post-concussion symptom expression; however, the temporal effects of activity demand on post-concussion symptoms in adults with persistent post-concussion symptoms (PPCS) are unclear. The purpose of this study was to examine activity demand and time-of-day effects of post-concussion symptoms in individuals with PPCS using ecological momentary assessment (EMA). We enrolled 40 adults (60.5% female; mean age = 42.53 ± 11.36 years) with PPCS in our prospective observational study with repeated measures. Participants completed a 20-day EMA period in which they responded to a smartphone app five times per day to report PPCS symptoms and the activities they were currently engaged in. PPCS symptoms were reported using the Post-Concussion Symptom Scale (PCSS), a 22-item symptom inventory that includes total symptoms (possible range = 0-132) and symptom clusters: cognitive-migraine-fatigue (possible range = 0-66), affective (0-18), sleep (0-12), and somatic (0-12). For each activity reported by participants, they were asked to characterize it as mentally demanding, physically demanding, both, or neither. Descriptive statistics captured PCSS scores and characterizations of activity demand. Linear mixed-effects models (LMMs) examined the effects of time of day and activity demand on PCSS symptom scores. During the EMA period, PCSS scores were in the clinically significant range (mean = 24.68 ± 21.04; range = 0-106). Mean symptom domain scores were 16.53 ± 13.84 for cognitive-migraine-fatigue (range = 0-63), 3.25 ± 4.05 for affective (range = 0-18), 1.69 ± 2.59 for sleep (range = 0-12), and 1.05 ± 1.72 for somatic symptoms (range = 0-10). Across all observations (n = 2,984), among the four activity characterization options, activities were most frequently characterized as neither mentally nor physically demanding (n = 1,675, 44.3%), and most participants (n = 26, 68.4%) characterized activities in this category most frequently. Open-ended responses elaborating on activities in this category included "doing nothing," "sleeping/relaxing," "watching TV," and "eating." Linear mixed-effects model (LMM) results (based on 38 participants with >33% response rates) showed that activity demands were significantly associated with symptoms. Mentally demanding activities were associated with increases in total and cognitive-migraine-fatigue symptoms, whereas physically demanding activities were associated with decreases in these symptoms. Mentally demanding and combined mentally and physically demanding activities were also associated with increased affective symptoms. Additionally, time of day was significantly associated with cognitive-migraine-fatigue symptoms, with increases in symptoms later in the day compared with early in the morning. The present findings extend existing literature by demonstrating the utility of EMA for capturing real-time associations between contextual factors and symptom expression in traumatic brain injury populations. We also provide evidence that time-of-day and activity demands are associated with symptom expression in individuals with PPCS. Collectively, these findings have implications for informing symptom management strategies in PPCS.
Cerebral gliomas represent a heterogeneous group of tumours that pose unique diagnostic and therapeutic challenges. Adolescents and young adults (AYAs, 15-39 years) often fall into a clinical gap, receiving care modelled on paediatric or adult oncology, which may not address their distinct biological and psychosocial needs. A review was conducted to systematically map the existing literature on cerebral gliomas in AYAs and identify evidence gaps in diagnosis, treatment, and prognosis. Our scoping review was conducted following PRISMA-SR guidelines, using PubMed and Scopus to identify studies on gliomas in AYAs. Eligibility criteria consisted of articles focused on gliomas in AYAs, published in English between 2000 and 2024. Studies exclusively focused on AYA populations, as well as studies including AYAs within mixed populations, were considered eligible. Extracted data included study characteristics, population, interventions, and outcomes (survival, quality of life, molecular markers), which were synthesised thematically into epidemiology, molecular/histological profiles, treatments, outcomes, and psychosocial impacts. Our systematic review identified 33 studies on gliomas in AYAs. Most of the included studies (62.5%, n = 20) were published between 2020 and 2024. Geographically, the studies were primarily conducted in the USA (25%, n = 8), followed by Canada (9.4%, n = 3) and Europe (9.4%, n = 3). From an epidemiological perspective, gliomas were the most common cerebral tumours. Molecular analyses revealed overlap between pediatric- and adult-type alterations, emphasising diagnostic ambiguity and the need for comprehensive profiling. Treatment reports underscored surgery as central, with emerging roles for proton therapy, targeted agents, and immunotherapy, although the lack of AYA-specific trials remains a barrier. Prognostic and psychosocial studies highlight survival disparities associated with molecular markers and socioeconomic factors, as well as unmet needs related to fertility preservation, neurocognition outcomes, and palliative care. The review identified major gaps, such as heterogeneous adoption of advanced diagnostic approaches, the absence of age-specific treatment protocols, and scarce research on long-term outcomes and quality of life in AYAs with gliomas. Addressing these issues requires AYA-focused clinical trials within a multidisciplinary care framework. • Gliomas in adolescents and young adults (AYAs) present overlapping molecular and clinical features of paediatric and adult-type gliomas, determining diagnostic and therapeutic challenges in everyday care. • Current management of glioma in AYAs is usually extrapolated from paediatric or adult populations, with limited AYA-specific trials, without the presence of evidence-based guidlines. • Our review has the aim to map the existing literature on cerebral gliomas in AYAs and to identify the major gaps in diagnosis, molecular profiling, treatment, outcome, and psychosocial aspects. • There is an urgent need to develop AYA-specific molecularly informed, multidisciplinary treatment strategies and clinical studies for gliomas focused on management and long-term outcomes.
In this secondary analysis of a randomized controlled trial, individuals aged 18-65 with a psychotic disorder and paranoid ideation were recruited. Ninety-eight participants were randomized to maximally 16 sessions of VR-CBTp (n = 48) or CBTp (n = 50). Self-rated symptom severity, functional impairment, and clinician-rated illness severity were assessed at each therapy session. Analyses on change scores between the first and final session were performed to assess overall improvement, and multilevel regression models explored in-depth session differences. Clinician-rated paranoia and avoidance improved more rapidly in VR-CBTp than CBTp, with differences emerging from session 3. Patients reported similar progress in both groups over time on symptoms and functional impairment. A greater proportion of VR-CBTp participants completed treatment early, requiring fewer sessions than the CBTp group. Therapists observed faster symptom recovery in paranoia and avoidance in VR-CBTp while requiring fewer sessions than standard CBTp. These findings suggest that VR-CBTp may be more efficient in duration, while broader effects on access and therapist workload remain to be determined.