[Comment] Beyond diagnosis: can fluid tau biomarkers stage Alzheimer’s disease? Lessons from down syndrome

The introduction of blood-based biomarkers (BBMs) for Alzheimer’s disease (AD) represents one of the most transformative advances in neurodegenerative disease research over the past decade.1,2 For the first time, biological evidence of AD pathology can be obtained through a minimally invasive, scalable blood test, opening new opportunities for early diagnosis, patient triage, and implementation of disease-modifying therapies.3 Among the available biomarkers, phosphorylated tau (p-tau) species, particularly plasma p-tau217, have consistently shown excellent diagnostic performance across the AD continuum, recently culminating in regulatory approval of plasma p-tau217-based assays in both the USA and Europe.

<![CDATA[Clinical AI in psychiatry falters when designers miss ward realities; better ethnographic UX research reduces alert fatigue, cognitive load, and boosts meaningful adoption.]]>
<![CDATA[Clinical AI in psychiatry falters when designers miss ward realities; better ethnographic UX research reduces alert fatigue, cognitive load, and boosts meaningful adoption.]]>

Comparison of subject-to-template registration schemes using CT and MR radiotherapy images with brain lesions

IntroductionVoxel-based analyses have been used more widely in radiotherapy in recent years. The purpose of this study is to compare eight different methods of registering images on to a template space for such analyses. A novel way, using both CT and MR data, is proposed.MethodsCT and MR brain images from 85 participants in the CoDe-B-Rad study (NCT06466720) were registered on an age-specific template. The registration schemes used included sCT-Template (linear and non-linear); MR-Template (linear, non-linear, masked, and enantiomorphic); and Dual-Template (linear and non-linear). The registrations were compared qualitatively and quantitatively against the template MR images with scores ranging from 1 (lowest) to 5 (highest) and quantitatively (via Jaccard, ASD, and HD95).ResultsQualitatively, the best registration scheme was the Dual-Template-non-linear registration, with 60 participants scoring above 4. The second best was the MR-Template-enantiomorphic, with 53 participants scoring above 4. Quantitatively, the Dual-Template-non-linear method outperformed on the mean (±SD) for the ASD and HD95, with 0.918 (±0.1774) and 2.965 (±0.5392) respectively. For ASD the difference compared to other methods was significant (p = 0.03). The MR-Template-masked outperformed on the Jaccard mean (±SD), median (IQR), and ASD, achieving values of 0.567 (±0.0557), 0.555 (0.055), and 0.808 (0.162) respectively. The Dual-Template-non-linear and MR-Template-masked and non-linear had the same result for the median HD95: 2.639. The performance of all linear schemes was inadequate both quantitatively and qualitatively. All non-linear registration schemes had issues with distortions of tissue and landmarks, however, for the Dual-Template scheme these were minimal.ConclusionThe Dual-Template-non-linear registration scheme is a new way of registering lesioned brain images for use with voxel-wise techniques in radiotherapy, which utilises both CT and MR image data. The scheme provides fidelity of the underlying soft tissue as well as the surrounding skull, minimising anatomical and dosimetric distortions.

Spinal cord stimulation for concurrent improvement of consciousness and spasticity following severe traumatic brain injury: a case study

BackgroundSpasticity frequently complicates disorders of consciousness (DoC) after severe brain injury, yet effective treatments addressing both conditions remain limited. Spinal cord stimulation (SCS) has shown promise in treating each condition independently, but its application in patients with concurrent DoC and spasticity has rarely been systematically investigated.MethodsWe report a 30-year-old man with prolonged DoC and severe limb spasticity following traumatic brain injury who underwent dual-level percutaneous SCS lead implantation. Frequency screening was performed to identify optimal stimulation parameters, followed by 21 days of continuous stimulation. Assessments included the Coma Recovery Scale–Revised (CRS-R), Modified Ashworth Scale (MAS), Hip Adductor Tone Scale (HATS), surface electromyography (sEMG), electroencephalography (EEG), and transcranial magnetic stimulation (TMS).ResultsFrequency screening identified 80 Hz as the optimal parameter for spasticity reduction. After 21 days of stimulation, the CRS-R score increased from 5 to 10, MAS improved from 3–4 to 1–1+ , and HATS decreased from 3 to 1. sEMG showed reduced muscle activity and spectral shifts consistent with decreased spasticity. EEG demonstrated enhanced frontotemporal functional connectivity and increased spectral power. TMS motor evoked potential latency was significantly shortened. Clinical improvements were sustained at the 6-month follow-up.ConclusionThis case suggests that 80 Hz SCS may be associated with concurrent improvement in consciousness and spasticity in patients with DoC following severe brain injury, accompanied by electrophysiological correlates of altered neural connectivity and corticospinal function.

Seeing clearly with CLARI-O: a window into cellular architecture, interactions, and morphology of organoid models

Cortical organoids (COs) represent a powerful in vitro model system that recapitulates key aspects of human brain development, enabling the study of neurodevelopmental processes, cellular diversity, and disease mechanisms in a physiologically relevant 3D environment. However, traditional histological analysis of COs relies on tissue sectioning, which limits the ability to capture the full spatial complexity of organoid architecture. In this study, we establish a framework for applying CLARI-O, an improved tissue-clearing technique, for intact COs and organoid-based systems, enabling comprehensive 3D visualization and analysis of 3D organizational features. Using CLARI-O in combination with high-resolution imaging, we demonstrate the utility of tissue clearing for studying glial populations, including oligodendrocytes and microglia, considered to be underrepresented in COs, and their interactions with neurons. Additionally, we apply this method to forebrain assembloids (FAs) to visualize cellular heterogeneity and the interface between ventral and dorsal regions. Finally, we use CLARI-O to study mouse brains containing xenotransplanted COs (MB-COs) to evaluate human cell integration, migration, vascularization, and structural connectivity. This is the first study to demonstrate how tissue clearing can be used after functional assays such as calcium imaging to correlate neural activity with post hoc structural analysis in MB-COs. Together, this work establishes CLARI-O as a powerful tool for advancing 3D structural and functional interrogation of human CO-derived systems, enhancing their value for disease modeling, drug screening, and translational neuroscience.

EEG oscillatory changes following rehabilitative tactile and thermal stimulation in disorders of consciousness: a longitudinal and pilot study

IntroductionRecent advances in the understanding of sensory processing in disorders of consciousness (DoC) have highlighted the potential of exteroceptive stimuli, particularly tactile stimulation. Unlike auditory or visual inputs, tactile stimuli engage primary somatosensory pathways that may be preserved even in severely brain injured patients. The aim of our study is to identify cortical neurophysiological markers for diagnosis, prognosis, and structured rehabilitative planning.MethodsSeven patients were included. EEG was recorded at baseline (T0) and after 1 month of repeated tactile and thermal stimulation administered in a randomized manner to both hands (T1). Spectral power changes were computed by contrasting stimulation-related activity with resting state and analyzed across frequency bands and cortical regions.ResultsAt T0, sensory stimulation elicited weak and spatially limited EEG modulation, predominantly involving slow-frequency activity, consistent with reduced cortical responsiveness. Following the stimulation period (T1), EEG responses showed increased amplitude and spatial extent, characterized by a relative suppression of slow oscillations and enhanced modulation of higher-frequency activity over fronto-central and parietal regions.ConclusionRepeated tactile and thermal stimulation were associated with longitudinal changes in EEG oscillatory patterns, reflecting possible modulation of cortical responsiveness associated with sensory stimulation. The assessment of stimulation-induced EEG oscillatory changes may represent exploratory neurophysiological indicators of residual cortical responsiveness that could support future studies on sensory processing in DoC patients.

The relationship between trait mindfulness and psychotic-like experiences in a brief AI-generated music listening context: the roles of presence, perceived interactivity, and emotional arousal

Background and objectiveWithin the interdisciplinary field of cyberpsychology and mental health, trait mindfulness has been associated with lower levels of subclinical anomalous symptoms, such as Psychotic-Like Experiences (PLEs), has gained increasing attention. However, in the context of daily digital human-computer interactions (e.g., listening to AI-generated music), the specific pathways through which Mindfulness operates (the involvement with Presence and Perceived Interactivity) and the boundary conditions of physiological arousal, remain to be clarified. This study aims to explore the direct predictive relationship between mindfulness and individuals’ PLEs, and to investigate the multipath effect of brief AI-generated music listening context (with Presence and Perceived Interactivity), along with the moderating effect of Arousal.MethodsWith a cross-sectional survey design, self-reported multimodal data were collected from 527 Chinese participants. Structural equation modeling (SEM) was conducted using Mplus 8.3 to empirically test the main effects (path coefficients) of the theoretical hypotheses and the moderation model.ResultsBoth the measurement and structural models demonstrated good fit. The path analysis results indicated that: (1) trait trait mindfulness was significantly and negatively associated with PLEs (p < 0.001); (2) regarding the main effect paths of brief AI-generated music listening context, mindfulness significantly and positively predict individuals’ Presence and Perceived Interactivity, while both significantly and negatively predict PLEs; (3) Arousal played a significant moderating role in the relationship between mindfulness and brief AI-generated music listening context, exhibiting a synergistic enhancement effect. Higher levels of Arousal significantly amplified the positive prediction of Mindfulness on both Presence and Perceived Interactivity (p < 0.01).ConclusionsWith the help the SEM, this study maps out the underlying multipath network through which mindfulness is associated with lower PLEs within a brief AI-generated music listening context. The observed associations suggest that presence and perceived interactivity may function as pivotal correlational nodes relevant to mental health correlates, while these results also nuance classic cognitive load assumptions by indicating a potential synergistic association between trait mindfulness and emotional arousal. These results provide a solid empirical foundation and prospective insights, for the mental health-oriented design of AI music products, such as the immersive acoustic environment construction and dynamic, arousal-based interaction recommendations.

RutiSafeNet: a behavioral risk and nursing workload monitoring tool for open-door acute inpatient mental health units

IntroductionOpen-door policies for acute inpatient mental health units (AIMHU) have shown promising results in reducing coercive measures, but concerns remain among patients and staff regarding increased workload, constant surveillance, and potential safety risks associated with these policies. This study aims to develop a monitoring tool to facilitate safety management in AIMHUs by monitoring behavioral risks and nursing workload.MethodsThis study employed a qualitative approach using the content analysis method. Data were collected through three in-depth interviews and two focus groups involving staff (n=19) from the AIMHU of the hospital.Results34 items were identified to define behavioral risks related to self-harm and suicide, aggressiveness, and absconding, alongside factors affecting nursing workload. These items were categorized into three levels of risk: low, moderate, and high.DiscussionRutiSafeNet is a preliminary, observation-based monitoring prototype intended to support, rather than to predict, structured risk and workload monitoring in acute inpatient mental health units. As a qualitatively developed instrument, it requires psychometric validation, including inter-rater reliability, construct and criterion validity, predictive value, and clinical feasibility, before it can be implemented as a validated scale in clinical practice.

Psychometric properties of the Chinese version of the school refusal assessment scale–revised in a clinical sample of adolescents and their caregivers with depressive disorders

School refusal behavior (SRB) is a prevalent and functionally heterogeneous problem among children and adolescents that can lead to serious academic, social, and psychological consequences. The School Refusal Assessment Scale–Revised (SRAS-R) is the most widely used instrument for identifying the functional motivations underlying school refusal, yet its psychometric properties have not been examined in Chinese clinical populations. The present study aimed to translate and culturally adapt the SRAS-R into Chinese and to evaluate its psychometric properties in a clinical sample of adolescents with depressive disorders. A total of 171 adolescent outpatients (age range 12–19 years; M = 15.5, SD = 1.90; 67.3% female) diagnosed with DSM-5 depressive disorders and meeting criteria for school refusal behavior completed both child and parent versions of the Chinese SRAS-R. Confirmatory factor analysis (CFA) using diagonally weighted least squares estimation was conducted. After removing Items 20 and 24, the four-factor model yielded strong CFI and RMSEA values for both parent (CFI = 0.99, RMSEA = 0.021, SRMR = 0.094) and child reports (CFI = 0.98, RMSEA = 0.028, SRMR = 0.097), although SRMR values were marginally above the prespecified threshold. Internal consistency reliability ranged from marginal to good across subscales (Cronbach’s α: parent = 0.664–0.815; child = 0.700–0.864), with parent-reported Factor 4 showing the weakest reliability. Factor 1 (avoidance of aversive school situations) obtained the highest mean scores for both informants, consistent with the depression-related negative affectivity characteristic of this clinical sample. Cross-informant discrepancy analyses revealed that children reported significantly higher scores than parents on Factor 2 (escape from social/evaluative situations; p = .017, d = 0.18) and Factor 4 (pursuit of tangible reinforcement; p <.001, d = 0.27), suggesting that parents may underestimate internally driven motivations. Intraclass correlation coefficients indicated fair to good parent–child agreement (ICC = 0.45–0.62), with the highest agreement for Factor 1 and the lowest for Factor 4. The findings provide initial internal-structure and reliability evidence for the Chinese SRAS-R in this single-site clinical sample and underscore the need for multi-informant assessment, while future studies should examine convergent, discriminant, criterion-related, and predictive validity in more diverse samples.