---
title: "Neurology Clinical Research Feed | MedicHelpline"
specialty: "Neurology"
specialty_slug: "neurology"
canonical_url: "https://medichelpline.com/clinical-feed/neurology"
content_type: "clinical_feed_specialty"
page: 1
articles_in_batch: 30
generated_at: "2026-09-05T23:52:17.836Z"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Neurology — Clinical Research Feed
## Specialty Overview: Neurology
Latest peer-reviewed clinical trials, guidelines, and observational research in **Neurology**, indexed and structured for clinical intelligence and AI reasoning.
## Latest Neurology Publications
### 1. [VR Headset Pupillometry Detects RAPD and Pathological Anisocoria: Study Results](https://medichelpline.com/clinical-feed/medrxiv-1-pupil-symmetry-and-swinging-light-test-performed-with-vr-headset-for-detection.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-05
- **Detail Markdown URL:** [VR Headset Pupillometry Detects RAPD and Pathological Anisocoria: Study Results](https://medichelpline.com/clinical-feed/medrxiv-1-pupil-symmetry-and-swinging-light-test-performed-with-vr-headset-for-detection.md)

> **Executive GIST:** - Purpose: The study evaluated sensitivity of **VR pupillometry** using the HP Reverb G2 Omnicept headset to detect **anisocoria** and **relative afferent pupillary defect (RAPD)** compared with routine clinical pupil exam. - Design: Prospective clinical evaluation including 29 patients in two diagnostic groups and 19 healthy controls; procedures included a **Pupil symmetry test** and a **Swinging light test** implemented in the VR headset. - Cohorts: Group I — asymmetric optic neuropathy (N=21); Group II — suspected pathological anisocoria (N=8); Controls N=19. - Detection of RAPD: Both VR pupillometry and standard exam identified RAPD in 16 of 21 Group I patients. Five Group I patients had relative afferent pupillary asymmetry (RAPA) within the control range (0.1–0.2 mm). - Correlations: RAPA/RAPD metrics correlated with inter-eye differences in visual acuity and visual field mean deviation (MD) with R=0.58 and R=0.68 respectively (p 5.8 dB inter-eye MD difference had RAPD by testing. - Anisocoria detection: In Group II, **pathological anisocoria** (>0.8 mm) was detected by VR pupillometry in all relevant cases; only 1 of 8 was detected on standard exam. - Controls: Anisocoria between 0.4–0.8 mm was seen in 37% (7/19) of controls; anisocoria was larger in the dark (mean additional 0.2 mm). - Performance summary: VR pupillometry matched conventional exam for RAPD detection and exceeded it for detecting pathological anisocoria. Longitudinal pupillary constriction data were proposed as potentially useful for diagnosis and monitoring. - Availability and ethics: Data available on request. Ethical approval and patient consent were obtained; funding sources declared. - Note: This is a medRxiv preprint not yet peer reviewed and should not guide practice without further validation.

### 2. [After Ultragenyx Angelman drug failure, experts say other antisense therapies still hold promise](https://medichelpline.com/clinical-feed/stat-news-1-stat-after-failure-of-angelman-syndrome-drug-experts-see-hope-in-other.md)
- **Source:** STAT News | **Published:** 2026-09-04
- **Detail Markdown URL:** [After Ultragenyx Angelman drug failure, experts say other antisense therapies still hold promise](https://medichelpline.com/clinical-feed/stat-news-1-stat-after-failure-of-angelman-syndrome-drug-experts-see-hope-in-other.md)

> **Executive GIST:** - Ultragenyx announced that its experimental drug for **Angelman syndrome** failed in a late-stage clinical trial, a setback for patients and the company. - The failed trial was described in STAT News coverage; specific trial results, endpoints, and numerical data were not reported in the source article. - Experts quoted in the article emphasized that a single unsuccessful trial does not necessarily invalidate the therapeutic approach under study. - Mark Zylka, an Angelman researcher at the University of North Carolina, is quoted saying the failed trial does not mean the mechanism is inherently flawed. - The article notes that other companies — including **Ionis** and **Oak Hill Bio** — are developing their own **antisense** treatments for Angelman syndrome and that those programs remain ongoing. - Observers in the piece suggested continued reason for cautious optimism that similar experimental medicines could succeed in restoring functions such as cognition and communication in patients with intellectual disabilities. - The STAT article is a STAT+ exclusive; the published item referenced another STAT story reporting Ultragenyx’s failed trial but withheld many trial-specific details behind the subscription. - The source emphasized broader implications: success or failure in Angelman trials could influence development of genetic medicines for other neurological conditions, but the article did not provide definitive conclusions or new data. - Multiple contextual items in the source (subscription prompts, author contact information, and site navigation) are present but do not add clinical detail about the trials. - Several important details — including the specific therapeutic modality used by Ultragenyx, trial design, patient numbers, safety findings, and timelines for rival programs — were not reported in the source article and therefore are not available here.

### 3. [Temple-Worn Optical Wearable Shows Temporal Concordance With Transcranial Doppler During Exercise](https://medichelpline.com/clinical-feed/medrxiv-3-concordance-between-a-temple-worn-optical-wearable-and-transcranial-doppler.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Temple-Worn Optical Wearable Shows Temporal Concordance With Transcranial Doppler During Exercise](https://medichelpline.com/clinical-feed/medrxiv-3-concordance-between-a-temple-worn-optical-wearable-and-transcranial-doppler.md)

> **Executive GIST:** - The study evaluated a temple-worn optical wearable, Temple, which reports a proprietary, dimensionless **Brain Flow index** as a proxy for relative cerebral hemodynamic changes. - Reference standard was **transcranial Doppler (TCD)** ultrasound measuring middle cerebral artery blood-flow velocity (**MCAv**). - Twenty-three healthy adults were enrolled; twenty participants were analyzed for each protocol (exercise and postural transition). - Two physiological challenges were used: a cycle-ergometer **exercise** protocol and a stand-to-supine **postural transition** protocol, chosen because they produce distinct, acute cerebral hemodynamic responses. - The Brain Flow index tracked MCAv with strong within-subject temporal correlations: median Pearson r = 0.795 for exercise and 0.799 for postural transition (p < 0.001 for both). - Transition responses were directionally concordant and statistically significant for both increases and decreases in flow between devices. - Bland–Altman analysis of normalized transition responses showed small mean biases, indicating similar relative response shapes; signals were standardized within session so comparisons reflect relative-shape concordance rather than absolute-unit agreement. - The Brain Flow index reproduced the direction and time course of MCAv in both perturbations, including the postural transition where heart rate moved oppositely. - Authors conclude further studies with complementary modalities and additional cerebrovascular reactivity challenges are required to define clinical use cases and evaluate cerebral specificity of the Brain Flow index. - Ethical oversight: Institutional Human Ethics Committee of LLRM Medical College, Chaudhary Charan Singh University, Meerut approved the study (approval SC-1/2025/9370 dated 16 December 2025). Funder: Temple Pvt. Ltd., Gurugram, India.

### 4. [Prevalence and causes of secondary psychosis in adults with first-episode psychosis in Hong Kong](https://medichelpline.com/clinical-feed/medrxiv-15-secondary-causes-among-adult-patients-presenting-with-first-episode-psychosis.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Prevalence and causes of secondary psychosis in adults with first-episode psychosis in Hong Kong](https://medichelpline.com/clinical-feed/medrxiv-15-secondary-causes-among-adult-patients-presenting-with-first-episode-psychosis.md)

> **Executive GIST:** - This retrospective review examined adults aged 18–64 with **first-episode psychosis (FEP)** referred to consultation psychiatry at a tertiary acute teaching hospital in Hong Kong between January 2015 and April 2025. - The cohort included 384 patients (mean age 40.0 ± 13.7 years; 69% female). Patients with delirium were excluded. - **Secondary causes** of psychosis were identified in 9.6% (n = 37) of the cohort. - **Substance use** was the single most common secondary cause overall (n = 11; 2.9% of all FEP presentations). - In 16 patients with secondary psychoses, the underlying condition was revealed only by medical workup performed because of the FEP presentation. - Among those conditions uncovered by FEP-related workup, **autoimmune encephalitis** (definitive or probable) was identified in five patients and **early-onset dementia** in four patients; these were the most frequent diagnoses detected by investigation. - The authors report that the observed prevalence of secondary psychoses in this Hong Kong FEP cohort is lower than published international figures. - The study highlights the need for clinicians to recognise clinical features that raise suspicion for **autoimmune encephalitis** and **early-onset dementia** in FEP patients with otherwise unremarkable history and toxicology. - Ethical approval was obtained from the Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee. Data are available on request. No competing interests were declared.

### 5. [GAMLSS versus Linear Regression for Neuropsychological Norms: Comparable Clinical Outcomes](https://medichelpline.com/clinical-feed/medrxiv-14-smooth-curves-similar-conclusions-comparing-linear-regression-and-gamlss.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [GAMLSS versus Linear Regression for Neuropsychological Norms: Comparable Clinical Outcomes](https://medichelpline.com/clinical-feed/medrxiv-14-smooth-curves-similar-conclusions-comparing-linear-regression-and-gamlss.md)

> **Executive GIST:** - The study compared traditional **linear regression (LR)**–based normative scores with norms derived from **Generalized Additive Models for Location, Scale and Shape (GAMLSS)** for a brief cognitive battery used in the Norwegian Dementia Disease Initiation (DDI) cohort. - Norms were constructed for the CERAD word list test (including delayed recall), Trail Making Test (TMT) A and B, FAS phonemic fluency, and VOSP Silhouettes using the same normative samples as the original LR norms. - Expected low-score frequencies and empirical base rates were evaluated in a normative subsample (n = 131); clinical implications were assessed in the DDI clinical cohort (n = 643). - **GAMLSS** produced lower frequencies of low scores compared with LR norms, an effect largely driven by the **CERAD delayed recall** measure. - Overall concordance between the two normative methods was high (kappa = 0.91), with 4.2% of classifications discordant between approaches. - Two-year diagnostic stability and change in the clinical cohort were broadly similar regardless of whether LR or GAMLSS norms were applied. - Cerebrospinal fluid (CSF) biomarker profiles did not clearly favor either normative method when relating biomarker status to cognitive classifications. - Authors conclude **GAMLSS** more accurately models bounded and non-normal score distributions, but downstream clinical differences in classification and prognostic indicators were modest in this dataset. - Ethical approvals were obtained for the DDI, TronderBrain, and Gothenburg MCI studies; all participants provided written informed consent. Data are not freely available due to ethical restrictions. - Funding sources included the EU Joint Programme – Neurodegenerative Disease Research, The Research Council of Norway, and Helse Nord.

### 6. [Exercise raises NODDI-derived neurite density across white matter in healthy older adults](https://medichelpline.com/clinical-feed/medrxiv-14-physical-exercise-increases-the-noddi-derived-neurite-density-index-across.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Exercise raises NODDI-derived neurite density across white matter in healthy older adults](https://medichelpline.com/clinical-feed/medrxiv-14-physical-exercise-increases-the-noddi-derived-neurite-density-index-across.md)

> **Executive GIST:** - This secondary analysis of the FIT4BRAIN randomized controlled trial evaluated whether an 8-week, remotely delivered multicomponent physical exercise program alters white matter microstructure in older adults using NODDI metrics. - The diffusion MRI sample included 66 participants (mean age 66.4 ± 3.6 years; 43 females). Participants were randomized to the physical activity group (PAG, n = 34) or an active control group (CON, n = 32). - Primary imaging outcomes were NODDI-derived **neurite density index (NDI)** and **orientation dispersion index (ODI)** measured across major white matter tracts. - Statistical analyses used linear mixed-effects and Bayesian multilevel models adjusted for age and sex to test Timepoint × Group interactions for NDI and ODI. - A significant Timepoint × Group interaction was observed for **NDI** (p = 0.003), indicating a greater increase in NDI in the exercise group across 22 white matter tracts; no significant interaction was found for **ODI** (p = 0.785). - The standardized composite **VO2 max** score increased within the exercise group from pre- to post-intervention, but the Timepoint × Group interaction for VO2 max did not reach significance (p = 0.079). - Across all participants, pre-to-post changes in mean NDI correlated positively with changes in VO2 max, but this correlation did not differ between groups. - The authors conclude that short-term multicomponent physical exercise can modify white matter microstructure in older adults, as indexed by increased NDI. Ethical approval and trial registration were reported; competing interests were declared absent.

### 7. [Episodic Memory and Functional Tests Best Predict 24‑Month MCI → Alzheimer’s Progression in ADNI C](https://medichelpline.com/clinical-feed/medrxiv-13-comparative-value-of-cognitive-and-functional-assessments-for-predicting-24.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Episodic Memory and Functional Tests Best Predict 24‑Month MCI → Alzheimer’s Progression in ADNI C](https://medichelpline.com/clinical-feed/medrxiv-13-comparative-value-of-cognitive-and-functional-assessments-for-predicting-24.md)

> **Executive GIST:** - This ADNI cohort study analyzed 2,430 participants with baseline **mild cognitive impairment (MCI)** to identify which clinical assessments best predict progression to **Alzheimer’s disease (AD)** over 24 months. - Models used Extreme Gradient Boosting (XGBoost) with repeated stratified 5-fold cross‑validation (10 repetitions) and compared demographics/genetics, global cognition scales, domain-specific cognitive measures, functional scales, and Everyday Cognition (ECog) questionnaires. - A baseline clinical model (age, sex, education, **APOE ε4** status) achieved AUC = 0.692. - **Episodic memory** measures showed the highest predictive performance as a domain (AUC = 0.915). - The **Functional Activities Questionnaire** performed nearly as well alone (AUC = 0.913), indicating substantial predictive value of functional assessment. - Combining episodic memory, functional assessment, and executive function produced the best multivariable performance (AUC = 0.943; sensitivity = 0.857; specificity = 0.889). - Among individual memory tests, Logical Memory Delayed Recall had the highest standalone AUC (0.896); RAVLT Learning added minimal incremental value. - The authors conclude that streamlined batteries emphasizing **episodic memory** and **functional status** could improve efficient risk stratification for memory clinics and AD clinical trials. - Data used are available from ADNI to qualified investigators; this report is a preprint and has not been peer reviewed.

### 8. [SniffCell: Cell-type-resolved somatic variant discovery from bulk long-read sequencing](https://medichelpline.com/clinical-feed/medrxiv-11-cell-type-resolved-somatic-variant-discovery-from-bulk-long-read-sequencing.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [SniffCell: Cell-type-resolved somatic variant discovery from bulk long-read sequencing](https://medichelpline.com/clinical-feed/medrxiv-11-cell-type-resolved-somatic-variant-discovery-from-bulk-long-read-sequencing.md)

> **Executive GIST:** - Researchers developed **SniffCell**, a method that leverages native long-read DNA methylation patterns to assign variant-supporting molecules from bulk long-read whole-genome sequencing to **methylation-resolvable cell types**. - SniffCell constructs cell-type-discriminatory methylation signatures across eight tissues, then assigns long reads to cell types and performs **cell-type-specific variant calling**. - The method was benchmarked in peripheral blood mononuclear cells and brain tissue, recovering sorted cell identities and validating assignments using purified immune-cell, neuronal, and oligodendrocyte fractions. - In blood, SniffCell identified lineage-restricted antigen receptor rearrangements and localized a somatic tandem-repeat expansion specifically to **T cells**. - In frontal cortex samples, SniffCell detected recurrent **neuron-specific tandem-repeat expansions** in genes including FGF14, LRRC7 and SH3RF3. - Across three brain cohorts totaling 172 donors, recurrent neuron-associated expansions were enriched for **GAA-rich motifs**; neuron-associated alleles diverged more from inherited repeat length than oligodendrocyte-associated alleles, which tended to track inherited length. - SniffCell converts native bulk long-read genomes into a cell-type-aware resource for somatic variant discovery, revealing recurrent somatic instability in human tissues at **cell-type resolution**. - Software and analysis scripts are publicly available (SniffCell and mTRplotter repositories); several data releases are noted for controlled access; detailed cohort depositions and accession locations were reported in the source.

### 9. [CAID Syndrome as a Monogenic Cause of Cerebral Small Vessel Disease with Early Cerebellar Microble](https://medichelpline.com/clinical-feed/medrxiv-1-chronic-atrial-and-intestinal-dysrhythmia-syndrome-a-distinct-monogenic-cause.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [CAID Syndrome as a Monogenic Cause of Cerebral Small Vessel Disease with Early Cerebellar Microble](https://medichelpline.com/clinical-feed/medrxiv-1-chronic-atrial-and-intestinal-dysrhythmia-syndrome-a-distinct-monogenic-cause.md)

> **Executive GIST:** - This retrospective cross-sectional study describes the neurological and neuroimaging features of **Chronic Atrial and Intestinal Dysrhythmia (CAID) syndrome** in 16 genetically confirmed French-Canadian patients. - Median age at last evaluation was 34 years (range 19–60); 62.5% were women. - Comprehensive neurological assessment was performed in all patients; brain MRI was available for 14 patients and imaging markers were rated using **STRIVE-2** criteria by an expert neuroradiologist. - Neurological symptoms included migraines in 44.4% of patients, mild cerebellar signs in 16.7%, and ischemic or hemorrhagic cerebrovascular events in 12.5%. - MRI abnormalities were frequent: white matter hyperintensities in 92.9% of imaged patients, lacunes in 50.0%, and **cerebral microbleeds** in 85.7%. - Lesions affected deep, lobar, and infratentorial regions with a marked **cerebellar predominance** (11/12; 91.7% among those with infratentorial involvement). - Five patients showed innumerable microbleeds. Despite a relatively young cohort, moderate-to-severe **cerebral small vessel disease (CSVD)** was common (median SVD score 1.5, IQR 0–4). - Patients with countless microbleeds were older than those with discrete lesions (46.2 vs. 31.2 years; p = 0.043). - Coexisting congenital cardiac disease and arrhythmias pose combined ischemic and hemorrhagic risks; atrial fibrillation management required individualized approaches, including **left atrial appendage closure** for some. - Authors conclude that CAID represents a novel monogenic cause of **CSVD**, and they recommend systematic neurological evaluation and MRI, especially before initiating antithrombotic therapy. - Study approvals were obtained from CHU Sainte-Justine and CHU de Québec ethics committees. Anonymized clinical and derived neuroimaging data are available on request from the corresponding author.

### 10. [Computational model demonstrates distinct functions of the two dentate gyrus blades](https://medichelpline.com/clinical-feed/biorxiv-7-a-computational-model-of-the-two-dentate-gyrus-blades.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Computational model demonstrates distinct functions of the two dentate gyrus blades](https://medichelpline.com/clinical-feed/biorxiv-7-a-computational-model-of-the-two-dentate-gyrus-blades.md)

> **Executive GIST:** - The Dentate Gyrus (DG) is a critical hippocampal substructure whose damage is linked to context overgeneralization, affective dysregulation, and epileptogenic effects. - Traditional DG models emphasize **pattern separation** for downstream CA3 memory storage; recent experiments implicate additional functions including precise binding of objects/events to space and integration across episodes. - Experimental evidence indicates functional specialization across the two DG blades: the **suprapyramidal** blade biases toward pattern separation, while the **infrapyramidal** blade biases toward integration. - The authors propose the first computational model that implements this blade-specific division: an exemplar-based k-WTA architecture for the suprapyramidal DG (DGSUP) to support pattern separation and episode-specific codes, and a gradual heterosynaptic plasticity architecture for the infrapyramidal DG (DGINF) to support integration across episodes. - Both coding regimes were evaluated on two input domains: MNIST digit data and neurally plausible entorhinal cortex inputs, suggesting domain generality of the mechanisms tested. - With entorhinal cortex inputs, the model produces place fields in the two blades that either remap or retain stable codes, consistent with empirical results differentiating remapping behavior across blades. - The model incorporates novel inputs (novel digit classes or novel spatial episodes) via a neurogenesis-inspired turnover and recruitment mechanism to add new representations. - The dual processing streams enable comparison between ongoing experience (episode-specific representations) and generalized expectations (integrated representations), yielding prediction errors that guide selective memory storage for poorly predicted experiences and forgetting of well-predicted ones. - The proposed learning rules are described as biologically plausible and expand the conceptual role of the DG beyond sole pattern separation, potentially supporting iterative construction of spatial cognitive maps that encode location-dependent expectations while preserving episodic traces. - Funding sources and declarations reported: Max Planck Society, Max Planck School of Cognition, European Research Council, The Kavli Foundation, Kristian Gerhard Jebsen Foundation Helse Midt Norge; authors declared no competing interests.

### 11. [Diurnal and Seasonal Variation in Brain mu-Opioid and Dopamine D2 Receptor Signaling](https://medichelpline.com/clinical-feed/biorxiv-6-diurnal-and-seasonal-regulation-of-brain-mu-opioid-and-dopamine-d2-receptor.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Diurnal and Seasonal Variation in Brain mu-Opioid and Dopamine D2 Receptor Signaling](https://medichelpline.com/clinical-feed/biorxiv-6-diurnal-and-seasonal-regulation-of-brain-mu-opioid-and-dopamine-d2-receptor.md)

> **Executive GIST:** - The study analyzed historical PET data to examine daily and seasonal rhythms in human neurotransmission, focusing on **mu-opioid receptor (MOR)** and **dopamine D2 receptor (D2R)** availability. - Scans included 188 healthy participants with [11C]carfentanil for MOR and 184 with [11C]raclopride for D2R. - Time-of-day (TOD) of scanning was used as the primary predictor of receptor availability to assess diurnal patterns. - Results showed an afternoon increase in **MOR availability** and an afternoon decrease in **D2R availability** compared with morning scans, indicating opposing diurnal trajectories for the two systems. - Seasonal variation (daylength) modulated the TOD effect for **MOR** but not for **D2R**, with MOR changes spanning anterior cingulate, dorsomedial and dorsolateral prefrontal cortex, insula, and striatum. - The diurnal variation in MOR availability within those regions was also sensitive to participants’ trait-anxiety levels. - Authors conclude that opioidergic and dopaminergic neurotransmission display distinct daily rhythms and that the MOR system uniquely mediates both diurnal and seasonal regulation and relates to behavioral trait measures. - The article is a preprint; the authors declared no competing interests and reported multiple funders. Specific numerical effect sizes, statistical parameters, and detailed methods beyond the PET tracers, sample sizes, and predictors were not reported in the supplied source text.

### 12. [Heart rate deceleration during reaching signals violation of movement expectations](https://medichelpline.com/clinical-feed/biorxiv-4-heart-rate-deceleration-reflects-expectation-violation-during-reaching.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Heart rate deceleration during reaching signals violation of movement expectations](https://medichelpline.com/clinical-feed/biorxiv-4-heart-rate-deceleration-reflects-expectation-violation-during-reaching.md)

> **Executive GIST:** - The study used a reaching task with a robotic manipulandum in male and female human participants to separate effects of **movement outcome** and **expectation violation** on heart rate responses. - **Heart rate (HR) deceleration** was confirmed following visuomotor perturbations that induce movement errors, consistent with prior reports. - When contextual cues predicted upcoming movement outcomes, HR deceleration occurred during movement preparation rather than after an error, implicating **expectation** in HR modulation. - Across varying expectation levels for different movement outcomes, HR deceleration correlated with **unexpected** outcomes rather than with the negative valence of outcomes. - Manipulating target width to allow successful reaches despite visuomotor rotations showed HR deceleration was more strongly linked to **task error** (failure to achieve task goal) than to **sensory prediction error** (mismatch in sensory feedback). - Authors conclude that HR responses during movement are more closely tied to violations of movement expectation than to movement error per se. - The findings propose that HR may serve as a physiological marker of expectation-related processing during sensorimotor behavior. - Funding sources and competing interests were declared: several Japan Society for the Promotion of Science grants and Japan Science and Technology Agency; authors declared no competing interests.

### 13. [Transcriptional and Anatomical Map of Sensory Vagus Neurons in Danionella cerebrum](https://medichelpline.com/clinical-feed/biorxiv-3-transcriptional-subtypes-anatomical-organization-and-sexual-dimorphism-of.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Transcriptional and Anatomical Map of Sensory Vagus Neurons in Danionella cerebrum](https://medichelpline.com/clinical-feed/biorxiv-3-transcriptional-subtypes-anatomical-organization-and-sexual-dimorphism-of.md)

> **Executive GIST:** - The study establishes the transparent miniature fish **Danionella cerebrum** as a model to study the adult vertebrate sensory vagus nerve, enabling direct anatomical and molecular analysis. - Researchers generated a **transgenic line** labeling D. cerebrum cranial sensory ganglia to visualize and map vagal projections that are otherwise difficult to access. - Anatomical mapping revealed a **somatotopic layout** of the vagal ganglia, indicating spatial organization of sensory inputs. - Single-cell transcriptional profiling of the sensory vagus identified diverse conserved sensory subtypes, including **nutrient-sensing**, **mechanoreceptive**, **nociceptive**, and **thermosensitive** neurons, plus polymodal combinations. - Marker-gene expression allowed visualization of somatotopic-specific sensory subtypes, linking molecular identity to anatomical position. - The sensory vagus in D. cerebrum is dynamic: it becomes **sexually dimorphic** during sexual maturation and shows ongoing **adult neurogenesis**. - The study produced a molecular and anatomical atlas of the sensory vagus that provides a platform for future functional studies of body–brain communication in this species. - Competing interest: A.F.S. is a scientific advisor to Novartis. Funders included the Jane Coffin Childs Memorial Fund for Medical Research and the University of Basel Research Fund for Excellent Junior Researchers. - The report is a bioRxiv preprint (doi: https://doi.org/10.64898/2026.09.01.748112) posted September 04, 2026; the full manuscript and supplementary files were made available with a CC-BY-NC-ND 4.0 license.

### 14. [Visual Impairment Has Limited Impact on Color-Based Attention BCIs Despite ERP Changes](https://medichelpline.com/clinical-feed/biorxiv-3-the-effect-of-visual-impairment-on-the-controllability-of-a-brain-computer.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Visual Impairment Has Limited Impact on Color-Based Attention BCIs Despite ERP Changes](https://medichelpline.com/clinical-feed/biorxiv-3-the-effect-of-visual-impairment-on-the-controllability-of-a-brain-computer.md)

> **Executive GIST:** - The study evaluated how different forms of **visual impairment** affect event-related potentials (ERPs) and the controllability of a **brain-computer interface** (BCI) driven by covert visual spatial attention in healthy participants. - Participants directed covert attention to peripheral visual stimuli while researchers recorded ERPs and assessed BCI decoding performance under varied viewing conditions. - The investigators simulated vision degradation (blurred vision) and compared monocular versus binocular viewing to model different stages of visual impairment. - Early attention-sensitive visual ERP components differed between monocular and binocular vision, indicating altered early visual processing with monocular viewing. - Simulated degraded vision produced reductions in ERP amplitude in the **P300** time range, showing diminished late attention-related responses under degraded acuity. - Despite measurable ERP differences across viewing conditions, BCI decoding accuracy was not meaningfully affected when **color** was the discriminative target feature. - The data indicate that a gaze-independent, non-invasive BCI that uses color as a distinguishing stimulus can remain controllable even with certain visual impairments. - This approach could enable communication for paralyzed persons who have reduced visual acuity or impaired gaze control, by relying on attention to identifiable visual features rather than gaze shifts. - The authors declared no competing interests and reported funding from the Deutsche Forschungsgemeinschaft. Specific participant numbers, detailed stimulus parameters, and quantitative accuracy values were not reported in the source summary. - The preprint was posted September 04, 2026; methodological specifics and full data are presented in the source preprint but were not detailed in the abstract-level summary used here.

### 15. [Retrieval Uncertainty Drives Rapid Consolidation of Confabulated Memories in Retrosplenial Cortex](https://medichelpline.com/clinical-feed/biorxiv-3-retrieval-uncertainty-drives-rapid-consolidation-of-confabulated-memories-in.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Retrieval Uncertainty Drives Rapid Consolidation of Confabulated Memories in Retrosplenial Cortex](https://medichelpline.com/clinical-feed/biorxiv-3-retrieval-uncertainty-drives-rapid-consolidation-of-confabulated-memories-in.md)

> **Executive GIST:** - The study tested whether uncertainty during retrieval of past memories can generate and rapidly consolidate fabricated or **confabulated memories** for events that were never directly experienced. - Using chemogenetics, in vivo imaging, behavioral assays, and a new mapping method, the authors examined how higher order associations (HOA) form and become consolidated across brain regions. - Acquisition of HOA depended on activity of **dorsal CA1 parvalbumin interneurons** in an intact **hippocampus**, while retrieval of these confabulated associations required the **retrosplenial cortex (RSc)**. - The team developed Large-scale Brainwide Correlated Activity Mapping (**LaBCAM**) to identify functional connectivity changes across brain regions during uncertain retrieval; LaBCAM indicated that only uncertain remote retrieval engages canonical fear circuitry. - Longitudinal imaging of **dendritic spines** in RSc showed different patterns of spine reorganization during acquisition versus rapid systems consolidation of HOA, implicating structural plasticity in RSc in confabulation consolidation. - Confabulated HOA appeared early in an Alzheimer’s disease model (APP/PS1) and were also present in aged animals, suggesting early vulnerability of this mechanism in disease and aging. - The authors conclude that retrieval uncertainty can transfer conditioning to novel contexts and that such fabricated memories undergo rapid consolidation involving RSc circuitry and spine remodeling. - Specific experimental parameters, quantitative effect sizes, sample sizes, and full methodological details were reported in the source but are not reproduced here; the preprint provides supplemental material for those details.

### 16. [Chronic stress drives sex-specific Type 1, 2, and 17 responses in brain-resident lymphocytes](https://medichelpline.com/clinical-feed/biorxiv-22-chronic-stress-promotes-sex-divergent-type-1-2-and-17-responses-in-brain.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Chronic stress drives sex-specific Type 1, 2, and 17 responses in brain-resident lymphocytes](https://medichelpline.com/clinical-feed/biorxiv-22-chronic-stress-promotes-sex-divergent-type-1-2-and-17-responses-in-brain.md)

> **Executive GIST:** - The study used unpredictable chronic mild stress (UCMS), a validated mouse model of depression, to investigate how chronic stress alters immune signatures in brain-resident lymphocytes. - UCMS induced depressive-like behaviors in both male and female mice, but produced different neuropathological changes: reduced regional synaptic density in females and decreased neuron counts in male hippocampi. - Single-cell RNA sequencing of brain lymphocytes revealed sex- and stress-regulated enrichment of T helper cytokine programs across distinct tissue-resident lymphocyte lineages. - Female brain-resident **γδT cells** were enriched for **type 2** and **type 17** signatures and showed higher expression of inflammasome genes including **Nlrp3** and **Il1b**. - Male brain lymphocytes, notably **αβT cells** and NKT cells, displayed enrichment for **type 1** signatures with higher **Cxcr3** and **Il27ra** expression. - Chronic stress amplified these sex differences, increasing the **type 1** response and **IFNγ** production preferentially in males at both transcript and protein levels. - Type 17 cytokines (IL-17A and IL-17F) were also increased after UCMS, but with sex-divergent polarization: IL-22 decreased in female and increased in male brain lymphocytes. - Mechanistic changes included stress-associated suppression of **P4ha1** in male and **Zfp36** in female brain tissue-resident lymphocytes; P4HA1 has been linked to mitochondrial restriction of type 1 responses, and ZFP36 suppresses inflammatory cytokine translation. - Ex vivo CD3-dependent stimulation of brain immune cells showed stress-dependent increases in cytokine production with sex-specific effects, supporting functional relevance of transcriptomic findings. - The authors present a cellular and molecular framework for how chronic stress dysregulates tissue-resident lymphocytes in the brain with a pronounced sex bias; this work is a preprint and has not been peer-reviewed.

### 17. [Validity of Multidimensional Scaling for Low-Dimensional Representation of Whole-Body Movements](https://medichelpline.com/clinical-feed/biorxiv-2-validity-of-low-dimensional-representation-of-whole-body-movements.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Validity of Multidimensional Scaling for Low-Dimensional Representation of Whole-Body Movements](https://medichelpline.com/clinical-feed/biorxiv-2-validity-of-low-dimensional-representation-of-whole-body-movements.md)

> **Executive GIST:** - The study evaluated whether a low-dimensional **state space** derived by multidimensional scaling (MDS) can validly summarize **whole-body movements** for impression evaluation. - Researchers used recorded exercises from Radio Calisthenics No. 1 as the movement dataset and applied MDS to generate a low-dimensional representation of postures and movements. - The analysis tested whether distances among points in the MDS state space reflected exercise category more than individual performer identity. - Results indicated that distances in the MDS-derived state space corresponded more strongly to **exercise category** than to performer identity, implying MDS captures intra-exercise posture similarity. - The patterns of distances between conditions were not uniform across all exercise categories; distance relationships varied by exercise type. - Authors conclude that an MDS-based state-space is a valid and interpretable way to summarize whole-body movement, but they note limitations. - The paper calls for further validation using a broader range of whole-body movements and a more diverse participant sample before generalizing the findings. - No competing interests were declared; funding was provided by the Japan Science and Technology Agency (JPMJMS2291).

### 18. [CAMSAP3 loss-of-function evidence implicates gene in generalized genetic epilepsy](https://medichelpline.com/clinical-feed/biorxiv-1-camsap3-loss-of-function-models-suggest-causative-role-in-generalized-genetic.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [CAMSAP3 loss-of-function evidence implicates gene in generalized genetic epilepsy](https://medichelpline.com/clinical-feed/biorxiv-1-camsap3-loss-of-function-models-suggest-causative-role-in-generalized-genetic.md)

> **Executive GIST:** - Next-generation sequencing revealed predicted pathogenic CAMSAP3 variants in two patients with **generalized epilepsy**, prompting functional follow-up. - CAMSAP3 encodes a regulator of non-centrosomal microtubule dynamics important for axonal differentiation and migration. - Overexpression of patient-derived CAMSAP3 variants in cultured HEK cells caused **protein degradation** and altered **microtubule acetylation**, indicating disrupted protein stability and cytoskeletal regulation. - A Camsap3 knockout zebrafish model showed elevated axonal **microtubule acetylation**, paralleling the cell-culture phenotype and supporting a loss-of-function mechanism. - Knockout zebrafish displayed behavioral and electrophysiologic hallmarks of epilepsy: seizure-like swimming behaviors and **epileptiform** activity recorded by local field potential. - Development of inhibitory interneurons was abnormal in Camsap3 knockout zebrafish, suggesting a developmental mechanism that could contribute to network hyperexcitability. - The convergence of human genetic data, cellular assays, and an animal knockout model supports a causative role for **CAMSAP3** in at least some forms of generalized genetic epilepsy. - The authors declare no competing interests and acknowledge funding from the National Institute of Neurological Disorders and Stroke and other listed sources. - These results provide functional validation for CAMSAP3 as an epilepsy-associated gene but further clinical and mechanistic studies were not reported in the source and remain necessary to inform patient management.

### 19. [Persistent anti-ganglioside autoantibodies in recovered Guillain-Barré syndrome show reduced neuro](https://medichelpline.com/clinical-feed/biorxiv-1-autoantibodies-from-recovered-guillain-barre-syndrome-patients-exhibit-altered.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-04
- **Detail Markdown URL:** [Persistent anti-ganglioside autoantibodies in recovered Guillain-Barré syndrome show reduced neuro](https://medichelpline.com/clinical-feed/biorxiv-1-autoantibodies-from-recovered-guillain-barre-syndrome-patients-exhibit-altered.md)

> **Executive GIST:** - Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy often triggered by infection, most commonly **Campylobacter jejuni**, through anti-ganglioside antibodies that cross-react with neuronal gangliosides. - In most patients, neuropathy resolves as anti-ganglioside antibody titers decline and immune stimulation wanes. - The study found that approximately **10%** of clinically confirmed GBS patients retained high circulating anti-ganglioside antibody titers more than a decade after clinical recovery. - Despite persistent titers, sera from recovered patients did not induce neuropathy in a human pluripotent stem cell-derived sensory neuron model when tested with human complement, in contrast to paired acute-phase sera from the same patients. - Comparative analyses of paired acute and recovered sera revealed changes in **IgG** subclass distribution and antibody glycoforms between disease and recovery. - Isolated anti-GM1 ganglioside antibodies from recovered patients showed **anti-inflammatory glycoform modifications**, distinguishing them from pathogenic acute-phase antibodies. - The data support a model in which patients selectively maintain **non-pathogenic variants of autoantibodies** that lack neuron-damaging effector functions but could retain protective activity against C. jejuni. - Methods reported include use of paired acute and recovered sera and a human stem cell-derived sensory neuron plus human complement assay to assess neurotoxic potential. - Funding sources and competing interests were disclosed; specific institutional or experimental protocol details beyond those reported were not provided in the source.

### 20. [FDA approves Zanvastro, the first disease-modifying drug for Alexander disease](https://medichelpline.com/clinical-feed/stat-news-0-stat-ionis-wins-fda-approval-for-first-drug-for-alexander-disease-a-rare-and.md)
- **Source:** STAT News | **Published:** 2026-09-03
- **Detail Markdown URL:** [FDA approves Zanvastro, the first disease-modifying drug for Alexander disease](https://medichelpline.com/clinical-feed/stat-news-0-stat-ionis-wins-fda-approval-for-first-drug-for-alexander-disease-a-rare-and.md)

> **Executive GIST:** - Ionis Pharmaceuticals received FDA approval for **Zanvastro**, the first disease-modifying therapy for **Alexander disease**, a rare and often fatal neurologic disorder. - The approval covers use in both children and adults. - In the pivotal trial, patients treated with Zanvastro showed stability in **walking speed**, while the control group experienced a 33% decline in that measure. - Trial data also suggested that treating younger children may lead to improvements in motor function rather than just stabilization. - Zanvastro was described as generally safe in the trial; serious adverse events occurred more often in the control group than in treated patients. - Because Alexander disease is extraordinarily rare, Ionis used an **unusual testing approach** to evaluate the drug; specific details of that approach were not reported in the source. - The source did not report additional details such as full trial size, duration, dosing, long-term outcomes, or specific labeling and postmarketing requirements. - This approval represents the first FDA-recognized disease-modifying option for this patient population, marking a notable regulatory milestone for a very rare neurologic condition.

### 21. [FDA Approves Zanvastro (zilganersen) for Alexander Disease — First Disease-Targeting Therapy](https://medichelpline.com/clinical-feed/fda-news-releases-0-fda-approves-first-drug-to-treat-alexander-disease.md)
- **Source:** FDA News Releases | **Published:** 2026-09-03
- **Detail Markdown URL:** [FDA Approves Zanvastro (zilganersen) for Alexander Disease — First Disease-Targeting Therapy](https://medichelpline.com/clinical-feed/fda-news-releases-0-fda-approves-first-drug-to-treat-alexander-disease.md)

> **Executive GIST:** - The FDA approved **Zanvastro (zilganersen)** injection on September 3, 2026, as the first therapy specifically approved to treat **Alexander disease**, a rare progressive neurological disorder. - Alexander disease is caused by mutations in the gene encoding **glial fibrillary acidic protein (GFAP)**; abnormal GFAP accumulates in supportive brain cells and damages the nervous system. - Zanvastro is an **antisense oligonucleotide** that reduces production of the abnormal GFAP protein and is administered by injection into the spinal canal every three months by a trained healthcare professional. - The approval was supported by a multicenter, randomized, controlled clinical study (NCT04849741) enrolling 49 patients aged 2 years and older, plus an open-label substudy of four patients under 2 years. - In patients aged 5 and older with baseline walking impairment, Zanvastro produced significantly better walking speed at 61 weeks versus no treatment. In children aged 2–4 years, a composite motor assessment showed improvement with Zanvastro while controls declined. - Data for patients under 2 were limited; pharmacokinetic modeling and safety data from four infants and the older pediatric cohort supported extending the indication to patients under 2 years. - Common adverse reactions included vomiting, back pain, cough, headache, and post-lumbar puncture syndrome; aseptic meningitis has been reported and should prompt evaluation. - Zanvastro received Orphan Drug, Fast Track, Breakthrough Therapy, Rare Pediatric Disease, and Priority Review Voucher designations; approval was granted to Ionis Pharmaceuticals, Inc. - The FDA emphasized that prior to this approval only supportive care was available and framed the approval as addressing the underlying cause of disease progression.

### 22. [2026 Stroke Rehabilitation Guideline: Start Early and Address Physical, Cognitive, and Mental Heal](https://medichelpline.com/clinical-feed/medical-news-today-0-stroke-rehab-guidelines-emphasize-early-support-for-physical-cognitive-and.md)
- **Source:** Medical News Today | **Published:** 2026-09-03
- **Detail Markdown URL:** [2026 Stroke Rehabilitation Guideline: Start Early and Address Physical, Cognitive, and Mental Heal](https://medichelpline.com/clinical-feed/medical-news-today-0-stroke-rehab-guidelines-emphasize-early-support-for-physical-cognitive-and.md)

> **Executive GIST:** - New 2026 guideline from the American Stroke Association (published in Stroke) recommends starting **stroke rehabilitation** as soon as a patient is medically stable, ideally within 48 hours, while avoiding moderate- to high-intensity exercise in the first 24 hours. - Rehabilitation plans should be individualized and address physical, cognitive, communication, and mental health needs rather than focusing on physical recovery alone. - Early mobilization (sitting, standing, walking) between 24 and 48 hours is emphasized; mobilization earlier than 24 hours may be associated with worse outcomes in some studies. - A coordinated, **multidisciplinary team**—including neurologists, rehab nurses, occupational and physical therapists, speech-language pathologists, social workers, psychologists, and recreational therapists—should guide recovery and tailor care to the survivor’s goals. - Rehab settings can vary: inpatient rehabilitation, skilled nursing facilities, long-term care hospitals, outpatient therapy, home-based care, and telehealth options depending on stroke severity and patient needs. - Mental health is highlighted as an integral part of recovery: about one in three people may experience **post-stroke depression** and up to a quarter may experience anxiety; routine screening and treatment for mental health are recommended alongside physical rehab. - The guideline updates 2016 recommendations and expands or adds recommendations in areas including cognition, mental health, sleep, post-stroke fatigue, and recreation/leisure based on evidence published since the prior guideline. - The overarching goal is helping stroke survivors achieve the highest possible independence and quality of life, with caregiver support and attention to life changes such as employment, relationships, sleep, pain, and sexual function.

### 23. [Complement and Complement-Targeted Therapeutics in Neurological Diseases](https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-role-of-complement-and-complement-targeted-therapeutics-in-neurological-diseases.md)
- **Source:** Nature Reviews Neurology | **Published:** 2026-09-03
- **Detail Markdown URL:** [Complement and Complement-Targeted Therapeutics in Neurological Diseases](https://medichelpline.com/clinical-feed/nature-reviews-neurology-0-role-of-complement-and-complement-targeted-therapeutics-in-neurological-diseases.md)

> **Executive GIST:** - The **complement** system is a set of plasma and membrane proteins that bridge innate and adaptive humoral immunity and also contributes to brain development and nervous system homeostasis. - Dysregulated or inappropriate complement activation is implicated across many autoimmune and **neurodegenerative** neurological disorders, including conditions affecting the central nervous system (CNS), peripheral nervous system (PNS) and muscle. - Several **FDA-approved** complement-targeted agents exist, primarily for diseases driven by complement-fixing pathogenic antibodies (for example, **myasthenia gravis** and **neuromyelitis optica spectrum disorder**), and numerous additional biologic agents are in ongoing phase I–III trials. - Experimental data indicate that some complement components can have tissue-protective roles in CNS diseases such as **Alzheimer disease** and **multiple sclerosis**, supporting the need for selective modulation of pathways rather than broad complement blockade. - Emerging therapies increasingly target proximal complement components (for example, **C1**), but proximal blockade carries heightened concerns about invasive infections and disruption of physiological complement functions. - Future development requires nuanced drug design, attention to risks versus benefits, and systematic diagnostic guidance that integrates reliable, disease-specific biomarkers to enable personalized complement-targeted therapy. - The review includes schematic representations of complement pathways (Fig. 1) and the expanding range of complement therapeutics (Fig. 2), and cites foundational and recent literature on complement function, synapse pruning, neuroinflammation and therapeutic strategies. - Overall, anti-complement therapeutics are poised to reshape treatment paradigms in autoimmune neurologic conditions amid a crowded biologic landscape targeting multiple immune mechanisms.

### 24. [Hippocampal gene and epigenetic alterations link impaired neurogenesis to major depressive disorder](https://medichelpline.com/clinical-feed/nature-1-gene-alteration-in-human-brain-suggests-genetic-and-epigenetic-roots-of-major.md)
- **Source:** Nature Medicine | **Published:** 2026-09-03
- **Detail Markdown URL:** [Hippocampal gene and epigenetic alterations link impaired neurogenesis to major depressive disorder](https://medichelpline.com/clinical-feed/nature-1-gene-alteration-in-human-brain-suggests-genetic-and-epigenetic-roots-of-major.md)

> **Executive GIST:** - A large, multimodal molecular study of the adult human **hippocampus** reports evidence for sustained **adult neurogenesis** in humans and identifies a disrupted or stalled neurogenic process in people with **major depressive disorder (MDD)**. - The study used cell- and circuit-specific molecular characterization to map alterations associated with MDD; findings implicate coordinated **genetic** and **epigenetic** changes. - Multiple biological domains were implicated, including **stress**-related pathways, **immune** signalling, **metabolic** processes and **synaptic** mechanisms, all linked to impaired hippocampal plasticity. - Results connect altered genes in the human hippocampus with psychiatric disorders and show depleted adult neurogenesis in MDD (illustrated in Fig. 1 of the briefing). - The authors propose that these cell- and circuit-level molecular signatures provide a framework for **disease subtyping** and may guide future **therapeutic development**. - The Research Briefing summarizes and contextualizes the open-access Nature Medicine article by Peng et al., Dysregulated adult hippocampal neurogenesis in major depressive disorder. - The briefing cites prior work linking adult neurogenesis to memory and stress resilience in animal models (for example, studies by Chen et al. and Anacker et al.) and situates the new human molecular data within that broader literature. - Detailed experimental methods, cohort details and specific gene lists were reported in the source article and are not reproduced in full in this briefing.

### 25. [Expansion of Unimodal-to-Transmodal Cortical Hierarchy Precedes Psychosis in Clinical High-Risk In](https://medichelpline.com/clinical-feed/medrxiv-4-altered-unimodal-to-transmodal-cortical-hierarchy-before-transition-to.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [Expansion of Unimodal-to-Transmodal Cortical Hierarchy Precedes Psychosis in Clinical High-Risk In](https://medichelpline.com/clinical-feed/medrxiv-4-altered-unimodal-to-transmodal-cortical-hierarchy-before-transition-to.md)

> **Executive GIST:** - Study used **connectome gradient mapping** to examine baseline cortical hierarchical organization along the unimodal-to-transmodal axis in 580 individuals from the NAPLS-3 cohort. - Participant groups included clinical high-risk converters (CHR-C, n = 56), clinical high-risk non-converters (CHR-NC, n = 434), and healthy controls (HC, n = 90). - CHR-C individuals showed bidirectional, regionally selective alterations along the sensorimotor-to-association gradient: reduced gradient values in the **visual network** and elevated values in the **default mode network** compared with CHR-NC and HC. - At the whole-brain level, CHR-C exhibited increased explained variance, increased range, and increased variation of the primary unimodal-to-transmodal gradient, interpreted as **hierarchical expansion** of cortical organization. - Greater explained variance of the gradient correlated with shorter time to conversion to **psychosis** among converters; increased gradient range and variation were associated with greater positive symptom severity across CHR participants. - Findings indicate that expansion and greater separation between sensory and transmodal systems exist before illness onset in those who later develop psychosis, suggesting early macroscale network reorganization may characterize progression from clinical high-risk to psychotic illness. - Data were drawn from NAPLS-3 and are available via the NIMH Data Archive under applicable access procedures; ethical approvals and participant consents were reported by the authors.

### 26. [Phenotypic age, metabolic health, and dementia risk: Mendelian randomisation and network analysis](https://medichelpline.com/clinical-feed/medrxiv-3-causal-roles-of-phenotypic-age-and-metabolic-health-on-dementia-a-mendelian.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [Phenotypic age, metabolic health, and dementia risk: Mendelian randomisation and network analysis](https://medichelpline.com/clinical-feed/medrxiv-3-causal-roles-of-phenotypic-age-and-metabolic-health-on-dementia-a-mendelian.md)

> **Executive GIST:** - This study examined whether composite measures of biological ageing (**PhenoAgeAccel**) and metabolic health (**MetaboHealth**) have causal effects on all-cause **dementia** using genetic instruments and structure learning. - Analyses used UK Biobank participants of White British genetic ancestry to derive exposures: MetaboHealth from NMR metabolomics (n=272,568) and PhenoAgeAccel from clinical biomarkers plus chronological age (n=274,077). - Genome-wide association studies (GWAS) identified 126 independent genome-wide significant variants for MetaboHealth and 141 for PhenoAgeAccel; 109 and 141 variants were retained as genetic instruments respectively. - Two-sample Mendelian randomisation (MR) used FinnGen all-cause dementia summary statistics, with inverse-variance weighting as the primary MR method and multiple sensitivity and robust MR methods for confirmation. - MR provided no evidence that genetically predicted MetaboHealth (OR per unit 0.83, 95% CI 0.49–1.42; p=0.51) or PhenoAgeAccel (OR per year 0.99, 95% CI 0.95–1.02; p=0.44) causally influence all-cause dementia. - Causal network analysis of constituent biomarkers highlighted lower **lymphocyte percentage** and higher **NMR-derived glucose** as having direct relationships with dementia in the joint biomarker network. - The authors interpret results as evidence that the composite exposures themselves were not causal for dementia in MR, while specific constituent biomarkers may warrant further study. - Data and summary statistics will be deposited in the GWAS Catalog upon publication; individual-level UK Biobank data available via application. Funding sources and ethical approvals are reported; authors declared no competing interests.

### 27. [Psychometric validation of the revised Hungarian Autism Spectrum Quotient (AQ-50-HU-R)](https://medichelpline.com/clinical-feed/medrxiv-17-measuring-autistic-traits-in-hungarian-adults-psychometric-evaluation-of-the.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [Psychometric validation of the revised Hungarian Autism Spectrum Quotient (AQ-50-HU-R)](https://medichelpline.com/clinical-feed/medrxiv-17-measuring-autistic-traits-in-hungarian-adults-psychometric-evaluation-of-the.md)

> **Executive GIST:** - The study evaluated the Hungarian translation and a revised version, the **AQ-50-HU-R**, to measure **autistic traits** in adults using two samples (N1 = 1,967; N2 = 423) that included autistic and non-autistic participants. - The AQ-50-HU-R demonstrated **high internal consistency** and good **test–retest reliability**; exact alpha and reliability coefficients were not reported in the source abstract. - Confirmatory factor analysis favored a **bifactor model** (χ2[1125] = 1650.433, p < 0.001) with excellent fit indices: CFI = 0.991, TLI = 0.990, RMSEA = 0.033 (90% CI = 0.030–0.037), SRMR = 0.083. - In that model, 71% of shared variance was attributable to a **general autistic traits factor**, supporting interpretation of the total score as the primary indicator. - The AQ-50-HU-R total score differentiated clinically verified autistic participants from those reporting no ASD diagnosis with good accuracy (AUC = 0.906); the suggested screening cutoff was 25. - Associations between AQ-50-HU-R scores and ADOS (Autism Diagnostic Observation Schedule) scores were reported as weak or nonsignificant. - The authors conclude the measure is best used as a **reliable total-score screening tool** to support referral for comprehensive diagnostic assessment rather than as a diagnostic substitute. - Ethical approvals were obtained from Semmelweis University Regional and Institutional Committee of Science and Research Ethics and the Medical Research Council (approval numbers: RKEB 158/2021, RKEB 159/2021, BM/14269-3/2025); participants gave electronic written informed consent. - Data and code supporting CFA and ROC analyses are available on OSF at the provided anonymous view-only link. - The preprint was posted on medRxiv on September 03, 2026, DOI: 10.64898/2026.09.01.26361970; authors are affiliated with Semmelweis University.

### 28. [Limits of Trial-Adaptive Neural Language Fusion in P300-Speller Brain–Computer Interfaces](https://medichelpline.com/clinical-feed/medrxiv-17-limits-of-trial-adaptive-neural-language-fusion-across-large-language-models-in.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [Limits of Trial-Adaptive Neural Language Fusion in P300-Speller Brain–Computer Interfaces](https://medichelpline.com/clinical-feed/medrxiv-17-limits-of-trial-adaptive-neural-language-fusion-across-large-language-models-in.md)

> **Executive GIST:** - The study reanalyzed 3,373 archived selections from a P300-speller dataset (BigP3BCI) collected from 47 people with ALS to test whether trial-by-trial reliability estimates improve language model fusion. - Researchers compared a tuned **fixed weight** fusion baseline against an **adaptive fusion** policy, using a fair, matched-search-space methodology and out-of-fold tuning. - Evaluation covered 22 language-model priors spanning parameter scales up to **46.7B** parameters. - Two representative priors — **GPT-2** and a classical **5-gram** model — were analyzed further with naive and mechanistic approaches. - Across the fair comparison, no prior's 95% confidence interval favored adaptive fusion over a tuned fixed weight, despite the presence of oracle headroom at all scales. - Under **GPT-2**, a naive comparison showed adaptive fusion performed significantly worse; both naive and tuned anchors converged toward a degenerate or near-degenerate fair-comparison solution. - Additional controllers applied to the representative priors failed to convert the observable oracle headroom into practical benefit. - The fixed-fused posterior's output probability was better at flagging high-risk or erroneous selections, showing a 2.8- to 3.8-fold enrichment versus the best tested controller. - The authors conclude that a tuned fixed weight is a robust default across the tested model-family and scale range, and that trial-adaptive reliability estimation provided no deployable advantage in this dataset. - The report emphasizes that adaptive weighting schemes should be validated against a fairly tuned baseline across model families and scales; data and code are available at the cited GitHub repository.

### 29. [Childhood Maltreatment, Poor Sleep, and Fear of Relapse in Multiple Sclerosis: A Clinical Summary](https://medichelpline.com/clinical-feed/medrxiv-1-exploring-the-negative-triad-of-childhood-maltreatment-fear-of-relapse-and-low.md)
- **Source:** medRxiv (Clinical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [Childhood Maltreatment, Poor Sleep, and Fear of Relapse in Multiple Sclerosis: A Clinical Summary](https://medichelpline.com/clinical-feed/medrxiv-1-exploring-the-negative-triad-of-childhood-maltreatment-fear-of-relapse-and-low.md)

> **Executive GIST:** - This preprint investigated the interrelations among **childhood maltreatment (CM)**, **sleep quality**, and **fear of relapse (FoR)** in people with **multiple sclerosis (MS)** using an online survey. - The study sampled N = 48 participants and assessed sleep with the **Pittsburgh Sleep Quality Index (PSQI)**, FoR with the **Fear-of-Relapse Scale (FoR)**, and CM with the **Childhood Trauma Questionnaire (CTQ)**; timing of CM subtypes was additionally queried. - In the overall cohort, worse **sleep quality** was significantly associated with greater **fear of relapse**; the interaction between CM and sleep did not significantly predict FoR across the whole sample. - Exploratory sex-stratified analyses found a significant interaction between **CM** and **sleep** predicting FoR among male participants, but this interaction was not significant among female participants. - Authors interpret that both a history of **childhood maltreatment** and impaired **sleep quality** may act as additional psychosocial stressors influencing illness management and the subjective experience of relapse risk in MS. - The dataset is available from the corresponding author on reasonable request; institutional ethics approval was obtained (Review Board for Issues of Ethics in Scientific Research, Department of Psychology, University of Innsbruck; Certificate #45/2025). - The manuscript is a medRxiv preprint and has not been peer reviewed; authors declared no competing interests and confirmed adherence to reporting and ethical guidelines. - Findings are preliminary given sample size and preprint status; the authors call for additional research and tailored support services to address CM and sleep problems within MS care.

### 30. [FibrilNet: semantic network mapping of conserved and tissue-specific molecular environments in sys](https://medichelpline.com/clinical-feed/biorxiv-2-fibrilnet-maps-conserved-and-tissue-specific-molecular-environments-across.md)
- **Source:** bioRxiv (Biomedical Preprints) | **Published:** 2026-09-03
- **Detail Markdown URL:** [FibrilNet: semantic network mapping of conserved and tissue-specific molecular environments in sys](https://medichelpline.com/clinical-feed/biorxiv-2-fibrilnet-maps-conserved-and-tissue-specific-molecular-environments-across.md)

> **Executive GIST:** - The study introduces **FibrilNet**, a network framework that integrates experimentally defined amyloid proteomes with a human protein–protein interaction graph and Gene Ontology–derived semantic information. - FibrilNet compares topology-only random walk with restart (RWR) to an **ontology-aware semantic RWR** in frozen leave-one-out module reconstruction and precursor-seeded prioritization tasks. - The human interaction graph used contains 17,997 proteins and 925,977 physical interactions; interaction context is encoded in a 9-dimensional **semantic representation**. - In expanded cardiac transthyretin amyloidosis (**ATTR**), semantic-RWR raised mean reciprocal rank (MRR) from 0.00167 to 0.05015 and Recall@100 from 0.0199 to 0.3377, improving reconstruction for 132 of 151 held-out targets. - Significant semantic improvements were also reported for renal serum amyloid A amyloidosis (**AA**) and leukocyte chemotactic factor 2 amyloidosis (**ALECT2**). - Across compact ATTR, light-chain amyloidosis (**AL**), AA and ALECT2 modules, **APCS**, **VTN** and **TIMP3** formed a direct four-disease recurrent core; **APOE** appeared in three of four modules. - A tissue-aware ATTR analysis showed limited overlap between cardiac and neurologic modules (19 shared proteins; Jaccard 0.0569), indicating tissue specificity of amyloid-associated environments. - In a hTTR-A97S peripheral-nerve model, semantic-RWR significantly improved reconstruction of the 202-protein neurologic module, with strongest evidence concentrated in the downregulated proteomic program. - TTR-seeded propagation benefited from semantic information but remained weak in absolute terms, suggesting a separation between **precursor identity** and the distributed downstream molecular environment. - Authors conclude a multilayer model: a restricted conserved amyloid environment coexists with precursor-, tissue- and disease-specific organization. - The authors declared no competing interests; data/code referenced via a Zenodo record per the source.

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