European Journal of Neuroscience

Objective: To examine how medial plantar nerve shear wave speed (Cs) and viscosity coefficient (Vi) are associated with the severity of diabetic peripheral neuropathy (DPN), and to assess their ability to differentiate adjacent severity categories. Materials and Methods: Based on TCSS, the 113 patients with type 2 diabetes mellitus were assigned to the non-DPN (n = 33), mild DPN (n = 46), and moderate DPN (n = 34) groups. Medial plantar nerve Cs and Vi were measured using shear wave elastography and viscosity imaging. Receiver operating characteristic analysis evaluated Cs, Vi, and their logistic regression-based combination; areas under the curves (AUCs) were compared using DeLong tests. Results: Cs and Vi increased progressively across the three groups (both P < 0.001). For non-DPN versus mild DPN, the AUCs of Cs, Vi, and the combined model were 0.688 (95% CI, 0.604-0.772), 0.741 (0.660-0.822), and 0.745 (0.665-0.826), respectively, without significant pairwise differences. For mild versus moderate DPN, the corresponding AUCs were 0.707 (0.625-0.789), 0.794 (0.724-0.865), and 0.799 (0.731-0.867). The combined model outperformed Cs (P = 0.045), whereas Cs versus Vi and Vi versus the combined model did not differ significantly (P = 0.162 and 1.000, respectively). Conclusion: Medial plantar nerve Cs and Vi increased with DPN severity. Their combination improved discrimination between mild and moderate DPN compared with Cs alone but not with Vi alone. Quantitative medial plantar nerve viscoelastic assessment may complement clinical severity grading.

Abstract Objective: Glaucoma is a chronic disorder that impairs ocular health and may exacerbate ocular surface disease leading to tear film instability, dry eye symptoms and decreased quality of life. This study compared changes in tear quantity among glaucoma subjects living with and without diabetes mellitus, attending an eye clinic in Nigeria. Methods: A comparative cross sectional research design was used. 157 subjects which comprised 74 glaucoma subjects living with diabetes mellitus and 83 glaucoma subjects living without diabetes mellitus participated in the study. Tear quantity assessment included the Schirmer I test and tear meniscus height (TMH) measurement. Descriptive statistics, independent samples t-test and Chi-square test were used to examine the data at 0.05 level of significance. Results: Glaucoma subjects living with diabetes mellitus showed substantially decreased tear production (11.4 +/- 6.8 mm) compared with glaucoma subjects living without diabetes mellitus (19.6 +/- 9.6 mm; p < 0.001). Tear meniscus height in glaucoma subjects living with diabetes mellitus (0.8 +/- 0.3 mm) was significantly greater than in subjects living without diabetes mellitus (0.7 +/- 0.3 mm; p = 0.034). Conclusion: Diabetes mellitus dramatically deteriorates the ocular surface function in glaucoma subjects by decreasing tear production, altering the tear meniscus height and increasing the severity of ocular surface symptoms. Routine glaucoma care, especially in patients with diabetes mellitus, should include a full ocular surface evaluation including Schirmer I test, TBUT, TMH, and OSDI assessment to allow early detection and management of ocular surface disease, better treatment adherence, and improved visual outcomes. Keywords: Glaucoma, Diabetes Mellitus, Tear production, Tear Meniscus Height, Ocular Surface Disease.

Background: Bipolar disorder is associated with persistent social, cognitive, and functional impairment during euthymia, yet the neural mechanisms underlying these deficits remain unclear. Alterations to self-referential processing are a candidate mechanism, but existing electrophysiological studies rely on emotionally valenced paradigms that potentially confound self-processing with emotional biases. Methods: We analysed electroencephalography from 28 patients with bipolar disorder (type I or II) and 28 age- and sex-matched healthy controls during an emotionally neutral colour judgment task with self-related (preference) and non-self-related (similarity) conditions. Late positive potentials, temporal generalisation decoding, and frequency band decoding (theta, alpha, beta) were used to characterise the temporal dynamics and oscillatory correlates of self versus non-self processing. Results: Controls showed higher overall event-related potential amplitudes and greater self versus non-self differentiation than patients (condition by group interaction, 337 to 946 ms). Broadband temporal generalisation decoding revealed extensive cross-temporal generalisation of the self versus non-self representation in controls, spanning most of the trial, but no significant generalisation in patients. Frequency analyses showed that alpha and beta carried self versus non-self information in both groups, with broader extent in controls, and that anterior theta carried this information in patients but not controls. Exploratory correlations linked decoding measures to rumination and anxiety but not to manic symptoms. Conclusions: The neural representation distinguishing self-referential from externally guided processing was both smaller in amplitude and less temporally sustained in bipolar disorder. Reduced persistence is not detectable by conventional amplitude analyses, and may bear on the self-related and social cognitive difficulties reported in this population.

Parkinsons disease (PD) arises through disruption of multiple interconnected cellular processes, but the genetic contributions to these processes may differ across ancestries. We investigated functional convergence among genes harboring pathogenic or likely pathogenic (P/LP) variants and variants of uncertain significance (VUS) in a multicenter Indian cohort recruited through the Genetics of Parkinsons Disease in India Young Onset Parkinsons Disease project (GOPI YOPD). The cohort included 668 participants (463 males 69.3%) with a mean age at motor onset of 39.4+/-8.8 years. P/LP variants and VUS identified through previously reported whole-exome or whole genome sequencing were retained as separate evidential categories. The P/LP-associated gene set comprised 11 unique genes and the VUS associated set comprised 40 unique genes. Separate STRING functional-enrichment analyses evaluated Gene Ontology Biological Process, Molecular Function and Cellular Component terms, KEGG pathways, WikiPathways and STRING local network clusters. Terms meeting a Benjamini Hochberg false discovery rate threshold of <0.05 were organized into eight non-mutually-exclusive ontology/pathway categories. Gene to pathway mappings were subsequently projected to individual participants to estimate pathway representation and examine clinical associations. At least one reportable P/LP variant or VUS was identified in 336/668 participants (50.3%): 35 had a P/LP variant alone, 282 had VUS alone and 19 had a P/LP variant together with VUS in one or more additional genes. The most frequently represented categories were mitochondrial organization (247/336, 73.5%), autophagy related processes (228/336, 67.9%) and regulation of synaptic vesicle transport (201/336, 59.8%). PRKN was the most frequent P/LP-associated gene, occurring in 29/54 P/LP carriers, followed by PLA2G6 and PINK1. Lysosomal transport was represented exclusively by VUS-associated genes, particularly GBA1, VPS13C and LRRK2. Among P/LP carriers, additional VUS in distinct genes were not associated with age at onset (P = 0.81) or family history (52.6% versus 31.4%; P = 0.15). No pathway phenotype association remained significant after correction for multiple testing. Genetic findings in this Indian cohort converged across an interconnected mitochondrial autophagic lysosomal vesicular network, with different contributions from P/LP-associated and VUS associated gene sets. This study provides the first pathway resolved South Asian genetic profile and a framework for comparative studies across populations.

Mitochondria are central hubs for cellular metabolism and mitochondrial dysfunction is a hallmark of many chronic diseases. Consequently, changes in mitochondrial DNA copy number (mtDNA-CN), the number of mtDNA genomes per cell or tissue sample, are associated with diseases ranging from cancer and obesity to psoriasis and all-cause mortality. MtDNA-CN especially holds promise as a biomarker for neurodegenerative diseases, but whether and how mtDNA-CN changes with neurodegeneration is controversial. Here, we performed a systematic review and meta-analysis of 76 studies including 156 comparisons of mtDNA-CN in populations with or without a neurodegenerative disease to identify overall trends and potential moderators that explain variation among studies. Overall, mtDNA-CN was not statistically different with neurodegeneration, but heterogeneity among studies was extreme (I2 = 99.5%). The diagnosed disease explained the most variation. For example, Alzheimer's patients showed a 21% decrease in mtDNA-CN, but there was no change in mtDNA-CN with Parkinson's disease. Decreases in mtDNA-CN during neurodegeneration were also more extreme at older ages. Surprisingly, the tissue sampled for mtDNA-CN was not particularly influential, except for certain diseases. Studies published in earlier years also showed more extreme decreases in mtDNA-CN with neurodegeneration. Excessive heterogeneity persisted even after accounting for all moderators and their interactions (I2 = 85.7%). We conclude that the general perception of decreased mtDNA-CN with neurodegeneration is a vast oversimplification that may stem from legacy effects of early studies. However, mtDNA levels offer great promise as biomarkers for neurodegeneration, other diseases, and general health metrics, assuming appropriate complications can be considered.

Children and adolescents with hearing loss frequently encounter reduced auditory access and delayed language development, factors that may influence the maturation of executive functions. This study examined developmental differences in planning, a core executive function, in 98 children and adolescents with hearing loss or normal hearing aged 7 to18 years using the Tower of London task. Compared to normal hearing peers, participants with hearing loss made more unnecessary moves and rule violations and initiated problem-solving more rapidly, suggesting reduced preplanning efficiency and increased impulsivity. These group differences were most pronounced in adolescents, who showed faster initiation and greater movement inefficiency than age-matched normal hearing participants. Within the hearing loss group, adolescents displayed higher accuracy and longer initiation times than children, reflecting developmental improvements despite persistent gaps relative to hearing peers. Language development age did not alter the main effects. Findings indicate that reduced early auditory and language access may contribute to differences in planning development, highlighting the need for targeted executive functions support in educational and clinical settings for youth with hearing loss.

Purpose: Lower-limb prosthesis use involves interacting physical, psychosocial, and device-related outcomes that may not be fully captured by conventional clinical assessment. This study aimed to develop and evaluate a stakeholder-informed framework of outcome domains relevant to meaningful everyday prosthesis use. Materials and Methods: A mixed-methods participatory design comprised a structured synthesis of selected clinically relevant content from five established patient-reported outcome measures; semi-structured interviews and importance and actionability ratings with 18 contributors (12 prosthesis users, four clinicians, and two industrial partners); and integration of the synthesis, qualitative, and rating findings. Interview records were analysed using reflexive thematic analysis, and ratings were analysed descriptively. Results: The resulting framework comprised four interrelated domains: Mobility, Physical Function, Psychosocial Wellbeing, and Prosthesis Experience. Mobility showed the clearest convergence across stakeholder perspectives. Prosthesis users showed the largest importance actionability gap for Prosthesis Experience (4.5 vs 3.0), whereas clinicians showed the largest gap for Psychosocial Wellbeing (5.0 vs 3.0). Interviews highlighted day-to-day variability in prosthesis use and the influence of confidence, fatigue, comfort, environmental conditions, social context, and device usability. Conclusions: Meaningful outcome assessment in prosthetic rehabilitation should extend beyond mobility alone to consider physical function, psychosocial wellbeing, and prosthesis experience within everyday contexts. The proposed framework provides a stakeholder-informed foundation for multidimensional outcome assessment in prosthetic rehabilitation.

Impaired gait performance and stability is a key symptom often defining disease outcome in people with Multiple Sclerosis. Step-by-step foot placement control in response to variations in the center-of-mass kinematic state is a crucial gait stability mechanism, especially in the mediolateral direction. Even though it is known that people with Multiple Sclerosis are at an increased risk of falling, step-by-step foot placement control remains to be characterized in this population. Here, we explored characteristic foot placement control in ten people with early stage Multiple Sclerosis, compared to 21 controls walking at a similar average gait speed, during 1-minute steady-state treadmill walking. Kinematic data were analyzed using a linear feedback model that correlated foot placement with the center-of-mass kinematic state during the preceding swing phase. People with Multiple Sclerosis demonstrated step-by-step foot placement control in both the mediolateral and anteroposterior directions. No differences were found in foot placement precision between groups. However, foot placement responses to variations in center-of-mass velocity proved stronger in people with Multiple Sclerosis. Moreover, the contribution of mediolateral center-of-mass velocity feedback to the control mechanism was higher in people with Multiple Sclerosis as compared to neurologically healthy controls. Our results suggest that foot placement control is still retained in early clinically evident stages of Multiple Sclerosis, but is realized through differently weighted sensory feedback control.

A dental AI system and a dentist reading the same radiographs form a paired comparison. Published comparative studies often report the two arms separately against a reference standard, leaving the joint pattern of correctness between them unavailable for secondary paired inference. We show what that omission costs. The accuracy difference remains exactly identified; its sampling variance does not, so the report contains the estimate and not its uncertainty. On a study of 282 units, two published accuracies are consistent with 38 distinct joint tables whose confidence intervals differ in width by a factor of 2.5. The consequence is a three-zone decision map rather than a single threshold: differences at or below 1.06 points are non-significant under every compatible table, differences at or above 6.03 points are significant under every compatible table, and in between the published numbers cannot decide. We then show the omission is repairable at negligible cost. One additional integer, the number of units both arms classify correctly, identifies the joint table exactly and restores standard paired inference. For a panel of readers the pairwise dependences must arise from one joint distribution, a constraint that binds once three readers are present; publishing each reader's joint-correct count against a single reference reader cannot widen and may tighten every pairwise bound, and in a 7-arm experiment reduced them by a median of 37% even for pairs excluding that reference. Where the integer was never published we give DentalPair-Cert, an interval with finite-sample coverage uniformly over every admissible within-unit AI-dentist dependence under the independent-sampling-unit model, certified in both the nuisance maximization and the inversion. Across 4,200,000 simulated comparisons an independence analysis falls to 74.5% coverage with 12.2% type-I error; in a purposive sample of 9 recent comparative studies, 1 reported a paired test on discordant units.

Dopamine replacement therapy (DRT) alleviates motor symptoms in Parkinson's disease (PD) but can trigger hallucinations in a subset of patients, yet the neural basis of this selective vulnerability is unknown. Hallucinations are among the most disabling non-motor symptoms of PD, linked to social isolation, dementia and institutionalization. Using a validated robotic paradigm to induce and quantify hallucinations in real-time, combined with resting-state fMRI in a crossover On/Off DRT design, we studied patients with PD with (PD-H) and without (PD-nH) hallucinations. DRT selectively amplified sensitivity to robot-induced hallucinations in patients with pre-existing hallucinatory phenotype (PD-H, but not PD-nH) and was accompanied by cortico-striatal and large-scale network hyperconnectivity. Rather than supporting a uniform hallucinogenic effect of dopamine in PD, these findings indicate that DRT interacts with an intrinsic neural vulnerability that varies in patients. Prospective studies will establish whether this pharmacological-behavioural signature identifies patients at risk before clinical hallucinations emerge.

Background: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic risk factor for Parkinson's disease (PD). G2019S, the most common pathogenic variant, has been linked to milder motor symptoms, but the effects of other LRRK2 variants on disease trajectory remain incompletely characterized. R1441G, the second most common pathogenic variant, co-occurs with the PD risk variant M1646T on a shared haplotype. Whether this haplotype confers a distinct rate of motor progression has not been established. Methods: We analyzed up to 12 years of longitudinal data from 603 participants in the Parkinson's Progression Markers Initiative (PPMI) with PD and available whole-genome sequencing data: 394 sporadic PD, 169 G2019S carriers, 20 R1441G+M1646T carriers, and 20 M1646T carriers. Motor symptom progression (MDS-UPDRS III) was assessed using linear mixed-effects models with genotype-by-time interactions, adjusted for age at onset, disease duration at baseline, sex, race, baseline score, and levodopa equivalent daily dose. Results: R1441G+M1646T carriers exhibited 76% slower progression in OFF-state MDS-UPDRS III than sporadic PD (0.50 vs. 2.04 points/year; {beta}=-1.54 [95% CI: -2.48, -0.60]; p=0.001). G2019S carriers exhibited 26% slower progression (1.52 points/year; {beta}=-0.52 [-0.99, -0.06]; p=0.03). M1646T carriers did not differ from sporadic PD (p=0.60). Slower progression in R1441G+M1646T carriers was characterized by attenuated bradykinesia (64% slower; p=0.008), axial decline (76% slower; p=0.002), and a lack of orofacial symptom progression (p<0.001). R1441G+M1646T carriers also exhibited 55% slower self-reported motor decline (MDS-UPDRS II; p=0.04) Conclusions: R1441G+M1646T carriers exhibit substantially slower motor progression than sporadic PD while M1646T carriers do not.

Mood fluctuations in major depressive disorder are difficult to anticipate. The biological neural rhythms that organize mood dynamics over days to weeks remain unknown. In individuals implanted with a chronic neural sensing and stimulation device for treatment-resistant depression, we collected years-long intracranial neural recordings alongside daily mood ratings. Both mood and limbic neural activity fluctuated cyclically with multiday (multidien) periodicities of 2-34 days. An individual's daily phase position within mood cycles tracked depression severity, distinguishing whether symptoms were rising, peaking, or resolving. Neural rhythms led mood cycles and forecast an individual's mood trajectory up to 30 days in advance, outperforming models based on raw neural activity. Electrical stimulation reshaped these rhythms, shifting individuals away from the peak-depression phase of their multidien cycle. Our results identify multidien rhythms as an organizing principle of mood in depression and a forecastable, modifiable target for chronotherapeutic neuromodulation.

Introduction Hearing loss (HL) affects over 1{middle dot}5 billion people globally and India shares a disproportionately high burden including Disabling Hearing Loss (DHL). HL affects an Individual socio-economically, but there are limited studies on the broader societal economic consequences of HL in India.Methods Using Cost-of-Illness (COI) approach, we studied the societal economic burden of HL in India. This study uses epidemiological and macroeconomic data and modelling to estimate the loss of Gross National Income (GNI) due to HL and DHL across three economic pathways. Uncertainty is evaluated using deterministic and Probabilistic Sensitivity Analyses (PSA).Results The model estimates that there are in India, 289 million and 85{middle dot}9 million people with HL and DHL respectively. Direct Loss of GNI and Indirect Loss of GNI (Caregiver burden) are estimated as INR 4,648{middle dot}4 billion (USD 55{middle dot}6 billion) and INR 3,268 billion (USD 39 billion) respectively. The Loss of GNI due to Low Education amongst those with HL is estimated as INR 1,041{middle dot}9 billion (USD 12{middle dot}45 billion).Discussion Economic burden of HL is presented across three pathways with Direct Loss of GNI due to DHL being the greatest. It also presents age stratified caregiver economic burden. The findings of the study help in estimating similar cost pathways, advocacy, and policy decisions towards reducing HL prevalence in India and LMICs. This study also highlights the need for India specific estimations related to the HL attributable low education, state-wise disaggregates, and prevalence studies. Funding This study has not received any funding.

Background: The Centiloid (CL) scale standardizes global amyloid PET quantification and is widely used to define amyloid positivity. As a global summary measure, however, CL may not fully reflect the regional distribution of amyloid deposition, which can carry additional prognostic information about the rate of cognitive decline. Objective: To develop and externally validate a fixed, regional amyloid PET composite score that complements CL for predicting cognitive decline in Alzheimer's disease. Methods: The Regional Amyloid PET Score (RAPS) was derived from 82 FreeSurfer regions using machine learning with bootstrap stability selection to predict the rate of change in CDR-Sum of Boxes (CDR-SB) in 433 amyloid-positive ADNI [18F]florbetapir participants. The fixed nine-region weights were applied without retraining in a cross-tracer ADNI [18F]florbetaben subset (N = 71; largely overlapping the discovery participants) and two external validation cohorts, NACC SCAN (N = 1531; four tracers) and OASIS-3 (N = 428). Results: RAPS comprised nine regions. In ADNI, RAPS correlated more strongly with CDR-SB slope than CL and showed higher discrimination of rapid decliners (AUC 0.813 vs 0.713). Performance was directionally consistent across validation cohorts; in NACC SCAN, RAPS and CL independently predicted clinical progression. Cross-cohort meta-analysis of the three independent cohorts supported incremental discrimination beyond CL (pooled {Delta}AUC +0.066; I2 = 0%). Conclusions: RAPS, a fixed regional amyloid PET-derived score, may complement CL for prognostic stratification in Alzheimer's disease research.

Light reaching the retina is a primary regulator of human circadian physiology, acting largely through melanopsin-expressing retinal ganglion cells with peak short-wavelength sensitivity. Delivering known, repeatable retinal doses outside the laboratory is difficult because conventional light sources leave viewing geometry, gaze, and ambient conditions uncontrolled. Consumer extended-reality (XR) glasses fix a bright binocular display in constant geometry relative to the eye, but their suitability as calibrated photic stimulators has not been established. Here we validate a commercial micro-OLED XR display (VITURE Luma Ultra) for controlled retinal photostimulation. A purpose-built host application renders exact 8-bit RGB stimuli while independently controlling hardware brightness and logging all intensity-determining state; spectral radiance was measured at the retinal position of a 3D-printed phantom head with an open-source miniature spectroradiometer, anchored to absolute units by a luminance transfer calibration. The blue primary peaks at 461 nm (FWHM 43 nm), is spectrally invariant across a >10-fold intensity range, and at maximum output delivers an estimated 299 lx melanopic equivalent daylight illuminance, above consensus daytime recommendations, while remaining roughly two orders of magnitude below photobiological safety limits. The red primary is visually effective with minimal melanopic drive (melanopic DER 0.10), enabling spectrally shifted evening stimulation. Unlike the immersive virtual-reality headsets previously used for calibrated light delivery, the see-through form factor preserves the wearer's view of the surroundings--relevant for clinical monitoring in supervised settings such as the intensive care unit. These results show that consumer XR glasses can serve as a dose-calibrated platform for wearable photostimulation using an open-source measurement chain, and provide groundwork for application-layer dose-response studies.

Despite extensive knowledge of the progressive sequence of cognitive and functional deficits in Alzheimer's Disease (AD), the impact of neurodegeneration on the conscious experience of patients remains largely unexplored. Understanding how the content of consciousness, particularly perceptual awareness, changes with the progression of AD is crucial to enable meaningful person-centred care. This is especially important in severe AD when impairments in language and other cognitive domains mean people are unable to report their experiences. We investigated whether electrophysiological (EEG) and fMRI signatures of perceptual awareness described in healthy older people are present in people with mild-moderate and severe AD using two "no-report" paradigms. Firstly, a visual masking paradigm examined visual awareness negativity (VAN) and late positive (LP) electrophysiological responses and activation in visual cortex and fronto-parietal regions that are characteristically associated with conscious perception of faces; and second, a complex audio-visual (movie) task examined activation in fronto-parietal networks previously associated with perceptual awareness. In healthy older controls we found cortical responses characteristic of awareness in both EEG and fMRI modalities, with VAN and LP markers and widespread occipital, fusiform face area and fronto-parietal activation. In people with mild-moderate AD, there were significant reductions in VAN and LP markers and reduced fronto-parietal activation. In participants with severe AD, who were behaviourally minimally responsive, there was only limited evidence of presence of frontoparietal markers of perceptual awareness, however this may reflect attentional and task insensitivity in people with advanced dementia. These results demonstrate that the brain mechanisms associated with perceptual awareness become increasingly impaired with progression of AD. Specifically, involvement of frontoparietal networks is reduced in AD, which may reflect reduced higher-level awareness. This suggests AD should be considered a disorder of consciousness and should motivate further investigation into the dimensions of awareness affected by the disorder with implications for treatment and management of people with dementia.

Background: Hippocampal sclerosis (HS) is a common cause of drug-resistant focal epilepsy (DRFE) and amenable to neurosurgical treatment. Detection relies on MRI but can be challenging. 7 Tesla (T) ultra-high field MRI and automated MRI post-processing tools have independently been shown to improve radiological diagnosis of HS. However, combining these approaches remains underexplored. This study evaluated whether AID-HS, a tool for HS detection developed using 3T MRI, generalises to 7T MRI data. Methods: We collated a dataset of paired 3T and 7T T1-weighted MRI from four epilepsy centres, including 23 patients with HS, 39 healthy controls, and 23 individuals with focal cortical dysplasia as disease controls. Histopathology served as the gold standard for defining HS where available (n=7), otherwise radiological findings (n=16). AID-HS was applied to images acquired at both field strengths, and sensitivity and specificity for detection and lateralisation of HS were compared. Additionally, agreement of hippocampal features across 3T and 7T was evaluated. Results: We found no evidence of a difference in performance of AID-HS between 3T and 7T. Sensitivity for detection of unilateral HS was 63% (12/19) at 3T and 68% (13/19) at 7T (McNemar's exact test p=1.0). Specificity in controls was 97% (60/62) at 3T and 100% (62/62) at 7T (p=0.5). Bilateral HS was correctly flagged in 3 of 4 cases using feature-based criteria, with high specificity in controls. Quantitative hippocampal features showed moderate to good agreement across field strengths (ICC 0.70 to 0.98), with small differences observed for volume and thickness estimates. Conclusion: AID-HS provides robust detection and lateralisation of HS across multiple 7T MRI centres, highlighting its potential to enhance lesion detection. Future work is needed to investigate whether models trained on 7T data can leverage the improved image quality for further gains in HS detection performance.

Introduction: Continuous glucose monitoring (CGM) offers an advancement over traditional self-monitoring of blood glucose (SMBG) for people living with type 1 diabetes (T1D). However, evidence on the acceptability and feasibility of different CGM use cases in African populations remains limited. Methods: This was a pragmatic three-arm, randomised controlled trial on CGM conducted among people living with T1D in three public healthcare clinics in South Africa. Participants were assigned to Arm 1 (continuous CGM), Arm 2 (periodic CGM), or Arm 3 (SMBG). Diabetes education was provided at all study visits. Feasibility was assessed by adherence to CGM use and through the Glucose Monitoring Satisfaction Survey (GMSS). Diabetes distress was measured by the Diabetes Distress Scale (DDS), health-related quality of life (HRQoL) by the EQ-5D scales, and acceptability using the Theoretical Framework of Acceptability (TFA). Surveys were collected on paper and transferred to OpenClinica. Analyses were performed in R. The trial was registered in the Clinical Trials Registry (NCT05944718) on July 13, 2023. Results: A total of 83 participants were included in Arm 1, 85 in Arm 2, and 80 in Arm 3. CGM mean active time was 55% in Arm 1 versus 69% in Arm 2. The proportion of participants meeting the [&ge;]70% active time threshold was higher in Arm 2 (52%) than in Arm 1 (34%). Diabetes' distress declined across arms during the intervention period, with no significant difference between arms; distress increased slightly six months post-intervention but remained below baseline. At 6 months, glucose monitoring satisfaction was significantly higher in both CGM arms than in the SMBG arm, and satisfaction increased over time in CGM arms. Health-related quality of life remained stable across arms during the intervention period with no significant difference between arms. High acceptability was observed in both CGM arms, with higher ratings in the periodic arm. Conclusions: CGM was acceptable to people living with type 1 diabetes and feasible to use in public-sector clinics in South Africa, with high acceptability under continuous and periodic use. Health-related quality of life remained stable across arms, and diabetes-related distress declined, during the intervention period, across arms. Glucose monitoring satisfaction rose significantly in both CGM arms compared to SMBG. Periodic CGM might be a promising and potentially more scalable option than continuous use for public-sector care.

Objective: Published P300-speller fusion schemes fix prior trust regardless of trial reliability; we tested whether a reliability estimate improves on it. Methods: We reanalyzed 3,373 archived P300-speller selections from 47 people with ALS (BigP3BCI). A fair, matched-search-space comparison, tuning both a fixed weight and an adaptive policy out-of-fold, was evaluated across 22 evaluable language-model priors up to 46.7B parameters. Two representative priors, GPT-2 and a classical 5-gram, additionally received detailed naive and mechanistic analyses. Results: No prior's 95% CI favored adaptive fusion under the fair comparison, despite unexploited oracle headroom at every scale. Under GPT-2, the naive comparison was significantly worse for adaptive fusion; both anchors converged to a degenerate or near-degenerate fair-comparison solution. For the representative anchors, three further controllers failed to convert that headroom into benefit; the fixed-fused posterior's output probability outperformed the best controller for flagging errors (2.8- to 3.8-fold enrichment). Conclusion: A tuned fixed weight is a difficult-to-beat default across the tested scale range; reliability estimation gave no deployable adaptive advantage. Significance: Adaptive weighting should be validated against a fairly tuned baseline across model families and scales; in this dataset, the fused output's confidence identified high-risk selections better than the tested purpose-built ranker.

Integrating multisensory and behavioral information is essential for sensory perception. In the auditory system, multisensory and behavioral influences emerge early in subcortical structures. Descending projections from non-auditory cortical areas are well positioned to convey such signals, yet how they shape subcortical auditory processing remains poorly understood. Here, we investigated corticocollicular projections from the primary somatosensory (S1) and motor (M1) cortices to the inferior colliculus (IC), a principal integration center in the auditory midbrain. We found that trunk- and limb-related regions of S1 and M1 form prominent monosynaptic projections to the IC, and that optogenetic activation of these projections robustly drives IC activity. Notably, a substantial population of cortical-responsive neurons did not respond to sound. In sound-responsive neurons, concurrent cortical stimulation enhanced sound-evoked responses, whereas cortical activation preceding sound onset suppressed them. Furthermore, both cortical-responsive IC neurons and deep-layer S1 and M1 neurons exhibited locomotion-related modulation and anticipatory activity prior to movement onset, suggesting that these descending pathways convey movement-related signals to the IC. Together, our findings identify a descending sensorimotor circuit that integrates body- and movement-related information with auditory processing in the auditory midbrain.