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Annals of the New York Academy of Sciences

Wiley

Preprints posted in the last 30 days, ranked by how well they match Annals of the New York Academy of Sciences's content profile, based on 12 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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Exploring Auditory Biofeedback Paradigms for Gait Training in Children with Cerebral Palsy: A User-Centered Design Study

Kantan, P. R.; Hansen, M. B.; Foldager, J. J.; Fjeldgaard, F. S.; Dahl, S.; Spaich, E. G.

2026-05-29 rehabilitation medicine and physical therapy 10.64898/2026.05.29.26353852 medRxiv
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Purpose: To identify, through iterative user-centered design, the auditory biofeedback requirements and sound preferences supporting gait training in children with cerebral palsy (CP), and to determine which feedback variables, sound mappings, and sound types yield clinically viable and movement-interpretable paradigms. Methods: The iterative process spanned two prototype phases. Prototype A comprised seven paradigms demonstrated to two experienced physiotherapists (Workshop 1A). Two of these were subsequently discarded owing to poor sound-movement interpretability and two were modified. Six paradigms were added to Prototype B, demonstrated to four children, five parents, and one therapist (Workshop 1B) and two therapists (Workshop 2B). Data were analyzed using systematic text condensation. Results: Within-child sound preferences varied with energy level and sensory state on a given day. Sound-movement interpretability tended to suffer for paradigms with greater acoustic complexity (e.g. computer-generated music). Therapists endorsed a repertoire spanning both movement quality and movement quantity targets. Participants independently proposed paradigms rewarding restrained and controlled movement, a feedback category absent from the current prototype. Conclusions: Session-level calibration is preferable to fixed sound profiles, requiring real-time interface support for paradigm adjustment. Acoustic complexity must remain subordinate to movement-sound interpretability. Paradigms targeting movement restraint are a development priority unaddressed in the literature.

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Modulating supplementary motor area excitability enhances groove-related pleasure during music listening

Etani, T.; Takemi, M.; Samma, T.; Nitta, J.; Homma, S.; Ueda, K.; Yoshida, K.; Hayashida, K.; Fujimaki, T.; Kondoh, S.; Kudo, K.; Fujii, S.

2026-05-11 neuroscience 10.64898/2026.05.09.722456 medRxiv
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Pleasurable urge to move to music is often referred to as groove. Although previous studies have shown an association between the supplementary motor area (SMA) and the groove experience, its causal role remains unclear. Here, we investigated whether the SMA is causally involved in groove experience during music listening using repetitive transcranial magnetic stimulation. Fifteen healthy participants completed three sessions on separate days: excitatory stimulation (intermittent theta burst stimulation; iTBS) over the SMA, inhibitory stimulation (continuous theta burst stimulation; cTBS) over the SMA, and sham stimulation (iTBS or cTBS) over the vertex. After each stimulation session, participants listened to five high-groove and five low-groove musical excerpts and rated urge-to-move and pleasure on a 0-100 scale. Heart rate was additionally recorded as an exploratory physiological measure during music listening. Linear mixed-effects models (LMM) showed that pleasure ratings, but not urge-to-move ratings, were higher following both iTBS and cTBS compared with sham stimulation. In exploratory LMMs, reduced log-transformed heart rate variability (HRV) significantly predicted higher pleasure ratings. These findings suggest that SMA stimulation modulates the pleasurable component of the groove experience, likely via network-level mechanisms rather than a simple linear relationship between SMA excitability and pleasure. They also raise the possibility that reduced parasympathetic activity, reflected by lower HRV, mediates the stimulation-related increase in musical pleasure. Future studies should investigate the causal roles of other brain regions as well as clarify the directionality between autonomic changes and the groove experience.

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Greater gray matter volume in somatosensory and parietal regions in elite skiers compared with other athletes

Nakagawa, K.; Kanosue, K.

2026-05-13 neuroscience 10.64898/2026.05.10.724084 medRxiv
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Elite athletes exhibit sport-specific neural adaptations, yet it remains unclear whether such changes reflect general effects of training or the unique demands of individual sports. Skiing requires postural control and whole-body coordination under dynamically unstable environments, placing high demands on somatosensory processing and sensorimotor integration. The present study aimed to identify structural brain characteristics specific to elite skiers by comparing them with athletes from other sports disciplines and non-athletes. T1-weighted MRI data were analyzed using voxel-based morphometry in 13 skiers, 23 non-ski control athletes and 25 non-athletes. Whole-brain analysis comparing skiers with non-ski athletes revealed a significant cluster showing greater gray matter volume in skiers compared with non-ski athletes in the left postcentral gyrus, extending into the superior parietal lobule. The identified cluster primarily encompassed cytoarchitectonic Areas 2 and 5L. These regions are involved in higher-order somatosensory processing and multisensory integration. Importantly, region-of-interest analysis demonstrated that gray matter volume within this cluster was greater in skiers compared with non-ski athletes and non-athletes, with no difference between non-ski athletes and non-athletes. These findings highlight the relative prominence of structural adaptations within somatosensory-parietal networks, reflecting the unique integration of proprioceptive and other sensory information required for elite skiing. Overall, these findings provide evidence for sport-specific structural brain differences in elite athletes and highlight the importance of somatosensory and parietal regions in sensorimotor integration relevant to skiing. These findings may have implications for understanding neural markers of expertise and may inform future approaches to training and performance evaluation in skiing.

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Characterizing reward sensitivity to natural singing: an individual differences approach

Segura, E.; Lorenzo-Seva, U.; Zatorre, R.; Kleber, B. A.; Rodriguez-Fornells, A.

2026-05-07 neuroscience 10.64898/2026.05.04.722621 medRxiv
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Singing is an innate human behaviour present across cultures and the lifespan. Despite lacking direct biological advantages, its ubiquity suggests that it is intrinsically rewarding. This research aimed to investigate the underlying factors that explain variability in sensitivity to deriving reward and enjoyment from natural singing in the general population. In Study 1 (n = 606), an initial pool of items describing daily, non-professional singing behaviours were administered to an international adult sample. Exploratory factor analysis revealed a unidimensional structure of 20 items with acceptable model fit, organized into five facets representing distinct domains of singing-related rewards: 1) pleasure and emotional evocation, 2) social singing reward, 3) singing frequency, 4) mood regulation through singing, and 5) inattentional singing during routine tasks. In Study 2 (n = 430), confirmatory factor analysis in a new sample supported this structure. When both samples were combined (n = 1036), the unidimensional model defined by these five facets showed acceptable to excellent goodness-of-fit indices, supporting the conceptualization of singing reward as a multidimensional construct with differentiated facets. This led to the Barcelona-Aarhus Natural Singing Engagement Questionnaire (BANSEQ), which demonstrated excellent reliability ( = .94) and population-level stability. Study 3 (n = 1036) tested the convergent validity of BANSEQ with measures of music reward and engagement and identified sociodemographic and psychological correlates across the five facets of singing reward. Overall, these findings characterize the sources of individual differences in the hedonic experience of natural singing and propose BANSEQ as a robust psychometric tool for its assessment in the general population.

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Remote Cognitive-Motor Training Combining Mental and Physical Practice for Freezing of Gait in Parkinson Disease: a Randomized Controlled Trial

Silva, P. R. d.; Honda, k. Y. T.; Santos, L. B. R. d.; Garcia, J. M.; Silva, B. H. T. d.; Aranha, L. d. M.; Piemonte, M. E. P.

2026-05-10 rehabilitation medicine and physical therapy 10.64898/2026.05.07.26352678 medRxiv
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BACKGROUNDFreezing of gait (FOG) is a disabling feature of Parkinsons disease (PD). Although physical practice (PP) improves gait, maintaining gains remains challenging. Mental practice (MP), including Dynamic Neuro-Cognitive Imagery (DNI), may enhance gait control, but evidence on remote combined interventions is limited. PURPOSETo investigate whether adding MP grounded in DNI principles to remote physical practice supports greater and more sustained improvements than remote physical practice alone in people with PD and FOG. METHODSA prospective, single-blind, parallel-group randomized controlled trial was conducted. Forty-three participants with idiopathic PD and FOG were randomized to an experimental group (EG, n = 20) or control group (CG, n = 23), stratified by cognitive performance. Both groups received 10 remote sessions over 6 weeks. All performed structured physical practice targeting gait components; the EG additionally performed MP based on DNI, while the CG performed time-matched seated stretching. Assessments were conducted at baseline (BI), post-intervention (AI), and 30-day follow-up (FU). The primary outcome was Rapid Turns Test performance; secondary outcomes included FOG severity, motor aspects of daily living, mobility-related quality of life, and global cognition. RESULTSAll randomized participants were included in intention-to-treat analyses; 38 completed all assessments. Significant group x time interactions were found for Rapid Turns Test duration (p = 0.0019) and FOG time (p = 0.0108). Both groups improved short-term, but only the EG maintained gains at follow-up. Additional interactions favored the EG for mobility-related quality of life (p = 0.001) and global cognition (p = 0.0018). Self-reported FOG improved over time in both groups (p < 0.001) without between-group differences, while motor aspects of daily living showed a time effect only (p = 0.001). CONCLUSIONMP based on DNI principles may enhance retention of gains when combined with remote physical practice, supporting its use as an adjunct in FOG rehabilitation. Trial registrationThis trial is registered at ClinicalTrials.gov with trial registration number NCT06957405 (registered on April 25, 2025). Protocol and statistical analysis planThe full trial protocol and statistical analysis plan are available upon request from the corresponding author. Data sharingThe datasets generated, used and analyzed during the trial are or will be available from the corresponding author upon reasonable request. Funding and conflicts of interestThis article was produced as part of the activities of FAPESP Research, Innovation and Dissemination Center for Neuromathematics (grant #2013/07699-0, Sao Paulo Research Foundation). Co-author PRS received individual support from FAPESP (grant number 2025/14403-7). The authors declare no conflict of interest.

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Disability, Fatigue, and Mental Health in Acute versus Chronic Spinal Pain Patients in the Gaza Strip: A Comparative Cross-Sectional Study

Salama, M.; Najim, A.; Shabana, M.; Almukbel, R.; Mokbel, K.

2026-05-15 rehabilitation medicine and physical therapy 10.64898/2026.05.12.26353046 medRxiv
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Background: Spinal pain, including neck pain and low back pain (LBP), is a common musculoskeletal condition and major contributor to disability worldwide. Evidence comparing disability, fatigue and mental health across acute and chronic stages remains limited, particularly in conflict-affected and low-resource settings. This study assessed these outcomes among patients with acute and chronic neck pain and LBP in the Gaza Strip. Methods: A comparative cross-sectional study was conducted among 410 adults attending outpatient physical therapy at Nasser Medical Complex, Khan Younis, Gaza Strip. Participants included 204 with neck pain and 206 with LBP, classified as acute neck pain (n=101), chronic neck pain (n=103), acute LBP (n=102) and chronic LBP (n=104). Disability, fatigue, psychological distress and sleep disturbance were assessed using the Neck Disability Index (NDI)/Oswestry Disability Index (ODI), Fatigue Severity Scale (FSS), Patient Health Questionnaire-4 (PHQ-4) and PROMIS Sleep Disturbance Short Form 8a. Independent t-tests, adjusted linear regression, correlation analyses, clinical-threshold analyses and binary logistic regression were performed. Results: Chronic neck pain and chronic LBP were associated with significantly higher disability, fatigue and psychological distress than acute pain. Chronic neck pain patients had higher NDI, FSS and PHQ-4 scores than acute neck pain patients; chronic LBP patients had higher ODI, FSS and PHQ-4 scores than acute LBP patients (all p<0.001). Sleep disturbance did not differ significantly between groups. Female participants reported higher psychological distress in both pain groups, with higher fatigue in neck pain and higher disability in LBP. Adjusted analyses confirmed that chronic pain status remained associated with higher disability, fatigue and psychological distress. Fatigue was the most consistent factor independently associated with chronic pain status. Conclusions: Chronic spinal pain was associated with greater disability, fatigue and psychological distress than acute spinal pain, while sleep disturbance was common across groups. These findings support early multidimensional assessment, including screening for fatigue and psychological distress. Longitudinal studies are needed to clarify whether these factors contribute to transition from acute to chronic spinal pain.

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How do we align in good conversation? Investigating the link between interaction quality and multimodal interpersonal coordination

Dominguez-Arriola, M. E.; Lam, P. C. H.; Perez, A.; Pell, M. D.

2026-05-11 neuroscience 10.64898/2026.05.09.723997 medRxiv
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Conversations can feel effortlessly engaging or, conversely, difficult and unrewarding. Multiple factors contribute to the experienced quality and outcomes of a conversation, among them how interlocutors align with each other. The present study investigated speech-to-speech, brain-to-speech, and brain-to-brain coordination as markers of interpersonal alignment, examining their relationship with jointly perceived interaction quality and mutual affinity between conversational partners. Pairs of previously unacquainted participants (dyads) engaged in multiple short, free-form conversations on topics of varying interest while their vocal and neural activity were simultaneously recorded in a dual-EEG ("hyperscanning") setup. We analyzed interlocutors prosodic adaptation, neural speech tracking, and neural coordination during each conversation. At the speech-to-speech level, our findings reveal that partners with more positive mutual impressions became more similar in their volume and voice quality over the course of the experiment session, reflecting greater prosodic convergence. At the brain-to-speech level, we found no reliable effect of interaction quality on neural tracking of unfolding speech within any individual region, although topographical differences suggested relative modulation across scalp sites. Finally, at the brain-to-brain level, our findings show that higher perceived interaction quality enhanced inter-brain relationships across frequency bands (alpha and theta) and temporal dependencies (concurrent/near-instantaneous and recurrent/listener-lagging), with the strongest effects observed for concurrent alpha-band coupling. These findings suggest that distinct coordination processes are involved in how interlocutors experience an interaction and how they establish relational affinity, casting new light into the mechanisms that make a conversation worthwhile.

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Meditation Styles Are Highly Discriminable from EEG at the Subject Level With Limited Generalization Across the Population: A Machine-Learning Study

Hayat, S.; Goretti, F.; Fabbri, R.; Noferini, C.; Cravero, E.; Mori, P.; Scaglione, A.; Pavone, F. S.

2026-05-19 neuroscience 10.64898/2026.05.15.725404 medRxiv
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Meditation has been associated with improvements in attention, emotional regulation, and mental well-being, motivating increasing interest in objective methods for assessing meditative states. In this study, we investigate whether EEG-based machine learning can reliably distinguish between multiple meditation styles and mind-wandering states. EEG data were recorded from experienced meditators performing three meditation styles, Shamatha, Vipassana, and Metta, together with an eyes-closed mind-wandering condition. EEG signals were preprocessed to remove artifacts, and features were extracted from frequency, time-frequency, and time domains. Classification was evaluated using both intra-subject and inter-subject strategies with multiple machine learning classifiers. Results demonstrate high intra-subject classification accuracy across meditation-versus-mind-wandering and meditation-style comparisons, indicating strongly discriminative subject-specific neural signatures. In contrast, inter-subject performance decreased substantially, particularly for distinguishing meditation styles, suggesting considerable inter-individual variability in meditation-related EEG patterns. Furthermore, temporal analysis revealed that classification performance increase over time, indicating that the neural distinctions between meditation states become increasingly pronounced over time. Additionally, t-SNE visualization showed clear within-subject clustering but increased overlap across subjects, explaining the reduced inter-subject generalization. Overall, these findings highlight the potential of EEG-based machine learning for personalized assessment and monitoring of meditative states while emphasizing the challenges of developing subject-independent meditation classification systems.

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Investigating the Usability, Feasibility, and Effect of a Virtual Reality Cognitive Training System on Brain Cancer Patients with Mild Cognitive Impairment: A Quasi-Experimental (Single-Arm) Pilot Study

Faiola, A.; Villano, J. L.; Soroya, S. H.

2026-05-19 neurology 10.64898/2026.05.18.26353031 medRxiv
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(1) Background: Brain cancer is the ninth leading cause of cancer death in the US, with approximately 76,000 newly diagnosed cases annually. Studies show that at time of diagnosis, up to six-months post-treatment, 50%-80% of brain cancer survivors (BCS) report cognitive dysfunction. Mild cognitive impairment (MCI) has gained increasing attention as a persistent disability experienced by up to 75% of all BCS, which affects memory, concentration, executive function, etc. Studies show cognitive training with computerized gaming as improving cognitive function for patients with stroke, dementia, and Parkinsons. It is of significant clinical interest to develop innovative interventions that reduce MCI. Aim: To improve cognitive performance of BCS suffering with MCI by evaluating the feasibility, acceptability and effect of a Virtual Reality Cognitive Rehabilitation Training (VR-CRT) platform during four weeks of cognitive training. (2) Methods: We employed a quasi-experimental pretest/posttest non-randomized/non-blinded single-arm design for 4 weeks, with an experimental group (n=6, after attrition) using VR-CRT. Participants were selected based on convenience sampling using the electronic medical record to identify qualified patients, guided by inclusion/exclusion criteria. Feasibility was defined by retention as >80%, with usability testing using the System Usability Scale (SUS) and NASA-TLX surveys. The Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) test, and Trail Making A-B (TM-A/B) test were used to measure cognitive performance, comparing baseline to post week-four. (3) Results: The feasibility criteria of >80% was met. All SUS and NASA scores were in the higher index, suggesting a high degree of usability, with low workload demand. For effect, the COWA findings showed a significant improvement (41.38%), with a paired sample T-Test confirming that the participants COWA scores improved significantly from pre- to post-intervention (p = 0.03), indicating enhanced verbal fluency and executive functioning after intervention. HVLT (combined) showed improvements of 18.75% for Form A and 11.32% for Form B, which also showed a significant improvement (p = .04) in the retention discrimination index from pre- to post-test. The TM-A/B test showed an improvement (25.97%), suggesting that the participants spent less time completing both parts A and B, but was not statistically significant. (4) Conclusion: This study fulfilled our aim to demonstrate modest to significant cognitive improvement using VR-CRT with brain cancer patients with MCI. Despite the small sample size, we believe the use of virtual reality will lead to important advances for patients with MCI, particularly the frontal lobe brain region, expressed in executive function.

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Overground suspension walkers elicit more and higher quality stepping than treadmills: A longitudinal study of pre-walking infants with Down syndrome

Hospodar, C. M.; Enriques, F. A.; Paez, A. I.; Feldner, H. A.; Looper, J. E.; Kretch, K. S.

2026-05-12 rehabilitation medicine and physical therapy 10.64898/2026.05.05.26352150 medRxiv
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ImportanceChildren with Down syndrome (DS), a genetic condition associated with neuromotor impairments, walk [~]1 year later than typically developing peers. Treadmill training is the most successful known intervention for accelerating walking onset in DS. Overground stepping with mobility devices better mimics critical properties of real-world walking, but it is unknown how overground stepping develops in pre-walking infants with DS. ObjectiveWe aimed to characterize the developmental trajectory of stepping quantity and quality in supported overground stepping compared to supported treadmill stepping. We also measured infants ability to self-propel in the walker. Finally, we assessed caregivers perspectives on both devices. DesignWe tested infants at 10, 13, 16, and/or 19 months of age. SettingThis study occurred in a university laboratory in the United States. ParticipantsWe tested 31 pre-walking infants with Down syndrome across 69 sessions. ExposureAt each session, infants completed four trials per task (treadmill and walker) and a test of self-propulsion in the walker. Main Outcomes and MeasuresWe measured step quantity (overall step rate and alternating step rate), step quality (percentage of steps that were alternating, forward, and flat-landing), the ability to self-propel the walker, and caregiver perspectives on both devices. ResultsStep quantity increased with age and varied by task--infants took more steps per minute in the walker compared to the treadmill. Moreover, steps were of equal or higher quality in the walker. By 16 months, about half of infants could self-propel. Caregivers viewed both devices favorably, though the majority preferred the walker for home and/or community use. ConclusionsOverground walkers promote more stepping than a treadmill in pre-walking infants with DS, with stepping of similar or higher quality. Caregivers feel positively about overground walkers. RelevanceOverground stepping using a suspension walker shows promise as an intervention for pre-walking infants with Down syndrome.

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Reliability and Concurrent Validity of a Computer Vision-Based Tool for Quantitative Finger Movement Analysis

Maharshi, A.; Ladha, B.; Malani, R.; Palaskar, P.

2026-06-01 rehabilitation medicine and physical therapy 10.64898/2026.05.21.26353446 medRxiv
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Background: Accurate evaluation of fine motor abilities is a key aspect of neurological rehabilitation. However, conventional approaches like goniometry are limited by variations among raters and their difficulty in detecting active movement. On the other hand, computer vision-based software delivers non-invasive and quantitative analysis of hand movements. An innovative computer-vision-based software tool, F.A.I.R. Chance(C), was developed to track and analyze individual finger joint movements on a camera-equipped laptop and give real-time numerical feedback. However, its metrics require validation in a healthy population before the tool can be used for clinical purposes. Objective: To assess the reliability and validity of finger movement assessment by the F.A.I.R. Chance computer vision-based tool in healthy adult participants. Methods: An observational cross-sectional study was done at MGM School of Physiotherapy, comprising 30 healthy participants between 18 and 60 years of age. Finger movements like flexion, extension, abduction, and adduction were measured with a standard handheld goniometer. These same finger movements were then measured with the tool at two time points separated by a 30-minute interval to determine the test-retest reliability. The tool's measurements were compared with the goniometric measurements to determine its concurrent validity. Test retest reliability was checked by the Intra-class Correlation Coefficient ICC (2,1), while concurrent validity was tested through Pearson's correlation coefficients. Results: Metacarpophalangeal and proximal interphalangeal joint motions demonstrated moderate to good test-retest reliability (ICC: 0.716-0.953) for the F.A.I.R. Chance tool. However, distal interphalangeal joint movements had lower consistency. Good reliability (ICC: 0.754-0.908) was seen for movements of abduction and adduction in the fingers. Strong concurrent validity for extension movements of the metacarpophalangeal joints (r=0.760-0.914) and moderate concurrent validity for flexion movements of the metacarpophalangeal joints (r=0.427-0.604) was demonstrated for all fingers for the F.A.I.R. Chance tool. Concurrent validity for adduction and abduction movements demonstrated a low to fair correlation with goniometric measurements (r=0.210-0.440). This is consistent with previous research showing poor agreement between goniometry and adduction-abduction movements of the fingers. Conclusion: The F.A.I.R. Chance tool shows good reliability and acceptable concurrent validity to assess fine motor movements in the healthy adult population. This sets a basis for further clinical study of the tool in the target population with fine motor impairments. Keywords: artificial intelligence; assistive technology; computer vision; fine motor evaluation; hand function;

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microRNA expression during early development in the coral Acropora digitifera

Grinblat, M.; Fridrich, A.; Cooke, I.; Moran, Y.; Huerlimann, R.; Brunner, R.; Andrade, N.; Ueda, N.; Ball, E.; Miller, D. J.

2026-05-13 developmental biology 10.64898/2026.05.09.724056 medRxiv
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Acropora spp. are the dominant reef-builders of the Indo-Pacific but are also amongst the most stress-sensitive corals. For these reasons, Acropora spp. have become the most studied of corals, two species (A. digitifera and A. millepora) often essentially serving as the basis for understanding molecular responses and processes across the sub-order Refertina and corals in general. The early development of these species has been well-characterised in terms of morphology and gene expression but as yet we have a limited understanding of how transcription is regulated during development. In "higher" animals (bilaterians) microRNAs (miRNAs) are critical regulators of gene expression but until now their involvement in coral development has not been investigated. Building on the existing developmental data for Acropora spp., we catalogued microRNAs (miRNAs) expressed during the early development of Acropora digitifera and profiled their expression in 21 stages from unfertilised eggs to 24h after treatment with a natural settlement cue (CCA chips). 157 miRNAs were recognised, many of which ([~]60%) were novel. These fell into three distinct groups, corresponding to three distinct developmental phases: (1) those present in eggs through to gastrulation (2) a larvally expressed group and (3) those expressed following settlement induction. Exposure of competent larvae to a natural settlement inducer resulted in major changes in the miRNA profile within 10 minutes, indicating that miRNAs may be particularly important in mediating the larva/polyp transition but are also likely to play important regulatory roles throughout early coral development in addition to possible roles in disease resistance.

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Spatiotemporal dynamics of flow experience: an EEG microstate analysis

Khoshnoud, S.; Alvarez Igarzabal, F.; Wittmann, M.

2026-05-14 neuroscience 10.64898/2026.05.11.724329 medRxiv
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Flow, as defined by Mihalyi Csikszentmihalyi (1975), is a holistic sensation experienced when individuals are fully immersed in an activity, resulting in a mental state characterized by a diminished sense of self and altered perception of time. To investigate the global neural dynamics underlying flow, we employed EEG microstate analysis to capture the spatial and temporal properties of dominant transient global brain states (Lehmann et al., 1998). In a study involving 43 participants playing the video game Thumper for 25 minutes, we extracted three four-minute EEG segments from each session corresponding to reported experiences of flow, boredom, and frustration, as determined by self-reports and performance metrics. Across conditions, six distinct microstate topographies (A-F) accounted for most of the global variance. Given that reduced self-referential processing is a key feature of flow, we hypothesized that flow would modulate the properties of microstates C and E, which have been associated with brain regions resembling the default mode network (DMN). Compared to boredom and frustration, the flow condition showed significantly decreased global explained variance, mean duration, time coverage, and occurrence frequency of microstate E, as well as reduced mean duration and time coverage of microstate C. These findings suggest that microstates associated with self-referential processing are shorter and less frequent during flow than during boredom and frustration. This supports the notion that the flow experience modulates global brain dynamics, particularly within the DMN. Furthermore, our results align with previous research reporting reduced DMN activity during meditative and psychedelic states, reinforcing the idea of diminished self-awareness in such conditions.

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How sensory load shapes the neural processing and perception of visual durations

Bellotti, F. I.; Zanon, M.; Bueti, D.

2026-05-12 neuroscience 10.64898/2026.05.08.723690 medRxiv
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The sensory content and temporal structure of stimuli have been shown to consistently bias duration perception. Temporal intervals filled with continuous sensory input ("filled intervals"), are often perceived as lasting longer than intervals marked only by their onset and offset ("empty intervals"). Despite this robust behavioral finding, it remains unclear whether filled and empty intervals rely on similar or distinct neural mechanisms and, more generally, how sensory format shapes the neural processing of millisecond time. To address this question, we asked twenty-one healthy participants to reproduce visual durations across different stimulus configurations while high-density scalp EEG was recorded. Behavioral results revealed differences in performance across stimulus configurations. Event-related potentials (ERPs) recorded at occipito-parietal and fronto-central electrodes between 0.1 and 0.4 s after duration offset were modulated in amplitude by both stimulus duration and format. These modulations scaled with the sensory load of the stimulus and its duration, suggesting a common underlying mechanism. A Representational Similarity Analysis (RSA) of the ERP data showed that perceived time was represented more strongly than physical time particularly at occipito-parietal electrodes, but only within the 0.2-0.3 s post-offset window, where stimulus format exerted a pronounced effect on the ERP signal. These findings highlight the role of sensory processing in shaping duration perception and its neural coding, and reveal an early neural signature of perceived time in occipito-parietal electrodes. 1 Significance statementOur perception of subsecond durations is distorted by the sensory content of stimuli. Here, we investigated how stimulus configuration shapes the neural correlates of visual duration perception. Specifically, we asked whether temporal intervals filled with continuous sensory input are processed differently from those lacking such content. We found that, between 0.2 and 0.3 s after interval offset, ERP amplitudes were modulated by stimulus content, and in this same temporal window the EEG signal reflected the perceptual bias. These findings support the view that duration processing and perception are deeply rooted in sensory processing.

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Advancing brain health equity after traumatic brain injury: A multi-stakeholder global priority-setting study

Mollayeva, T.; SantAna, T. T.; Shaikh, U.; Spouge, R.; Hanafy, S.; Fuller-Thomson, E.; McDonald, M.; Colantonio, A.; Cee, D.; McGettrick, G.; Lawlor, B.

2026-05-27 neurology 10.64898/2026.05.19.26353566 medRxiv
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The impact of social parameters on brain health among people with traumatic brain injury (TBI) has been extensively documented. However, translation of this evidence into policy and clinical practice remains limited. This may reflect a lack of coordinated and equity-driven approaches to brain health that integrate diverse stakeholder perspectives, limiting progress toward equity-oriented research and service delivery models. We conducted a convergent parallel mixed-methods study guided by the REporting guideline for PRIority SEtting of health research (REPRISE). We utilized the PROGRESS-Plus framework (Place of residence, Race/ethnicity, Occupation, Gender/sex, Religion, Education, Socioeconomic status, Social capital, and context-specific parameters) to ensure systematic consideration of social parameters in the study. For Objective 1, we synthesized existing evidence on social parameters and brain health outcomes. For Objective 2, we surveyed people with lived experience of TBI, family members/friends, clinicians, researchers, and community leaders across the globe to assess their prioritization of social parameters relevant to brain health. For Objective 3, we integrated evidence synthesis and stakeholder input through a structured Round Robin consensus activity to prioritize actionable areas for feasibility and impact. The activity culminated in the development of a knowledge mobilization agenda designed to inform equity-centred policy, research, and clinical practice. In Objective 1, we identified 59 publications with evidence on the effect of PROGRESS-Plus parameters on brain health outcomes following TBI. Meta-research highlighted that education, age, and country-level indicators are prognostic for brain health after TBI. In Objective 2, the highest-ranked priorities of 113 stakeholders across four continents (North America, Europe, Africa, and Oceania) were education, access to benefits, and income. These priorities were at the centre of discussion in Objective 3, which comprised idea sharing, refinement and thematic clustering, and a final prioritization poll. The resulting final 15 priorities were organized into two tracks: Track A, actions feasible in the short term, and Track B, longer-term implementation priorities. Building on this priority-setting process, co-created with stakeholders around the globe, the findings provide a roadmap for integration of social parameters in TBI research, knowledge exchange, policy, and practice.

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Physiotherapist and Patient Perspectives on a Snack-based Physical Activity Application and Tracking Device for People with Chronic Non-specific Low Back Pain: A Qualitative Study

Alali, A.; Soundy, A.; Falla, D.; Deane, J.

2026-05-06 rehabilitation medicine and physical therapy 10.64898/2026.04.29.26351862 medRxiv
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ObjectivesTo explore patients and physiotherapists perspectives on a snack-based physical activity (PA) approach and mobile health technologies (mHealth) for non-specific chronic low back pain (NSCLBP). Snack-based PA refers to short, frequent bouts of activity (2-5 minutes) integrated into daily routines. DesignQualitative study using Interpretative Phenomenological Analysis (IPA) of semi-structured online interviews. SettingCommunity-based recruitment in the United Kingdom. Interviews were conducted online via Microsoft Teams between May and November 2024. ParticipantsSixteen participants were purposively sampled: eight adults with NSCLBP (lasting [&ge;]3 months in the previous year) and eight physiotherapists with [&ge;]2 years experience managing people with NSCLBP. ResultsThree shared themes were identified across both groups: (1) understanding the needs and requirements of PA; (2) perceptions of snack-based activity; and (3) factors influencing mobile health application use. Five subthemes were identified within themes one and three, together with two additional subthemes reported only by patients, relating to data sharing and technical issues. Both groups valued the time-efficiency and practical integration of snack-based activity, while highlighting the need for personalisation, age-appropriate content, accessibility and affordability. ConclusionsPhysiotherapists and patients emphasised the potential value of the snack-based PA approach in terms of adherence. However, both groups agreed that future intervention development should prioritise personalisation, user-friendly design, and equitable digital access. STRENGTHS AND LIMITATIONS OF THIS STUDYO_LIThis study uses Interpretative Phenomenological Analysis (IPA) to provide in-depth, dual-perspective insights from both people with non-specific chronic low back pain (NSCLBP) and physiotherapists on a novel snack-based physical activity approach for chronic non-specific low back pain. C_LIO_LIReporting adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ) 32-item checklist to ensure methodological transparency. C_LIO_LIThe sample included variation in patient age, ethnicity and physiotherapist experience, which broadened the range of views captured. C_LIO_LIAll participants were UK-based, which may limit the transferability of findings to other healthcare systems and cultural contexts. C_LIO_LIThe small sample size, although consistent with IPA methodology, and the use of single online interviews, may not capture longitudinal perspectives on sustained engagement. C_LI

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Rotating Letters in the Mind's Eye: Behavioral and electro-cortical associations with 3D Mental-Rotation Ability

Khan, R.; Bekiari, S.; Hierck, B.; Salvatori, D.; Kenemans, L.

2026-05-14 neuroscience 10.64898/2026.05.11.724360 medRxiv
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Mental rotation in 3D is a key cognitive skill involving dynamic spatial transformations, for which pronounced individual differences have been documented. Here we ask whether individual differences in 3D abilities can be explained by analogous differences in 2D abilities. 3D mental-rotation was assessed by the Vandenberg & Kruse Mental Rotation Test (3D-MRT) and examined for association with performance and underlying electrocortical mechanisms during a 2D letter rotation task. Participants (N=40) first completed the MRT and then performed a computerized 2-D letter rotation task in which they had to identify whether letters were oriented in a standard or a mirrored direction (parity judgment) when rotated at 0{degrees}, 60{degrees}, 120{degrees}, and 180{degrees} while EEG was recorded. Reaction times (RTs) and error rates increased with angular disparity. The angular disparity effect on RT was smaller for mirrored letters. Low, relative to high, 3D-MRT scoring participants showed more pronounced accuracy declines at higher rotation angles. An EEG Event Related Potential (ERP) known as the Rotation-Related Negativity (RRN) became more pronounced with increasing angular disparity. High 3D-MRT scores were associated with a stronger RRN response at central-parietal sites. In addition, the ERP-P3b wave was more pronounced at central-parietal sites for low 3D-MRT scorers, independent of angular disparity. It is concluded that 3D rotational ability is positively associated with 2D mental rotation performance, and more strongly with enhanced recruitment of neural visual-spatial cortical representations than with enhanced recruitment of more general cognitive resources.

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Transcranial direct current stimulation-augmented cognitive training for post-COVID-19 cognition: A phase IIb randomized controlled trial

Trujillo Llano, C.; Fromm, A. E.; Lingemann, L.; Grittner, U.; Meinzer, M. F.; Fleischmann, R.; Brakemeier, E.-L.; Antonenko, D. F.; Floeel, A.

2026-05-14 neurology 10.64898/2026.05.11.26352906 medRxiv
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BackgroundCognitive dysfunction is a prevalent and debilitating symptom of post-COVID-19 condition with limited evidence-based interventions. Here, we assessed the efficacy of cognitive training (CT) alone and combined with transcranial direct current stimulation (tDCS) for cognitive enhancement in post-COVID-19 patients. MethodsNeuromod-COV was a phase IIb, prospective, randomized, open-label, blinded-endpoint trial conducted at University Medicine Greifswald, Germany. The tDCS intervention was evaluated through a double-blind, sham-controlled design. Adults aged 18-60 with confirmed SARS-CoV-2 infection [&ge;] 6 weeks prior and post-infection cognitive complaints were eligible. Participants were randomly assigned (1:1:1) to CT with active tDCS (CT+AtDCS), CT with sham tDCS (CT+StDCS), or progressive muscle relaxation (PMR, non-cognitive control intervention) with sham tDCS. Intervention consisted of nine 20-minute sessions over three weeks of CT (letter updating task) or PMR with 2 mA tDCS (active/sham) applied over the left dorsolateral prefrontal cortex. The primary outcome was untrained working memory (WM; measured by N-back task accuracy) comparing CT with PMR at post-intervention. Secondary outcomes included trained and untrained WM, visuospatial memory, and self-report measures at post-intervention and 1-month follow-up comparing CT vs. PMR and CT+AtDCS vs. CT+StDCS. The trial was registered at ClinicalTrials.gov (NCT04944147). ResultsBetween October 1, 2021, and August 7, 2024, 60 participants were randomized (76.7% female) to CT+AtDCS (n = 20), CT+StDCS (n = 20), or PMR (n = 20). CT did not improve untrained WM at post-intervention compared with PMR (primary outcome: {beta} = 1.59, 95% CI - 1.30 to 4.48, p = 0.278; 1-back: {beta} = 2.52, 95% CI -1.27 to 6.31, p = 0.191; 2-back: {beta} = 0.66, 95% CI -3.12 to 4.44, p = 0.732). However, CT+AtDCS enhanced untrained WM at post-intervention and follow-up, and visuospatial memory at post-intervention compared with CT+StDCS (secondary outcomes). No intervention improved self-report outcomes. No serious adverse events occurred and incidence rate ratios were similar between groups. ConclusionCT alone did not improve untrained WM performance. However, CT with tDCS enhanced untrained WM and visuospatial memory, suggesting potential benefits of combined neuromodulation approaches for cognitive enhancement in post-COVID-19 patients.

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Cortical activation in healthy young adults performing a verbal fluency task during gait: A near-infrared functional spectroscopy (f-NIRS) study.

Mendes, F. A. d. S.; Silva, P. R. d.; Garcia, D. F.; Miamoto, M. S.; Macena, R. G.; Santos, L. B. R.; Aranha, L. d. M.; Santos, G. V.; Sato, J. R.; Piemonte, M. E. P.

2026-05-15 neurology 10.64898/2026.05.12.26353003 medRxiv
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BACKGROUND: Dual task walking requires simultaneous management of cognitive and motor demands and is associated with changes in gait and cortical activation. However, the relationship between task related cortical recruitment and dual task related gait adjustments in healthy young adults remains unclear. This study aimed to investigate the effects of dual tasking on gait performance and cortical activation, and to examine the association between changes in cortical activity and dual-task costs. METHODS: This cross sectional study included 33 healthy young adults. Participants performed three conditions: single task walking, cognitive single task (verbal fluency), and dual task walking. Each condition was repeated 10 times using a repeated short block design with randomized trial presentation. Gait performance was assessed using an instrumented walkway, and cortical activation was measured using functional near infrared spectroscopy. Dual task costs were calculated for gait and cognitive outcomes. Statistical analysis included repeated measures analysis of variance (ANOVA) and Wilcoxon signed rank tests, with false discovery rate correction for multiple comparisons. Associations between changes in cortical activation and dual task costs were examined using correlation analyses. RESULTS: Dual task walking resulted in significant changes in gait, including reduced speed, step and stride length, and increased base of support, stance, and double support (all p < 0.05), while cognitive performance remained unchanged. Dual tasking was associated with increased cortical activation in left prefrontal and motor related regions. Greater increases in cortical activation were associated with lower dual task costs across most gait parameters, with significant correlations observed in the left dorsolateral prefrontal cortex (r {approx} 0.42 to 0.47 for speed and stride length; p < 0.05). Double support showed a distinct pattern, suggesting a specific temporal adjustment within the gait cycle. CONCLUSIONS: Dual task walking in young adults is associated with coordinated behavioral and cortical adaptations. Increased cortical recruitment is linked to reduced motor interference, suggesting that broader engagement of cortical networks may contribute to performance under cognitive motor load.

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A Pre-Post Single-Arm Trial of a Multicomponent Intervention for Self-Efficacy Enhancement among an Online Support Group of Primary Caregivers of Children with Neuro Muscular Disorders: SEE-NMD Protocol

Aziz, N. I.; Khalid, W.; Khan, S.

2026-05-06 neurology 10.64898/2026.05.04.26352405 medRxiv
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IntroductionSpinal Muscular Atrophy (SMA) and Duchenne Muscular Dystrophy (DMD) are progressive genetic neuromuscular disorders imposing substantial caregiving demands on families. In Pakistan, where disease-modifying therapies remain largely inaccessible, care is predominantly supportive, frequently resulting in psychological distress and diminished caregiver confidence. An individuals belief in their capacity to execute required behaviours, self-efficacy, is a recognised determinant of caregiving quality, yet evidence on caregiver self-efficacy in SMA and DMD within low-resource settings remains sparse. This study aims to evaluate the effect of a multicomponent, digitally delivered intervention on self-efficacy among primary caregivers of children with SMA and DMD in Pakistan. Methods and AnalysisThis single-group, pre-post study will recruit 30 primary caregivers of children with SMA or DMD enrolled in the Treat-NMD Registry of Pakistan. An eight-week intervention will be delivered via online support groups, comprising educational video clips, expert-led live sessions, pictorial guides, and progressively tapering audio reminders. The primary outcome, self-efficacy, will be measured using a culturally adapted, content-validated Urdu version of the DMD Caregiver Self-Efficacy Scale (DMD-CSES), assessed at baseline (T0) and eight weeks post-intervention (T1). Pre-post scores will be compared using a paired t-test or Wilcoxon signed-rank test depending on data distribution, with analyses conducted in STATA Version 17. Ethics and DisseminationEthical approval has been granted by the Ethics Review Committee of Aga Khan University (2025-11875-37040). Verbal informed consent will be obtained from all participants, with confidentiality maintained throughout. Findings will be disseminated via peer-reviewed publication, conference presentations, and shared with the Treat-NMD registry network. Trial registration numberNCT07356063, Date of registration: 11/January/2026