Scientific Reports

In humans, theta ({theta}) band activity (defined as 4-8 or 5-7 Hz), measured over the frontal midline of the scalp, is an important EEG correlate of voluntary and conscious self-control. Theta waves specifically reflect the workings of the frontal lobes, and can therefore be useful in distinguishing cortical from more ancient control mechanisms. In dogs, inhibitory self-control is extensively studied, but mostly through behavioural tests. Here, we present a first inquiry into a possible EEG correlate of cognitive control in the domestic dog, by comparing short ([~]30-second-long) EEG recordings from two conditions: passive wakefulness (baseline) versus a delayed gratification challenge (test). Both were recorded alternating, under similar conditions for each dog within the same session. In total, we collected and analysed 226 short recordings from fourteen dogs. Within and across animals, we found an increase in activity (test > baseline) that resembles human cognitive theta in frequency range (5-7 Hz) and scalp localization. Our results are a first demonstration that frontal midline theta in awake dogs can peak under similar conditions to those in humans. These findings indicate that compliant behaviour in dogs is under prefrontal control.

In this study, we investigate the individuality and information content of infrared molecular profiles derived from blood samples in a large, longitudinal health-profiling cohort and compare them to a standard clinical laboratory panel. Using Fourier-transform infrared spectroscopy, we obtained comprehensive molecular fingerprints from 4,704 self-reported healthy individuals over five visits spanning 1.5 years, alongside routine clinical laboratory measurements. We show that infrared profiles are highly individual-specific and remarkably stable over time, with intra-individual variability significantly lower than inter-individual differences--paralleling the characteristics observed in clinical laboratory data. To quantify and compare the information content of these molecular datasets, we employ individual identification as a proxy for Shannon entropy. In this framework, higher identification accuracy reflects a higher amount of information. Infrared profiles outperform the clinical laboratory panel in identifying individuals at scale, suggesting higher intrinsic information content. Furthermore, combining infrared and clinical laboratory data substantially improves identification performance (the identification of less than 3000 individuals by the clinical laboratory panel is boosted to more than 4000 by incorporating the infrared spectroscopic markers), highlighting the value of integrating complementary data modalities. These findings suggest a practical framework, rooted in information theory, for comparing molecular profiling approaches and emphasize the potential of infrared spectroscopy as a complementary tool in personalized medicine.

The human startle reflex has primarily been characterized by its repeatable, coordinated, and temporally patterned somatomotor responses. In this study, we assessed whether startle-evoked sympathetic nervous system (SNS) responses might also constitute a repeatable, coordinated, and temporally structured output. Using a noninvasive tactile startle stimulus, we simultaneously recorded startle-evoked electrodermal activity, photoplethysmography-derived blood volume indices, heart rate, blood pressure, stroke volume, and cardiac output in healthy participants. Our results demonstrate that startle elicits a reproducible and patterned constellation of SNS responses - a multimodal SNS startle signature - with conserved temporal relationships across effector systems. The SNS startle signature was composed of robust bilateral peripheral responses, including palmar sweating, cutaneous vasoconstriction, and biphasic cutaneous venous-capillary blood volume changes, in addition to more mild central hemodynamic changes. In contrast to previous startle reflex studies, there was no influence of biological sex or cardiac-cycle gating on responses. Lastly, the SNS startle signature exhibited features of a potentially attractive diagnostic, associated with robust responder discrimination and high response reliability across repeated trials. Overall, these findings fill a critical knowledge gap and also suggest the potential utility of this multimodal signature for assessing autonomic dysfunction.

Zebrafish have been used a prominent model for high-throughput phenotypic screens of candidate risk gene mutations for several disorders. This also includes models for attention deficit/hyperactivity disorder (ADHD). Traditional behavioural tests, such as the forced light/dark assay, concentrate on basic locomotion measures. However, recently developed visually-driven locomotion assays, for example closed-loop systems using virtual reality, have allowed extraction of richer data on animal locomotion and decision-making under different sensory stimuli. Here, we have used such a system to assess the behaviour in adgrl3.1 mutant fish, an established model for ADHD. Our results show that mutants exhibit a higher baseline excitability and a lower threshold for initiating motor events, demonstrating that collecting behavioural responses in an interactive environment enables a more precise characterisation of ADHD-relevant phenotypes associated with adgrl3.1 disruption. More generally, we establish a scalable translational platform to screen gene-function relationships and possible therapeutic interventions, not only for ADHD but multiple neurodevelopmental disorders.

Genitourinary infections (GUIs) during pregnancy are a significant clinical concern linked to maternal morbidity. While Streptococcus is a common gut commensal and a known urogenital pathobiont, whether gut-resident Streptococcus plays a causal role in the etiology of pregnancy-related infections remains unclear due to confounding in observational studies. To investigate the potential causal effect of gut Streptococcus abundance on the risk of maternal genitourinary infection during pregnancy using Mendelian randomization (MR). We performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) summary statistics. Genetic instruments for gut Streptococcus abundance were obtained from the MiBioGen consortium (N=18,340). Outcome data for maternal genitourinary infection (ICD-10 O23.x) were sourced from the FinnGen consortium (N=111,731). The inverse-variance weighted (IVW) method was used as the primary analysis, supplemented by sensitivity analyses (MR-Egger, weighted median, MR-PRESSO). We further assessed potential mediation via systemic inflammation (C-reactive protein, interleukin-6) and associations with eleven major adverse pregnancy outcomes (APOs). Genetically predicted higher gut Streptococcus abundance was associated with a reduced risk of maternal genitourinary infection (IVW odds ratio [OR] = 0.63, 95% confidence interval [CI]: 0.43-0.93, p = 0.020). Sensitivity analyses supported this protective association, with no evidence of horizontal pleiotropy (MR-Egger intercept p = 0.942) or significant heterogeneity. No causal effects were observed on systemic inflammatory markers (CRP, IL-6, all p > 0.05) or on major APOs, including postpartum haemorrhage, placental abruption, etc. This MR study provides genetic evidence supporting a causal, protective role of gut Streptococcus against the risk of clinically diagnosed genitourinary infection during pregnancy. This effect appears specific and is not mediated through the systemic inflammatory pathways examined, suggesting a localized mechanism within the genitourinary tract.

This study examines the temporal dynamics of expressive piano performance by means of a quantitative analysis of motor timing in an elite pianist, with particular reference to stylistic contrasts between Baroque and Romantic repertoire. In line with kinematic models of expressive timing, which describe musical performance as reflecting principles of biological motion, we examined whether a common temporal structure underlies stylistically divergent executions. Despite marked differences in structural complexity and gesture density, both performances exhibited a shared low-frequency oscillatory pattern ([~]0.36 Hz) in beat-level timing variability. This infra-delta rhythmic modulation is consistent with the presence of an underlying motor timing scaffold and suggests a common temporal organization across expressive behaviors. These findings support the hypothesis that musical performance relies on a rhythmically structured control architecture, potentially shared with other complex motor activities such as speech and locomotion.

The human hand has a refined mechanical sensitivity, allowing it to play crucial roles in tactile exploration and object manipulation. Despite its fundamental and clinical relevance, a comprehensive characterization of mechanical sensitivity across the human palm is still lacking. Here, we mapped the spatial distribution of innocuous and noxious mechanical sensitivity across the palmar surface of the human hand. We examined 66 hands from 33 healthy adults, dividing the palm into 27 areas, in each of which we measured the mechanical detection threshold, the mechanical pain threshold and the pain intensity evoked by a standard 300 g pinprick stimulus. We found distal areas (i.e., fingertips) to exhibit higher tactile sensitivity than proximal areas (i.e., the wrist). Notably, the sensitivity to innocuous and noxious mechanical stimuli were inversely correlated across areas, such that areas with higher tactile sensitivity displayed higher pain thresholds. In addition, the dominant hand was less sensitive than the non-dominant one, and women displayed higher sensitivity than men. Together, this work provides the first detailed spatial characterization of mechanical sensitivity across the human hand and introduces a systematic methodology for its assessment. These findings set the stage for future studies of the neurophysiological mechanisms of touch and pain in the human hand and for clinical research into pathological conditions involving the altered hand sensitivity.

Genetic mosaicism can arise from in vivo CRISPR-Cas9 gene editing, especially in the embryos. This study evaluates the extent of genetic mosaicism resulted from CRISPR-Cas9-mediated knockout for 11 genes in the freshwater microcrustacean Daphnia magna, D. pulex, and D. sinensis. Based on extensive genotyping data of the asexually produced progenies of successfully edited females, we find strong evidence of mosaicism in 9 of these genes. The genotyping data also suggest the gene editing activity can take place as early as the one-cell embryo stage and extends into the 32-cell and later stages. This study establishes genetic mosaicism as an important feature of Cas9-mediated gene editing in Daphnia.

Whether qualitative aspects of consciousness, or qualia in short, are equivalent across individuals is a foundational scientific question. Testing this is challenging because one cannot assume a shared mapping between stimuli and private experience (my "red" may be your "green") [1-3]. Previously, we proposed a structural characterization of qualia [4, 5] and the quantitative assessment of structural correspondences through an unsupervised alignment method [4, 6], which does not presuppose such correspondence. Using this approach, our previous work focused on identifying optimal mappings between relational structures of color qualia at the group level [4]. Given known perceptual diversities [7], however, it remained unknown whether any two individuals structures could be empirically aligned. Here, we resolve this by collecting 4,371 pairwise similarity ratings for 93 colors-from 11 individuals, enabling direct individual-to-individual alignment. We reveal two fundamental, coexisting features. First, we identified two clusters of individuals showing robust within-cluster alignment, corresponding to color-neurotypicals and atypicals. Second, we uncovered a continuous spectrum of diversity: some participants who showed normal color discrimination ability in terms of the Total Error Score (TES) on Farnsworth-Munsell 100 hue test nevertheless failed to align with either cluster, revealing idiosyncratic structures that defy simple categorization. Together, these findings suggest a novel structure-based taxonomy of divergent color qualia that complements conventional performance-based classification. Our method is generalizable to other sensory modalities, and opens a path to the scientific investigation of both shared and idiosyncratic qualitative aspects of consciousness.

Intergenerational social programs provide opportunities for people of all ages to form new relationships. Furthermore, existing qualitative and behavioural evidence from such programs points to health and wellbeing benefits, yet the physiological consequences of repeated intergenerational encounters remain unknown. A deeper understanding of how such programs shape dyadic physiological responses will illuminate the mechanisms of relationship formation. Across a six-session collaborative drawing program, we tracked cardiac synchrony within 31 intergenerational (older/younger adult) and 30 same generation (younger adult) dyads. Each session dyads completed self-report measures, then drew together and alone, while we recorded participants actions with motion capture and physiological signals (neural and cardiac) using fNIRS. Collaborative behaviour, self-reported social closeness, and interpersonal distance (i.e., proximity) showed group-specific patterns, whereby interpersonal distance emerged as a promising objective measure of relationship development. Cardiac synchrony did not covary with group, task, an interaction thereof or any measure of behaviour or social closeness-yet there was a trending relationship between collaboration while drawing together and cardiac synchrony for intergenerational dyads only. In summary, cardiac synchrony pointed to marginally enhanced arousal during active collaboration between older and younger adults. Relationship development was better characterised, in this study, by behaviour and self-report measures than cardiac synchrony.

The rat vestibular system plays a critical role in anti-gravity responses such as the tail-lift reflex and the air-righting reflex. In a previous study in male rats, we obtained evidence that these two reflexes depend on the function of non-identical populations of vestibular sensory hair cells (HC). Here, we caused graded lesions in the vestibular system of female rats by exposing the animals to several different doses of an ototoxic chemical, 3,3-iminodipropionitrile (IDPN). After exposure, we assessed the anti-gravity responses of the rats and then assessed the loss of type I HC (HCI) and type II HC (HCII) in the central and peripheral regions of the crista, utricle and saccule. As expected, we recorded a dose-dependent loss of vestibular function and loss of HCs. The relationship between hair cell loss and functional loss was examined using non-linear models fitted by orthogonal distance regression. The results indicated that both the tail-lift reflex and the air-righting reflexes mostly depend on HCI function. However, a different dependency was found on the epithelium triggering the reflex: while the tail-lift response is sensitive to loss of crista and/or utricle HCIs, the air-righting response rather depends on utricular and/or saccular integrity.

Humans can predict an objects motion better if its movements are consistent with gravity. Here we investigate whether this may be due to an internalized strong Earth gravity prior or to vestibular cues reporting instantaneous information about gravity. These two directions can be separated using virtual reality by providing strong visual cues to the direction of up which may or may not be aligned with true gravity. Participants were presented with a ball travelling on a parabola path simulated with either downward acceleration created by simulated Earths gravity (1g) or inverted gravity (-1g) resulting in the ball curving upwards. In both types of trial, the ball disappeared at between 57.5% and 75% of its full trajectory - after it had started its descent in the case of 1g or ascent in the case of -1g. Participants pressed a mouse button when they judged the ball to have got back to the height at which it was launched. Participants were either standing or supine. There were no differences in the estimated time to reach the indicated level between the 1g and -1g simulations, however, we found an overestimation of the perceived time for the ball to reach target height when observers were lying supine compared to when they were standing upright independent of the gravity condition simulated. A control experiment confirmed that this was not due to a general slowing of reaction times while lying supine versus while upright. To explore whether these observations might reflect posture-related changes in vestibular activity, participants completed the task under both simulated gravity conditions while seated upright in the presence of disruptive galvanic vestibular stimulation (dGVS) or during sham stimulation. As when lying supine, the perceived time for the ball to reach the target height was significantly longer in the presence of dGVS compared to during sham stimulation. Overall, participants were no better at anticipating 1g motion compared to -1g motion, but we provide compelling evidence that the state of vestibular signalling can impact the prediction of object motion.

Balancing exploration and exploitation is a fundamental challenge for adaptive behavior, yet it remains unclear whether visual sampling and spatial locomotion reflect a single cross-domain trait or operate independently. We addressed this question by recording head-mounted eye-tracking and full-body motion tracking while 26 participants freely navigated "Westbrook", a large-scale virtual city for a total of 150 min across five sessions. From the movement trajectories we derived three spatial descriptors: median walking speed, occupancy entropy, and the proportion of explorative route choices. From the gaze data, we computed 38 robust visual descriptors encompassing fixation dynamics, pupil size, saccadic amplitude, gaze-head alignment, and transition entropy. Principal-component analysis reduced the visual descriptors to three components that captured 58 % of variance, with the first component (PC1) reflecting "gaze dynamism" (frequent shifts, larger saccades, higher transition entropy). Canonical correlation analysis revealed a strong coupling between spatial and visual behaviours: the first pair of canonical variates correlated at r = 0.68 (cross-validated r = 0.45), driven primarily by the association of high walking speed and occupancy entropy with elevated gaze dynamism. In contrast, the proportion of explorative route choices contributed little to this coupling. These findings demonstrate that individual differences in low-level locomotor speed and spatial coverage co-vary with an exploratory visual style, supporting the existence of a domain-general "exploration" factor that shapes both how people move through, and attend to, complex environments.

For eye-hand coordination, predictions of sensory movement consequences may already be issued, and adjusted, during action preparation. In this pre-registered study, we combined a delayed-movement paradigm with a virtual reality-based hand-eye tracking task to investigate the oculomotor correlates of planning and executing coordinated hand-eye movements under standard vs nonstandard visual hand movement feedback. We measured pupil dilation and gaze-hand tracking during action preparation and subsequent task execution, where visual movement feedback violated or matched cued expectations: Participants prepared and, after a delay period, executed hand movements. Their movements were reflected by congruent or incongruent (inverted) movements of a glove-controlled virtual hand model, which they had to follow with their gaze. In the preceding delay period, visual cues could specify the to-be-executed movement (or leave it unspecified), and the visuomotor mapping (congruent or incongruent, 75% cue validity). We found that during the delay, pupil diameter increased more strongly when the movement was pre-cued (compared to left unspecified), and when nonstandard compared to standard visual movement feedback was expected. During execution, gaze-hand tracking performance decreased under nonstandard mappings, but significantly less so when the to-be-executed movement was pre-cued. Expectation violation trials produced a strong pupil dilation, particularly when congruent (standard) visuomotor expectations were violated, but also when incongruent mappings were cued but congruent ones observed. Furthermore, expectation violation impaired tracking performance; again, stronger for pre-cued movements with standard mapping. Our results indicate that oculomotor responses during delay encode processes related to motor planning and flexible forward prediction of sensory action consequences ahead of execution, i.e. increased mental effort and expectations of sensory conflict. Moreover, the results demonstrate that the strength of these (updated) predictions affects eye-hand coordination and pupillary responses during subsequent execution of the planned action.

Previous investigations have explored the effects of hypermagnetic fields, that is, fields in excess of the Earths background geomagnetic field strength of approximately 50 {micro}T, on Escherichia coli (E. coli). Conversely, this study investigates the effects of hypomagnetic field conditions, that is, fields below the geomagnetic background intensity, on the growth of E. coli K12 by using a hypomagnetic chamber to shield cultures, with a measured residual magnetic field inside the chamber of 19 nT. When grown in rich media from a semi-anaerobic, stationary-phase starting culture under geomagnetic and hypomagnetic conditions, the lag phases of E. coli were approximately 86 minutes and 132 minutes, respectively. Despite this increase in lag phase, exceeding two E. coli doubling times, the log-phase growth rate of E. coli was identical under both geomagnetic and hypomagnetic conditions. In addition to demonstrating a biologically relevant sensitivity to magnetic field parameters in the hypomagnetic direction, this represents a much greater absolute magnetosensitivity, with a deviation of only 50 {micro}T between the hypomagnetic and geomagnetic conditions, than has previously been demonstrated for E. coli.

OBJECTIVES: Compare results of the Pediatric Outcomes Data Collection Instrument (PODCI) in children ages 2-18 years with cerebral palsy (CP) across all severity levels of the Gross Motor Function Classification System (GMFCS) with children in the General Population, confirming discriminant validity as a performance assessment tool and health-related quality of life (HRQOL) measure. METHODS: Cross-sectional study: single response PODCI proxy survey databases of 5238 children ages 2-18 years in GP and 2470 in the Population with CP were analyzed. Statistical methods included Analysis of Variance (ANOVA), Analysis of Covariance (ANCOVA), Linear Trend Test, and Standard Error Assessment. RESULTS: A statistically significant difference exists between PODCI subscales in General Population and Population with CP across age groups and GMFCS levels. Motor scales and Global Functioning increase with age in both populations and are inversely proportional to GMFCS level in the Population with CP. HRQOL measures decrease with age in both populations with Happiness decreasing more in the General Population than those with CP as age increases. CONCLUSIONS: PODCI demonstrates a statistically significant difference in motor performance and HRQOL in children ages 2-18, between the General Population and the population with CP. PODCI is a valid performance assessment tool for use in CP ages 2-18 across all GMFCS levels. KEYWORDS: Cerebral Palsy, General Population, PODCI, ICF, Performance

The clitoris is one of the least studied organs of the human body. The detailed anatomy of the clitoris is challenging to address through a gross dissection, as most of its parts are embedded internally, surrounded by pubic bone and several pelvic organs. While clinical imaging methods such as magnetic resonance imaging can capture the gross 3D morphology, they lack the spatial resolution required to resolve the detailed structures. In this study, we generated micron-scale computed tomography images of the female pelvises, leveraging a synchrotron radiation X-ray source. This unique data revealed the complex trajectory of the dorsal nerve of the clitoris, the main sensory nerve of the clitoris. Notably, the nerve trunks within the clitoral glans were revealed, with the maximum diameter ranging from 0.2 to 0.7 mm. They showed a tree-like branching pattern projecting towards the surface of the glans. We also revealed that some branches of the dorsal nerve of the clitoris ramify to innervate the clitoral hood and mons pubis. Finally, the posterior labial nerve, a branch of the perineal nerves, was shown to innervate the surroundings of the clitoris and the labial structures. These findings have an immediate impact on operations performed around the vulva area, such as gender-affirmation surgery and reconstruction surgery after genital mutilation.

Mitochondrial diseases are a diverse group of inherited neuromuscular disorders leading to progressive disability and early mortality. Mitochondrial myopathy is a common feature of mitochondrial disorders, affecting most patients. Assessment of disease progression and treatment efficacy in mitochondrial disease trials has often relied on muscle biopsies, however, these are increasingly considered unfavourable by patients. Imaging biomarkers of disease could reduce the patient burden, enabling non-invasive longitudinal monitoring of molecular information. Photoacoustic imaging combines the molecular sensitivity of light absorption with the deep tissue imaging capabilities of ultrasound, enabling a safe and fast imaging technique. Tuning the wavelength of light allows for the detection of molecular constituents such as oxy- and deoxy-haemoglobin, lipids, and water. These signatures may reflect underlying pathophysiological alterations and serve as valuable indicators of disease state and progression. We conducted an exploratory study of a photoacoustic imaging dataset in patients with mitochondrial myopathy due to the m.3243A>G mt-tRNALeu mutation and compared to healthy volunteers. We generated photoacoustic measurements at wavelengths in the near infrared, comparing absolute values and ratios derived in the bicep muscle. Confounding factors such as skin colour and sex were considered, and we ensured that these parameters were matched in healthy volunteers and patients. We identified significant differences between patients and controls, revealing changes in ratios between water and total haemoglobin, lipid and total haemoglobin, and lipid and water content. This study highlights the promise of photoacoustic imaging as a novel imaging biomarker in mitochondrial myopathies, paving the way for larger scale studies.

A substantial body of evidence demonstrates that measures from mammograms are predictive of breast cancer risk. In this matched case-control study, mammograms acquired near the time of diagnosis were analyzed to investigate bilateral breast asymmetry as measure of short-term risk prediction. Specifically, contralateral breast images were compared with measures derived in the Fourier domain (FD); this technique summarizes power in concentric radial bands that cover the Fourier plane. Equivalently, this approach can be described as a multiscale characterization of the image. The summarized power difference between respective contralateral bands produces an asymmetry measure. Full field digital mammography (FFDM) and synthetic two-dimensional images from digital breast tomosynthesis (DBT) were investigated for women that had both types of mammograms acquired at the same time. Odds ratios (ORs) and the area under the receiver operating curves (Azs) were generated from conditional logistic regression modeling with 95% confidence intervals. Raw unprocessed FFDM images produced significant findings: OR = 1.90 (1.58, 2.29) and Az = 1.72 (0.67, 0.76) per one standard deviation unit. Associations were significant but attenuated for both clinical FFDM and DBT images: OR = 1.31 (1.11, 1.54) and Az = 0.63 (0.58, 0.67); and OR = 1.48 (1.25, 1.76) and Az = 0.65 (0.60, 0.70), respectively. Results suggest that clinical FFDM and DBT images are inferior to raw FFDM images in capturing breast asymmetry with information loss for breast cancer risk prediction. Moreover, these DBT images have lower spatial resolution but produced stronger associations than the clinical FFDM images.

Radiation-induced intestinal injury is a widely used model for studying mechanisms regulating tissue injury and regeneration. Traditionally, Cesium (137Cs) radiation has been used in research applications, but over the past decade, X-ray irradiation has become increasingly favored due to its improved safety and non-radioactive profile. Since each type of radiation has distinct physical characteristics that drive its performance, we sought to systematically compare the effects of the X-ray and 137Cs irradiators on intestinal epithelial injury and regeneration. Using established in vitro models, including colorectal cancer cell lines such as HCT116, RKO, and DLD-1, and mouse intestinal organoids, alongside an in vivo model, Bmi1-CreER;Rosa26eYFP, we evaluated differences in transcriptional, protein, and histopathological responses to irradiation. Our results demonstrate that X-ray produced intestinal injury and regenerative responses comparable to those induced by 137Cs, supporting its reliability as an alternative modality for studying intestinal radiation.