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bioRxiv2024

Physiological Processing of Aversiveness in the Mind's Ear: Comparing Audiovisual, Auditory and Imagined Auditory Affective Stimuli

Understanding the somatovisceral responses to auditory affective imagery has important implications in disorders like misophonia. The current study compared physiological responses to aversive and nonaversive states across three modalities: audiovisual, auditory, and auditory imagery. Electromyographic activity over corrugator supercilii (EMGc) and zygomaticus major (EMGz), electrodermal activity (EDA), heart rate (HR), and finger skin temperature (SKT) were measured. There was significant differentiation in EMGc, EDA, and HR deceleration between aversive and nonaversive audiovisual stimuli. EMGc potentiation was the only physiological measure showing consistent differentiation across the three modalities. Cross-modal aversiveness classification results revealed a similar physiological response pattern between audiovisual and auditory modalities. The physiological response pattern during auditory affective imagery was useful for predicting the aversiveness in audiovisual modality but not the other way around. Vividness in auditory imagery correlated with subjective hedonic valence ratings, but not physiological responses. Taken together, the current data suggest that the aversiveness of auditory imagery is differentiable in subjective affective experience and facial muscle potentiation. These results of the physiological responses to imagined aversive sounds in nonclinical population would serve as a comparison baseline for the study of misophonia.

physiology↗

bioRxiv2025

Non-invasive assessment of integrated cardiorespiratory network dynamics after physiological stress in humans

BackgroundPhysiological variables provide critical insights into the integrated control of the cardiorespiratory system, reflecting the bodys real-time responses to internal and external perturbations. Visualizing the exchange of information between different components of the cardiorespiratory system is beneficial for monitoring individuals in various clinical settings and extreme environments. This study aimed to develop a non-invasive method, using principles of information theory, to visualize the flow of information between physiological variables, with a focus on the integrated cardiorespiratory responses to different physiological stressors. MethodsHeart rate, respiratory rate, minute ventilation, respiratory frequency, tidal volume, capillary oxygen saturation (SpO2), end-tidal oxygen, and end-tidal carbon dioxide concentrations were recorded from 22 healthy participants. Transfer entropy, which reflects measures of causal relationships between parallel time-series, was used to compute the flow of information between cardiorespiratory signals into network maps. Network mapping was performed after rest in a control condition and following exposure to the isolated and combined effects of normobaric hypoxia (FIO2: 0.12), moderate intensity cycling exercise (100W), and overnight sleep deprivation. For each intervention, 10-minute segments of physiological signals (from minutes 5 to 15 after the commencement of hypoxia and/or exercise) were used for analysis. ResultsEach physiological stressor was associated with a distinctive pattern of information flow between physiological variables. Hypoxia led to the engagement of SpO2 a hub in the network, facilitating the exchange of information with end-tidal oxygen concentration and heart rate. Sleep deprivation was associated with a shift in the flow of information from SpO2 to other nodes, such as respiratory rate, during hypoxia. During exercise, heart rate emerged as the central node for receiving information, while SpO2 acted as the primary node disseminating information to other nodes. Increased connectivity within the networks was observed during exercise alone or when combined with other stressors. ConclusionThis non-invasive network mapping technique visualizes the interaction of various cardiorespiratory variables following exposure to physiological stressors. By mapping normative responses, this approach may help identify outliers associated with various disease states.

physiology↗

bioRxiv2026

Increases in therapist-patient physiological synchrony after dog-patient contact in canine-assisted psychotherapy: an exploratory pilot study

Introduction: Canine-assisted psychotherapy (CAP) introduces a therapy dog into the therapist-patient relationship and may influence interpersonal processes underlying therapeutic change. This exploratory pilot study investigated whether direct patient-dog contact is associated with changes in autonomic arousal and therapist-patient physiological synchrony. Methods: Skin conductance was recorded from 18 patients with depressive disorders and one therapist during 53 routine CAP sessions. A total of 192 episodes of direct patient-dog contact were identified from video recordings. Three-minute periods before and after each contact onsets were compared. Skin conductance level (SCL), skin conductance fluctuations (SCF), and therapist-patient physiological synchrony were assessed using zero-lag correlation and maximum cross-correlation. Sliding-window analyses examined temporal changes in synchrony, while randomly selected pseudo-events served as controls. Results: SCL increased significantly following dog contact in both patients and the therapist, whereas SCF rate over 3 min did not change significantly. Therapist-patient physiological synchrony increased significantly after dog contact, as indicated by both zero-lag correlation and maximum cross-correlation. Sliding-window analyses confirmed these increases and showed a reduction in the temporal lag between the two physiological signals. Importantly, increases in synchrony were significantly greater following genuine dog-contact events than following pseudo-events. Discussion: Direct physical contact between patients and therapy dogs is followed by increased autonomic arousal and enhanced therapist-patient physiological synchrony. These findings suggest that dog-patient contact may function as an interactional event that promotes physiological coordination and interpersonal attunement within the therapeutic dyad.

physiology↗

bioRxiv2020

Comparative physiology of five tropical montane songbirds reveals differential seasonal acclimatisation and cold adaption

The physiology of tropical birds is poorly understood, particularly in how it relates to local climate and changes between seasons. This is particularly true of tropical montane species, which may have sensitive thermal tolerances to local microclimates. We studied metabolic rates (using open flow respirometry), body mass and haemoglobin concentrations of five sedentary Mesoamerican songbirds between the summer and winter at two elevations (1550 m and 1950 m, respectively). We asked whether there were uniform seasonal shifts in physiological traits across species, and whether higher elevation species displayed evidence for cold tolerance. Seasonal shifts in metabolic rates differed between the three species for which data were collected. Basal metabolic rates in one species - black-headed nightingalethrushes Catharus mexicanus - were up-regulated in summer (~19% increase of winter metabolism), however two other species displayed no seasonal regulation. No species exhibited shifts in haemoglobin concentrations across season or across elevation, whereas body mass in two species was significantly higher in the summer. One species restricted to higher elevations - ruddy-capped nightingale-thrushes C. frantzii - displayed physiological traits indicative of cold-tolerance. Although only summer data were available for this species (C. frantzii), metabolic rates were constant across temperatures tested (5-34{degrees}C) and haemoglobin concentrations were significantly higher compared to the other four species. Our results suggest that seasonal acclimatisation in physiological traits is variable between species and appear unrelated to changes in local climate. As such, the distinct physiological traits observed in ruddy-capped nightingale-thrushes likely relate to historic isolation and conserved physiological traits rather than contemporary climatic adaption.

ecology↗

bioRxiv2021

Social Touch is associated with Neural but not Physiological Synchrony in Naturalistic Mother-Infant Interactions

Caregiver touch plays a vital role in infants growth and development, but its role as a communicative signal in human parent-infant interactions is surprisingly poorly understood. Here, we assessed whether touch and proximity in caregiver-infant dyads are related to neural and physiological synchrony. We simultaneously measured brain activity and respiratory sinus arrhythmia of 4- to 6-month-old infants and their mothers (N=69 dyads) in distal and proximal joint watching conditions as well as in an interactive face-to-face condition. Neural synchrony was higher during the proximal than during the distal joint watching conditions, and even higher during the face-to-face interaction. Physiological synchrony was highest during the face-to-face interaction and lower in both joint watching conditions, irrespective of proximity. Maternal affectionate touch during the face-to-face interaction was positively related to neural but not physiological synchrony. This is the first evidence that touch mediates mutual attunement of brain activities, but not cardio-respiratory rhythms in caregiver-infant dyads during naturalistic interactions. Our results also suggest that neural synchrony serves as a biological pathway of how social touch plays into infant development and how this pathway could be utilized to support infant learning and social bonding. HighlightsO_LIMother-infant neural and physiological synchrony arise during mutual engagement. C_LIO_LIBehavioral correlates of neural and physiological synchrony diverge. C_LIO_LIInterpersonal neural synchrony is related to proximity and affective touch. C_LIO_LIInterpersonal physiological synchrony is related to infant negative affect. C_LI

neuroscience↗

bioRxiv2021

Can we harness digital technologies and physiology to hasten genetic gain in U.S. maize breeding?

Genetic gain in breeding programs depends on the predictive skill of genotype-to-phenotype algorithms and precision of phenotyping, both integrated with well-defined breeding objectives for a target population of environments (TPE). The integration of physiology and genomics could improve predictive skill by capturing additive and non-additive interaction effects of genotype (G), environment (E), and management (M). Precision phenotyping at managed stress environments (MSEs) can elicit physiological expression of processes that differentiate germplasm for performance in target environments, thus enabling algorithm training. Gap analysis methodology enables design of GxM technologies for target environments by assessing the difference between current and attainable yields within physiological limits. Harnessing digital technologies such as crop growth model-whole genome prediction (CGM-WGP) and gap analysis, and MSEs, can hasten genetic gain by improving predictive skill and definition of breeding goals in the U.S. maize production TPE. A half-diallel maize experiment resulting from crossing 9 elite maize inbreds was conducted at 17 locations in the TPE and 6 locations at MSEs between 2017 and 2019. Analyses over 35 families represented by 2367 hybrids demonstrated that CGM-WGP offered a predictive advantage (y) compared to WGP that increased with occurrence of drought as measured by decreasing whole-season evapotranspiration (ET; log(y) = 0.80({+/-}0.6) - 0.006({+/-}0.001) x ET; r2 = 0.59; df = 21). Predictions of unobserved physiological traits using the CGM, akin to digital phenotyping, were stable. This understanding of germplasm response to ET enables predictive design of opportunities to close productivity gaps. We conclude that enabling physiology through digital methods can hasten genetic gain by improving predictive skill and defining breeding objectives bounded by physiological realities.

plant biology↗

bioRxiv2021

Relationship between constitutive and acute gene regulation, and physiological and behavioral responses, mediated by the neuropeptide PACAP

Since the advent of gene knockout technology in 1987, insight into the role(s) of neuropeptides in centrally- and peripherally-mediated physiological regulation has been gleaned by examining altered physiological functioning in mammals, predominantly mice, after genetic editing to produce animals deficient in neuropeptides or their cognate G-protein coupled receptors (GPCRs). These results have complemented experiments involving infusion of neuropeptide agonists or antagonists systemically or into specific brain regions. Effects of gene loss are often interpreted as indicating that the peptide and its receptor(s) are required for the physiological or behavioral responses elicited in wild-type mice at the time of experimental examination. These interpretations presume that peptide/peptide receptor gene deletion affects only the expression of the peptide/receptor itself, and therefore impacts physiological events only at the time at which the experiment is conducted. A way to support real-time interpretations of neuropeptide gene knock-out is to demonstrate that the wild-type transcriptome, except for the deliberately deleted gene(s), in tissues of interest, is preserved in the knock-out mouse. Here, we show that there is a cohort of genes (constitutively PACAP-Regulated Genes, or cPRGs) whose basal expression is affected by constitutive knock-out of the Adcyap1 gene in C57Bl6/N mice, and additional genes whose expression in response to physiological challenge, in adults, is altered or impaired in the absence of PACAP expression (acutely PACAP-Regulated Genes, or aPRGs). Distinguishing constitutive and acute transcriptomic effects of neuropeptide deficiency on physiological function and behavior in mice reveals alternative mechanisms of action, and changing functions of neuropeptides, throughout the lifespan.

neuroscience↗

bioRxiv2021

Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of early adulthood population. In this article, we investigated the effect of six month exposure of either caloric restriction or intermittent fasting on a broad range of physiological traits in 960 one year old Diversity Outbred mice. We found caloric restriction and intermittent fasting affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilties ranged from 0.04-0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of early adult-hood mice following six months of dietary intervention.

genetics↗

bioRxiv2024

Investigating the variability of physiological response functions across individuals and brain regions in functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) is a valuable neuroimaging tool for studying brain function and functional connectivity between brain regions. However, the blood oxygen level dependent (BOLD) signal used to generate the fMRI images can be influenced by various physiological factors, such as cardiac and respiratory activity. These physiological effects, in turn, influence the resulting functional connectivity patterns, making physiological noise correction a crucial step in the preprocessing of fMRI data. When concurrent physiological recordings are available, researchers often generate nuisance regressors to account for the effect of heart rate and respiratory variations by convolving physiological response functions (PRF) with the corresponding physiological signals. However, it has been suggested that the PRF characteristics may vary across subjects and different regions of the brain, as well as across scans of the same subject. To investigate the dependence of PRFs on these factors, we examine the performance of several different PRF models, in terms of BOLD variance explained, using resting-state fMRI data from the Human Connectome Project (N=100). We examined both one-input (heart rate or respiration) and two-input (heart rate and respiration) PRF models and show that allowing PRF curves to vary across subjects and brain regions generally improves PRF model performance. For one-input models, the improvement in model performance gained by allowing spatial variability was most prominent for respiration, particularly for a subset of the subjects (about a third) examined. Allowing for subject-specific or regional variability in the cardiac response function resulted in a significant model performance improvement only when using a two-input PRF model. Overall, our results highlight the importance of considering spatial and subject-specific variability in PRFs when analyzing fMRI data, particularly regarding respiratory-related fluctuations.

bioengineering↗

bioRxiv2024

From phenotype to receptor: validating physiological clustering of Escherichia coli phages through comprehensive receptor analysis

Understanding the relationship between bacteriophage (phage) classification and target receptors is crucial for phage ecology and applied research. In this study, we compared 13 previously isolated Escherichia coli phages based on physiological characteristics, whole-genome sequences, and tail fiber protein phylogenetics. We improved our previously proposed physiological clustering method by optimizing the bacterial panel for host range assessment, implementing appropriate distance metrics for mixed data types, and applying silhouette coefficient analysis for objective determination of optimal cluster numbers. We combined genomic analysis and lipopolysaccharide (LPS) structural analysis of phage-resistant E. coli strains to identify target receptors of the phages. Complementation experiments further confirmed the direct involvement of identified genes in phage reception. The results revealed that phylogenetically distinct E. coli phages target different sites in the LPS R-core region (modified by WaaV, WaaW, WaaT, and WaaY), membrane proteins (NfrB, TolA, YhaH), or flagella. Our analysis revealed that, subtle chemical modifications of LPS (such as Heptose phosphorylation) were shown to be important for E. coli phage recognition. Furthermore, physiological characteristics, tail fiber phylogenetics, and whole genome analysis independently classified the phages with high correlation to target receptor specificity. The addition of three phages with known receptors further validated our approach. Our results suggest that grouping based on physiological characteristics (such as lysis dynamics and host range) and genotypes (tail fiber phylogenetics or whole genome analysis) independently classified phages with high correlation to target receptor specificity. Here, we elucidated the diversity and specificity of E. coli phage target receptors, providing new insights into the classification of E. coli phages and phage-host interactions. ImportancePhage therapy is gaining attention as an alternative treatment for antibiotic-resistant bacteria. Developing effective phage cocktails requires combining phages with different target receptors, but traditional methods for identifying target receptors are labor-intensive. This study demonstrates that E. coli phages targeting the TK001 strain with different target receptors can be grouped based on their physiological characteristics, tail fiber sequences, or whole genomes. Our approach was enhanced through systematic bacterial panel selection for host range assessment, optimized distance metrics for physiological characteristics, and objective cluster determination using silhouette coefficient analysis for all three classifications. This insight can be used to more efficiently create diverse phage cocktails. Additionally, we identified phages targeting diverse sites, including different regions of LPS, membrane proteins, and flagella. These findings deepen our understanding of phage host recognition mechanisms, enabling the rapid preparation of effective phage cocktails and contributing to new advancements in bacterial infection treatment.

microbiology↗

bioRxiv2024

Surviving in the mountains: Temperature and elevation have contrasting physiological effects on the hoverfly Eristalis tenax in the Himalayas

Insect populations are experiencing a global decline due to a variety of human-linked environmental changes. Among these changes, how insects physiology might be affected by predicted upslope migration due to climate change is unknown. Being ectotherms, insect physiology is impacted by abiotic factors like ambient temperature that change with elevation. Here, we performed in situ experiments to assess the sensory and cardiac physiology of an important generalist pollinating hoverfly Eristalis tenax (Diptera: Syrphidae), across different elevations in the eco-sensitive and biodiverse Himalayan mountains. We built a portable physiology setup and measured hoverfly antennal responses towards common floral volatiles at 3600 masl and 4200 masl. We also recorded their heart rate at 3000 masl, 3500 masl and 4000 masl. We report the first in situ physiology experiments performed in the high-altitude Himalayas. Our results show a contrasting impact of elevation and temperature on the sensory and cardiac physiology of hoverflies, with antennal sensitivity decreasing with increasing elevation, while average heart rate increased with temperature, independent of elevation. With upslope migration and climate warming, consequent sensory mismatches and cardiac stress could have deleterious effects on the health of both hoverflies and the vulnerable Himalayan ecosystem.

zoology↗

bioRxiv2025

Physiologic recovery of Mycobacterium tuberculosis from drug injury: A molecular study of post antibiotic effect in mice

Post-antibiotic effect (PAE) describes the delayed recovery of bacteria following antibiotic exposure. PAE is thought to underlie tuberculosis (TB) treatment forgiveness, i.e. the capacity of regimens to tolerate non-adherence. The basis of PAE in Mycobacterium tuberculosis (Mtb) remains poorly understood, partly because PAE has conventionally been measured based on change in Mtb burden in vitro rather than change in Mtb physiology in vivo. We investigated Mtb physiologic recovery in the BALB/c mouse model following sub-curative 2- and 4-week durations of the standard isoniazid, rifampin, pyrazinamide, ethambutol (HRZE) treatment. Measurement of rRNA synthesis via the RS ratio(R) and the entire transcriptome via SEARCH-TB elucidated the dynamics of physiologic recovery. Mtb burden did not increase over 28 days of drug-free post-treatment recovery, indicating prolonged PAE in vivo. The RS ratio indicated that Mtb ribosomal RNA synthesis resumed within four days of treatment interruption. However, transcriptional changes indicative of metabolic reactivation were delayed for over two weeks. Processes critical for replication, including expression of genes involved in protein and cell wall synthesis, remained suppressed throughout 28 days post-treatment. Longer treatment induced more extensive physiologic perturbation and was associated with slower and less complete recovery. Expression of processes that are typically induced by environmental stress (e.g., DosR regulon, universal stress proteins, and heat shock proteins) exhibited the reverse, decreasing during drug treatment and rising during recovery. These findings provide a new basis for understanding PAE based on drug-induced injury and physiologic recovery. Following relatively short durations of HRZE, physiologic recovery of Mtb was a slow, sequential and incomplete process in vivo. Our observation that longer treatment resulted in even slower recovery suggests that Mtb may progressively lose capacity to recover. This work establishes a tractable experimental framework for quantifying the forgiveness of new TB treatment regimens in vivo.

microbiology↗

bioRxiv2018

Genetic variation for ontogenetic shifts in metabolism underlies physiological homeostasis in Drosophila

Organismal physiology emerges from metabolic pathways and structures that can vary across development and among individuals. Here we tested whether genetic variation at one level of physiology can be buffered at higher levels during development by the inherent capacity for homeostasis in physiological systems. We found that the fundamental scaling relationship between mass and metabolic rate, as well as the oxidative capacity per mitochondria, differed significantly across development in the fruit fly Drosophila. However, mitochondrial respiration rate was maintained across development at similar levels. Furthermore, genotypes clustered into two types--those that switched to aerobic, mitochondrial ATP production before the second instar and those that relied on anaerobic production of ATP via glycolysis through the second instar. Despite genetic variation for the timing of this metabolic shift, second-instar metabolic rate was more robust to genetic variation than was the metabolic rate of other instars. We also found that a mitochondrial-nuclear genotype with disrupted mitochondrial function both increased aerobic capacity more through development and relied more heavily on anaerobic ATP production relative to wildtype genotypes. By taking advantage of both ways of making ATP, this genotype maintained mitochondrial respiratory capacity, but also generated more free radicals and had decreased mitochondrial membrane potential, potentially as a physiological-defense mechanism. Taken together, the data revealed that genetic defects in core physiology can be buffered at the organismal level via physiological compensation and that natural populations likely harbor genetic variation for distinct metabolic strategies in development that generate similar organismal outcomes.

genetics↗

bioRxiv2026

Leveraging DNA and RNA oscillatory dynamics to investigate the ecology and physiology of a freshwater microbial community

The dynamics of microbial communities in temporally varying environments are often mediated by the physiological responses of their members. However, physiological measurements remain difficult to obtain \textit{in situ} from diverse communities in nature, limiting our understanding of microbial community dynamics in changing environments. Here, we investigate the physiological dynamics of a microbial community by applying a macroecological approach to a multi-year timeseries of paired ribosomal RNA (rRNA) and DNA (rDNA) measurements from a freshwater community, interpreting their relationship by developing a model of microbial physiology. Leveraging the existence of seasonal oscillations, we developed a data-driven minimal model that provided macroecological predictions and interpretations of rDNA, rRNA, and their relationship. Using this model, we examined two macroecological patterns with physiological interpretations: 1) time averaged rRNA:rDNA as a measure of a community member's steady-state and 2) the temporal ordering of rRNA fluctuations relative to rDNA. We found that rRNA:rDNA increased with the number of 16S rRNA operon copies, which in the context of our model suggests a superlinear effect of copy number. Temporal fluctuations of rRNA tended to \textit{precede} those of rDNA, consistent with the view that increases in ribosomal content can lead to future biomass. We then identified environmental variables where rRNA and rRNA:rDNA displayed greater sensitivity than rDNA, reasoning that rRNA:rDNA, as a reflection of the growth rate, may respond more strongly to environmental change. The ratio rRNA:rDNA provided greater sensitivity than rDNA for the majority of the aquatic environmental variables tested, particularly those reflecting the degree of eutrophy vs. oligotrophy. The results of this work indicate that the ratio rRNA:rDNA may be underutilized as a measure of the physiological state of natural communities.

microbiology↗

bioRxiv2026

Infra-slow brain-heart-gut electrophysiological interactions reveal a coordinated multisystem physiological network in humans

Growing evidence indicates that brain continuously interacts with other physiological systems through neural and non-neural pathways. The brain-heart and brain-gut axes play a central role in homeostasis, allostasis and behaviour, but also in cognitive aspects including emotion and decision-making. Disruptions in these axes have been linked to a wide range of cardiovascular, neurological, and psychiatric disorders. Despite this evidence, triadic crosstalk between the brain, heart, and gut remains largely unexplored. Brain activity, cardiac autonomic fluctuations, and gastric rhythms all exhibit slow temporal components in resting state, suggesting that brain-heart-gut electrophysiological interactions may occur over timescales from the infra-slow (0.01-0.1 Hz) physiological range. Using non-invasive electrophysiological recordings from 28 healthy participants at rest, we extracted time-varying power dynamics describing the activity of the three organs: brain alpha power, cardiac sympathetic and parasympathetic indices, and the power of the gastric rhythm. Statistical associations among these organs were quantified using the maximal information coefficient across the extended temporal delay range. Physiological interactions were confirmed using surrogate-based testing, which allowed us to construct the network topology of interactions between the three organs. Our findings show that triadic brain-heart-gut interactions form a multi-directional network at infra-slow timescales, shaping resting state activity. This study offers one of the first insights into the physiology of brain-heart-gut interplay, providing a methodological baseline for the development of more comprehensive biomarkers based on network dynamics capable of linking pathological conditions to dysregulation across multiple organ systems. Abstract figure legend O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=90 SRC="FIGDIR/small/718683v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@6600d1org.highwire.dtl.DTLVardef@bfd404org.highwire.dtl.DTLVardef@1f85612org.highwire.dtl.DTLVardef@dac616_HPS_FORMAT_FIGEXP M_FIG C_FIG Simultaneous resting-state electroencephalographic (EEG), electrocardiographic (ECG), and electrogastrographic (EGG) recordings were processed to extract time-resolved physiological markers for each organ: EEG alpha-band power for the brain, cardiac sympathetic and parasympathetic indices (CSI, CPI) for the heart, and EGG power for the gastrointestinal tract. Coupling between time series was then quantified, and statistical significance was assessed using a surrogate-based method. Significant couplings were subsequently integrated to construct a large-scale network representation, summarizing the strength, temporal delays, and directionality of the predominant electrophysiological interactions among the three organs. Key points summaryO_LIFirst in-human, non-invasive investigation of parallel brain-heart-gut electrophysiological interactions in awake, healthy individuals. C_LIO_LIWe analysed simultaneous electroencephalographic (EEG), electrocardiographic (ECG) and electrogastrographic (EGG) recordings and quantified strength and temporal scale of the derived time-series associations, to construct a large-scale network of interactions. C_LIO_LIWe found that brain-heart-gut interactions extend into the infra-slow (0.01 - 0.1 Hz) range, indicating that spontaneous fluctuations in the electrophysiological activity of one organ at rest are typically followed by corresponding changes in the other two. C_LIO_LIWe found a consistent brain-heart-gut network topology across participants, with multidirectional interactions and bodily dynamics converging toward midline central-posterior brain regions. C_LIO_LIThese findings provide one of the first endeavours in understanding the physiology of brain-heart-gut interactions, and a methodology with strong biomarker development potential. C_LI

neuroscience↗

bioRxiv2026

Title: Zero-shot automated insulin delivery for type 1 diabetes via dynamic physiology-aware reinforcement learning

Insulin therapy in type 1 diabetes requires constant dose adjustment based on blood glucose, meals, physiological states, and physical activity. This demanding self-management imposes a substantial burden and increases dosing-error risk, underscoring the need for automated insulin delivery (AID) systems that reduce user intervention. However, many current systems depend on fixed, individualized parameters and may not fully adapt to rapid or unobserved physiological changes. We developed the Dynamic Physiology-Aware Reinforcement learning Controller (DPARC), a zero-shot insulin optimizer that infers latent physiological dynamics from recent continuous glucose monitoring (CGM) and insulin-delivery history without prior personalization, carbohydrate announcements, or preset subject-specific parameters. DPARC uses a rolling 24-hour CGM and insulin-history window, but closed-loop operation can begin after 1 hour of observed data by initializing unobserved history with neutral normalized padding and progressively replacing it with observations. In silico, a single frozen DPARC policy adapted within 1 hour, improved time in range compared with a total daily insulin-conditioned reinforcement learning baseline, and approached the upper-bound performance of a fully personalized model under stochastic unannounced meals with randomized timing, carbohydrate amounts, absorption variability, and meal skipping. In supervised porcine studies under unannounced meals, DPARC maintained high time in range without manual configuration, supporting large-animal feasibility while prospective human evaluation is needed before clinical efficacy can be established. Learned latent representations correlated with physiological markers including insulin sensitivity and plasma insulin concentration, supporting physiological alignment and explanatory anchors. Collectively, these findings support DPARC as a preclinical proof-of-concept zero-shot AID framework for future supervised human evaluation.

bioengineering↗

bioRxiv2026

The Effect of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Cardiorespiratory Physiology: Four Waveforms Trial with Tragus vs Earlobe Stimulation

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) depends on activating afferent vagal pathways, leading to central and physiological (parasympathetic) modulation. Explaining how taVNS changes cardiorespiratory physiology requires systematic characterization of the effects of electrode location and stimulation waveform using rigorous experimental controls. ObjectiveTo determine the acute effects of four taVNS stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz) on physiological markers of parasympathetic activation compared with configuration-matched earlobe stimulation in healthy subjects at rest. MethodsCustomized 8-mm ear-clip electrodes delivered monophasic 500 s pulses (anode anterior) to the tragus or a configuration-matched earlobe control across four stimulation configurations (left unilateral 25 Hz, 100 Hz, burst, and bilateral 25 Hz). Twenty-five healthy participants completed a randomized, single-blind, within-subject crossover study, undergoing both active and control stimulation for all four configurations (200 sessions total). Each session consisted of five 60-second stimulation blocks (1,000 stimuli total). Heart rate (HR), heart rate variability (HRV; RMSSD), and respiration were recorded continuously. Linear mixed-effects models compared physiological responses between tragus and earlobe stimulation during the first stimulation block (primary analysis), across 5-second HR intervals (secondary analysis), and averaged across all five stimulation blocks (post hoc analysis). ResultsDuring the first stimulation block, HRV was significantly higher during unilateral left 25 Hz tragus stimulation than during the matched earlobe control ({beta} = -10.34, t(33) = -2.63, p = .01, 95% CI [-18.05, -2.64]), consistent with increased parasympathetic activity. No significant differences were observed for HRV with the other stimulation configurations, or for HR or respiration under any configuration. Analysis of 5-second HR intervals likewise revealed no significant temporal effects for block one. Analysis of 5-second heart rate intervals across the five blocks identified differences between tragus and earlobe at discrete time points but did not show a consistent temporal pattern across the stimulation period. Across all five stimulation blocks, unilateral left 25 Hz tragus stimulation remained associated with higher HRV ({beta} = -6.56, t(124) = -3.85, p < .01, 95% CI [-9.90, -3.22]) and also produced an increase in HR relative to earlobe stimulation ({beta} = -1.05, t(24) = -2.57, p = .01, 95% CI [-1.85, -0.24]). Respiration was unaffected throughout. ConclusionIn this systematic study, unilateral left 25 Hz tragus stimulation produced physiological modulation consistent with vagal target engagement. These findings underscore the importance of rigorous dose-specific taVNS studies to establish reproducible physiological biomarkers.

bioengineering↗

bioRxiv2026

Multidimensional characterization of the physiological and behavioral effects of TCB-2 in mice

Background and PurposeSerotonergic psychedelics affect behavior and physiology, but the relationships among these effects remain poorly understood. In rodents, the head-twitch response is used as a measure of psychedelic-like activity, yet it does not capture changes in physiological state or the performance of learned behaviors. Here, we investigated the acute effects of the 5-HT2A receptor agonist TCB-2 across several behavioral and physiological measures and examined how these effects were modified by pretreatment with the 5-HT2A receptor antagonist volinanserin. Experimental ApproachMice were tested in head-fixed and freely moving conditions. During a learned auditory trace-conditioning task, we measured licking, pupil area, eye position, and blinking. We measured locomotor activity in an open field and quantified head-twitch responses using a DeepLabCut-based method. To examine the contribution of 5-HT2A receptors, mice were pretreated with the 5-HT2A receptor antagonist volinanserin. Key ResultsTCB-2 caused pupil constriction without detectable changes in eye position or blinking when administered alone. TCB-2 also reduced licking at the highest dose, but the cue-locked temporal pattern of licking remained evident. In freely moving mice, TCB-2 reduced locomotor activity and produced a dose-dependent increase in head-twitch responses. Volinanserin partially attenuated TCB-2-induced pupil constriction and reduced head-twitch responses under some conditions, but it did not consistently prevent the other effects of TCB-2. Conclusions and ImplicationsTCB-2 produced distinct effects across physiological and behavioral measures rather than a uniform disruption of behavioral function. Pronounced pupil constriction and head-twitch responses occurred without detectable changes in eye position or blinking, while the temporal organization of conditioned licking was retained despite a reduction in its magnitude. The incomplete and variable effects of volinanserin preclude definitive conclusions about the receptor mechanisms underlying each response. Combining automated head-twitch detection with physiological and task-related measurements provides a broader framework for comparing the pharmacological profiles of serotonergic compounds. What is already knownO_LIClassical psychedelics produce characteristic effects primarily through serotonin 5-HT2A receptor activation. C_LIO_LIHead-twitch responses capture only one dimension of psychedelic-like drug action. C_LI What this study addsO_LITCB-2 reduced locomotion and licking while preserving the cue-locked pattern of conditioned licking. C_LIO_LIPupil constriction occurred without detectable changes in eye position or blinking. C_LI Clinical significanceO_LIMultidimensional phenotyping can distinguish the physiological and behavioral profiles of serotonergic compounds. C_LIO_LIComplementary measures may improve preclinical evaluation of emerging serotonergic therapeutics. C_LI

pharmacology and toxicology↗