Biology subjects

Wen, W.

Publications and source records attributed to Wen, W..

At least 19 recordsLinked to original sources

bioRxiv2026

CD59 Promotes SNARE Complex Assembly via Interaction with the Proline-Rich N-Terminal Domain of VAMP2

ObjectiveThe complement regulatory protein CD59 has been shown to promote SNARE complex assembly, yet its interaction with vesicle-associated membrane protein 2 (VAMP2) remains poorly characterized. This study aims to identify the key domain in VAMP2 that mediates the CD59 interaction and to evaluate whether CD59 point mutations affect SNARE complex assembly. MethodsThe interaction between CD59 and VAMP2 was examined by immunofluorescence confocal microscopy and co-immunoprecipitation (co-IP). The effect of CD59 on SNARE complex assembly was assessed by co-expressing CD59 with the three core SNARE proteins (syntaxin-1, SNAP-25, and VAMP2) and detecting complex formation by western blotting. Four CD59 single-point mutants were generated and evaluated in SNARE assembly assays. AlphaFold3 was employed to predict the interaction between CD59 and individual VAMP2 domains (confidence threshold: ipTM + pTM [≥] 0.75). Truncated VAMP2 constructs were further characterized by molecular dynamics simulations and co-IP. Results(1) CD59 directly bound VAMP2 and promoted SNARE complex assembly without altering individual SNARE protein levels. (2) All four CD59 single-point mutants retained the ability to promote SNARE assembly at a level comparable to wild-type CD59, despite showing differential effects on binding stability in molecular dynamics simulations. (3) The proline-rich (P-rich) N-terminal domain of VAMP2 was identified as the key binding interface; its deletion abolished the CD59 interaction, whereas deletion of the SNARE motif did not. ConclusionCD59 promotes SNARE complex assembly through interaction with the P-rich N-terminal domain of VAMP2. The examined point mutations do not impair this function, suggesting that these sites may tolerate substitutions or that redundant contact residues maintain the interaction.

neuroscience↗

bioRxiv2026

Gut bacterial Infection drives Parkinsonian pathology in LRRK2 G2019S Knock-in Mice

The LRRK2 G2019S mutation is one of the most common genetic risk factors for Parkinsons disease (PD), yet LRRK2 G2019S knock-in (KI) mice rarely develop robust neurodegeneration under basal conditions, suggesting that additional environmental triggers are required for disease progression. Here, we established a clinically relevant gene-environment interaction mouse model of PD by subjecting LRRK2 G2019S KI mice to recurrent Citrobacter (C.) rodentium infection, a murine model of enteric bacterial inflammation. Repeated infection induced progressive PD-like phenotypes selectively in KI mice, including motor impairment, reduced locomotor activity, impaired motor coordination, selective nigrostriatal dopaminergic neurodegeneration, enhanced neuroinflammation, and pathological phosphorylated -synuclein (p-Syn) accumulation, whereas wild-type (WT) mice remained largely resistant. Mechanistically, infected KI mice developed markedly exacerbated colonic inflammation, epithelial barrier dysfunction, increased intestinal permeability, and enhanced inflammasome activation despite normal bacterial clearance, indicating that pathogenic LRRK2 signaling amplifies inflammatory responses rather than impairing antimicrobial defense. In parallel, recurrent infection induced pronounced intestinal p-Syn accumulation and expansion of pathology beyond the epithelial layer in KI mice, supporting a gut-brain axis mechanism linking intestinal inflammation to neurodegeneration. Collectively, these findings demonstrate that the LRRK2 G2019S mutation functions as a sensitizing factor that cooperates with recurrent enteric inflammation to drive PD- related pathology. This study establishes a physiologically relevant LRRK2 G2019S gene- environment interaction mouse model that recapitulates key behavioral, neuropathological, and inflammatory features of PD.

immunology↗

bioRxiv2026

Expectation triggers a change-like EEG response without acoustic change

Predictive processing theories posit that the auditory system continuously generates expectations and updates internal models when incoming evidence violates those expectations. Whether such updating can be expressed as a temporally precise, change-like neural response at a context-defined moment during continuous stimulation--without any physical change--has remained unclear. Using a transitional click-train paradigm in human EEG, we show that listeners reliably detect subtle midpoint transitions when click timing is fixed, whereas temporal uncertainty markedly weakens this sensory-driven detection. Strikingly, even in a physically unchanged stimulus, variable click timing elicits a robust response time-locked to the nominal midpoint. This endogenous change-like signal is stimulus-statistics dependent--absent in the fixed-timing no-change control--temporally confined to the early post-change window, and strongly state dependent, being amplified during active change detection relative to passive listening. Moreover, within identical no-change trials, the response tracks subjective change reports. Together, these findings show that temporal uncertainty and task engagement jointly gate predictive updating in continuous auditory streams, providing a compact assay to dissociate sensory-driven change responses from context- and state-dependent predictive signals.

neuroscience↗

bioRxiv2026

Deep Learning Reveals Persistent Individual Signatures in Bat Echolocation Calls of the Greater Leaf-nosed Bat

Intraspecific variation is a prerequisite for natural selection and can manifest in various phenotypic traits, including vocal signals. However, classifying individuals based on their vocalizations, or acoustic individual identification (AIID), remains a significant challenge. This is particularly true for species that use rapidly varying echolocation calls for orientation. Here, we demonstrate that deep learning can overcome the limitation of traditional methods and reveal persistent individual signatures within bat echolocation calls. We recorded echolocation calls from 34 individuals of the greater leaf-nosed bat (Hipposideros armiger) under controlled laboratory conditions, with 19 individuals recorded repeatedly over three months. We show that a convolutional neural network (CNN) dramatically outperforms a traditional method, achieving an average identification accuracy of 84% for single calls and 91% for call sequences. In contrast, the traditional Discriminant Functional Analysis method achieved accuracies of only 39% and 47%, respectively. Through systematically altering the temporal structure of echolocation calls in input sequences, we found that temporal patterning enhances individual classification accuracy, suggesting it contributes to the encoding of individual-specific information. This study revealed that echolocation calls of H. armiger can contain stable, individual identity that were previously undetectable. Our findings highlight the potential of deep learning for non-invasive AIID and provide a methodological basis for future studies aiming to monitor animals in more dynamic environments.

zoology↗

bioRxiv2026

Unified Multi-Cohort Harmonisation and Normative Modelling of Neuroimaging Data via Hierarchical GAMLSS

Large-scale neuroimaging studies increasingly pool data across multiple cohorts, scanners, and acquisition protocols, introducing technical between-cohort variation that must be addressed before meaningful biological inference can be drawn. Existing harmonisation methods, particularly ComBat-based approaches, have been widely adopted for this purpose. However, they remain limited by Gaussian assumptions and by their focus on location or location-scale correction. In this study, we propose a unified hierarchical Generalised Additive Models for Location, Scale and Shape (GAMLSS) framework for multi-cohort harmonisation and normative modelling of structural neuroimaging data. The framework models cohort effects directly within all fitted distributional parameters, accommodates any parametric family for which exact inverse mapping is available, and returns harmonised values on the original measurement scale through centile-based quantile mapping. Normative deviation scores are obtained as a direct by-product of the same fitted model, enabling harmonisation and normative inference to be conducted jointly. The method was evaluated in a pooled longitudinal dataset comprising 88,126 observations across 237 structural neuroimaging features from six cohorts spanning childhood to late life: ABCD, IMAGEN, NCANDA, LIFE, UK Biobank, and MAS. Harmonisation performance was compared with ComBat, ComBat-GAM, and ComBat-LS using complementary criteria assessing data retention, residual batch effects, preservation of age-related and sex-related biological signal, and coherence of post-harmonisation lifespan trajectories. GAMLSS achieved near-complete removal of residual cohort effects, retained almost all valid observations post-harmonisation, and showed the strongest overall preservation of biological signal across validation metrics. In particular, it better preserved biologically plausible age trajectories for distributionally complex features such as white matter hypointensity volume, while simultaneously providing harmonised native-scale values and normative deviation scores within a single framework. These findings suggest that hierarchical GAMLSS offers a flexible and practical alternative to existing ComBat-based methods for large-scale neuroimaging harmonisation, particularly for features with non-Gaussian residual distributions and settings where cohort effects extend beyond differences in mean and variance.

neuroscience↗

bioRxiv2026

Altered Motor Awareness in Parkinson's Disease with Progressive Micrographia

Micrographia, characterized by abnormally small handwriting, is a common motor symptom in Parkinsons disease (PD), and has been classified into consistent micrographia (CM) and progressive micrographia (PM), which may reflect different underlying mechanisms. However, the relative contributions of motor execution and sensorimotor processing to these subtypes remain unclear. In this study, forty-five people with Parkinsons disease (PwP) and twenty age-matched healthy controls (HCs) completed a handwriting task and a control detection task (CDT) assessing the ability to distinguish self-generated from externally generated movements. PwP were classified based on handwriting metrics as showing no micrographia, CM, and/or PM. CDT accuracy was significantly lower in PwP than in HCs (p < 0.01) and was particularly reduced in PwP with PM (p < 0.01). These findings indicate that PM is associated with impaired motor awareness, suggesting altered sensorimotor integration as a characteristic feature of this subtype.

neuroscience↗

bioRxiv2025

Temporal boundary gating of auditory sensitivity

Perception unfolds over time, but whether continuous sounds are sampled with uniform sensitivity is unknown. We combine human psychophysics, EEG and rodent neurophysiology to show that local auditory change detection is strongly gated by stimulus boundaries. In humans, brief perturbations inserted at different temporal positions within 0.5-1-s tones revealed an inverted U-shaped sensitivity profile: detection was attenuated near sound onset and offset and maximal mid-epoch, with EEG change responses showing a closely matching dependence on change timing. Electrocorticography in awake rats exhibited homologous temporal weighting, and analogous profiles for amplitude changes and visual motion demonstrated cross-feature and cross-modal generality. To uncover circuit mechanisms, we recorded single units along the inferior colliculus-medial geniculate body-auditory cortex pathway together with laminar local field potentials in A1. Onset-locked suppression of change responses emerged in midbrain and was progressively amplified in thalamus and cortex, whereas the full start-end profile was expressed in granular-layer alpha-gamma power. A simple biophysically grounded model in which onset responses saturate and cortical populations integrate over finite temporal windows recapitulates this pattern, explaining how stimulus boundaries disrupt prospective and retrospective integration and thereby degrade change detection near the beginning and end of sounds.

neuroscience↗

bioRxiv2025

Associations between volumes of grey matter regions and white matter hyperintensities with cognitive empathy in oldest-old adults

OBJECTIVESTo study the differential associations of regional volumes of grey matter (GM) and white matter hyperintensities (WMH) with behavioural and informant-reported measures of cognitive empathy (CE), especially in brain regions understood to have functional connectivity involvement with CE abilities. METHODSCommunity-dwelling participants from the Sydney Memory and Ageing Study (Sydney MAS) underwent whole brain MRI. Regional cortical GM volumes were derived using FreeSurfer v7.1 for, and WMH volumes were derived using UBO Detector. On follow-up four years later, CE was indexed via the Reading the Mind in the Eyes Test (RMET; a behavioural task) and Interpersonal Reactivity Index - Perspective Taking subscale (IRI-PT; an informant-reported measure). RESULTSIn 129 participants (mean age 87.01 years), Structural equation modelling (SEM) showed associations between insula GM volumes and RMET scores (p=0.001), and between supramarginal gyrus (SMG) GM volumes and IRI-PT scores (p=0.016). Associations remained significant after inclusion of covariates accounting for age, global cognition, affective symptoms, and social networks. DISCUSSIONCE abilities assessed with RMET (a behavioural task) were positively associated with insula GM volumes. CE abilities on the IRI-PT (an informant-reported measure) were positively associated with SMG GM volumes. No associations between WMH volumes and CE measures were found. These findings may inform clinical workflows that use structural MRI investigations looking at social cognitive disturbances in older adults and provide further evidence of the divergent nature of behavioural and self-report measures of CE.

neuroscience↗

bioRxiv2025

Walking Selectively Modulates Behaviorally Relevant Auditory Responses According to Stride Cycle Phase

Perception in natural environments unfolds while the body is in motion, yet how locomotion shapes cortical computations for fine-grained and dynamic scene analysis remains unclear. Here, we combined over-ground walking with mobile EEG and a transitional click-train paradigm to test how natural locomotion influences auditory processing in humans. Participants listened to two-segment click trains in which a subtle inter-click-interval (ICI) change signaled a pitch shift and performed a task-engaged change-detection task while either sitting or walking; an independent cohort also completed a passive-listening version. Walking elevated behavioral detection thresholds and slowed responses, indicating reduced sensitivity to fine temporal changes. Neurally, locomotion produced a response-component-specific attenuation: activity time-locked to the ICI transition--the change response previously linked to temporally integrative updating of an ongoing auditory object--was strongly reduced, whereas the offset response was largely preserved and onset responses were only modestly affected. Critically, this modulation persisted during passive listening and was selectively amplified near the perceptual threshold during task-engaged detection, revealing an interaction between motor state and cognitive demand. Thus, natural locomotion does not uniformly degrade hearing; instead, it preferentially down-weights a behaviorally critical, temporally demanding stage of auditory processing, offering a framework for understanding how motor-cognitive state shapes auditory scene analysis in the moving brain.

neuroscience↗

bioRxiv2025

Deficiency of Mesencephalic Astrocyte-derived Neurotrophic Factor Aggravates Acute Pancreatitis in Mice

Acute pancreatitis (AP) is a complex and potentially severe inflammatory disorder of the pancreas and is one of the most common causes of gastrointestinal hospitalization. Although environmental risk factors such as alcohol and gallstones are well recognized, only a subset of exposed individuals develop AP, suggesting that intrinsic factors, including genetic susceptibility, influence disease onset and progression. Endoplasmic reticulum (ER) stress has emerged as a key mechanism in AP pathogenesis, because ER is essential for protein synthesis, folding, degradation and secretion (proteostasis). Mesencephalic astrocyte-derived neurotrophic factor (MANF), an ER stress-inducible protein highly expressed in the pancreas, plays a critical role in maintaining proteostasis, yet its involvement in AP remains unclear. To investigate the functional role of MANF in AP, we generated pancreas-specific MANF knockout (MANF-KO) mice using the Cre/loxP system and subjected them to moderate experimental AP, that is caerulein- or alcohol-induced AP in mice. In the caerulein model, MANF deficiency exacerbated pancreatic injury in both sexes, as indicated by increased apoptosis (cleaved caspase-3, caspase-12), ER stress markers (eIF2, p-eIF2, GRP78), inflammation (IL-6, TNF), regenerative activity (Ki67), and pancreatic lipase levels. Notably, male MANF-KO mice exhibited enhanced inflammation (HMGB1), macrophage infiltration (CD68), and oxidative stress (DNP, HNE), which were not observed in females. In the alcoholic AP model, both male and female MANF-KO mice showed increased ER stress (p-IRE1, p-eIF2, GRP78), apoptosis, inflammation, macrophage infiltration, regeneration, and lipase levels, whereas elevated HMGB1 expression and oxidative stress again predominantly occurred in male MANF-KO mice. Together, these findings reveal a critical and sex-specific role for MANF in regulating pancreatic stress responses and inflammatory injury, supporting its potential contribution as a genetic factor in AP pathogenesis.

pathology↗

bioRxiv2025

Age-Related Alterations in the Expression of Mesencephalic Astrocyte-derived Neurotrophic Factor in the Brain and Their Impact on Neurobehavioral Functions

Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic protein localized in the endoplasmic reticulum (ER) and pivotally involved in maintaining ER homeostasis. MANF plays an important role in mitigating neurodegenerative processes. Aging, the primary risk factor for neurodegenerative diseases (NDDs), is associated with significant alterations in ER function. The ER, central to protein synthesis, folding, degradation and secretion (proteostasis), experiences considerable stress in NDDs, which activates the unfolded protein response (UPR). We hypothesized that MANF and UPR is crucial for maintaining proteostasis during aging, but their efficacy declines with age, therefore increasing vulnerability to NDDs. We measured MANF levels in the brain and plasma of 1-, 4-, 11-, and 22-month-old male and female mice. A progressive decline of MANF levels was observed, with the lowest levels detected in 22 months. Reduced MANF expression was found in aged mice across several brain areas, including the cerebral cortex, olfactory bulb, thalamus, hypothalamus, hippocampus, and cerebellum. There was a sex difference in MANF levels in aged mice. Aging also altered the expression of UPR and MANF interacting proteins. Using cerebellar Purkinje cell (PC)-specific MANF deficient mice, we showed that MANF deficiency impaired motor coordination in female, but not male mice. MANF deficiency weakened spatial learning and memory in both male and female mice. Male MANF deficient mice displayed increased sociability, whereas female mice exhibit social withdrawal. Taken together, MANF expression in the brain declined with age and MANF deficiency impacted neurobehaviors in the aging animal in a sex-specific manner.

neuroscience↗

bioRxiv2025

Complementary role of frontal theta and parietal alpha activity in resolving visual competition

Attention plays a central role in selecting information for conscious perception. Because natural environments are structured, prior knowledge about relevant and irrelevant features can guide this selection. However, prior knowledge about distractors can enhance their neural representation, raising the question of how the brain prevents such enhancement from interfering with behavior. We addressed this question by combining a binocular rivalry paradigm with frequency-tagged stimuli to independently track target and distractor signals during sustained perceptual competition. We identified a sequential pattern of oscillatory dynamics underlying stable perception. Early parietal alpha activity (8-12 Hz) was associated with the segregation of competing inputs without altering sensory gain. This was followed by frontal theta activity (3-7 Hz), which was linked to the reactive suppression of distractors representations. Importantly, alpha-mediated gating effects are most pronounced under high perceptual uncertainty, where they facilitated the stabilization of weak target signals and promoted their access to conscious awareness. Together, these findings demonstrate that perceptual competition is resolved through a coordinated sequence of proactive gating and reactive suppression.

neuroscience↗

bioRxiv2025

Spatial Transcriptomics Analysis Uncovers ER stress in MANF-deficient Purkinje Cells Underlying Alcohol-induced Cerebellar Vulnerability in Mice

Cerebellar Purkinje cells (PCs) are among the most vulnerable neurons to alcohol neurotoxicity. Alcohol can induce endoplasmic reticulum (ER) stress and alter the structure and function of PCs. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an ER stress inducible protein highly expressed in PCs. It is neuroprotective in various pathological conditions where ER stress is induced. However, it is unknown whether MANF plays a role in protecting PCs from alcohol induced ER stress. In this study, we generated PC-specific MANF knockout (KO) mouse model to test the hypothesis that MANF deficient PCs are more susceptible to binge alcohol exposure induced ER stress and neurodegeneration in the adult brain. We found that PC-specific MANF KO animals show moderate motor function deficit, which was exacerbated by alcohol exposure. Interestingly, female KOs were more sensitive than male KOs to alcohol-induced motor function impairments. In accordance with the behavior changes, alcohol exposure also caused UPR activation, increased intranuclear expression of calcium binding protein Calbindin, and PC degeneration in female but not male MANF KO mice. Spatial transcriptomics and high throughput in situ analyses demonstrated that MANF deficiency altered the transcriptomic landscape in PCs in a sex-specific manner and triggered the expression of genes involved in protein folding and response to ER stress. These results suggests that MANF KO PCs may be predisposed with a higher risk to UPR activation and ER stress in a sex dependent manner, contributing to their vulnerability to alcohol neurotoxicity.

molecular biology↗

bioRxiv2025

Alcohol Disrupts Neural Differentiation Through Endoplasmic Reticulum Stress and PERK Pathway Activation

Prenatal alcohol exposure (PAE) can lead to fetal alcohol spectrum disorder (FASD), a condition marked by developmental brain defects that result in neurobehavioral and cognitive impairments. However, the underlying molecular mechanisms remain poorly understood. Brain development is a highly regulated process, with neurogenesis playing a crucial role. A key stage in this process is neural differentiation, which is essential for proper brain function. This study aims to investigate how alcohol disrupts neural differentiation. NE-4C cells, a neural stem cell line derived from the mouse embryonic brain, were utilized as an in vitro model. As an in vivo model, pregnant mice were exposed to alcohol between gestation days 14 and 16, after which newly formed neurons in the ventricular zone (VZ) were analyzed. To examine the role of endoplasmic reticulum (ER) stress, tunicamycin (TM), and MANF-deficient NE-4C cells were employed. Neural differentiation was assessed using immunofluorescence, immunoblotting and flow cytometry. Alcohol impaired the differentiation of NE-4C cells into neurons and astrocytes without impacting cell migration. It also induced ER stress, preferably activating the PERK pathway. Similarly, ER stress caused by TM and MANF deficiency disrupted neural differentiation and activated PERK. Inhibiting PERK mitigated alcohol-induced impairment of neuronal differentiation. PAE decreased the number of newly formed neurons in the VZ of fetal brain while having little effects on cell survival and proliferation. Inhibiting PERK partially reversed the reduction of new neurons caused by PAE. Thus, alcohol-induced ER stress, particularly PERK activation, may contribute to impaired neurogenesis linked to FASD.

pharmacology and toxicology↗

bioRxiv2025

Effects of alcohol on gut microbiome in adolescent and adult MMTV-Wnt1 mice

Breast cancer is the most commonly diagnosed cancer in women worldwide, with alcohol consumption recognized as a significant risk factor. While epidemiological studies consistently show a positive correlation between alcohol consumption and increased breast cancer risk, the underlying mechanisms remain unclear. Recent evidence suggests that the gut microbiome--the diverse collection of microorganisms, including bacteria, viruses, and fungi, residing in the gastrointestinal tract--plays a pivotal role in systemic health and disease. This is achieved through its regulation of key physiological processes such as metabolism, immune function, and inflammatory responses. Disruption of the gut microbiome (dysbiosis) has recently been implicated in the development of breast cancer. We hypothesized that alcohol exposure induces gut dysbiosis, which in turn drives systemic inflammation and carcinogenic processes. Previously, we demonstrated that alcohol exposure promotes mammary tumor growth and aggressiveness in MMTV-Wnt1 (Wnt1) transgenic mice, an established model for investigating mechanisms of alcohol-induced tumor promotion. In this study, we sought to determine whether alcohol exposure induces gut dysbiosis in adolescent and adult Wnt1 transgenic mice and their wild-type FVB counterparts. Our findings revealed that alcohol exposure significantly reduced microbiome richness in adult Wnt1 and FVB mice. Alcohol exposure also markedly altered microbiome composition in adolescents and adults in both strains. Additionally, we identified specific microbial taxa that were significantly affected by alcohol exposure. These results demonstrate that alcohol disrupts the gut microbiome in a preclinical breast cancer model, providing insights into the potential role of gut dysbiosis in alcohol-induced mammary tumor promotion and offering avenues for future research.

cancer biology↗

bioRxiv2025

An Enhanced Conditional Variational Autoencoder-Based Normative Model for Neuroimaging Analysis

Normative modelling in neuroimaging provides a powerful framework for quantifying individual deviations from expected brain measures as a function of relevant covariates. While most established approaches have focused on analysing distinct variables in isolation, there is a growing need for deep learning-based methods capable of handling multiple response variables simultaneously. Conditional variational autoencoders (cVAEs) have previously been applied in this context; however, existing inference methods still face challenges in providing reliable probabilistic predictions. In this study, we introduce an enhanced cVAE-based framework for normative modelling of neuroimaging data. Our key contribution is the development of a novel inference method that integrates latent space sampling and bootstrapping. This method directly leverages the generative nature of cVAEs to estimate the conditional distributions of brain measures. We demonstrate the effectiveness of this approach using white matter hyperintensity (WMH) volumes as a test case for developing, testing, and validating the model. Our dataset includes 8,551 normotensive and 18,180 hypertensive participants from the UK Biobank. We evaluated our method against three well-established and popular normative modelling techniques, including Generalised Additive Models for Location, Scale, and Shape (GAMLSS), Multivariate Fractional Polynomial Regression (MFPR), and Hierarchical Bayesian Regression (HBR). Our results indicate that the proposed cVAE-based framework achieves comparable performance across various metrics, while capturing individual deviations that correlate with the severity of hypertension. The model is particularly well-suited for high-dimensional, non-linear data, making it a robust tool for assessing individual deviations in brain structure. This enhanced normative modelling architecture paves the way for more nuanced and reliable assessments of brain health, with potential implications for personalised medicine and early detection of neurological disorders.

neuroscience↗

bioRxiv2024

A signal of temporal integration in the human auditory brain: psychological insights, EEG evidence, and clinical application

Temporal integration, the process by which the auditory system combines sound information over a curtain period to form a coherent auditory object, is essential for coherent auditory perception, yet its neural mechanisms remain underexplored. We use a "transitional click train" paradigm, which concatenates two click trains with slightly differing inter-click intervals (ICIs), to investigate temporal integration in the human cortex. Using a 64-channel electroencephalogram (EEG), we recorded responses from 42 healthy participants exposed to regular and irregular transitional click trains and conducted change detection tasks. Regular transitional click trains elicited significant change responses in the human cortex, indicative of temporal integration, whereas irregular trains did not. These neural responses were modulated by ICI length, ICI contrast, and regularity. Behavioral data mirrored EEG findings, showing enhanced detection for regular conditions compared to irregular conditions and pure tones. Furthermore, variations in change responses were associated with decision-making processes. Temporal continuity was critical, as introducing gaps between click trains diminished both behavioral and neural responses. In clinical assessments, 22 coma patients exhibited diminished or absent change responses, effectively distinguishing them from healthy individuals. Our findings identify distinct neural markers of temporal integration and highlight the potential of transitional click trains for clinical diagnostics.

neuroscience↗

bioRxiv2024

Reconcile sensory attenuation and enhancement: The temporal dynamics of self-generated sensory feedback

Self-generated touches are often perceived as weaker than externally generated ones, a phenomenon known as sensory attenuation. However, recent studies have challenged this view by providing evidences that actions could also enhance predicted touch. To investigate this paradox, we examined the temporal dynamics of perceptual processing using steady-state somatosensory evoked potentials (SSSEP) and sliding time window analysis. Results showed that SSSEP in the very early window was smaller in the no-delay and active conditions compared to the delayed and passive condition, respectively, consistent with sensory attenuation. However, this attenuation soon disappeared and reversed in the later windows and onward, indicating an early attenuation followed by a later enhancement. This study resolves the paradox of sensory attenuation and enhancement in self-generated sensory signals by demonstrating that these processes occur at different phases of sensory processing. The findings reveal a sophisticated dynamic balance in sensory processing, facilitating optimal interaction with the environment.

neuroscience↗