Biology subjects

Jiang, Z.

Publications and source records attributed to Jiang, Z..

At least 127 records · Page 7Linked to original sources

bioRxiv2024

Architecture of intact mammalian pyruvate dehydrogenase complex revealed by in-situ structural analysis

The multi-enzyme pyruvate dehydrogenase complex (PDC) links glycolysis to the citric acid cycle by converting pyruvate into acetyl-coenzyme A and is essential for cellular energy metabolism. Although individual components have been characterized, the structure of intact PDC remains unclear, hampering our understanding of its composition and multi-step catalytic reactions. Here, we report the in-situ architecture of intact PDC within mammalian mitochondria by cryo-electron tomography. The organization of peripheral E1 and E3 multimers varies substantially among PDCs. We discovered 1-46 E1 heterotetramers surrounding each PDC core, and up to 12 E3 dimers locating primarily along the pentagonal openings. Furthermore, we observed dynamic interactions of the substrate translocating lipoyl domains (LDs) with both E1 and E2, implicating the mechanism of substrate channeling. Our findings reveal the intrinsic dynamics of PDC peripheral compositions, suggesting an additional model in which the number of assembled E1 heterotetramer, E3 dimer, and functional LDs of PDC may be regulated to further control its catalytic activity.

cell biology↗

bioRxiv2024

Bacterial exonuclease III expands its enzymatic activities on single-stranded DNA

Bacterial exonuclease III (ExoIII), widely acknowledged for specifically targeting double-stranded DNA (dsDNA), has been documented as a DNA repair-associated nuclease with apurinic/apyrimidinic (AP)-endonuclease and 3'[->]5' exonuclease activities. Due to these enzymatic properties, ExoIII has been broadly applied in molecular biosensors. Here, we demonstrate that ExoIII (Escherichia coli) possesses highly active enzymatic activities on ssDNA. By using a range of ssDNA fluorescence-quenching reporters and fluorophore-labelled probes coupled with mass spectrometry analysis, we found ExoIII cleaved the ssDNA at 5'-bond of phosphodiester from 3' to 5' end by both exonuclease and endonuclease activities. Additional point mutation analysis identified the critical residues for the ssDNase action of ExoIII and suggested the activity shared the same active center with the dsDNA-targeted activities of ExoIII. Notably, ExoIII could also digest the dsDNA structures containing 3'-end ssDNA. Considering most ExoIII-assisted molecular biosensors require the involvement of single-stranded DNA (ssDNA) or nucleic acid aptamer containing ssDNA, the activity will lead to low efficiency or false positive outcome. Our study revealed the multi-enzymatic activity and the underlying molecular mechanism of ExoIII on ssDNA, illuminating novel insights for understanding its biological roles in DNA repair and the rational design of ExoIII-ssDNA involved diagnostics.

biochemistry↗

bioRxiv2023

Unveiling Elevated Spontaneous Mutation Rates in Phyllostachys edulis (Moso Bamboo) through Whole Genome Sequencing (WGS) and Investigating the Impact of Atmospheric and Room Temperature Plasma (ARTP) Induced Mutagenesis

Moso bamboo, recognized for its wide distribution and economic importance, encounters challenges in varietal enhancement due to its protracted sexual reproduction cycle. This study employed whole-genome resequencing to uncover spontaneous mutations in Moso bamboo and investigated mutagenesis using atmospheric and room temperature plasma (ARTP). Through the sequencing results, we identified the population of flowering bamboo as an asexual breeding line. Notably, the flowering Moso bamboo population, exclusively derived from asexual reproduction, exhibited a high spontaneous mutation rate (4.54 x 10-4 to 1.15 x 10-3/bp) during sexual reproduction, considering parental and cross-pollination effects. Genetic disparities between offspring and parents exhibited a bimodal distribution, indicating a substantial cross-pollination rate. ARTP mutagenesis increased structural variations in offspring, while changes in SNPs and INDELs were less pronounced. Sanger sequencing validated a gene subset, providing a foundation for spontaneous mutation rate investigation via whole-genome sequencing. These insights, particularly from mutagenized offspring sequencing, contribute to Moso bamboo breeding strategies. HighlightMoso bamboo breeding revolutionized--high spontaneous mutations in asexually derived flowering population. ARTP mutagenesis boosts structural variations, shaping innovative breeding approaches.

genetics↗

bioRxiv2023

Genomic evidence for hybridization and introgression between blue peafowl and green peafowl and selection for white plumage

The blue peafowl (Pavo cristatus) and the green peafowl (Pavo muticus) have significant public affection due to their stunning appearance, although the green peafowl is currently endangered. Some studies have suggested introgression between these the two species, although evidence is mixed. In this study, we successfully assembled a high-quality chromosome-level reference genome of the blue peafowl, including the autosomes, Z and W sex chromosomes as well as a complete mitochondria DNA sequence. Data from 77 peafowl whole genomes, 76 peafowl mitochondrial genomes and 33 peahen W chromosomes genomes provide the first substantial genetic evidence for recent hybridization between green and blue peafowl. We found three hybrid green peafowls in zoo samples rather than in the wild samples, with blue peafowl genomic content of 16-34%. Maternal genetic analysis showed that two of the hybrid female green peafowls contained complete blue peafowl mitochondrial genomes and W chromosomes. Hybridization of endangered species with its relatives is extremely detrimental to conservation. Some animal protection agencies release captive green peafowls in order to maintain the wild population of green peafowls. Therefore, in order to better protect the endangered green peafowl, we suggest that purebred identification must be carried out before releasing green peafowls from zoos into the wild in order to preventing the hybrid green peafowl from contaminating the wild green peafowl. In addition, we also found that there were historical introgression events of green peafowl to blue peafowl in four Zoo blue peafowl individuals. The introgressed genomic regions contain IGFBP1 and IGFBP2 genes that could affect blue peafowl body size. Finally, we identified that the nonsense mutation (g.4:12583552G>A) in the EDNRB2 gene is the genetic causative mutation for white feather color of blue peafowl (also called white peafowl), which prevents melanocytes from being transported into feathers, such that melanin cannot be deposited.

genomics↗

bioRxiv2023

Early Embryonic Establishment of Constitutive Heterochromatin Involves H3K14ac-mediated Recruitment of Eggless/SetDB1

Constitutive heterochromatin, built on various types of repetitive DNA, is a fundamental feature of eukaryotic nucleus essential for transposon silencing and genome stability. However, the molecular programs driving its de novo establishment during early embryogenesis remain poorly understood. Here, we show that histone H3 lysine 14 acetylation (H3K14ac) is maternally inherited and partially colocalizes with hallmarks of constitutive heterochromatin, H3 lysine 9 trimethylation (H3K9me3) and its methyltransferase Eggless/SetDB1, around the mid-blastula transition in Drosophila early embryos. Concealing H3K14ac by either antibody injection or maternal knockdown of Gcn5 diminishes Eggless/SetDB1 nuclear foci and reduces the deposition of H3K9me3. Structural analysis reveals that Eggless/SetDB1 recognizes H3K14ac via its tandem Tudor domains, and disrupting the binding interface causes defects in Eggless/SetDB1 distribution and derepression of a subset of transposons. Therefore, H3K14ac, a histone modification associated with active transcription, is a crucial piece of the maternal programs that introduce constitutive heterochromatic features to the newly formed zygotic genome.

developmental biology↗

bioRxiv2023

Application of slow-controlled release fertilizer coordinates the carbon flow in carbon-nitrogen metabolism to effect rice quality

Slow-controlled release fertilizers are experiencing a popularity in rice cultivation due to their effectiveness in yield and quality with low environmental costs. However, the underlying mechanism by which these fertilizers regulate grain quality remains inadequately understood. This study investigated the effects of five fertilizer management practices on rice quality in a two-year field experiment: CK, conventional fertilization, and four applications of slow-controlled release fertilizer (UF, urea formaldehyde; SCU, sulfur-coated urea; PCU, polymer-coated urea; BBF, controlled-release bulk blending fertilizer). In 2020 and 2021, the yields of UF and SCU groups showed significant decreases when compared to conventional fertilization, accompanied by a decline in nutritional quality. Additionally, PCU group exhibited poorer cooking and eating qualities. However, BBF group achieved increases in both yield (10.8 t hm-2 and 11.0 t hm-2) and grain quality reaching the level of CK group. The sufficient nitrogen supply in both the PCU and BBF groups during the grain-filling stage led to a greater capacity for the accumulation of proteins and amino acids in the PCU group compared to starch accumulation. Intriguingly, BBF group showed better carbon-nitrogen metabolism than that of PCU group. The optimal nitrogen supply present in BBF group suitable boosted the synthesis of amino acids involved in the glycolysis/ tricarboxylic acid cycle, thereby effectively coordinating carbon-nitrogen metabolism. The application of the new slow-controlled release fertilizer, BBF, is advantageous in regulating the carbon flow in the carbon-nitrogen metabolism to enhance rice quality.

plant biology↗

bioRxiv2023

Increased FAN1 expression by mRNA-LNP attenuates CAG repeat expansion in Huntington patients' iPSC-derived astrocytes

Expansion of repeat sequences within the human genome can lead to disease pathogenesis, such as Huntingtons Disease, primarily affecting the nervous system. Genome-wide association studies (GWAS) of age-at-onset in Huntingtons disease (HD) patients demonstrated DNA mismatch repair (MMR) genes are modifiers of somatic expansion and may be potential therapeutic targets for repeat expansion (RE) disorders. FAN1, a Fanconi anemia-associated nuclease, has been reported as an influencer of repeat expansion in the RE mouse models. Here, we show the first demonstration that FAN1 knock-out in HD patient-derived fibroblasts and results in increased CAG repeat length. We also develop a robust novel cell-based platform using stem cell technology to produce the HD patients iPSC-derived astrocytes (iAstro). This platform is a disease-relevant system and has a significantly wider assay window, making it more suitable to assess the effect of gene modulation on CAG repeats. A substantial and exponential increase in repeat instability was exhibited in this HD patients iPSC-derived astrocytes platform. Over-expression of FAN1 protein via FAN1 plasmid transfection in this platform reduced CAG repeat instability, suggesting that upregulation of FAN1 protein may have a potential protective effect in CAG repeat expansion for a therapeutic setting. We leveraged the mRNA-LNP modality to enhance FAN1 protein expression and revealed that codon-optimized FAN1 mRNA-LNP robustly prevented increased CAG repeat in HD patients iPSC-derived astrocytes platform. The data from these cell-based platforms highlight that FAN1 plays a protective role in attenuating expanded somatic HTT CAG repeats and shed light on new therapeutic directions against repeat expansion disorders.

neuroscience↗

bioRxiv2023

A dipteran parasite regulates 20E synthesis and antibacterial activity of the host for development through inducing host nitric oxide production

Parasites primarily rely on the host to survive, and have evolved diverse survival strategies. In the present study, we report a specific survival strategy of a dipteran parasite Exorista sorbillans (Diptera: Tachinidae), which is a potential biological control agent for agricultural pests and a pest in sericulture. We found that the expression levels of host nitric oxide synthase (NOS) and nitric oxide (NO) production were increased after E. sorbillans infection. Reducing NOS expression and NO production with a NOS inhibitor (L-NAME) in infected hosts significantly impeded the growth of E. sorbillans larvae. Moreover, the 20-hydroxyecdysone (20E) biosynthesis of infected hosts was elevated with increasing NO production, and inhibiting NOS expression also lowered 20E biosynthesis. More importantly, induced NO synthesis was required to eliminate intracellular bacterial pathogens that presumably competed for shared host resources. Inhibiting NOS expression down-regulated the transcription of antimicrobial peptide genes and increased the number of bacteria in infected hosts. Collectively, this study revealed a new perspective on the role of NO in host-parasite interactions and a novel mechanism for parasite regulation of host to support its development. Author summaryParasites are ubiquitous on earth and diverse, and have evolved various strategies to match their own specific requirements for survival within the host. In this study, we found that Exorista sorbillans, an endoparasite of many agricultural pests and the main insect pest in sericulture, used a novel strategy to manipulate its host NO synthesis for survival within its host Bombyx mori. Specifically, NOS expression and the production of NO in the host were up-regulated by E. sorbillans infection, which benefited larval E. sorbillans development. Meanwhile, increased NO production in host activated 20E synthesis of parasitized hosts and triggered the expression of AMPs against the invasion of pathogenic bacteria to avoid nutritional competence in the host. Our study provides innovative insights into the mechanisms by which a parasite manipulates host NO production for development and may help to expand our knowledge of other parasitic systems.

pathology↗

bioRxiv2023

OpenNucleome for high resolution nuclear structural and dynamical modeling

The intricate structural organization of the human nucleus is fundamental to cellular function and gene regulation. Recent advancements in experimental techniques, including high-throughput sequencing and microscopy, have provided valuable insights into nuclear organization. Computational modeling has played significant roles in interpreting experimental observations by reconstructing high-resolution structural ensembles and uncovering organization principles. However, the absence of standardized modeling tools poses challenges for furthering nuclear investigations. We present OpenNucleome--an open-source software designed for conducting GPU-accelerated molecular dynamics simulations of the human nucleus. OpenNucleome offers particle-based representations of chromosomes at a resolution of 100 KB, encompassing nuclear lamina, nucleoli, and speckles. This software furnishes highly accurate structural models of nuclear architecture, affording the means for dynamic simulations of condensate formation, fusion, and exploration of non-equilibrium effects. We applied OpenNucleome to uncover the mechanisms driving the emergence of "fixed points" within the nucleus--signifying genomic loci robustly anchored in proximity to specific nuclear bodies for functional purposes. This anchoring remains resilient even amidst significant fluctuations in chromosome radial positions and nuclear shapes within individual cells. Our findings lend support to a nuclear zoning model that elucidates genome functionality. We anticipate OpenNucleome to serve as a valuable tool for nuclear investigations, streamlining mechanistic explorations and enhancing the interpretation of experimental observations.

biophysics↗

bioRxiv2023

Oligodendroglial precursors orchestrate immune network instigating early demyelination in experimental autoimmune encephalomyelitis

The immunomodulatory cellular network that triggers early inflammation and demyelination, the key steps in multiple sclerosis (MS) pathogenesis remains poorly characterized. Here, we demonstrate that overactivation of Wnt pathway promotes pathological transformation of oligodendrocyte precursor cells (OPCs) to replicate pathological OPCs in human MS. In mouse experimental autoimmune encephalomyelitis (EAE), pathological OPCs attract CD4+ T-helper 1 (Th1) cells into the spinal cord and brain through CC-chemokine ligand 4 (CCL4), whilst OPCs cooperate with Th1 cells inducing transformation of cytotoxic macrophages that execute early demyelination. Simultaneously, Th1 cells and cytotoxic macrophages upregulate Wnt signaling and CCL4 expression in OPCs, thus exerting positive feedback onto the OPC-immune cascade and establishing a vicious cycle propagating EAE pathogenesis. Breaking this cascade by targeting CCL4 reduces immune cell infiltration, alleviates demyelination, and attenuates EAE severity. Our findings demonstrate a closely coordinated network of OPCs and immune cells therefore providing an alternative insight into MS pathophysiology.

neuroscience↗

bioRxiv2023

Neuroplasticity of speech-in-noise processing in older adults assessed by functional near-infrared spectroscopy (fNIRS)

Functional near-infrared spectroscopy (fNIRS), a non-invasive optical neuroimaging technique that is portable and acoustically silent, has become a promising tool for evaluating auditory brain functions in hearing- vulnerable individuals. This study, for the first time, used fNIRS to evaluate neuroplasticity of speech-in-noise processing in older adults. Ten older adults, most of whom had moderate-to-mild hearing loss, participated in a 4-week speech-in-noise training. Their speech-in-noise performances and fNIRS brain responses to speech (auditory sentences in noise), non-speech (spectrally-rotated speech in noise) and visual (flashing chequerboards) stimuli were evaluated pre- (T0) and post-training (immediately after training, T1; and after a 4-week retention, T2). Behaviourally, speech-in-noise performances were improved after retention (T2 vs. T0) but not immediately after training (T1 vs. T0). Neurally, we intriguingly found brain responses to speech vs. non-speech decreased significantly in the left auditory cortex after retention (T2 vs. T0 and T2 vs. T1) for which we interpret as suppressed processing of background noise during speech listening alongside the significant behavioural improvements. Meanwhile, functional connectivity within and between multiple regions of temporal, parietal and frontal lobes was significantly enhanced in the speech condition after retention (T2 vs. T0). We also found neural changes before the emergence significant behavioural improvements. Compared to pre-training, responses to speech vs. non-speech in the left frontal/prefrontal cortex were decreased significantly both immediately after training (T1 vs. T0) and retention (T2 vs. T0), reflecting possible alleviation of listening efforts. Finally, connectivity was significantly decreased between auditory and higher-level non-auditory (parietal and frontal) cortices in response to visual stimuli immediately after training (T1 vs. T0), indicating decreased cross-modal takeover of speech-related regions during visual processing. The results thus showed that neuroplasticity can be observed not only at the same time, but also before behavioural changes in speech-in- noise perception. To our knowledge, this is the first fNIRS study to evaluate speech-based auditory neuroplasticity in older adults. It thus provides important implications for current research by illustrating the promises of detecting neuroplasticity using fNIRS in hearing-vulnerable individuals.

neuroscience↗

bioRxiv2023

An atypical endomembrane localized CNL-type immune receptor with a conserved deletion in the N-terminal signaling domain functions in cell death and immunity

Plants have evolved intracellular nucleotide-binding leucine rich repeat receptors (NLRs) to induce a superior immune response. Upon activation, coiled-coil (CC) domain containing NLRs (CNLs) oligomerize to form apparent cation channels that promote calcium influx and cell death induction, with the alpha-1 helix of the individual CC domains penetrating membranes. Some members of a monophyletic subclass of CNLs, the ancient and autonomous NLRs (ANLs), are characterized by putative N- myristoylation and S-acylation sites at the N-terminus of their CCG10/GA domain, potentially mediating permanent membrane association. Whether these Potentially Membrane Localized NLRs (PMLs) mediate cell death upon activation in a similar way as reported for other CNLs has been unknown. We integrated phylogenetic, cell- biological, and functional studies to uncover the cell death function of an atypical but conserved Arabidopsis PML, PML5, which has a 113 amino acid deletion in its CCG10/GA domain. Active PML5 oligomers localize in Golgi membranes and the tonoplast, changes vacuolar morphology, and induce cell death, with the short N- terminus being sufficient for cell death. Mutant analysis supports a potential key role of PMLs in plant immunity. Similar deletions as in Arabidopsis PML5 are found in several Brassicales paralogs, pointing to the evolutionary importance of this innovation. PML5 is thus a naturally occurring CNL variant with a minimal signaling domain and its further study should help in understanding the functional importance of this minimal domain for NLR signaling.

plant biology↗

bioRxiv2023

PRO-LDM: Protein Sequence Generation with Conditional Latent Diffusion Models

AbstractsDeep learning-driven protein design holds enormous potential despite the complexities in sequences and structures. Recent developments in diffusion models yielded success in structure design, but awaits progress in sequence design and are computationally demanding. Here we present PRO-LDM: an efficient framework combining design fidelity and computational efficiency, utilizing the diffusion model in latent space to design proteins with property tuning. The model employs a joint autoencoder to capture latent variable distributions and generate meaningful embeddings from sequences. PRO-LDM (1) learns representations from biological features in natural proteins at both amino-acid and sequence level; (2) generates native-like new sequences with enhanced diversity; and (3) conditionally designs new proteins with tailored properties or functions. The out-of-distribution design enables sampling notably different sequences by adjusting classifier guidance strength. Our model presents a feasible pathway and an integratable tool to extract physicochemical and evolutionary information embedded within primary sequences, for protein design and optimization.

bioengineering↗

bioRxiv2023

Assigning mutational signatures to individual samples and individual somatic mutations with SigProfilerAssignment

Analysis of mutational signatures is a powerful approach for understanding the mutagenic processes that have shaped the evolution of a cancer genome. Here we present SigProfilerAssignment, a desktop and an online computational framework for assigning all types of mutational signatures to individual samples. SigProfilerAssignment is the first tool that allows both analysis of copy-number signatures and probabilistic assignment of signatures to individual somatic mutations. As its computational engine, the tool uses a custom implementation of the forward stagewise algorithm for sparse regression and nonnegative least squares for numerical optimization. Analysis of 2,700 synthetic cancer genomes with and without noise demonstrates that SigProfilerAssignment outperforms four commonly used approaches for assigning mutational signatures. SigProfilerAssignment is freely available at https://github.com/AlexandrovLab/SigProfilerAssignment with a web implementation at https://cancer.sanger.ac.uk/signatures/assignment/.

bioinformatics↗

bioRxiv2023

The pathogenic T42A mutation in SHP2 rewires interaction specificity and enhances signaling

Mutations in the tyrosine phosphatase SHP2 are associated with a variety of human diseases. Most mutations in SHP2 increase its basal catalytic activity by disrupting auto-inhibitory interactions between its phosphatase domain and N-terminal SH2 (phosphotyrosine recognition) domain. By contrast, some disease-associated mutations located in the ligand-binding pockets of the N- or C- terminal SH2 domains do not increase basal activity and likely exert their pathogenicity through alternative mechanisms. We lack a molecular understanding of how these SH2 mutations impact SHP2 structure, activity, and signaling. Here, we characterize five SHP2 SH2 domain ligand-binding pocket mutants through a combination of high-throughput biochemical screens, biophysical and biochemical measurements, and molecular dynamics simulations. We show that, while some of these mutations alter binding affinity to phosphorylation sites, the T42A mutation in the N-SH2 domain is unique in that it also substantially alters ligand-binding specificity, despite being 8-10 [A] from the specificity-determining region of the SH2 domain. This mutation exerts its effect on sequence specificity by remodeling the phosphotyrosine binding pocket, altering the mode of engagement of both the phosphotyrosine and surrounding residues on the ligand. The functional consequence of this altered specificity is that the T42A mutant has biased sensitivity toward a subset of activating ligands and enhances downstream signaling. Our study highlights an example of a nuanced mechanism of action for a disease-associated mutation, characterized by a change in protein-protein interaction specificity that alters enzyme activation. Significance StatementThe protein tyrosine phosphatase SHP2 is mutated in a variety of human diseases, including several cancers and developmental disorders. Most mutations in SHP2 hyperactivate the enzyme by destabilizing its auto-inhibited state, but several disease-associated mutations do not conform to this mechanism. We show that one such mutation, T42A, alters the ligand binding specificity of the N-terminal regulatory domain of SHP2, causing the mutant phosphatase to be more readily activated by certain upstream signals than the wild-type phosphatase. Our findings reveal a novel mode of SHP2 dysregulation that will improve our understanding of pathogenic signaling. Our study also illustrates how mutations distal to the specificity-determining region of a protein can alter ligand binding specificity.

biochemistry↗

bioRxiv2023

The canonical single-stranded DNA binding protein SSB is not an essential replication protein but an RNA chaperon in the hyperthermophilic archaeon Saccharolobus islandicus REY15A

Single-stranded DNA binding proteins (SSBs) have been regarded as indispensable factors in all three domains of life since they play vital roles in DNA replication. Herein, we report that genes coding for the canonical SSB (SisSSB) and the non-canonical SSB (SisDBP) in the hyperthermophilic archaeon Saccharolobus islandicus REY15A can both be deleted. The growth is not affected, and the cell cycle progression and genome stability of the deletion strains is not impaired, suggesting that SisSSB and SisDBP are not essential for cell viability. Interestingly, at a lower temperature (55{degrees}C), the protein level of SisSSB increases [~]1.8 fold in the wild type and the growth of {Delta}Sisssb and {Delta}Sisssb{Delta}Sisdbp is retarded. SisSSB exhibits melting activity on dsRNA and DNA/RNA hybrid in vitro and unwinding RNA hairpin in Escherichia coli. Furthermore, the core SisSSB domain is able to complement the absence of the cold shock proteins CspABGE in E. coli, suggesting that SisSSB functions as RNA chaperon. We show that a two-fold overexpression of SisSSB is beneficial to the cell growth at lower temperature, but it has detrimental effect on the cell growth and cell cycle progression at normal growth temperature, which differs from bacterial Csp proteins. Importantly, these in vitro and in vivo activities are conserved in SSB subtype SSB-1 in Crenarchaeota species that lack bacterial Csp homologs. Overall, we have clarified the function of the archaeal canonical SSB which does not function as a DNA processing factor, but plays a role in processes requiring dsRNA or DNA/RNA hybrid unwinding.

microbiology↗

bioRxiv2023

Prestimulus neural variability affects behavioral performances mediated by poststimulus-evoked responses at the intraindividual and interindividual levels

There are significant intra-individual and inter-individual variabilities in audiovisual temporal perception. Previous studies have shown that prestimulus neural variability could reflect behavioral variabilities. We aimed to investigate whether prestimulus neural variability can predict behavioral variability in audiovisual temporal perception. Furthermore, We also explored whether prestimulus neural variability directly influences behavioral responses or indirectly impacts perceptual decisions through post-stimulus-evoked responses. We analyzed the electroencephalography (EEG) data from a paradigm where the twenty-eight human subjects performed a simultaneity judgment (SJ) task in the beep-flash stimulus. The prestimulus weighted permutation entropy (WPE) was the indicator of neural variability in this study. We found that prestimulus frontal WPE could predict the individuals TBW in auditory- and visual-leading conditions. In addition, increased prestimulus parietal WPE was associated with more asynchronous responses. Prestimulus frontal WPE may be associated with top-down cognitive control, while parietal WPE may be related to bottom-up cortical excitability. Furthermore, poststimulus evoked responses could mediate the relation between prestimulus WPE and the individuals TBW or perceptual responses. These results suggested that prestimulus WPE was a marker in reflecting intra-individual and inter-individual variabilities in audiovisual temporal perception. Significantly, prestimulus WPE might influence perceptual responses by affecting poststimulus sensory representations.

neuroscience↗

bioRxiv2023

Not alpha power: prestimulus beta power predicts the magnitude of individual temporal order bias for audiovisual stimuli

Individuals exhibit significant variations in audiovisual temporal order perception. Previous studies have investigated the neural mechanisms underlying these individual differences by analyzing ongoing neural oscillations using stimuli specific to each participant. This study explored whether these effects could extend to different paradigms with the same stimuli across subjects in each paradigm. The two human participants groups performed a temporal order judgment (TOJ) task in two experimental paradigms while recording EEG. One is the beep-flash paradigm, while the other is the stream-bounce paradigm. We focused on the correlation between individual temporal order bias (i.e., point of subjective simultaneity (PSS)) and spontaneous neural oscillations. In addition, we also explored whether the frontal cortex could modulate the correlation through a simple mediation model. We found that the beta band power in the auditory cortex could negatively predict the individuals PSS in the beep-flash paradigm. Similarly, the same effects were observed in the visual cortex during the stream-bounce paradigm. Furthermore, the frontal cortex could influence the power in the sensory cortex and further shape the individuals PSS. These results suggested that the individuals PSS was modulated by auditory or visual cortical excitability depending on the experimental stimuli. The frontal cortex could shape the relation between sensory cortical excitability and the individuals PSS in a top-down manner. In conclusion, our findings indicated that the prefrontal cortex could effectively regulate an individuals temporal order bias, providing insights into audiovisual temporal order perception mechanisms and potential interventions for modulating temporal perception.

neuroscience↗