Biology subjects

Du, Y.

Publications and source records attributed to Du, Y..

At least 181 records · Page 10Linked to original sources

bioRxiv2023

Compensation or preservation? Different roles of functional lateralization in speech perception in older non-musicians and musicians

Musical training can offset age-related decline of speech perception in noisy environments. However, whether functional compensation or functional preservation the older musicians adopt to counteract the adverse effects of aging is unclear yet, so do older non-musicians. Here, we employed the fundamental brain organization feature named functional lateralization, and calculated network-based lateralization indices (LIs) of resting-state functional connectivity (FC) in 23 older musicians (OM), 23 older non-musicians (ONM), and 24 young non-musicians (YNM). OM outperformed ONM and almost equalized YNM in speech-in-noise/speech tasks. In parallel, ONM exhibited reduced lateralization than YNM in LI of intrahemispheric FC (LI_intra) in cingulo-opercular network (CON) and interhemispheric heterotopic FC (LI_he) in language network (LAN). Moreover, OM showed higher neural alignment to YNM (i.e., similar lateralization pattern) than ONM in LI_intra in CON, LAN, frontoparietal network (FPN) and default mode network (DMN) and LI_he in DMN. These findings suggest that musical training contributes to the preservation of youth-like lateralization in older adults. Furthermore, stronger left-lateralized and lower alignment-to-young of LI_intra in somatomotor network (SMN) and dorsal attention network (DAN) and LI_he in DMN correlated with better speech performance in ONM. In contrast, stronger right-lateralized LI_intra in FPN and DAN and higher alignment-to-young of LI_he in LAN correlated with better performance in OM. Thus, functional preservation and compensation of lateralization may play different roles in speech perception in noise for the elderly with and without musical expertise, respectively. Our findings provide insight into successful aging theories from the unique perspective of functional lateralization and speech perception. Significance statementAs a positive lifestyle which contributes to neural resource enrichment, musical training experience may mitigate age-related decline in speech perception in noise through both functional compensation and preservation. What is unknown is whether older musicians rely more on one of these mechanisms, and how is it different from older non-musicians. From a unique perspective of functional lateralization, we found that high-performing older musicians showed stronger preservation of youth-like lateralization with a more right-lateralized pattern whereas high-performing older non-musicians were associated with stronger scaffolding of compensatory networks with a more left-lateralized pattern. Our findings suggest that older musicians and non-musicians exhibit different coping strategies in terms of functional lateralization against aging, which would largely enrich aging theories and inspire training intervention.

neuroscience↗

bioRxiv2023

A longitudinal resource for population neuroscience of school-age children and adolescents in China

During the past decade, cognitive neuroscience has been calling for population diversity to address the challenge of validity and generalizability, ushering in a new era of population neuroscience. The developing Chinese Color Nest Project (devCCNP, 2013-2022), a ten-year pilot stage of the lifespan CCNP (2013-2032), is an ongoing project focusing on brain-mind development. The project aims to create and share a large-scale, longitudinal and multimodal dataset of typically developing children and adolescents (ages 6.0-17.9 at enrolment) in the Chinese population. The devCCNP houses not only phenotypes measured by demographic, biophysical, psychological and behavioural, cognitive, affective, and ocular-tracking assessments but also neurotypes measured with magnetic resonance imaging (MRI) of brain morphometry, resting-state function, naturalistic viewing function and diffusion structure. This Data Descriptor introduces the first data release of devCCNP including a total of 864 visits from 479 participants. Herein, we provided details of the experimental design, sampling strategies, and technical validation of the devCCNP resource. We demonstrate and discuss the potential of a multicohort longitudinal design to depict normative brain growth curves from the perspective of developmental population neuroscience. The devCCNP resource is shared as part of the "Chinese Data-sharing Warehouse for In-vivo Imaging Brain" in the Chinese Color Nest Project (CCNP) - Lifespan Brain-Mind Development Data Community (https://www.scidb.cn/en/c/ccnp) at the Science Data Bank. Design TypesO_LIAccelerated longitudinal design C_LIO_LIBrain-mind development C_LIO_LIPopulation imaging C_LIO_LIBrain chart C_LIO_LIRepeated measure C_LI MeasurementsO_LIPsychological behaviours C_LIO_LIBiophysical and physical measures C_LIO_LIIntelligence quotient measure C_LIO_LINeuroimaging C_LI Sample Characteristic - OrganismO_LIHomo sapiens C_LI Sample Characteristic - EnvironmentO_LISchool- and community-based sample C_LI Sample Characteristic - LocationO_LIChongqing and Beijing, China C_LI DurationO_LI10 years (2013-2022) C_LI

neuroscience↗

bioRxiv2023

Structural insights into ligand recognition and selectivity of the human hydroxycarboxylic acid receptor HCAR2

Hydroxycarboxylic acid receptor 2 (HCAR2) belongs to the family of class A G-protein-coupled receptors with key roles in regulating lipolysis and free fatty acid formation in humans. It is deeply involved in many pathophysiological processes and serves as an attractive target for the treatment of neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases. Here, we report four cryo-EM structures of human HCAR2-Gi1 complexes with or without agonists, including the drugs niacin and acipimox, and the highly subtype-specific agonist MK-6892. Combined with molecular docking and functional analysis, we have revealed the recognition mechanism of HCAR2 for different agonists and summarized the general pharmacophore features of HCAR2 agonists, which are based on three key residues R1113.36, S17945.52, and Y2847.43. Notably, the MK-6892-HCAR2 structure shows an extended binding pocket relative to other agonist-bound HCAR2 complexes. In addition, the key residues that determine the ligand selectivity between the HCAR2 and HCAR3 are also illuminated. Our findings provide structural insights into the ligand recognition, selectivity, activation, and G protein coupling mechanism of HCAR2, which sheds light on the design of new HCAR2-targeting drugs for greater efficacy, higher selectivity, and fewer or no side effects.

cell biology↗

bioRxiv2023

Bioactive Natural Product Discovery via Deuterium Adduct Bioactivity Screening

The discovery of bioactive natural products lies at the forefront of human medicine. The continued discovery of these molecules is imperative in the fight against infection and disease. While natural products have historically dominated the drug market, discovery in recent years has slowed significantly, partly due to limitations in current discovery methodologies. This work demonstrates a new workflow, Deuterium Adduct Bioactivity Screening (DABS), which pairs untargeted isotope labeling with whole cell binding assays for bioactive natural product discovery. DABS was validated and led to the discovery of a new isoprenyl guanidine alkaloid, zillamycin, which showed anti-cancer and anti-microbial activities. DABS thus represents a new workflow to accelerate discovery of natural products with a wide range of bioactive potential.

microbiology↗

bioRxiv2023

Constitutively synergistic multiagent drug formulations targeting MERTK, FLT3, and BCL-2 for treatment of AML

Although high-dose, multi-agent chemotherapy has improved leukemia survival rates in recent years, treatment outcomes remain poor in high-risk subsets, including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) in infants. Development of new, more effective therapies for these patients is therefore an urgent, unmet clinical need. To address this challenge, we developed a nanoscale combination drug formulation that exploits ectopic expression of MERTK tyrosine kinase and dependency on BCL-2 family proteins for leukemia cell survival in pediatric AML and MLL-rearranged precursor B-cell ALL (infant ALL). In a novel, high-throughput combination drug screen, the MERTK/FLT3 inhibitor MRX-2843 synergized with venetoclax and other BCL-2 family protein inhibitors to reduce AML cell density in vitro. Neural network models based on drug exposure and target gene expression were used to identify a classifier predictive of drug synergy in AML. To maximize the therapeutic potential of these findings, we developed a combination monovalent liposomal drug formulation that maintains ratiometric drug synergy in cell-free assays and following intracellular delivery. The translational potential of these nanoscale drug formulations was confirmed in a genotypically diverse set of primary AML patient samples and both the magnitude and frequency of synergistic responses were not only maintained but were improved following drug formulation. Together, these findings demonstrate a systematic, generalizable approach to combination drug screening, formulation, and development that maximizes therapeutic potential, was effectively applied to develop a novel nanoscale combination therapy for treatment of AML, and could be extended to other drug combinations or diseases in the future.

bioengineering↗

bioRxiv2023

Histone modifications regulate pioneer transcription factor cooperativity

Pioneer transcription factors have the ability to access DNA in compacted chromatin. Multiple transcription factors can bind together to a regulatory element in a cooperative way and cooperation between pioneer transcription factors Oct4 and Sox2 is important for pluripotency and reprogramming. However, the molecular mechanisms by which pioneer transcription factors function and cooperate remain unclear. Here we present cryo-EM structures of human Oct4 bound to a nucleosome containing human Lin28B and nMatn1 DNA sequences, which bear multiple binding sites for Oct4. Our structural and biochemistry data reveal that Oct4 binding induces changes to the nucleosome structure, repositions the nucleosomal DNA and facilitates cooperative binding of additional Oct4 and of Sox2 to their internal binding sites. The flexible activation domain of Oct4 contacts the histone H4 N-terminal tail, altering its conformation and thus promoting chromatin decompaction. Moreover, the DNA binding domain of Oct4 engages with histone H3 N-terminal tail, and posttranslational modifications at H3K27 modulate DNA positioning and affect transcription factor cooperativity. Thus, our data show that the epigenetic landscape can regulate Oct4 activity to ensure proper cell reprogramming.

biophysics↗

bioRxiv2023

Human Vascularized Bile Duct-on-a Chip: A multi-cellular micro-physiological system for studying Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease in which the bile ducts of the liver become inflamed and scarred. Scarred bile ducts eventually narrow and obstruct and can cause additional liver pathology including liver failure, repeated infections, and tumors. The pathogenesis of PSC remains largely unknown, partly due to difficulty in obtaining cholangiocytes and partly due to a paucity of in vitro models that capture the various factors contributing to disease progression. Here we report the development of a human vascularized bile duct-on-a-chip that models blood vessels and bile ducts structurally and functionally in three dimensions and includes cholangiocytes derived from control and PSC patient tissue and bile. The flow of blood and bile was modeled by perfusion of cell-lined channels, and cholangiocytes and endothelial cells displayed differential responses to perfusion. Normal and PSC cholangiocytes polarized normally, formed mature tight junctions and displayed similar permeability, comparable to ex vivo measurements. The model with PSC cholangiocytes, however, became more inflammatory than the normal under the stimulation of IL-17A, which induced PBMC and differentiated Th17 cells in the vascular channel to transmigrate more through the endothelial layer of the vascular compartment. In sum, this human vascularized bile duct-on-a-chip recapitulated the vascular-biliary interface structurally and functionally and represents a novel multicellular platform to study inflammatory and fibrotic cholangiopathies such as PSC.

bioengineering↗

bioRxiv2023

Molecular architecture and platelet-activating properties of small immune complexes assembled on intact heparin and their possible involvement in heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an adverse reaction to heparin leading to a reduction in circulating platelets with an increased risk of thrombosis. It is precipitated by polymerized immune complexes consisting of pathogenic antibodies that recognize a small chemokine platelet factor 4 (PF4) bound to heparin, which trigger platelet activation and a hypercoagulable state. Characterization of these immune complexes is extremely challenging due to the enormous structural heterogeneity of such macromolecular assemblies and their constituents (especially heparin). We use native mass spectrometry to characterize small immune complexes formed by PF4, heparin and monoclonal HIT-specific antibodies. Up to three PF4 tetramers can be assembled on a heparin chain, consistent with the results of molecular modeling studies showing facile polyanion wrapping along the polycationic belt on the PF4 surface. Although these assemblies can accommodate a maximum of only two antibodies, the resulting immune complexes are capable of platelet activation despite their modest size. Taken together, these studies provide further insight into molecular mechanisms of HIT and other immune disorders where anti-PF4 antibodies play a central role.

biochemistry↗

bioRxiv2023

USP39 promotes hepatocellular carcinogenesis through regulating alternative splicing in cooperation with SRSF6/HNRNPC

Abnormal alternative splicing (AS) caused by alterations in spliceosomal factors is implicated in cancers. Standard models posit that splice site selection is mainly determined by early spliceosomal U1, U2 snRNPs. Whether and how other mid/late-acting spliceosome components such as USP39 modulate tumorigenic splice site choice remain largely elusive. We observed that hepatocyte-specific knock-in of USP39 promoted hepatocarcinogenesis and potently regulated splice site selection. In human liver cancer cells, USP39 promoted tumor proliferation in a spliceosome-dependent manner. USP39 depletion deregulated hundreds of AS events, including the oncogenic splice-switching of KANK2. Mechanistically, we developed a novel RBP-motif enrichment analysis and found that USP39 modulated exon inclusion/exclusion by interacting with SRSF6/HNRNPC in both humans and mice. Our data represent a paradigm for the control of splice site selection by mid/late-acting spliceosome proteins and their interacting RBPs. USP39 and possibly other mid/late-acting spliceosome proteins may represent potential prognostic biomarkers and targets for cancer therapy. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=97 SRC="FIGDIR/small/525324v1_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@34cbc1org.highwire.dtl.DTLVardef@2d0ee2org.highwire.dtl.DTLVardef@2c4bd6org.highwire.dtl.DTLVardef@26db00_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2023

Engineering synthetic CopT/A-based genetic circuits for miRNA imaging and functional gene regulation

Synthetic genetic circuits that can operate at the transcriptional and translation levels have been widely applied in the control of cellular behaviors and functions. However, the regulation of genetic circuits is often accompanied by the introduction of exogenous substances or the endogenous generation of inhibitory products, which would bring uncontrollable hazards for biological safety and reduce the efficiency of the system. Here, we described a miRNA-responsive CopT-CopA (miCop) genetic circuit system to realize real-time monitoring the intracellular expression of miRNA-124a during neurogenesis or miRNA-122 under the stimulation of extracellular drugs in living cells and animals. Furthermore, to prove the modularity of the system, we engineered this mipCop to tune the expression of DTA (diphtheria toxin A) gene, and showed the powerful capacity of killing cancer cells by inducing apoptosis and cell cycle arrest based on miRNA response. This study provides an effective means to couple miRNA sensing with miRNA-responsive gene modulation, which may open up new diagnostic or therapeutic applications.

synthetic biology↗

bioRxiv2022

Language models generalize beyond natural proteins

Learning the design patterns of proteins from sequences across evolution may have promise toward generative protein design. However it is unknown whether language models, trained on sequences of natural proteins, will be capable of more than memorization of existing protein families. Here we show that language models generalize beyond natural proteins to generate de novo proteins. We focus on two protein design tasks: fixed backbone design where the structure is specified, and unconstrained generation where the structure is sampled from the model. Remarkably although the models are trained only on sequences, we find that they are capable of designing structure. A total of 228 generated proteins are evaluated experimentally with high overall success rates (152/228 or 67%) in producing a soluble and monomeric species by size exclusion chromatography. Out of 152 experimentally successful designs, 35 have no significant sequence match to known natural proteins. Of the remaining 117, sequence identity to the nearest sequence match is at median 27%, below 20% for 6 designs, and as low as 18% for 3 designs. For fixed backbone design, the language model generates successful designs for each of eight experimentally evaluated artificially created fixed backbone targets. For unconstrained generation, sampled proteins cover diverse topologies and secondary structure compositions, and have high experimental success rate (71/129 or 55%). The designs reflect deep patterns linking sequence and structure, including motifs that occur in related natural structures, and motifs that are not observed in similar structural contexts in known protein families. The results show that language models, though only trained on sequences, learn a deep grammar that enables the design of protein structure, extending beyond natural proteins.

synthetic biology↗

bioRxiv2022

Injury and a program of fetal wound healing in the fetal and neonatal extrahepatic bile duct

IntroductionBiliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause; however, the response of the fetal EHBD to injury remains unknown. The objective of this study was to define the fetal response to EHBD injury and to determine whether it follows a fetal wound healing paradigm. MethodsMouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes. ResultsA wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland (PBG) hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device. ConclusionThe fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with high levels of HA typical of the regenerative, scarless program termed fetal wound healing. Although generally beneficial, the expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD.

physiology↗

bioRxiv2022

Mechanical regulation of retinal vascular inflammation and degeneration in diabetic retinopathy

Vascular inflammation is known to cause degeneration of retinal vessels in early diabetic retinopathy (DR). Past studies investigating these diabetes-induced vascular abnormalities have focused primarily on the role of molecular or biochemical cues. Here we show that retinal vascular inflammation and degeneration in DR are also mechanically regulated by retinal vascular stiffening that is caused by overexpression of collagen-crosslinking enzyme lysyl oxidase (LOX) in retinal vessels. Treatment of diabetic mice with LOX inhibitor BAPN prevented the increase in retinal vascular stiffness, vascular ICAM-1 overexpression, and leukostasis. Consistent with these anti-inflammatory effects, BAPN treatment of diabetic mice blocked the upregulation of proapoptotic caspase-3 in retinal vessels, which concomitantly reduced retinal vascular degeneration and the diabetes-induced loss of contrast sensitivity in these mice. Finally, we show that increasing substrate stiffness alone increases the adhesiveness and neutrophil elastase-induced death of cultured retinal endothelial cells. By uncovering a link between LOX-dependent vascular stiffening and the development of retinal vascular and functional defects in diabetes, these findings offer unique insights into DR pathogenesis that has important translational potential.

pathology↗

bioRxiv2022

Distinct immune responses associated with vaccination status and protection outcomes after malaria challenge

Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malaria infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with interferon responses and T and B cell signatures were increased and decreased, respectively, in protected vaccinees as early as one day following CHMI. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of v{delta}2+{gamma}{delta} T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that protective immunity by PfRAS is associated with early changes in interferon and adaptive immune responses. Author summaryMalaria poses a significant global health threat, causing over half a million deaths annually. Effective vaccines are critically needed to prevent malaria disease. Our incomplete understanding of immune mechanisms that mediate malaria protection is hampering the development of effective vaccines. Irradiated sporozoite vaccines can induce highly sterilizing protection against malaria and are a valuable tool for the analysis of immune protection. Here, we aimed to characterize correlates of immune protection in individuals vaccinated with a suboptimal dose of irradiated sporozoite and subsequently challenged with live malaria parasite. Blood samples were taken before and after malaria challenge, and gene expression and cell type profiles were measured. We observed that the trajectories of immune response after malaria challenge is highly distinct between protected and non-protected vaccinees. We observed early perturbations in interferon response and adaptive immune cells in protected vaccinees whereas inflammatory and innate cell response were unique to non-protected vaccinees. We also observed that the immune profile after malaria challenge was distinctly similar between non-protected vaccinees and mock-vaccinated individuals. Our study sheds light on the dynamics of vaccine-induced immune responses that are associated with protection from malaria after CHMI.

immunology↗

bioRxiv2022

DiffDomain enables identification of structurally reorganized topologically associating domains

Topologically associating domains (TADs) are critical structural units in three-dimensional genome organization of mammalian genome. Dynamic reorganizations of TADs between health and disease states are associated with transcription and other essential genome functions. However, computational methods that can identify reorganized TADs are still in the early stages of development. Here, we present DiffDomain, an algorithm leveraging high-dimensional random matrix theory to identify structurally reorganized TADs using chromatin contact maps. Method comparison using multiple real Hi-C datasets reveals that DiffDomain outperforms alternative methods for FPRs, TPRs, and identifying a new subtype of reorganized TADs. The robustness of DiffDomain and its biological applications are demonstrated by applying on Hi-C data from different cell types and disease states. Identified reorganized TADs are associated with structural variations and changes in CTCF binding sites and other epigenomic changes. By applying to a single-cell Hi-C data from mouse neuronal development, DiffDomain can identify reorganized TADs between cell types with reasonable reproducibility using pseudo-bulk Hi-C data from as few as 100 cells per condition. Moreover, DiffDomain reveals that TADs have differential cell-to-population variability and heterogeneous cell-to-cell variability. Therefore, DiffDomain is a statistically sound method for better comparative analysis of TADs using both Hi-C and single-cell Hi-C data.

bioinformatics↗

bioRxiv2022

Soft and stretchable organic bioelectronics for continuous intra-operative neurophysiological monitoring during microsurgery

Continuous intra-operative neurophysiological monitoring (CINM) that provides precise mapping of neural anatomy through the entire microsurgery process is essential to preserve the structural and functional integrity of the nerve. However, bulky and rigid electrodes used currently in clinics are usually unable to reliably maintain continuous and stable contacts with the vulnerable and complex nerve networks, thus often resulting in detrimental post-operative complications, such as hemiplegia and sensory disturbances. Here, we describe a biomechanically compatible, suture-free, and individually reconfigurable CINM based on soft and stretchable organic electronic materials. Due to both low impedance and modulus of our conducting polymer electrodes, we achieved for the first time continuous recording of near-field action potential with high signal-to-noise ratio and minimal invasiveness during microsurgeries. Utilizing this unprecedented CINM modality, in conjunction with localized neurostimulation, we further demonstrated our approach in enabling optimal post-operative prognosis in preclinical animal models by preserving normal neural functions after a variety of tumor resection surgeries.

bioengineering↗

bioRxiv2022

Neural correlates of probabilistic information processing in gesture-speech integration

Semantic representation emerges from distributed multisensory modalities, yet a comprehensive understanding of the functional changing pattern within convergence zones or hubs integrating multisensory semantic information remains elusive. In this study, employing information-theoretic metrics, we quantified gesture and speech information, alongside their interaction, utilizing entropy and mutual information (MI). Neural implementation of these information-theoretic representations was characterized across three complementary experiments using high-definition transcranial direct current stimulation (HD-tDCS), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG). HD-tDCS demonstrated a causal contribution of the left inferior frontal gyrus (IFG) and posterior middle temporal gyrus (pMTG) to neural representations associated with gesture-speech MI. fMRI revealed that MI is represented across IFG and pMTG through distinct mechanisms: IFG preserves the relational structure predicted by MI, whereas pMTG supports discrimination of different levels of MI. EEG further showed that entropy primarily reflects transient modality-specific dynamics, whereas MI emerges during the N400-associated integration period. Cross-modal EEG-fMRI analyses demonstrated convergent MI-related neural representations with complementary temporal and spatial signatures. Together, these findings reveal a progressive organization of multisensory semantic integration, in which neural representations systematically track stimulus-level information-theoretic structure, with modality-specific uncertainty and cross-modal shared information expressed at different neural scales. This work establishes an information-theoretic framework that links the statistical structure of sensory information with its neural organization, providing new insights into how distributed inputs are coordinated to form coherent semantic representations.

neuroscience↗

bioRxiv2022

Musical expertise enhances neural alignment-to-young in sensorimotor regions that predicts older adults' audiovisual speech-in-noise perception

Musical training can offset age-related decline in speech-in-noise perception. However, how lifelong musical expertise affects the functional reorganization of older brain in speech-in-noise perception has not yet been systematically investigated. Here, we address this issue by analyzing fMRI responses of older musicians, older non-musicians and, young non-musicians identifying noise-masked audiovisual syllables. First, we confirmed that older musicians outperformed older non-musicians and even equaled young non-musicians. Then, we showed that both older groups showed decreased auditory activation and increased visual activation compared to young non-musicians, while older musicians showed higher activation in speech motor regions and greater deactivation of default mode network (DMN) regions than older non-musicians. Next, we revealed that musical expertise counteracted the age-related neural dedifferentiation of speech representation, making older musicians exhibit higher neural alignment-to-young in bilateral sensorimotor areas. Finally, we disentangled that greater activation in speech motor areas and stronger deactivation in DMN regions were correlated with higher neural alignment in sensorimotor areas, which strongly predicted better performance in older adults. Together, long-term musical expertise mitigates age-related deficits in audiovisual speech-in-noise processing through enhanced compensatory scaffolding that reserves youth-like representation in sensorimotor areas. Our findings provide a comprehensive perspective on understanding age- and experience-related brain reorganization during speech perception.

neuroscience↗