Biology subjects

Yamaguchi, S.

Publications and source records attributed to Yamaguchi, S..

At least 19 recordsLinked to original sources

bioRxiv2026

YAP-TEAD-driven CPA4 promotes NF2-deficient meningioma growth

Neurofibromin 2 (NF2) deficiency is a driver of meningioma and other cancers, yet transcriptional effectors that sustain NF2-deficient tumors remain poorly defined. We identify carboxypeptidase A4 (CPA4) as an effector of YAP-TEAD signaling in NF2-deficient meningioma. Transcriptomic profiling identified CPA4 as a consistently upregulated effector. Across patient cohorts and specimens, CPA4 expression was enriched in NF2-mutant and chromosome 22q-deleted meningiomas and associated with higher tumor grade and chromosome 1p loss. CPA4 depletion impaired proliferation, disrupted cell-cycle, DNA-replication, and DNA-repair programs, suppressed intracranial tumor growth, and prolonged survival. Integrated epigenomic and functional assays identified CPA4 as a direct YAP-TEAD transcriptional target. CPA4-high meningioma models exhibited preferential sensitivity to YAP-TEAD inhibition, while verteporfin and the clinical-stage TEAD inhibitor VT3989 reduced CPA4 expression, suppressed orthotopic tumor growth, and prolonged survival. These findings uncover a targetable YAP-TEAD-CPA4 dependency in NF2-deficient meningioma and identify CPA4 as a potential biomarker for TEAD- directed therapy. STATEMENT OF SIGNIFICANCECPA4 links NF2 loss to oncogenic YAP-TEAD transcription, sustains meningioma growth, and marks tumor sensitivity to pharmacologic TEAD inhibition. These findings establish CPA4 as a tumor-promoting effector and potential biomarker of an actionable pathway shared across NF2- deficient cancers.

cancer biology↗

bioRxiv2026

Comprehensive dissection of GPCR signaling using a NanoBiT-based platform

G-protein-coupled receptors (GPCRs) signal through multiple heterotrimeric G proteins, {beta}-arrestins, GPCR kinases (GRKs), and downstream effectors, whose combinatorial interactions shape cellular responses. These events are typically measured with separate assay formats that each capture only part of the network, making comparison across signaling layers difficult. Here, we consolidate a broad set of previously reported GPCR signaling interactions and assay concepts, together with newly designed sensors, into a single NanoBiT split-luciferase framework, allowing multiple layers of signal transduction to be examined side by side in living cells. We show that rational sensor engineering, in particular the positioning of NanoBiT fragments and targeted modification of the tagged proteins, is essential for detecting transient protein-protein interactions. The framework implements assays for G-protein dissociation, {beta}-arrestin recruitment, conformational activation and trafficking, and GRK recruitment, and extends to G-protein-effector and inter-effector interactions across diverse G, G{beta}, G{gamma}, {beta}-arrestin, GRK, adenylyl cyclase, PLC{beta}, and RhoGEF subtypes. It also enables real-time monitoring of the difficult-to-access G12/13-RhoGEF-RhoA pathway. Together, these assays provide a unified NanoBiT readout for systematic, side-by-side dissection of GPCR signaling.

pharmacology and toxicology↗

bioRxiv2026

Human interferon stimulated genes target ancient features of animal and bacterial viral replication

Animal and bacterial cells defend against viral infection by rapidly activating antiviral restriction factors. In human cells, antiviral immunity is initiated by interferon signaling that results in expression of hundreds of interferon-stimulated genes (ISGs)1,2,3,4,5,6. Complex regulatory networks and co-evolution of viral evasion strategies complicate analysis of immune proteins under native conditions and the function of most individual ISGs remains unknown7,8,9,10,11,12. Here we discover that heterologous expression of ISGs in bacteria is sufficient to protect against infection by diverse bacteriophages demonstrating properties of antiviral restriction preserved across billions of years of viral evolution. A screen of 306 human ISGs against 11 E. coli phages reveals that ISGs can restrict phage replication with potency equal to endogenous bacterial defense systems. We select for phage mutants that escape ISG restriction and identify the phage DNA primase-helicase complex as a target of human SPSB1. A 2.0 [A] crystal structure of the SPSB1-primase complex uncovers a recognition mechanism of foreign DxNxN protein motifs found in many animal and bacterial viral replication proteins. We show that SPSB1 in human cells recognizes and induces degradation of protein targets containing this motif from norovirus and poxvirus pathogens. Our results establish a cross-kingdom approach to studying immune function and reveal that human ISGs target features of viral replication common across kingdoms of life.

immunology↗

bioRxiv2026

Male odor preference in female mice is modulated across reproductive stages via the posteroventral medial amygdala.

Male odor induces various behavioral and physiological responses across the reproductive cycle in female mice. Although male odor preference in females is reduced during pregnancy, how it changes across later stages of the reproductive cycle, including nursing and weaning, remains unclear. Here, we found that male odor preference is lost during pregnancy and nursing. To identify the olfactory systems involved in these changes, we examined neural activity using c-Fos immunohistochemistry. Male odor exposure during nursing increased neural activity in the accessory olfactory bulb and the posteroventral medial amygdala (MeApv), a key node of the accessory olfactory system, as well as in subdivisions of the central amygdala, but not in the ventromedial hypothalamus or the bed nucleus of the stria terminalis. Finally, lesions of the MeApv prevented the loss of male preference during nursing, indicating that the MeApv is required for suppression of male preference during this stage.

neuroscience↗

bioRxiv2026

IMAGENE: Single-cell association of live cell imaging and gene expression profiles of non-adherent cells through photoactivatable adhesives

Live cell imaging is uniquely placed to study cell behavior as it preserves spatial context and enables non-destructive observations over time. Integrating live cell imaging and molecular phenotypes with single-cell resolution is key to uncovering the relationship between the behavioral and morphological signatures of cells, and their molecular states. Non-adherent cells - as are most immune cells - however, present unique challenges in linking live cell imaging and fixed cell assays with single-cell resolution due to the difficulty of identifying individual cells across experimental modalities. To overcome this issue, we developed IMAGENE, an experimental and computational pipeline that leverages previously reported photoactivatable biocompatible adhesive material (PA-BAM) coatings for on-the-fly cell immobilization. We demonstrate the IMAGENE experimental and computational pipeline by generating a dataset of label-free time-lapse videos of primary human naive CD8+ T cells following 24 hours of polyclonal stimulation. Individual cells, including highly motile cells, can be matched to expression profiles of genes of interest obtained through KrakenFISH, a modified version of the previously reported autoFISH setup for automated, single-molecule fluorescence in situ hybridization (smFISH) experiments that supports sample parallelization. We use this data to train explainable machine learning models that predict expression levels of individual genes, with variable performance, from hand-crafted dynamic and spatial features obtained from live cell imaging.

bioengineering↗

bioRxiv2026

Macrophage immunosenescence prolongs intraocular inflammation in aged mice via impaired induction of regulatory T cells

Immune-mediated intraocular inflammation, called uveitis, is a leading cause of global blindness, with the highest burden of visual impairment falling on older individuals. Immunosenescence, the functional changes in immune cells with aging, impacts the age-associated immune response, but how immunosenescence and the molecular regulators of the age-associated immune response affect the clinical course of uveitis remains unclear. In the murine model of experimental autoimmune uveitis (EAU), aged mice demonstrated a delayed onset and peak of intraocular inflammation compared to young mice. In contrast to the canonical monophasic inflammation that rapidly resolves in young mice, aged mice developed persistent, chronic inflammation. Transcriptomic and flow-cytometric analyses of immune cells and the receptor-ligand interactome revealed a dominant macrophage-CD4+ T cell signature. This signaling pathway was functionally altered on both ends: macrophages from aged mice had an impaired capacity to generate peripherally induced regulatory T cells (pTreg) through an IL-6 regulated pathway, while CD4+ T cells co-cultured with aged macrophages demonstrated increased proliferation. Our study establishes aging as a key regulator of the effector immune response in uveitis. Regulatory T cells, specifically pTreg, are essential for resolving inflammation in uveitis and an impaired ability to induce pTreg led to a sustained, chronic inflammatory uveitis phenotype in old mice, thereby linking immunosenescence to persistent neuroinflammation. These findings highlight potential therapeutic avenues for vision-threatening uveitis, especially in older patients.

immunology↗

bioRxiv2026

Parthenogenote-Derived Brain Unveils the Critical Role of Paternal Genome in Neural Development

Genomic imprinting, an epigenetic mechanism that governs parent-of-origin-specific gene expression, is essential for mammalian development, yet its role in late-stage development remains unclear due to the lethality of parthenogenetic (Pg) embryos. Here, we establish cell replacement with parthenogenote-derived cells (CReP), a blastocyst complementation strategy that enables survival and tissue-specific contribution of Pg-derived cells. Brain-targeted CReP showed that Pg-derived cells can participate in neural development but fail to maintain neuronal-glial balance due to aberrant activation of Notch signaling caused by the loss of the paternally expressed gene Dlk1. Restoration of Dlk1 normalized Notch activity and rescued neuronal differentiation. These findings reveal a critical role of the paternal genome, through Dlk1-mediated regulation of Notch signaling, in ensuring neural stem cell expansion and balanced cell fate decisions. The CReP model provides a powerful platform for investigating genomic imprinting and parental genome contributions in development and disease.

developmental biology↗

bioRxiv2025

Early pathogenesis of spinal and bulbar muscular atrophy uncovered by human iPSC-derived motor neurons highlights pathogenic neuropeptides as therapeutic targets

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disorder caused by the expansion of the polyglutamine tract in the androgen receptor (AR). Motor neurons (MNs) derived from patient-specific induced pluripotent stem cells (iPSCs) robustl y recapitulated early SBMA phenotypes driven by endogenous mutant AR in the absence of testosterone (dihydrotestosterone) and detectable mutant AR aggregation. Notably, endoplasmic reticulum stress markedly exacerbated SBMA pathology. Cross-species integrative analyses of patient-derived neurons and spinal cords of transgenic mouse models revealed high expression of multiple disease-associated neuropeptides, including urotensin II (UTS2), in patient spinal MNs that was correlated with disease onset and progression in iPSC-derived MNs. Downstream signaling analyses of these neuropeptides revealed convergent molecular pathways whose pharmacological inhibition rescued cellular phenotypes. Together, these results establish a human disease model harboring endogenous mutant AR that closely reproduces early SBMA pathology and provides molecular leads for elucidating disease mechanisms and biomarkers and developing therapeutic targets.

neuroscience↗

bioRxiv2025

A SABATH family enzyme regulates development via the gibberellin-related pathway in the liverwort Marchantia polymorpha

The SABATH family enzymes are a group of plant-specific methyltransferases that catalyze the methylation of many small molecules, including several plant hormones. While this family emerged anciently before the evolution of land plants from streptophyte algae, little is known about their biological function in plant lineages other than angiosperms. Here, we identified 12 SABATH family genes from the liverwort Marchantia polymorpha and found that MpSABATH2 is essential for its development. Mpsabath2 mutants were severely inhibited in thallus growth and gemma cup formation, while spontaneously forming sexual branches under non-inductive conditions. These phenotypes resembled the developmental responses to far-red light, which was also supported by transcriptome analysis. Further genetic analysis connected this phenomenon with gibberellin (GA)-related metabolism. Blocking GA biosynthesis partially rescued Mpsabath2 phenotypes, which were restored by treatment with the GA precursor, ent-kaurenoic acid. Given that bryophyte and angiosperm SABATH proteins fall into distinct phylogenetic clades, our findings suggest that SABATH family enzymes independently acquired roles in developmental regulation through convergent or parallel evolution in land plants.

plant biology↗

bioRxiv2025

Morning sickness-like changes during pregnancy in non-human primates and rodents

Nausea and vomiting of pregnancy (NVP), commonly referred to as "morning sickness," causes a range of symptoms including nausea, vomiting, weight loss, anorexia, and malaise in pregnant women during early pregnancy. Although NVP highly affects the quality of life of pregnant women, the absence of model animals has prevented us from revealing the underlying mechanisms. Here, to identify whether non-human animals may serve as models for studying NVP, we analyzed metabolic changes during pregnancy in common marmosets and mice. Marmosets exhibited a transient weight decrease during the period of placental development in approximately 22% of pregnancies. Some marmosets repeatedly showed transient weight loss across multiple pregnancies, suggesting individual variations in the likelihood of NVP-like symptoms. Although mice did not show apparent alteration in body weight, they exhibited a slowdown in food intake and alterations in locomotor activity during the corresponding phase. These shared alterations suggest that marmosets and mice may exhibit phenomena analogous to human NVP and could serve as useful models for investigating its biological basis. HighlightsO_LIMarmosets exhibited a transient weight loss during placental development in 22% of pregnancies. C_LIO_LIThere was individual variation in how often the transient weight loss occurred in marmosets. C_LIO_LIFood intake and activity in C57BL/6 mice are altered during the corresponding gestational phase. C_LIO_LIMultiple morning sickness-like phenomena were observed in non-human mammals. C_LI

physiology↗

bioRxiv2025

Activating and inhibiting nucleotide signals coordinate bacterial anti-phage defense

The cellular nucleotide pool is a major focal point of the host immune response to viral infection. Immune effector proteins that disrupt the nucleotide pool allow animal and bacterial cells to broadly restrict diverse viruses, but reduced nucleotide availability induces cellular toxicity and can limit host fitness(Ahmad et al., 1998; Goldstone et al., 2011; Hsueh et al., 2022; Itsko & Schaaper, 2014; Tal et al., 2022). Here we discover a bacterial anti-phage defense system named Clover that overcomes this tradeoff by encoding a deoxynucleoside triphosphohydrolase enzyme (CloA) that dynamically responds to both an activating phage cue and an inhibitory nucleotide immune signal produced by a partnering regulatory enzyme (CloB). Analysis of Clover phage restriction in cells and reconstitution of enzymatic function in vitro demonstrate that CloA is a dGTPase that responds to viral enzymes that increase cellular levels of dTTP. To restrain CloA activation in the absence of infection, we show that CloB synthesizes a dTTP-related inhibitory nucleotide signal p3diT (5'-triphosphothymidyl-3'5'-thymidine) that binds to CloA and suppresses activation. Cryo-EM structures of CloA in activated and suppressed states reveal how dTTP and p3diT control distinct allosteric sites and regulate effector function. Our results define how nucleotide signals coordinate both activation and inhibition of antiviral immunity and explain how cells balance defense and immune-mediated toxicity.

microbiology↗

bioRxiv2025

Visualizing the Chronicle of Multiple Cell Fate using a Near-IR Dual-RNA/DNA-Targeting Probe

Early detection and late-stage cell fate assessment are key factors to develop therapeutic strategies, although current methods cannot capture early responses or distinguish multiple injury states, especially in UV-vis-sensitive cells. Here, we introduce a method to simultaneously detect variations in RNA and DNA under near-infrared photoexcitation. Utilizing a pyrazinacene-based probe (TEG8-N14), we unexpectedly achieved discrimination of multiple cell states, including apoptosis, necrosis, necroptosis, and senescence, based on RNA-DNA changes. Specifically, TEG8-N14 selectively stains necrotic cells in live samples, while after fixation, it allows detection of ultra-early senescence in UV-vis-sensitive cells, providing approximately two-fold greater informational content than existing RNA or DNA fluorophores. These findings break current imaging barriers by enabling comprehensive visualization of single-cell fate histories without being affected by UV-vis or genetic manipulation.

bioengineering↗

bioRxiv2025

Natural variation modifies centromere proximal meiotic crossover frequency and segregation distortion in Arabidopsis thaliana

BackgroundCentromeres mediate chromosome segregation during cell division. In plants, centromeres are loaded with CENH3-variant nucleosomes, which direct kinetochore formation and spindle microtubule interaction. Plant centromeres are frequently composed of megabase-scale satellite repeat arrays, or retrotransposon nests. In monocentric genomes, such as Arabidopsis thaliana, extended regions of pericentromeric heterochromatin surround the CENH3-occupied satellite arrays. A zone of suppressed meiotic crossover recombination contains the centromere and extends into the pericentromeres. Here, we explore how Arabidopsis natural genetic variation influences centromere-proximal crossover frequency, and segregation distortion through meiosis, when homologous centromeres are structurally heterozygous. ResultsWe used fluorescent crossover reporters to survey the effect of natural variation on centromere-proximal recombination in twelve F1 hybrids, capturing Arabidopsis Eurasian and relict diversity. The majority of F1 hybrids showed either elevated or suppressed centromere-proximal crossovers (49 of 60), relative to inbreds. We relate hybrid crossover frequencies to patterns of centromeric structural variation, and in a subset of accessions, to epigenetic patterns of CENH3 loading and DNA methylation. The fluorescent reporters also allow segregation distortion through meiosis to be compared between inbred and hybrid strains. We observed a minority of hybrids (18 of 60) with distorted segregation through meiosis compared to inbreds, with and without simultaneous change to centromere-proximal crossover frequency. ConclusionsWe reveal a complex relationship between centromere structural variation, epigenetic state, crossover recombination, and segregation distortion. We propose a model for how Arabidopsis centromere structural heterozygosity may cause segregation distortion during female meiosis.

genetics↗

bioRxiv2024

Escherichia coli growth under low pH, low temperature, and high osmotic stress conditions requires the wzxE flippase for the enterobacterial common antigen intermediate

Colanic acid and enterobacterial common antigen (ECA) are cell surface polysaccharides that are produced by many E. coli isolates. Colanic acid is induced under low pH, low temperature, and hyperosmotic conditions and is important in E. coli resistance to these stresses; however, the role of the ECA is unclear. In this study, we observed that knockout of the flippase wzxE, which converts ECA intermediates from the cytoplasmic side of the inner membrane to the periplasmic side, resulted in low pH sensitivity in E. coli. The wzxE-knockout mutant showed reduced growth potential and viable counts in the extracts of several vegetables (cherry tomatoes, carrots, celery, lettuce, and spinach), which are known to be low pH environments. A double knockout strain of wzxE and wecF, which encodes an enzyme that synthesizes an ECA intermediate, did not show sensitivity to low pH, nor did a double knockout mutant of wzxE and wcaJ, which encodes a colanic acid synthase. The wzxE-knockout mutant was sensitive to low temperature or hyperosmotic conditions, which induced colanic acid synthesis, and these sensitivities were abolished by the additional knockout of wcaJ. These results suggest that ECA intermediates cause E. coli susceptibility to low pH, low temperature, and high osmotic pressure in a colanic acid-dependent manner, and that wzxE suppresses this negative effect. ImportancePolysaccharides covering bacterial cell surfaces, such as colanic acid, confer resistance to various stresses, such as low pH. However, the role of enterobacterial common antigens, carbohydrate antigens that are conserved throughout enterobacteria, in stress resistance is unclear. Our results suggest that lipid III enterobacterial common antigen, a substrate of flippase, causes sensitivity of Escherichia coli to low pH, low temperature, and high osmolarity in dependence on colanic acid synthesis, while wzxE inhibits this negative effect. The wzxE-knockout mutant was sensitive to crude vegetable extracts, suggesting that the creation of WzxE inhibitors could lead to new food poisoning prevention agents.

microbiology↗

bioRxiv2024

Lower-Limb Muscle Synergies in Musician's Dystonia: A Case Study of a Drummer

Musicians dystonia (MD) is a movement disorder characterized by involuntary muscle contractions specifically triggered by playing an instrument. This condition often leads to a loss of fine motor control, threatening the careers of affected musicians. While MD is commonly associated with the hands, it can also affect the lower limbs, particularly in drummers. Understanding the muscle coordination involved in MD is crucial for comprehending its neurological mechanisms, yet the muscle coordination of lower-limb dystonia has not been thoroughly explored. This study aimed to investigate the differences in lower-limb muscle synergies in a drummer with MD, utilizing Non-negative Matrix Factorization (NMF) to analyze coordinated muscle activity patterns during drumming tasks. A 36-year-old male professional drummer with lower-limb MD was instructed to play a drum set in time with a metronome set at 80 beats per minute. The task involved striking the bass drum pedal in time with the downbeat. Electromyographic (EMG) data were collected from ten muscles in the right lower limb. The data were analyzed using NMF to extract muscle synergies and compare the number of synergies, spatial modules, and temporal modules between the data with and without dystonia symptoms. The number of muscle synergies did not differ significantly between the data with and without symptoms. Notably, changes were observed in both the spatial and temporal modules of muscle synergies. Spatial modules revealed the appearance of dystonia-specific muscle synergy, which is considered related to compensatory movement. Temporal modules showed significant earlier overactivation in timing, which is considered the direct manifestation of dystonia symptoms. These findings indicate that lower-limb dystonia in drummers affects the spatial and temporal profiles of muscle synergies. This study underscores the importance of considering both spatial and temporal modules of muscle synergy in understanding and treating lower-limb dystonia in drummers. Further research is needed to validate these findings and apply muscle synergy analysis for the clinical assessment of lower-limb dystonia in drummers.

neuroscience↗

bioRxiv2024

Embryonic diversification of adult neural stem cells and ependymal cells

Both adult neural stem (type B) cells and ependymal (type E) cells in the mouse ventricular-subventricular zone (V-SVZ) are derived from slowly dividing (or quiescent) embryonic neural stem-progenitor cells (NPCs) that are set aside during development. However, it has remained unclear whether fate diversification between adult type B and type E cells actually occurs during embryogenesis. Here we performed single-cell transcriptomic analysis of slowly dividing embryonic NPCs and identified cell subpopulations transcriptionally similar to adult type B or type E cells. The type B- like embryonic cells appeared to emerge before embryonic day (E) 13.5, whereas the type E-like cells became evident between E13.5 and E16.5. Genes differentially expressed in B-like embryonic cells (versus E-like cells) included Tmem100, Cadm2, and bone morphogenetic protein (BMP)-induced genes. Forced expression of an active form of BMP receptor (ALK2QD), TMEM100, or CADM2 in embryonic NPCs resulted in preferential generation of adult type B cells relative to type E cells in the postnatal brain. Moreover, knockdown of TMEM100 resulted in relative enrichment of type E cells over type B cells. Our results indicate that the embryonic origin of adult type B cells and that of type E cells have already diverged molecularly during embryogenesis, and they have identified key molecular players in this fate bifurcation.

developmental biology↗

bioRxiv2024

Oral bioavailability of a noncoding RNA drug, TY1, that acts on macrophages

All approved RNA therapeutics require parenteral delivery. Here we demonstrate an orally bioavailable formulation wherein synthetic noncoding (nc) RNA, packaged into lipid nanoparticles, is loaded into casein-chitosan (C2) micelles. We used the C2 formulation to deliver TY1, a 24-nucleotide synthetic ncRNA which targets the DNA damage response pathway in macrophages. C2-formulated TY1 (TY1C2) efficiently packages and protects TY1 against degradative enzymes. In healthy mice, oral TY1C2 was well-tolerated and nontoxic. Oral TY1C2 exhibited disease-modifying bioactivity in 2 models of tissue injury: 1) rat myocardial infarction, where a single oral dose of TY1C2 was cardioprotective, on par with intravenously-delivered TY1; and 2) mouse acute lung injury, where a single dose of TY1C2 attenuated pulmonary inflammation. Mechanistic dissection revealed that TY1C2 is not absorbed into the systemic circulation but is, instead, taken up by intestinal macrophages, namely those of the lamina propria and Peyers patches. This route of absorption may rationalize why an antisense oligonucleotide against Factor VII, which acts on hepatocytes, is not effective when administered in the C2 formulation. Thus, some (but not all) ncRNA drugs are bioavailable when delivered by mouth. Oral RNA delivery and uptake, relying on uptake via the gastrointestinal immune system, has broad-ranging therapeutic implications. Graphical AbstractOral TY1C2 is taken up in the small intestine mainly by macrophages of the lamina propria and the Peyers patches. Macrophages that have taken up oral TY1C2 mediate disease-modifying bioactivity in 2 animal models of acute tissue injury. The blue + denotes the as-yet-uncertain mechanisms/mediators linking TY1 gut uptake to the drugs systemic therapeutic benefits. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/591474v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@8bfffdorg.highwire.dtl.DTLVardef@15379e5org.highwire.dtl.DTLVardef@167e9aaorg.highwire.dtl.DTLVardef@11dd317_HPS_FORMAT_FIGEXP M_FIG C_FIG

synthetic biology↗

bioRxiv2024

Drumming Performance and Underlying Muscle Activities in a Professional Rock Drummer with Lower-Limb Dystonia: A Case Study

Task-specific focal dystonia (TSFD), characterized by the loss of fine motor control and coordination, affects drummers lower-limb movements, yet it remains relatively understudied, leaving a gap in understanding its effects on drumming performance and underlying muscle activities. This study explores lower limb dystonias impact on drumming performance and underlying muscle activity in a professional rock drummer. The drummer executed an eight-beat pattern on a drum kit, emphasizing kicking the bass drum on the initial beat and performing syncopation of the third beat. Dystonia symptoms primarily manifested in the initial beat, with fewer symptoms on syncopation of the third beat. Analysis revealed decreased bass-drum sound peak amplitude during the initial beat and increased (becoming more negative) synchronization error. Electromyographic (EMG) measurements of ten muscles in the affected right lower limb showed significant changes in the Biceps Femoris (BF), Tibialis Anterior (TA), Extensor Digitorum Longus (EDL), and Extensor Digitorum Brevis (EDB) muscles during symptom onset. Notably, we observed 1) earlier overactivation of the TA and EDL muscles during the leg lift-up motion or preparatory phase of pedaling, 2) reduced activation of the EDB muscle, and 3) increased activation of the BF muscle during the final pedaling movement when symptoms occurred. These findings suggest that lower-limb dystonia symptoms are characterized by a reduction in amplitude and an increase in synchronization error, potentially due to premature overactivation of the ankle dorsiflexor muscles.

neuroscience↗