Biology subjects

Ryan, K.

Publications and source records attributed to Ryan, K..

At least 19 recordsLinked to original sources

bioRxiv2026

The basal cell state maintains pancreatic cancers by controlling an immunosuppressive circuit

Intra-tumoral heterogeneity is a cardinal feature of solid tumors, yet how distinct cancer cell states functionally contribute to malignant and stromal diversity in situ remains poorly understood. Using mouse models to lineage-trace or genetically ablate the two predominant cancer cell states in autochthonous pancreatic ductal adenocarcinoma (PDAC), we discover that basal cancer cells are highly plastic, whereas classical cancer cells exhibit limited plasticity. Strikingly, ablation of the basal, but not the classical, state induced rapid and durable tumor collapse, driven by loss of immunosuppressive cancer-associated fibroblasts, macrophage repolarization, and reprogramming of the tumor cytokine milieu, culminating in tumor destruction by cytotoxic lymphocytes. Knockout of a single cytokine, GM-CSF, specifically in basal cells recapitulated macrophage repolarization and lymphocyte recruitment observed upon basal state ablation and shrank tumors. These results reveal the basal cell state controls an immunosuppressive cell circuit critical for PDAC maintenance, motivating therapeutic targeting of the basal cells.

cancer biology↗

bioRxiv2025

Rapid Derivation of Cloning-Competent Cells from Peripheral Blood Advances Conservation Biobanking

I.Establishing viable cell lines from endangered species is essential for conservation, yet traditional fibroblast derivation from skin biopsies faces challenges including variable success rates, contamination risk, and extended culture timelines. We demonstrate that endothelial progenitor cells (EPCs) and pericytes isolated from peripheral blood represent superior alternatives for biobanking across three mammalian genera (Canis, Bison, and Equus). Blood-derived cells exhibited 2-3 fold faster doubling rates (15-20 hours versus >35 hours for fibroblasts) and reduced time to generate banked lines from 3-4 weeks to 1.5-2 weeks. Proteomic profiling of 32 canonical markers confirmed EPCs and pericytes represent distinct populations with lineage-specific molecular signatures. Optical genome mapping demonstrated equivalent genomic stability across all cell types with no detectable structural variants or aneuploidies. Critically, interspecific somatic cell nuclear transfer (iSCNT) experiments confirmed both EPCs and pericytes generate viable embryos with efficiency meeting or exceeding fibroblasts. Gray wolf blood-derived cells produced six viable fetuses with 15% implantation rate, while bison EPCs showed higher blastocyst formation (7%) than fibroblasts (3%) from the same individual. Blood collection during routine veterinary procedures offers minimally invasive sampling with reduced contamination compared to skin biopsies. These findings support integrating blood-derived cell banking into conservation programs, enabling opportunistic genetic preservation during standard management activities and expanding options for genetic rescue through assisted reproductive technologies.

cell biology↗

bioRxiv2025

Human colonization with Phytobacter co-harbouring blaIMP-4 and mcr-9.1 highlights its potential as emerging human pathogen.

Phytobacter is a recently delineated, frequently misidentified genus within the order Enterobacterales. Following two rare cases of patient colonization with multidrug resistant Phytobacter in Ireland, this study presents a genus-wide genomic analysis that aims to define the pathogenic potential of Phytobacter species, with emphasis on their role as emerging human pathogens and reservoirs of carbapenemases. Two carbapenemase-encoding isolates were recovered from rectal swabs in Ireland in 2024 and were initially identified as Phytobacter by MALDI-ToF. Whole-genome sequencing with in silico species typing (dDDH, ANI) provided definitive taxonomic resolution. A genus-wide maximum-likelihood core-genome phylogeny was reconstructed, and the plasmidome and resistome were bioinformatically profiled across all available Phytobacter genomes. Phenotypic susceptibility of the Irish isolates was determined through minimum inhibitory concentration (MIC) testing. The Irish isolates (P. diazotrophicus E787336 and P. ursingii E980862) are the first reported Phytobacter strains carrying both plasmid-borne blaIMP-4 and mcr-9.1 in the genus. MIC testing confirmed resistance to aztreonam, aminoglycosides, cephalosporins, fluoroquinolones, and the {beta}-lactam/{beta}-lactamase inhibitor combination piperacillin-tazobactam. Across 34 Phytobacter genomes examined, 22 distinct plasmid replicon types were identified in 22 isolates, often shared across species. The genus-wide resistome encompassed 71 genes, more than half predicted to be acquired, with carbapenemases detected in 26.5% (9/34) of the genomes. In summary, Phytobacter harbors a diverse, plasmid-borne resistome including carbapenemases, with documented cases of human colonization and infection. These findings support its recognition as an emerging pathogen and reservoir of antimicrobial resistance, underscoring the need for improved clinical identification, genomic surveillance, and preparedness for limited treatment options. Author summarySince Phytobacter was first characterized in 2007, this bacterial genus has mainly been associated with plant growth promotion. More recently, however, increasing reports of human infections have raised concerns about its potential as emerging bacterial pathogen. These are further underscored by the description of multidrug resistant isolates capable to withstand different classes of antimicrobials, including carbapenems which are often used as a last line of treatment. Following the rare finding of multidrug resistant Phytobacter in two patients in Ireland, we combined bioinformatics and laboratory testing to characterize the antimicrobial resistance profile of this overlooked bacterial genus. Our results uncover the variety of resistance determinants, including to carbapenems, which is encoded in the genomes of Phytobacter. This shows its potential as hidden reservoir of drug resistance and emerging bacterial pathogen. We encourage improved clinical recognition and monitoring of Phytobacter to better anticipate infections with limited therapeutic options.

genomics↗

bioRxiv2025

The dorsal/ventral subdivision of the hindbrain predates the tunicate/vertebrate split

While the CNSs of the chordate sister clades Tunicata and Vertebrata have unmistakable homology, the extent of their conservation is still being uncovered. We report that the hindbrain of the tunicate Ciona, like those of vertebrates, has functionally-distinct dorsal and ventral domains. The Ciona dorsal hindbrain functions as a relay and processing center for peripheral sensory neurons, while in vertebrates the dorsal hindbrain forms the cerebellum. Despite the different fates of dorsal hindbrains in Ciona versus vertebrates, we present evidence from analysis of gene expression, developmental mechanisms, and neural circuit architecture that they share a common origin. While it is generally agreed that the cerebellum evolved in vertebrates, our findings indicate that a dorsally-positioned precursor to the cerebellum has much deeper roots.

evolutionary biology↗

bioRxiv2025

Emergence of Dual β-lactam and Colistin Resistance via blaFRI-8 and mcr10.2 co-carriage on an IncFII Family Plasmid in Enterobacter vonholyi

ObjectivesEnterobacter vonholyi isolate E323169 represents a rare case of co-carriage of the antimicrobial resistance genes (ARGs) blaFRI-8, mcr-10.2. isolated from a clinical rectal swab. E323169 is one of only 12 available E. vonholyi genomes. To date, and across over two million pathogenic genomes scanned, only three harbour blaFRI-8 and two encode mcr-10.2, yet none exhibit both genes together. This study analyzes the genomic, phenotypic and epidemiological importance of this rare co-occurrence. MethodsSpecies-ID for E323169 was assigned by MALDI-TOF and then re-assigned and confirmed using a multifactorial genomic workflow. Antimicrobial susceptibilities were determined by MIC assay. The genome of E323169 was sequenced on an Illumina-NextSeq-1000, assembled, and annotated for ARGs, virulence factors, and plasmid replicons detection. Comparative phylogenomics used 12 E. vonholyi RefSeq assemblies, and NCBI metadata were analysed for plasmid distributions of blaFRI-8 and mcr-10.2. ResultsE323169 carried six ARGs: four chromosomally encoded (blaACT-91, fosA, oqxA10, oqxB9) and two plasmid-borne (blaFRI-8 and mcr-10.2) co-located on IncFII(p14)_1_p14 replicon. Additional plasmid replicons: Col(MG828)_1 and ColRNAI_1 were also identified. By mining the NCBI Pathogen Detection pipeline, we identified blaFRI-8 on IncFII replicon in E. asburiae JBIWA002, and mcr-10.2 on a multi-replicon (IncFIB/IncFII) plasmid in E. kobei 11778-yvys. ConclusionThis report documents the first E. vonholyi isolate co-harboring blaFRI-8 and mcr-10.2 on a single IncFII family plasmid, showing the widening host range of plasmid-mediated resistance to carbapenems/colistin. No prior similar co-occurrences reported, underscoring its rarity. These findings highlight the urgent need for enhanced clinical screening and genomic surveillance to curb the spread.

microbiology↗

bioRxiv2024

Dietary protein restriction diminishes sucrose reward and reduces sucrose-evoked mesolimbic dopamine signaling

ObjectiveA growing literature suggests manipulating dietary protein status decreases sweet consumption in rodents and in humans. Underlying neurocircuit mechanisms have not yet been determined, but previous work points towards hedonic rather than homeostatic pathways. Here we hypothesized that a history of protein restriction reduces sucrose seeking by altering mesolimbic dopamine signaling. MethodsWe tested this hypothesis using established behavioral tests of palatability and motivation, including the palatability contrast and conditioned place preference (CPP) tests. We used modern optical sensors for measuring real-time nucleus accumbens (NAc) dopamine dynamics during sucrose consumption, via fiber photometry, in male C57/Bl6J mice maintained on low-protein high-carbohydrate (LPHC) or control (CON) diet for [~]5 weeks. ResultsA history of protein restriction decreased the consumption of a sucrose dessert in sated mice by [~]50% compared to controls [T-test, p< 0.05]. The dopamine release in NAc during sucrose consumption was reduced, also by [~]50%, in LPHC-fed mice compared to CON [T-test, p< 0.01]. Furthermore, LPHC-feeding blocked the sucrose-conditioned place preference we observed in CON-fed mice [paired T-test, p< 0.05], indicating reduced motivation. This was accompanied by a 33% decrease in neuronal activation of the NAc core, as measured by c-Fos immunolabeling from brains collected directly after the CPP test. ConclusionsDespite ongoing efforts to promote healthier dietary habits, adherence to recommendations aimed at reducing the intake of added sugars and processed sweets remains challenging. This study highlights chronic dietary protein restriction as a nutritional intervention that suppresses the motivation for sucrose intake, via blunted sucrose-evoke dopamine release in NAc.

physiology↗

bioRxiv2024

Deep homologies in chordate caudal central nervous systems

Invertebrate chordates, such as the tunicate Ciona, can offer insight into the evolution of the chordate phylum. Anatomical features that are shared between invertebrate chordates and vertebrates may be taken as evidence of their presence in a common chordate ancestor. The central nervous systems of Ciona larvae and vertebrates share a similar anatomy despite the Ciona CNS having [~]180 neurons. However, the depth of conservation between the Ciona CNS and those in vertebrates is not resolved. The Ciona caudal CNS, while appearing spinal cord-like, has hitherto been thought to lack motor neurons, bringing into question its homology with the vertebrate spinal cord. We show here that the Ciona larval caudal CNS does, in fact, have functional motor neurons along its length, pointing to the presence of a spinal cord-like structure at the base of the chordates. We extend our analysis of shared CNS anatomy further to explore the Ciona "motor ganglion", which has been proposed to be a homolog of the vertebrate hindbrain, spinal cord, or both. We find that a cluster of neurons in the dorsal motor ganglion shares anatomical location, developmental pathway, neural circuit architecture, and gene expression with the vertebrate cerebellum. However, functionally, the Ciona cluster appears to have more in common with vertebrate cerebellum-like structures, insofar as it receives and processes direct sensory input. These findings are consistent with earlier speculation that the cerebellum evolved from a cerebellum-like structure, and suggest that the latter structure was present in the dorsal hindbrain of a common chordate ancestor.

neuroscience↗

bioRxiv2024

First endangered black-footed ferrets, Mustela nigripes, cloned for genetic rescue

An endangered black-footed ferret female that died in 1988 with no living descendants in the current population was successfully cloned from cryopreserved cells using cross-species somatic cell nuclear transfer, producing three healthy kits. Incorporating progeny from these clones would provide an 8th founder to the breeding program and increase genetic variation to the species limited gene-pool. This marks the first time a native U.S. endangered species has been cloned.

zoology↗

bioRxiv2024

Warfarin analogs target disulfide bond-forming enzymes and suggest a residue important for quinone and coumarin binding

Disulfide bond formation has a central role in protein folding of both eukaryotes and prokaryotes. DsbB and VKOR enzymes catalyze the oxidation of the oxidoreductase partner and the formation of de novo disulfide bonds using quinone as cofactor. We have used E. coli and a family of warfarin analogs to study de novo disulfide bond formation. We found that human VKORc1 can function in E. coli by removing two positive residues, allowing the search for novel anticoagulants. One analog was capable of inhibiting both bacterial DsbB and VKOR, and a second one antagonized only the mammalian enzymes. We identified the two amino acid residues responsible for binding. One of these is also essential for quinone binding in both DsbB and VKOR. Our studies highlight a conserved role of this residue in de novo disulfide-generating enzymes and enable the design of novel anticoagulants or antibacterials using coumarin as a scaffold.

microbiology↗

bioRxiv2024

A Phased, Chromosome-scale Genome for Malus domestica 'WA 38'

Genome sequencing for agriculturally important Rosaceous crops has made rapid progress both in completeness and annotation quality. Whole genome sequence and annotation gives breeders, researchers, and growers information about cultivar specific traits such as fruit quality, disease resistance, and informs strategies to enhance postharvest storage. Here we present a haplotype-phased, chromosomal level genome of Malus domestica, WA 38, a new apple cultivar released to market in 2017 as Cosmic Crisp (R). Using both short and long read sequencing data with a k-mer based approach, chromosomes originating from each parent were assembled and segregated. This is the first pome fruit genome fully phased into parental haplotypes in which chromosomes from each parent are identified and separated into their unique, respective haplomes. The two haplome assemblies, Honeycrisp originated HapA and Enterprise originated HapB, are about 650 Megabases each, and both have a BUSCO score of 98.7% complete. A total of 53,028 and 54,235 genes were annotated from HapA and HapB, respectively. Additionally, we provide genome-scale comparisons to Gala, Honeycrisp, and other relevant cultivars highlighting major differences in genome structure and gene family circumscription. This assembly and annotation was done in collaboration with the American Campus Tree Genomes project that includes WA 38 (Washington State University), dAnjou pear (Auburn University), and many more. To ensure transparency, reproducibility, and applicability for any genome project, our genome assembly and annotation workflow is recorded in detail and shared under a public GitLab repository. All software is containerized, offering a simple implementation of the workflow.

genomics↗

bioRxiv2022

RSV-induced Expanded Ciliated Cells Contribute to Bronchial Wall Thickening

Viral infection, particularly respiratory syncytial virus (RSV), causes inflammation in the bronchiolar airways (bronchial wall thickening, also known as bronchiolitis), reducing airflow through the bronchioles. This bronchial wall thickening is a common pathophysiological feature in RSV infection, but it causes more fatalities in infants than in children and adults. However, the molecular mechanism of RSV-induced bronchial wall thickening remains unknown, particularly in healthy adults. RSV infection in the airway epithelium of healthy adult bronchial cells reveals RSV-infects primarily ciliated cells. RSV infection expands the cell cytoskeleton substantially without compromising epithelial membrane integrity and ciliary functions. The RSV-induced actin cytoskeleton expansion increases ununiformly epithelial height, and cytoskeletal (actin polymerization), immunological (INF-L1, TNF-, IP10/CXCL10), and viral (NS2) factors are probably responsible. Interestingly, RSV-infected cell cytoskeletons expansion resembles a noncanonical inflammatory phenotype, which contributes to bronchial wall thickening, and is termed cytoskeletal inflammation. Author SummaryRSV infects everyone. Although RSV-induced fatal pathophysiology (e.g., bronchiolitis) is more common in infants than adults, this bronchiolitis (or bronchial wall thickening) is common in the lower respiratory tract due to RSV infection in all ages. To determine the molecular mechanism of RSV-induced bronchial wall thickening, we infected in vitro adult airway epithelium with RSV. We found that RSV-infection induced a substantial actin-cytoskeleton expansion, consequently increased the height of the epithelium. We identified actin polymerization, secretion of proinflammatory cytokines and chemokines, and viral proteins contribute to the RSV-induced cytoskeletal expansion. Our results suggest that RSV-induces a novel noncanonical epithelial host response termed cytoskeletal inflammation, which may contribute to bronchial wall thickening.

microbiology↗

bioRxiv2021

Automatic Detection and Neurotransmitter Prediction of Synapses in Electron Microscopy

This paper presents a deep-learning based workflow to detect synapses and predict their neurotransmitter type in the primitive chordate Ciona intestinalis (Ciona) EM images. Identifying synapses from electron microscopy (EM) images to build a full map of connections between neurons is a labor-intensive process and requires significant domain expertise. Automation of synapse detection and classification would hasten the generation and analysis of connectomes. Furthermore, inferences concerning neuron type and function from synapse features are in many cases difficult to make. Finding the connection between synapse structure and function is an important step in fully understanding a connectome. Activation maps derived from the convolutional neural network provide insights on important features of synapses based on cell type and function. The main contribution of this work is in the differentiation of synapses by neurotransmitter type through the structural information in their EM images. This enables prediction of neurotransmitter types for neurons in Ciona which were previously unknown. The prediction model with code is available on Github.

neuroscience↗

bioRxiv2021

Increased apoptotic priming of glioblastoma enables therapeutic targeting by BH3-mimetics

IDH wild-type glioblastoma (GBM) is the most prevalent malignant primary brain tumour in adults. GBM typically has a poor prognosis, mainly due to a lack of effective treatment options leading to tumour persistence or recurrence. Tackling this, we investigated the therapeutic potential of targeting anti-apoptotic BCL-2 proteins in GBM. Levels of anti- apoptotic BCL-xL and MCL-1 were consistently increased in GBM compared with non- malignant cells and tissue. Moreover, we found that relative to their differentiated counterparts, patient-derived GBM stem-like cells also displayed higher expression of anti- apoptotic BCL-2 family members. Surprisingly, high anti-apoptotic BCL-xL and MCL-1 expression correlated with heightened susceptibility of GBM to BCL-2 family protein- targeting BH3-mimetics. This is indicative of increased apoptotic priming. Indeed, GBM displayed an obligate requirement for MCL-1 expression in both tumour development and maintenance. Investigating this apoptotic sensitivity, we found that sequential inhibition of BCL-xL and MCL-1 led to robust anti-tumour responses in vivo, in the absence of overt toxicity. These data demonstrate that BCL-xL and MCL-1 pro-survival function is a fundamental prerequisite for GBM survival that can be therapeutically exploited by BH3- mimetics.

cancer biology↗

bioRxiv2020

Comparative genomics identified a genetic locus in plant-associated Pseudomonas spp. that is necessary for induced systemic susceptibility

Plant root-associated microbes promote plant growth and induce systemic resistance (ISR) to foliar pathogens. In an attempt to find novel growth-promoting and ISR-inducing strains, we previously identified strains of root-associated Pseudomonas spp. that promote plant growth but unexpectedly induced systemic susceptibility (ISS) rather than ISR to foliar pathogens. Here we demonstrate that the ISS-inducing phenotype is common among root-associated Pseudomonas spp. Using comparative genomics, we identified a single P. fluorescens locus that is unique to ISS strains. We generated a clean deletion of the 11-gene ISS locus and found that it is necessary for the ISS phenotype. Although the functions of the predicted genes in the locus are not apparent based on similarity to genes of known function, the ISS locus is present in diverse bacteria and a subset of the genes have previously been implicated in pathogenesis in animals. Collectively these data show that a single bacterial locus contributes to modulation of systemic plant immunity. ImportanceMicrobiome-associated bacteria can have diverse effects on health of their hosts, yet the genetic and molecular basis of these effects have largely remained elusive. This work demonstrates that a novel bacterial locus can modulate systemic plant immunity. Additionally, this work demonstrates that growth promoting strains may have unanticipated consequences on plant immunity and this is critical to consider when engineering the plant microbiome for agronomic improvement.

microbiology↗

bioRxiv2019

Modelling erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I)

We employ and extensively characterise an ex vivo culture system to study terminal erythroid maturation of CD34+ progenitors from the peripheral blood of normal individuals and patients with Congenital Dyserythropoietic Anaemia type 1 (CDA-I). Using morphological analysis, FACS analysis and the proteomic approach CyTOF, we analysed patient-derived erythroblasts stage-matched with those from healthy donors during the expansion phase and into early differentiation. In patient cells, aspects of disordered erythropoiesis manifest midway through differentiation, including increased proliferation and changes in the DNA accessibility profile. We also show that cultured erythroblasts from CDA-I patients recapitulate the pathognomic feature of this erythroid disorder with up to 40% of the cells having abnormal spongy chromatin morphology by electron microscopy, as well as upregulation of GDF15, a marker of ineffective erythropoiesis. In the tertiary phase of culture, patient cells show significantly less enucleation and there is persistence of earlier erythroid precursors. Furthermore, the enucleation defect appears to be more severe in patients with mutations in C15orf41, as compared to the other known causative gene CDAN1, indicating a genotype/phenotype correlation in CDA-I. Such erythroblasts are a valuable resource for investigating the pathogenesis of this disease and provide the opportunity for streamlining diagnosis for CDA-I patients and ultimately other forms of unexplained anaemia.

genetics↗

bioRxiv2019

Genome Sequencing Unveils a New Regulatory Landscape of Platelet Reactivity

Exaggerated platelet aggregation at the site of vascular injury is the underlying pathophysiology of thrombotic diseases. Here, we conduct the largest whole genome sequencing (WGS) effort to uncover the genetic determinants of platelet aggregation. Leveraging 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) individuals deeply phenotyped for platelet aggregation, we identify 18 loci using single-variant approaches. This includes the novel RGS18 locus encoding a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with eQTL signatures for RGS18 expression in platelets. A gene-based approach focusing on deleterious coding variants identifies the SVEP1 gene, previously shown to be associated with coronary artery disease, as a novel determinant of platelet aggregation. Finally, in an integrative approach leveraging epigenetic data on megakaryocytes, we find strong association between rare variants mapping to a super enhancer region for PEAR1. This is a novel finding implicating the importance of rare variants with regulatory potential in a previously documented GWAS-identified locus.

genomics↗

bioRxiv2019

A genome-wide association study identifies that the GDF5 and COL27A1 genes are associated with knee pain in UK Biobank (N = 171, 516)

ObjectiveKnee pain is one of the most common musculoskeletal complaints that brings people to medical attention. We sought to identify the genetic variants associated with knee pain in 171,516 subjects from the UK Biobank cohort and replicate them using cohorts from 23andMe, the Osteoarthritis Initiative (OAI), and the Johnston County Osteoarthritis Study (JoCo).\n\nMethodsWe performed a genome-wide association study of knee pain in the UK Biobank, where knee pain was ascertained through self-report and defined as \"knee pain in the last month interfering with usual activities\". A total of 22,204 cases and 149,312 controls were included in the discovery analysis. We tested our top and independent SNPs (P < 5 x 10-8) for replication in 23andMe, OAI, and JoCo, then performed a joint meta-analysis between discovery and replication cohorts using GWAMA. We calculated the narrow-sense heritability of knee pain using Genome-wide Complex Trait Analysis (GCTA).\n\nResultsWe identified 2 loci that reached genome-wide significance, rs143384 located in the GDF5 (P = 1.32 x 10-12), a gene previously implicated in osteoarthritis, and rs2808772, located near COL27A1 (P = 1.49 x 10-8). These findings were subsequently replicated in independent cohorts and increased in significance in the joint meta-analysis (rs143384: P = 4.64 x 10-18; rs2808772: P -11 = 2.56 x 10-1). The narrow sense heritability of knee pain was 0.08.\n\nConclusionIn this first reported genome-wide association meta-analysis of knee pain, we identified and replicated two loci in or near GDF5 and COL27A1 that are associated with knee pain.

genetics↗

bioRxiv2018

1H MR Spectroscopy of the Motor Cortex Immediately following Transcranial Direct Current Stimulation at 7 Tesla

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that may modulate cortical excitability, metabolite concentration, and human behaviour. The supplementary motor area (SMA) has been largely ignored as a potential target for tDCS neurorehabilitation but is an important region in motor compensation after brain injury with strong efferent connections to the primary motor cortex (M1). The objective of this work was to measure tissue metabolite changes in the human motor cortex immediately following tDCS. We hypothesized that bihemispheric tDCS would change levels of metabolites involved in neuromodulation including N-acetylaspartate, glutamate, and creatine. In this single-blind, randomized, cross-over study, fifteen healthy adults aged 21-60 participated in two 7T MRI sessions, to identify changes in metabolite concentrations by magnetic resonance spectroscopy. Immediately after 20 minutes of tDCS, there were no significant changes in metabolite levels or metabolite ratios comparing tDCS to sham. However there was a trend toward increased NAA/tCr concentration (p=0.08) in M1 under the stimulating cathode. There was a strong, positive correlation between the change in the absolute concentration of NAA and the change in the absolute concentration of tCr (p<0.001) suggesting an effect of tDCS. Both NAA and creatine are important markers of neurometabolism. Our findings provide novel insight into the modulation of neural metabolites in the motor cortex immediately following application of bihemispheric tDCS.

biophysics↗