bioRxiv : the preprint server for biology最新文献

{"title":"Mapping <i>Plasmodium</i> transitions and interactions in the <i>Anopheles</i> female.","authors":"Yan Yan, Lisa H Verzier, Elaine Cheung, Federico Appetecchia, Sandra March, Ailsa R Craven, Esrah Du, Alexandra S Probst, Tasneem A Rinvee, Laura E de Vries, Jamie Kauffman, Sangeeta N Bhatia, Elisabeth Nelson, Naresh Singh, Duo Peng, W Robert Shaw, Flaminia Catteruccia","doi":"10.1101/2024.11.12.623125","DOIUrl":"10.1101/2024.11.12.623125","url":null,"abstract":"<p><p>The human malaria parasite, <i>Plasmodium falciparum</i>, relies exclusively on <i>Anopheles</i> mosquitoes for transmission. Once ingested during blood feeding, most parasites die in the mosquito midgut lumen or during epithelium traversal¹. How surviving ookinetes interact with midgut cells and form oocysts is poorly known, yet these steps are essential to initiate a remarkable growth process culminating in the production of thousands of infectious sporozoites². Here, using single-cell RNA sequencing of both parasites and mosquito cells across different developmental stages and metabolic conditions, we unveil key transitions and mosquito-parasite interactions occurring in the midgut. Functional analyses uncover processes regulating oocyst growth and identify the transcription factor <i>Pf</i>SIP2 as essential for sporozoite infection of human hepatocytes. Combining shared mosquito-parasite barcode analysis with confocal microscopy, we reveal that parasites preferentially interact with midgut progenitor cells during epithelial crossing, potentially using their basal location as an exit landmark. Additionally, we show tight connections between extracellular late oocysts and surrounding muscle cells that may ensure parasites adherence to the midgut. We confirm our major findings in several mosquito-parasite combinations, including field-derived parasites. Our study provides fundamental insight into the molecular events characterizing previously inaccessible biological transitions and mosquito-parasite interactions, and identifies candidates for transmission-blocking strategies.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11601300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142742078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Digital Twin for the Win: Personalized Cardiac Electrophysiology.","authors":"Pei-Chi Yang, Mao-Tsuen Jeng, Deborah K Lieu, Regan L Smithers, Gonzalo Hernandez-Hernandez, L Fernando Santana, Colleen E Clancy","doi":"10.1101/2025.09.03.674034","DOIUrl":"10.1101/2025.09.03.674034","url":null,"abstract":"<p><p>Individual variability drives differences in cardiovascular disease manifestation, therapeutic response, and rare phenotypes. Traditional preclinical models minimize variability, limiting their ability to capture population heterogeneity and contributing to translational gaps and adverse drug reactions. Here, we present a computational, experimental, and machine learning framework for generating digital twins of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) that reproduce cell-specific electrophysiology from a single optimized voltage-clamp protocol. A synthetic population of iPSC-CMs was generated by varying 52 parameters across six ionic currents and used to train a neural network to infer parameters from current responses. Applied to experimental data, this approach produced digital twins that captured action potential diversity across temperatures and morphologies. Importantly, baseline variability in ionic current dynamics not only explained heterogeneity in spontaneous action potential waveforms but also predicted differential drug sensitivity, supporting digital twin application in cardiac safety pharmacology and precision medicine.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12424819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of Naturally Occurring Somatic Insertions in the Human Genome.","authors":"Chih-Lin Hsieh, Zarko Manojlovic, Timothy Okitsu, Cindy Okitsu, Jordan Wlodarczyk, Nick Shillingford, Ramzi Bawab, Yong Hwee Eddie Loh, Michael R Lieber","doi":"10.1101/2025.09.24.677890","DOIUrl":"10.1101/2025.09.24.677890","url":null,"abstract":"<p><p>Biochemical and genetic experimental systems permit precise definition of enzyme requirements and mechanistic steps in DNA repair. Comparison of these findings to repair events at naturally occurring breakage sites in multicellular organisms is valuable for confirming and extending these insights. However, heterogeneity in any cell population increases with each cell division, and the reliable detection of DNA breakage sites and their repair <i>in vivo</i> has been difficult due to technical limitations. Here, we examine somatic insertional mutations naturally occurring during normal metabolism and cell division in single human colon crypts using a novel whole-genome sequencing method. We find that replication slippage is a dominant mechanism for these events, and insertions larger than 10 bp are uncommon. Mechanistic features of these sites in physiologically normal cell clones, such as single human colon crypts, permits inferences about the DNA breakage repair zone and processing within natural chromatin, thereby permitting comparisons to experimental studies using <i>ex vivo</i> cellular and simplified biochemical systems.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12485854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating milk-derived extracellular vesicles as mediators of maternal stress and environmental intervention.","authors":"Julia Martz, Baila Hammer, Tristen J Langen, Benjamin Berkowitz, Benzion Berkowitz, Jasmyne A Storm, Jueqin Lu, Deepali Lehri, Sanoji Wijenayake, Jordan Marrocco, Amanda C Kentner","doi":"10.1101/2025.05.30.656911","DOIUrl":"10.1101/2025.05.30.656911","url":null,"abstract":"<p><p>Parental communication signals are transmitted through nursing and critically shape neurodevelopmental trajectories. Mirroring some well characterized effects of gestational challenges in rodents, maternal immune activation (MIA) during the lactational period disrupts maternal physiology, decreases lipid content, and is associated with adverse neurobehavioral outcomes in offspring. This occurs without MIA significantly affecting maternal care. While gestational MIA models are responsive to environmental interventions, which beneficially alter maternal milk composition and associated offspring outcomes, the bioactive mediators in milk underlying resilience remain poorly understood. Milk-derived extracellular vesicles (MEVs) transport and deposit biologically active cargo, including microRNAs (miRNAs) that induce post-translational regulation of candidate mRNA in the nursing offspring's tissues and cells. Using a rat model, we show that lactational MIA alters MEV-miRNA cargo and the expression of hippocampal miRNAs in offspring. Several miRNAs in MEVs were also found in the hippocampus of matching offspring. Remarkably, the miRNA changes in MEVs and the neonatal hippocampus were rescued when dams were raised in an enriched environment, suggesting environmental enrichment protected from the effects of MIA. This was supported by the behavioral phenotype. RNA-seq of adult offspring hippocampus showed long-term transcriptional changes associated with the gene targets of early-life regulated miRNAs. Our results position MEV-miRNA as dynamic programming signals by which maternal experience is communicated to offspring, encoding both stress-induced and protective cues that influence development. This suggests that breastfeeding interventions can regulate the genetic cargo of the milk, programming the life of developing infants.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the mesoscale resting-state functional connectivity of ocular dominance columns in humans using high-resolution functional MRI.","authors":"Marianna E Schmidt, Iman Aganj, Jason Stockmann, Berkin Bilgic, Yulin Chang, W Scott Hoge, Evgeniya Kirilina, Nikolaus Weiskopf, Shahin Nasr","doi":"10.1101/2025.03.27.645795","DOIUrl":"10.1101/2025.03.27.645795","url":null,"abstract":"<p><p>Despite their importance for visual perception, functional connectivity between ocular dominance columns (ODCs) in the human primary visual cortex (V1) remains largely unknown. Using high-resolution functional MRI (fMRI), we localized ODCs and assessed their resting-state functional connectivity (rs-FC) in 12 human adults. Consistent with anatomical studies in animals, we found stronger rs-FC in the middle compared to deep and superficial cortical depths and selectively stronger rs-FC between ODCs with alike compared to unalike ocular polarity. Beyond what was known from animal models, and consistent with human perceptual biases, intra- and interhemispheric rs-FC was stronger in peripheral (compared to central) and in dorsal (compared to ventral) V1 subregions. Lastly, rs-FC patterns correlated with ODC maps, suggesting that ODC maps can be predicted from rs-FC patterns within V1. These results highlight the heterogeneity in rs-FC between ODCs across cortical depths and V1 subfields, underscoring their likely association with human perceptual features.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quercetin as a Bitter Taste Receptor Agonist with Anticancer Effects in Head and Neck Cancer Cells.","authors":"Gavin Turner, Sarah M Sywanycz, Brianna L Hill, Robert D Wardlow, Robert J Lee, Ryan M Carey","doi":"10.1101/2025.09.17.676947","DOIUrl":"10.1101/2025.09.17.676947","url":null,"abstract":"<p><strong>Background/objectives: </strong>Quercetin is a bitter compound with demonstrated anticancer effects in preclinical models of head and neck squamous cell carcinoma (HNSCC). In taste transduction, bitter compounds activate bitter taste receptors (T2Rs), a group of G protein-coupled receptors with downstream signaling that includes cytosolic calcium (Ca ²⁺ ) release. T2Rs are expressed in HNSCC cells, where their activation induces apoptosis <i>in vitro</i> . Increased T2R expression in HNSCC also correlates with improved patient survival. The objective of this study was to investigate the role of quercetin as an anticancer T2R agonist in HNSCC cells <i>in vitro</i> and <i>ex vivo</i> .</p><p><strong>Methods: </strong>Quercetin-mediated Ca ²⁺ responses were assessed using live cell Ca ²⁺ imaging in the presence of the T2R14 antagonist LF1 and G-protein inhibitor YM-254980 (YM) in UM-SCC-47 and FaDu HNSCC cell lines. Cell viability was evaluated using crystal violet assays in cell lines and MTS assays in patient-derived tumor slices. Mitochondrial depolarization was measured with TMRE in the presence and absence of T2R pathway inhibitors.</p><p><strong>Results: </strong>Quercetin induced a Ca ²⁺ response in HNSCC cells, which was significantly reduced by LF1 and YM. Quercetin also decreased cell viability <i>in vitro</i> and showed a potential decrease in viability in tumor slices but was not statistically significant. Finally, quercetin caused mitochondrial depolarization, which was reduced in the presence of LF1 but not by YM.</p><p><strong>Conclusions: </strong>In HNSCC cells, quercetin causes a Ca ²⁺ response that is likely mediated by T2R14, decreases viability, and causes mitochondrial depolarization.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12458154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduced enteric BDNF-TrkB signaling drives stress-dependent glucocorticoid-mediated GI dysmotility.","authors":"Jared Slosberg, Srinivas N Puttapaka, Philippa Seika, Su Min Hong, Alpana Singh, Ainsleigh Scott, Subhash Kulkarni","doi":"10.1101/2024.12.13.628260","DOIUrl":"10.1101/2024.12.13.628260","url":null,"abstract":"<p><p>Stress is a key contributor to gastrointestinal (GI) dysmotility, particularly in patients with disorders of gut-brain interactions (DGBI). Since GI motility is governed by the enteric nervous system (ENS), stress may act by altering ENS function. While stress activates glucocorticoid signaling via the hypothalamic-pituitary-adrenal axis, the impact of stress-mediated glucocorticoid signaling on ENS biology remains poorly understood. In the central nervous system, glucocorticoids reduce specific isoforms of brain-derived neurotrophic factor (BDNF), impairing signaling through its receptor, TrkB, and contributing to behavioral dysfunction. However, the identity of ENS-specific <i>Bdnf</i> isoforms, their glucocorticoid sensitivity, and the effect of enhanced TrkB signaling on GI motility in stressed animals has not been characterized. Here, using male and female mice, we show that >85% of post-natal ENS <i>Bdnf</i> transcripts are glucocorticoid-responsive isoforms. We also demonstrate that both BDNF and its receptor TrkB ( <i>Ntrk2</i> ) are expressed by enteric neurons. In male mice, stress and administration of dexamethasone-a synthetic glucocorticoid receptor (GR) agonist-cause GI dysmotility, which we demonstrate is associated with significantly reduced <i>Bdnf</i> transcripts in the longitudinal muscle - myenteric plexus (LM-MP) tissue <i>in vivo</i> . Dexamethasone exposure also represses <i>Bdnf</i> transcript and mature protein levels in LM-MP tissue <i>in vitro</i> . Notably, treatment with HIOC, a selective TrkB agonist, rescues GI transit defects in dexamethasone-treated animals. These findings identify BDNF-TrkB signaling as a key modulator of stress-induced ENS dysfunction and highlight TrkB as a promising therapeutic target for GI dysmotility in DGBI.</p><p><strong>Significance statement: </strong>How stress causes gastrointestinal (GI) dysmotility is not well understood. GI motility is regulated by the enteric nervous system (ENS), which is responsive to brain-derived neurotrophic factor (BDNF), which signals through its receptor tropomyosin related kinase B (TrkB). By altering glucocorticoid signaling, stress modulates brain's BDNF levels to cause behavioral changes. However, if this pathway is similarly responsible for stress's effects on GI dysmotility is not well understood. Here, by identifying the nature of ENS-specific <i>Bdnf</i> isoforms, studying their response to stress and glucocorticoid signaling, and testing the effect of a TrkB agonist to improve gut motility in a model of glucocorticoid-driven dysmotility, we implicate altered BDNF-TrkB signaling as an important mechanism driving stress-associated dysmotility.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The specificity and structure of DNA crosslinking by the gut bacterial genotoxin colibactin.","authors":"Erik S Carlson, Raphael Haslecker, Chiara Lecchi, Miguel A Aguilar Ramos, Vyshnavi Vennelakanti, Linda Honaker, Alessia Stornetta, Estela S Millán, Bruce A Johnson, Heather J Kulik, Silvia Balbo, Peter W Villalta, Victoria D'Souza, Emily P Balskus","doi":"10.1101/2025.05.26.655968","DOIUrl":"10.1101/2025.05.26.655968","url":null,"abstract":"<p><p>Accumulating evidence has connected the chemically unstable, DNA-damaging gut bacterial natural product colibactin to colorectal cancer, including the identification of mutational signatures that are thought to arise from colibactin-DNA interstrand crosslinks (ICLs). However, we currently lack direct information regarding the structure of this lesion. Here, we combine mass spectrometry and nuclear magnetic resonance spectroscopy to elucidate the specificity and structure of the colibactin-DNA ICL. We find that colibactin alkylates within the minor groove of AT-rich DNA, explaining the origins of mutational signatures. Unexpectedly, we discover that the chemically unstable central motif of colibactin mediates the sequence specificity of crosslinking. By directly elucidating colibactin's interactions with DNA, this work enhances our understanding of the structure and genotoxic mechanisms of this cancer-linked gut bacterial natural product.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12154741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144277908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic pain is linked to a resting-state neural archetype that optimizes learning from punishments.","authors":"Francesco Scarlatti, Ludovic Dormegny-Jeanjean, Roman Schefzik, Tobias Banaschewski, Arun L W Bokde, Rüdiger Brühl, Sylvane Desrivières, Hugh Garavan, Penny Gowland, Antoine Grigis, Andreas Heinz, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Dimitri Papadopoulos Orfanos, Luise Poustka, Michael N Smolka, Sarah Hohmann, Nathalie Holz, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Gunter Schumann, Frauke Nees, Emanuel Schwarz, Martin Löffler, Jack R Foucher, Herta Flor","doi":"10.1101/2025.07.11.664303","DOIUrl":"10.1101/2025.07.11.664303","url":null,"abstract":"<p><p>Chronic pain is a leading cause of disability, yet its underlying susceptibility traits remain unclear. Disorders like chronic pain may stem from extreme neural types, or archetypes, optimized for specific cognitive strategies and reflected in patterns of resting-state networks. Here, we examined a sample from the general population ( <i>n</i> = 892) and three clinical samples with subacute back pain ( <i>n</i> = 76), chronic back pain ( <i>n</i> = 30), and treatment-resistant depression ( <i>n</i> = 24). Using the sample from the general population, we found three neural archetypes that prioritize different cognitive strategies. Clinical pain samples, compared to the sample from the general population, mapped close to an archetype optimized for punishment learning (Archetype P). We replicated these results by recomputing the archetypes starting from the clinical pain samples, additionally revealing an association between Archetype P and pain severity. These findings suggest a neural-cognitive trait underlying susceptibility to chronic pain.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12338593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144824525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical-layer EEG-fMRI at 7T: experimental setup and analysis pipeline to elucidate generating mechanisms of alpha oscillations.","authors":"Daniel C Marsh, Rodika Sokoliuk, Kevin M Aquino, Daisie O Pakenham, Ross Wilson, Rosa Sanchez Panchuelo, Matthew J Brookes, Simon Hanslmayr, Stephen D Mayhew, Susan T Francis, Karen J Mullinger","doi":"10.1101/2025.09.09.674189","DOIUrl":"10.1101/2025.09.09.674189","url":null,"abstract":"<p><p>Alpha band (8-13Hz) electroencephalography (EEG) oscillations play a key role in cognition, but their generating mechanisms are still poorly understood. Most studies investigating laminar origins of alpha oscillations have been conducted on animals using invasive intracranial recordings. To relate these findings to human alpha generation, non-invasive techniques need to be developed. Layer functional Magnetic Resonance Imaging (fMRI) at ultra-high field (UHF, 7T) allows for the interrogation of brain responses across cortical depths and combined with simultaneous EEG, provides the opportunity to gain new insight into human alpha generation mechanisms. This work establishes a framework to study the generating mechanisms of electrophysiological signals non-invasively in humans using simultaneous EEG layer-fMRI. Data were acquired on 10 participants during an eyes closed/eyes open paradigm. We showed that in 9/10 participants the quality of EEG and Blood Oxygenation Level Dependent (BOLD) fMRI data were sufficient to observe a significant negative correlation between EEG alpha power and the BOLD signal in visual cortex grey matter to the eyes open/eyes closed task. \"Deveining\" was performed to overcome the increase in BOLD signal toward the pial surface due to draining veins, and the effects of each of the steps in the deveining analysis on the cortical depth profiles of the negative alpha-BOLD correlations studied. The largest effect was dependent on the exclusion of voxels in the tissue immediately surrounding veins. Following deveining, the cortical depth profiles showed the negative alpha-BOLD correlations were significantly weaker in the middle depths compared with deep and superficial depths. When a boxcar rather than EEG alpha power was used to model the task, this depth-dependence was not seen, suggesting this was specific to spontaneous alpha-power modulations. In conclusion, we have established a method to non-invasively interrogate the origins of electrophysiological signals. Our alpha-BOLD depth profiles suggest the alpha signal to an eyes open-closed task is generated in superficial and deep layers suggesting top-down processes.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}