{"doi":"10.7554/elife.92805","title":"Brain-wide mapping of layer-specific functional connectivity in the human cortex at 3T using draining-vein-suppressed fMRI","abstract":"Layer-dependent functional magnetic resonance imaging (fMRI) is a promising yet challenging approach for investigating layer-specific functional connectivity (FC). Achieving a brain-wide mapping of layer-specific FC requires several technical advancements, including sub-millimeter spatial resolution, sufficient temporal resolution, functional sensitivity, global brain coverage, and high spatial specificity. Although gradient echo (GE)-based echo planar imaging (EPI) is commonly used for rapid fMRI acquisition, it faces significant challenges due to the draining-vein contamination. In this study, we addressed these limitations by integrating velocity-nulling (VN) gradients into a GE-BOLD fMRI sequence to suppress vascular signals from the vessels with fast-flowing velocity. The extravascular contamination from pial veins was mitigated using a GE-EPI sequence at 3T rather than 7T, combined with phase regression methods. Additionally, we incorporated advanced techniques, including simultaneous multi-slice (SMS) acceleration and NOise Reduction with DIstribution Corrected principal component analysis (NORDIC PCA) denoising, to improve temporal resolution, spatial coverage, and signal sensitivity. This resulted in a VN fMRI sequence with 0.9 mm isotropic spatial resolution, a repetition time (TR) of 4 s, and brain-wide coverage. The VN gradient strength was determined based on results from a button-pressing task. Using resting-state data, we validated layer-specific FC through seed-based analyses, identifying distinct connectivity patterns in the superficial and deep layers of the primary motor cortex (M1), with significant inter-layer differences. Further analyses with a seed in the primary sensory cortex (S1) demonstrated the reliability of the method. Brain-wide layer-dependent FC analyses yielded results consistent with prior literature, reinforcing the efficacy of VN fMRI in resolving layer-specific functional connectivity. Given the widespread availability of 3T scanners, this technical advancement has the potential for significant impact across multiple domains of neuroscience research.","journal":"eLife","year":2023,"id":415122,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9093,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314308,"name":"Weili Lin","orcid":"0000-0002-2900-8204","position":1,"is_corresponding":false},{"id":519436,"name":"Kelly S. Giovanello","orcid":"0000-0002-0855-0053","position":2,"is_corresponding":false},{"id":575842,"name":"Wei‐Tang Chang","orcid":"0000-0002-2918-1752","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T01:22:08.814145Z","pmid":"42012994","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}