{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:51:03Z","timestamp":1791287463711,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Cognitive deficits such as working memory impairment and peripheral inflammation frequently occur together in neuropsychiatric conditions, yet the relationship between them remains poorly understood. To address this gap, the present study examines these associations in healthy young adults to establish baseline relationships between peripheral immune cell subpopulations and neural activity without clinical confounds. The aim of this study is to investigate whether the relative proportions of peripheral immune cell subpopulations are associated with EEG asymmetry during a working memory task and with task performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EEG data were recorded from 24 healthy participants during a 2-back working memory task. Relative EEG asymmetry indices were computed for four frequency bands: alpha, beta, delta, and theta. 2-back task performance was also calculated. Peripheral blood was collected for DNA extraction and genome-wide DNA methylation analysis to estimate the relative proportions of immune cell subpopulations. Estimated proportions were Center Log-Ratio-transformed. Spearman\u2019s correlation and multiple linear regression were used to identify associations between EEG asymmetry, relative immune markers, and n-back task performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results &amp;amp; Discussion<\/jats:title>\n                    <jats:p>Our analysis revealed that theta asymmetry was associated with CLR-transformed proportions of natural killer cells (p=0.035) and CD4+ T cells (p = 0.027). 2-back task target accuracy was nearly correlated with granulocytes (p = 0.082) and CD8+ T cell proportions (p=0.016); however, these associations did not remain significant after Bonferroni correction. Despite this, both immune markers significantly predicted 2-back target accuracy across three multiple linear regression models (model 1: p = 0.005, model 2: p = 0.002, model 3: p = 0.002).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1810963","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:55:38Z","timestamp":1791284138000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["N-back electroencephalography asymmetry and peripheral immune cell subpopulation composition"],"prefix":"10.3389","volume":"17","author":[{"given":"Matisse","family":"Ducharme","sequence":"first","affiliation":[{"name":"Centre for Addiction and Mental Health, Schizophrenia Department","place":["Toronto, ON, Canada"]},{"name":"Department of Pharmacology & Toxicology, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Nader","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, Schizophrenia Department","place":["Toronto, ON, Canada"]},{"name":"Department of Pharmacology & Toxicology, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"De Luca","sequence":"additional","affiliation":[{"name":"Centre for Addiction and Mental Health, Schizophrenia Department","place":["Toronto, ON, Canada"]},{"name":"Department of Pharmacology & Toxicology, University of Toronto","place":["Toronto, ON, Canada"]},{"name":"Department of Psychiatry, University of Toronto","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","article-title":"EEG normal waveforms","volume-title":"StatPearls","author":"Nayak","year":"2025"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1109\/IEMBS.2011.6090952","article-title":"EEG-rhythm dynamics during a 2-back working memory task and performance","author":"Tsoneva","year":"2011"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fpain.2022.962722","article-title":"Frontal alpha asymmetry: A potential biomarker of approach-withdrawal motivation towards pain","volume":"3","author":"Silva-Passadouro","year":"2022","journal-title":"Front Pain Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"8029","DOI":"10.1038\/s41598-018-26133-w","article-title":"Asymmetric hemisphere activation in tenderness: Evidence from EEG signals","volume":"8","author":"Zhao","year":"2018","journal-title":"Sci Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00046.2024","article-title":"The relationship between frontal alpha asymmetry and behavioral and brain activity indices of reactive inhibitory control","volume":"132","author":"Akil","year":"2024","journal-title":"J Neurophysiol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2022.05.012","article-title":"EEG asymmetry and cognitive testing in MCI identification","volume":"177","author":"Martin","year":"2022","journal-title":"Int J Psychophysiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s10802-024-01191-z","article-title":"Examining conduct problems in a community sample during middle childhood: The role of frontal EEG asymmetry, temperament, and working memory","volume":"52","author":"Zerrouk","year":"2024","journal-title":"Res Child Adolesc Psychopathol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-11-73","article-title":"Peripheral inflammation is associated with remote global gene expression changes in the brain","volume":"11","author":"Thomson","year":"2014","journal-title":"J Neuroinflamm"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230253","article-title":"Mediation effect of brain volume on the relationship between peripheral inflammation and cognitive decline","volume":"95","author":"Zhuo","year":"2023","journal-title":"J Alzheimers Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1305790","article-title":"Peripheral inflammation and neurocognitive impairment: Correlations, underlying mechanisms, and therapeutic implications","volume":"15","author":"Tan","year":"2023","journal-title":"Front Aging Neurosci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2024.1453772","article-title":"Editorial: Neuroinflammation and cognitive impairment","volume":"16","author":"Li","year":"2024","journal-title":"Front Aging Neurosci"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05788-0","article-title":"Microglia-mediated T cell infiltration drives neurodegeneration in tauopathy","volume":"615","author":"Chen","year":"2023","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.trsl.2018.08.001","article-title":"DNA methylation as a transcriptional regulator of the immune system","volume":"204","author":"Morales-Nebreda","year":"2019","journal-title":"Trans Res"},{"key":"B14","first-page":"22","article-title":"The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10","volume":"59","author":"Sheehan","year":"1998","journal-title":"J Clin Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.2005.53221.x","article-title":"The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment","volume":"53","author":"Nasreddine","year":"2005","journal-title":"J Am Geriatr Soc"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state\u201d. A practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J Psychiatr Res"},{"key":"B17","volume-title":"MATLAB. 9.7.0.1190202 (R2018b)","year":"2018"},{"key":"B18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jneumeth.2003.10.009","article-title":"EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis","volume":"134","author":"Delorme","year":"2004","journal-title":"J Neurosci Methods"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/dev.22163","article-title":"Using different methods for calculating frontal alpha asymmetry (FAA) to study its development from infancy to 3 years of age in a large longitudinal sample","volume":"63","author":"Vincent","year":"2021","journal-title":"Dev Psychobiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-021-02399-1","article-title":"Frontal and parietal EEG alpha asymmetry: A large-scale investigation of short-term reliability on distinct EEG systems","volume":"227","author":"Metzen","year":"2022","journal-title":"Brain Struct Funct"},{"key":"B21","doi-asserted-by":"crossref","DOI":"10.4324\/9781410611147","volume-title":"Detection Theory: A User\u2019s Guide","author":"Macmillan","year":"2004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu049","article-title":"Minfi: A flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays","volume":"30","author":"Aryee","year":"2014","journal-title":"Bioinformatics"},{"key":"B23","volume-title":"RStudio: Integrated Development Environment for R","year":"2025"},{"key":"B24","volume-title":"IBM SPSS Statistics for Windows (Version 27.0)","year":"2020"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.68771","article-title":"Prefrontal, frontal, and temporal theta EEG asymmetries and self-reports of emotional regulation","volume":"16","author":"Cherenfant","year":"2024","journal-title":"Cureus"},{"key":"B26","article-title":"Innate immune system","volume-title":"Autoimmunity: From Bench to Bedside","author":"Aristiz\u00e1bal","year":"2013"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00832-3","article-title":"Neutrophils in chronic inflammatory diseases","volume":"19","author":"Herrero-Cervera","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13123","article-title":"Neutrophil modulation of behavior and cognition in health and disease: The unexplored role of an innate immune cell","volume":"311","author":"Coulibaly","year":"2022","journal-title":"Immunol Rev"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glad231","article-title":"Associations of blood absolute neutrophil count and cytokines with cognitive function in dementia-free participants: A population-based cohort study","volume":"79","author":"Fa","year":"2024","journal-title":"Journals Gerontology: Ser A"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3913","article-title":"Neutrophils promote Alzheimer\u2019s disease-like pathology and cognitive decline via LFA-1 integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1037\/0021-843X.114.4.599","article-title":"Working memory impairments in schizophrenia: A meta-analysis","volume":"114","author":"Lee","year":"2005","journal-title":"J Abnormal Psychol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.02.017","article-title":"Mechanisms of working memory impairment in schizophrenia","volume":"80","author":"Van Snellenberg","year":"2016","journal-title":"Biol Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.728990","article-title":"Is elevated neutrophil count and neutrophil-to-lymphocyte ratio a cause or consequence of schizophrenia?\u2014A scoping review","volume":"12","author":"Sandberg","year":"2021","journal-title":"Front Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/MS9.0000000000002744","article-title":"From immune response to mental health: Neutrophils in schizophrenia","volume":"87","author":"Obeagu","year":"2024","journal-title":"Ann Med Surg (Lond)"},{"key":"B35","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13024-024-00706-y","article-title":"Unraveling the dual nature of brain CD8+ T cells in Alzheimer\u2019s disease","volume":"19","author":"Hu","year":"2024","journal-title":"Mol Neurodegener"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01604-z","article-title":"CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer\u2019s disease pathology","volume":"24","author":"Su","year":"2023","journal-title":"Nat Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1810963\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T10:55:40Z","timestamp":1791284140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1810963\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2026.1810963"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1810963","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1810963"}}