{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T14:31:07Z","timestamp":1793716267467,"version":"4.6.1"},"reference-count":45,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"<jats:sec id=\"ab-zoi231499-4\"><jats:title>Importance<\/jats:title><jats:p>Temporal dynamic measures provide insight into the neurobiological properties of nicotine use. It is critical to determine whether brain-based measures are associated with substance use risk factors, such as childhood trauma\u2013related emotion dysregulation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-5\"><jats:title>Objective<\/jats:title><jats:p>To assess temporal dynamic differences based on smoking status and examine the associations between childhood trauma, alexithymia, nicotine smoking, and default mode network (DMN) states.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This cross-sectional study was conducted in the Baltimore, Maryland, area at the National Institute on Drug Abuse. Participants included individuals aged 18 to 65 years who smoked nicotine long term and matched controls with no co-occurring substance use or psychiatric disorders. Participants were enrolled from August 8, 2013, to August 9, 2022. Analysis was conducted from August 2022 to July 2023.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-7\"><jats:title>Exposure<\/jats:title><jats:p>Long-term nicotine smoking.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The main outcome was temporal dynamic differences based on smoking status. Coactivation pattern analysis was conducted based on 16-minute resting-state functional magnetic resonance imaging; total time in, persistence of, and frequency of transitions into states were evaluated. The associations between childhood trauma (Childhood Trauma Questionnaire), alexithymia (20-item Toronto Alexithymia Scale), and DMN temporal dynamics were assessed.<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-9\"><jats:title>Results<\/jats:title><jats:p>The sample included 204 participants (102 individuals who smoked nicotine and 102 control individuals) with a mean (SD) age of 37.53 (10.64) years (109 [53.4%] male). Compared with controls, individuals who smoked nicotine spent more time in the frontoinsular DMN (FI-DMN) state (mean difference, 25.63 seconds; 95% CI, 8.05-43.20 seconds; \u03b7<jats:sup>2<\/jats:sup><jats:italic><jats:sub>p<\/jats:sub><\/jats:italic>\u2009=\u20090.04; <jats:italic>P<\/jats:italic>\u2009=\u2009.004 after Bonferroni correction). In those who smoked nicotine, greater alexithymia was associated with less time spent in the FI-DMN state (<jats:italic>r<\/jats:italic>, \u22120.26; 95% CI, \u22120.44 to \u22120.07; <jats:italic>P<\/jats:italic>\u2009=\u2009.007). In a moderated mediation analysis, alexithymia mediated the association between childhood trauma and time spent in the FI-DMN state only in individuals who smoked nicotine (<jats:italic>c<\/jats:italic>\u2032\u2009=\u2009\u22120.24; 95% CI, \u22120.58 to \u22120.03; <jats:italic>P<\/jats:italic>\u2009=\u2009.02).<\/jats:p><\/jats:sec><jats:sec id=\"ab-zoi231499-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>Compared with controls, individuals who smoked nicotine spent more time in the FI-DMN state. Among those who smoked nicotine, childhood trauma\u2013related alexithymia was associated with less time spent in the FI-DMN state, indicating that considering trauma-related factors may reveal alternative neurobiological underpinnings of substance use. These data may aid in reconciling contradictory findings in prior literature regarding the role of FI-DMN regions in substance use.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.51132","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T16:00:44Z","timestamp":1704988844000},"page":"e2351132","source":"Crossref","is-referenced-by-count":9,"title":["Childhood Trauma, Emotional Awareness, and Neural Correlates of Long-Term Nicotine Smoking"],"prefix":"10.1001","volume":"7","author":[{"given":"Annika","family":"Quam","sequence":"first","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Biernacki","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Ross","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty Jo","family":"Salmeron","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy C.","family":"Janes","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"issue":"12","key":"zoi231499r1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/S2215-0366(18)30337-7","article-title":"The global burden of disease attributable to alcohol and drug use in 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.","volume":"5","author":"GBD 2016 Alcohol and Drug Use Collaborators","year":"2018","journal-title":"Lancet Psychiatry"},{"issue":"3","key":"zoi231499r3","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1016\/j.drugalcdep.2012.02.020","article-title":"Prefrontal and limbic resting state brain network functional connectivity differs between nicotine-dependent smokers and non-smoking controls.","volume":"125","author":"Janes","year":"2012","journal-title":"Drug Alcohol Depend"},{"key":"zoi231499r4","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.neuropharm.2013.02.015","article-title":"Dual role of nicotine in addiction and cognition: a review of neuroimaging studies in humans.","volume":"84","author":"Jasinska","year":"2014","journal-title":"Neuropharmacology"},{"key":"zoi231499r5","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.neuroimage.2013.05.079","article-title":"Dynamic functional connectivity: promise, issues, and interpretations.","volume":"80","author":"Hutchison","year":"2013","journal-title":"Neuroimage"},{"issue":"2","key":"zoi231499r6","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1002\/hbm.v36.2","article-title":"Spatial and temporal functional connectivity changes between resting and attentive states.","volume":"36","author":"Bray","year":"2015","journal-title":"Hum Brain Mapp"},{"issue":"9","key":"zoi231499r7","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1038\/s41386-019-0399-3","article-title":"Abnormal frontoinsular-default network dynamics in adolescent depression and rumination: a preliminary resting-state co-activation pattern analysis.","volume":"44","author":"Kaiser","year":"2019","journal-title":"Neuropsychopharmacology"},{"issue":"11","key":"zoi231499r8","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.bpsc.2020.07.006","article-title":"Temporal dynamics of large-scale networks predict neural cue reactivity and cue-induced craving.","volume":"5","author":"Wang","year":"2020","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"2","key":"zoi231499r9","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/hbm.v41.2","article-title":"Dynamic functioning of transient resting-state coactivation networks in the Human Connectome Project.","volume":"41","author":"Janes","year":"2020","journal-title":"Hum Brain Mapp"},{"key":"zoi231499r10","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103164","article-title":"Resting state brain dynamics: associations with childhood sexual abuse and major depressive disorder.","volume":"36","author":"Belleau","year":"2022","journal-title":"Neuroimage Clin"},{"issue":"7","key":"zoi231499r11","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.biopsych.2022.03.020","article-title":"Dynamic resting-state network biomarkers of antidepressant treatment response.","volume":"92","author":"Kaiser","year":"2022","journal-title":"Biol Psychiatry"},{"issue":"21","key":"zoi231499r12","doi-asserted-by":"publisher","first-page":"8081","DOI":"10.1523\/JNEUROSCI.3188-14.2015","article-title":"Interactions between the salience and default-mode networks are disrupted in cocaine addiction.","volume":"35","author":"Liang","year":"2015","journal-title":"J Neurosci"},{"key":"zoi231499r13","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.neuroimage.2019.06.036","article-title":"Brain default-mode network dysfunction in addiction.","volume":"200","author":"Zhang","year":"2019","journal-title":"Neuroimage"},{"issue":"1","key":"zoi231499r14","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.bpsc.2019.09.005","article-title":"Craving and cue reactivity in nicotine-dependent tobacco smokers is associated with different insula networks.","volume":"5","author":"Janes","year":"2020","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"2","key":"zoi231499r15","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.bpsc.2017.09.010","article-title":"Nicotine abstinence influences the calculation of salience in discrete insular circuits.","volume":"3","author":"Fedota","year":"2018","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"},{"issue":"5","key":"zoi231499r16","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1001\/jamapsychiatry.2013.4091","article-title":"Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function.","volume":"71","author":"Lerman","year":"2014","journal-title":"JAMA Psychiatry"},{"issue":"10","key":"zoi231499r18","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/j.tics.2019.07.003","article-title":"The default mode network\u2019s role in discrete emotion.","volume":"23","author":"Satpute","year":"2019","journal-title":"Trends Cogn Sci"},{"issue":"1","key":"zoi231499r19","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/0022-3999(94)90005-1","article-title":"The twenty-item Toronto Alexithymia Scale\u2013I: item selection and cross-validation of the factor structure.","volume":"38","author":"Bagby","year":"1994","journal-title":"J Psychosom Res"},{"key":"zoi231499r20","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.sbspro.2011.10.008","article-title":"Examination and comparison of alexithymia and self-regulation in patients with substance abuse disorder and normal individuals.","volume":"30","author":"Ghalehban","year":"2011","journal-title":"Procedia Soc Behav Sci"},{"issue":"7","key":"zoi231499r21","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1080\/10826084.2020.1729198","article-title":"The great disrupter: relationship of alexithymia to emotion regulation processes and smoking among pregnant women.","volume":"55","author":"Linn","year":"2020","journal-title":"Subst Use Misuse"},{"key":"zoi231499r22","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.jad.2021.09.085","article-title":"Why is alexithymia a risk factor for affective disorder symptoms? The role of emotion regulation.","volume":"296","author":"Preece","year":"2022","journal-title":"J Affect Disord"},{"issue":"5","key":"zoi231499r23","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1111\/sjop.v63.5","article-title":"Association between alexithymia and substance use: A systematic review and meta-analysis.","volume":"63","author":"Honkalampi","year":"2022","journal-title":"Scand J Psychol"},{"issue":"1","key":"zoi231499r24","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00213-013-3018-8","article-title":"Insula\u2019s functional connectivity with ventromedial prefrontal cortex mediates the impact of trait alexithymia on state tobacco craving.","volume":"228","author":"Sutherland","year":"2013","journal-title":"Psychopharmacology (Berl)"},{"issue":"10","key":"zoi231499r25","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1038\/nrn.2016.111","article-title":"The effects of childhood maltreatment on brain structure, function and connectivity.","volume":"17","author":"Teicher","year":"2016","journal-title":"Nat Rev Neurosci"},{"issue":"5-6","key":"zoi231499r26","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1037\/bul0000391","article-title":"Child maltreatment and alexithymia: a meta-analytic review.","volume":"149","author":"Ditzer","year":"2023","journal-title":"Psychol Bull"},{"issue":"1","key":"zoi231499r27","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1186\/s12888-021-03532-4","article-title":"Mediation role of alexithymia, sensory processing sensitivity and emotional-mental processes between childhood trauma and adult psychopathology: a self-report study.","volume":"21","author":"Karaca Din\u00e7","year":"2021","journal-title":"BMC Psychiatry"},{"issue":"3","key":"zoi231499r28","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.chiabu.2003.11.018","article-title":"Alexithymia as a mediator between childhood trauma and self-injurious behaviors.","volume":"28","author":"Paivio","year":"2004","journal-title":"Child Abuse Negl"},{"key":"zoi231499r29","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2022.109500","article-title":"Alexithymia mediates the association between childhood trauma and adolescent e-cigarette use.","volume":"236","author":"Sutherland","year":"2022","journal-title":"Drug Alcohol Depend"},{"issue":"20","key":"zoi231499r30","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.","volume":"310","author":"World Medical Association","year":"2013","journal-title":"JAMA"},{"issue":"6","key":"zoi231499r31","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1097\/EDE.0b013e3181577654","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.","volume":"18","author":"von Elm","year":"2007","journal-title":"Epidemiology"},{"issue":"9","key":"zoi231499r32","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1111\/add.1991.86.issue-9","article-title":"The Fagerstr\u00f6m test for nicotine dependence: a revision of the Fagerstr\u00f6m Tolerance Questionnaire.","volume":"86","author":"Heatherton","year":"1991","journal-title":"Br J Addict"},{"issue":"1","key":"zoi231499r35","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41592-018-0235-4","article-title":"fMRIPrep: a robust preprocessing pipeline for functional MRI.","volume":"16","author":"Esteban","year":"2019","journal-title":"Nat Methods"},{"issue":"8","key":"zoi231499r37","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.1176\/ajp.151.8.1132","article-title":"Initial reliability and validity of a new retrospective measure of child abuse and neglect.","volume":"151","author":"Bernstein","year":"1994","journal-title":"Am J Psychiatry"},{"issue":"4","key":"zoi231499r38","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00213-010-1848-1","article-title":"Meta-analysis of the acute effects of nicotine and smoking on human performance.","volume":"210","author":"Heishman","year":"2010","journal-title":"Psychopharmacology (Berl)"},{"issue":"3","key":"zoi231499r39","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/S0896-6273(02)01004-8","article-title":"Cognitive mechanisms of nicotine on visual attention.","volume":"36","author":"Lawrence","year":"2002","journal-title":"Neuron"},{"key":"zoi231499r41","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.neuroimage.2016.11.012","article-title":"Alterations of resting state functional network connectivity in the brain of nicotine and alcohol users.","volume":"151","author":"Vergara","year":"2017","journal-title":"Neuroimage"},{"issue":"1","key":"zoi231499r42","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.neuroimage.2005.12.002","article-title":"Self-referential processing in our brain\u2013a meta-analysis of imaging studies on the self.","volume":"31","author":"Northoff","year":"2006","journal-title":"Neuroimage"},{"issue":"3","key":"zoi231499r43","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/jcpp.2016.57.issue-3","article-title":"Annual research review: enduring neurobiological effects of childhood abuse and neglect.","volume":"57","author":"Teicher","year":"2016","journal-title":"J Child Psychol Psychiatry"},{"issue":"11","key":"zoi231499r44","doi-asserted-by":"publisher","first-page":"4622","DOI":"10.1002\/hbm.v36.11","article-title":"Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: a preliminary multimodal rsfMRI-fMRI-MRS-dMRI study.","volume":"36","author":"Duncan","year":"2015","journal-title":"Hum Brain Mapp"},{"issue":"6","key":"zoi231499r45","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1176\/appi.ajp.2013.12070950","article-title":"Decreased cortical representation of genital somatosensory field after childhood sexual abuse.","volume":"170","author":"Heim","year":"2013","journal-title":"Am J Psychiatry"},{"key":"zoi231499r2","volume-title":"Facing Addiction in America: The Surgeon General\u2019s Report on Alcohol, Drugs, and Health","year":"2016"},{"key":"zoi231499r17","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/B978-0-12-397025-1.00024-5","volume-title":"Brain Mapping: An Encyclopedic Reference","author":"Menon","year":"2015"},{"key":"zoi231499r33","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"1994"},{"key":"zoi231499r34","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","year":"2013"},{"key":"zoi231499r40","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/B978-0-12-805373-7.00028-1","volume-title":"Addictive Substances and Neurological Disease","author":"Brooks","year":"2017"},{"key":"zoi231499r36","unstructured":"Frederick? BB. capcalc. Version 1.3.5. Accessed January 13, 2023. https:\/\/github.com\/bbfrederick\/capcalc"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2813842\/quam_2024_oi_231499_1704316012.36601.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T16:00:52Z","timestamp":1704988852000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2813842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,11]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,2]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.51132","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,11]]}}}