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The current study examined the influence of standard classes of variance\u2013covariance structures in linear mixed effects (LME) modeling of fMRI data from patients with pediatric mild traumatic brain injury (pmTBI; <jats:italic>N<\/jats:italic>\u2009=\u2009181) and healthy controls (<jats:italic>N<\/jats:italic>\u2009=\u2009162). During two visits, participants performed a cognitive control fMRI paradigm that compared congruent and incongruent stimuli. The hemodynamic response function was parsed into peak and late peak phases. Data were analyzed with a 4\u2010way (GROUP\u00d7VISIT\u00d7CONGRUENCY\u00d7PHASE) LME using AFNI's 3dLME and compound symmetry (CS), autoregressive process of order 1 (AR1), and unstructured (UN) variance\u2013covariance matrices. Voxel\u2010wise results dramatically varied both within the cognitive control network (UN&gt;CS for CONGRUENCY effect) and broader brain regions (CS&gt;UN for GROUP:VISIT) depending on the variance\u2013covariance matrix that was selected. Additional testing indicated that both model fit and estimated standard error were superior for the UN matrix, likely as a result of the modeling of individual terms. In summary, current findings suggest that the interpretation of results from complex designs is highly dependent on the selection of the variance\u2013covariance structure using LME modeling.<\/jats:p>","DOI":"10.1002\/hbm.26699","type":"journal-article","created":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T10:39:11Z","timestamp":1715337551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A cautionary tale on the effects of different covariance structures in linear mixed effects modeling of <scp>fMRI<\/scp> data"],"prefix":"10.1002","volume":"45","author":[{"given":"Harm Jan","family":"van der Horn","sequence":"first","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik B.","family":"Erhardt","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Dodd","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasana","family":"Nathaniel","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey V.","family":"Wick","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"McQuaid","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1758-3391","authenticated-orcid":false,"given":"Sephira G.","family":"Ryman","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrei A.","family":"Vakhtin","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy B.","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin  Milwaukee Wisconsin USA"},{"name":"Department of Biomedical Engineering Medical College of Wisconsin  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2396-5609","authenticated-orcid":false,"given":"Andrew R.","family":"Mayer","sequence":"additional","affiliation":[{"name":"The Mind Research Network\/LBERI  Albuquerque New Mexico USA"},{"name":"Department of Psychiatry &amp; Behavioral Sciences University of New Mexico  Albuquerque New Mexico USA"},{"name":"Department of Psychology University of New Mexic  Albuquerque New Mexico USA"},{"name":"Department of Neurology University of New Mexico  Albuquerque New Mexico USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jml.2012.11.001"},{"key":"e_1_2_9_3_1","volume-title":"Time series analysis: Forecasting & control","author":"Box G. 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