{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T17:31:45Z","timestamp":1761845505478,"version":"3.41.2"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"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. Integr. Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Schizophrenia is a brain disorder characterized by diffuse, diverse, and wide-spread changes in gray matter volume (GM) and white matter structure (fractional anisotropy, FA), as well as cognitive impairments that greatly impact an individual\u2019s quality of life. While the relationship of each of these image modalities and their links to schizophrenia status and cognitive impairment has been investigated separately, a multimodal fusion <jats:italic>via<\/jats:italic> parallel independent component analysis (pICA) affords the opportunity to explore the relationships between the changes in GM and FA, and the implications these network changes have on cognitive performance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Images from 73 subjects with schizophrenia (SZ) and 82 healthy controls (HC) were drawn from an existing dataset. We investigated 12 components from each feature (FA and GM). Loading coefficients from the images were used to identify pairs of features that were significantly correlated and showed significant group differences between HC and SZ. MANCOVA analysis uncovered the relationships the identified spatial maps had with age, gender, and a global cognitive performance score.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three component pairs showed significant group differences (HC &amp;gt; SZ) in both gray and white matter measurements. Two of the component pairs identified networks of gray matter that drove significant relationships with cognition (HC &amp;gt; SZ) after accounting for age and gender. The gray and white matter structural networks identified in these three component pairs pull broadly from many regions, including the right and left thalamus, lateral occipital cortex, multiple regions of the middle temporal gyrus, precuneus cortex, postcentral gyrus, cingulate gyrus\/cingulum, lingual gyrus, and brain stem.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of this multimodal analysis adds to our understanding of how the relationship between GM, FA, and cognition differs between HC and SZ by highlighting the correlated intermodal covariance of these structural networks and their differential relationships with cognitive performance. Previous unimodal research has found similar areas of GM and FA differences between these groups, and the cognitive deficits associated with SZ have been well documented. This study allowed us to evaluate the intercorrelated covariance of these structural networks and how these networks are involved the differences in cognitive performance between HC and SZ.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnint.2021.755069","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T07:45:50Z","timestamp":1642664750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cognitive Implications of Correlated Structural Network Changes in Schizophrenia"],"prefix":"10.3389","volume":"15","author":[{"given":"Dawn M.","family":"Jensen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaheh","family":"Zendrehrouh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vince","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Turner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s12021-017-9338-9","article-title":"Multimodal neuroimaging in schizophrenia: description and dissemination.","volume":"15","author":"Aine","year":"2017","journal-title":"Neuroinformatics"},{"key":"B2","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1016\/j.neuroimage.2015.10.019","article-title":"An integrated approach to correction for off-resonance effects and subject movement in diffusion MR imaging.","volume":"125","author":"Andersson","year":"2016","journal-title":"NeuroImage"},{"journal-title":"Non-linear optimisation. FMRIB technical report TR07JA1.","year":"","author":"Andersson","key":"B3"},{"journal-title":"Non-linear registration, aka Spatial normalisation FMRIB technical report TR07JA2.","year":"","author":"Andersson","key":"B4"},{"key":"B5","doi-asserted-by":"crossref","first-page":"9985","DOI":"10.1073\/pnas.93.18.9985","article-title":"Schizophrenia and cognitive dysmetria: a positron-emission tomography study of dysfunctional prefrontal-thalamic-cerebellar circuitry.","volume":"93","author":"Andreasen","year":"1996","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"B6","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.neuron.2010.02.005","article-title":"Functional-anatomic fractionation of the brain\u2019s default network.","volume":"65","author":"Andrews-Hanna","year":"2010","journal-title":"Neuron"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83491-8","article-title":"Cellular correlates of gray matter volume changes in magnetic resonance morphometry identified by two-photon microscopy.","volume":"11","author":"Asan","year":"2021","journal-title":"Sci. Rep."},{"key":"B8","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","article-title":"Unified segmentation.","volume":"26","author":"Ashburner","year":"2005","journal-title":"NeuroImage"},{"key":"B9","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.psychres.2015.09.022","article-title":"Are negative symptoms really related to cognition in schizophrenia?","volume":"230","author":"Bagney","year":"2015","journal-title":"Psychiatry Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.scog.2018.02.001","article-title":"Cognitive and psychopathology correlates of brain white\/grey matter structure in severely psychotic schizophrenic inpatients.","volume":"12","author":"Banaj","year":"2018","journal-title":"Schizophrenia Res. Cogn."},{"key":"B11","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.tics.2011.11.015","article-title":"Cognition in schizophrenia: Core psychological and neural mechanisms.","volume":"16","author":"Barch","year":"2012","journal-title":"Trends Cogn. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.conb.2012.12.012","article-title":"Large-scale brain networks in affective and social neuroscience: Towards an integrative functional architecture of the brain.","volume":"23","author":"Barrett","year":"2013","journal-title":"Curr. Opin. Neurobiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0033291714001263","article-title":"Neurodevelopmental origin of cognitive impairment in schizophrenia.","volume":"45","author":"Bora","year":"2015","journal-title":"Psychol. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.schres.2010.12.020","article-title":"Neuroanatomical abnormalities in schizophrenia: A multimodal voxelwise meta-analysis and meta-regression analysis.","volume":"127","author":"Bora","year":"2011","journal-title":"Schizophrenia Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1109\/TITB.2008.923773","article-title":"Feature-based fusion of medical imaging data.","volume":"13","author":"Calhoun","year":"2009","journal-title":"IEEE Trans. Inform. Technol. Biomed."},{"key":"B16","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.bpsc.2015.12.005","article-title":"Multimodal fusion of brain imaging data: a key to finding the missing link(s) in complex mental illness.","volume":"1","author":"Calhoun","year":"2016","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroim."},{"key":"B17","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1177\/1073858414525995","article-title":"The frontoparietal control system: A central role in mental health.","volume":"20","author":"Cole","year":"2014","journal-title":"Neurosci. Rev. J. Bring. Neurobiol. Neurol. Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1080\/13546805.2012.730995","article-title":"How specific are negative symptoms and cognitive impairment in schizophrenia? An analysis of PANSS and SCoRS.","volume":"18","author":"Cruz","year":"2013","journal-title":"Cogn. Neuropsychiatry"},{"key":"B19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.schres.2015.11.021","article-title":"Interaction among subsystems within default mode network diminished in schizophrenia patients: A dynamic connectivity approach.","volume":"170","author":"Du","year":"2016","journal-title":"Schizophrenia Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1016\/j.jaac.2013.12.007","article-title":"White matter abnormalities and cognitive impairment in early-onset schizophrenia-spectrum disorders.","volume":"53","author":"Epstein","year":"2014","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"13507","DOI":"10.1073\/pnas.0705843104","article-title":"Development of distinct control networks through segregation and integration.","volume":"104","author":"Fair","year":"2007","journal-title":"Proc. Nat. Acad. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"18060","DOI":"10.1523\/JNEUROSCI.4735-11.2011","article-title":"Reduced white matter integrity is related to cognitive instability.","volume":"31","author":"Fjell","year":"2011","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrn.2018.16","article-title":"Dendritic structural plasticity and neuropsychiatric disease.","volume":"19","author":"Forrest","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"B24","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1176\/appi.ajp.2009.09060802","article-title":"International consensus study of antipsychotic dosing.","volume":"167","author":"Gardner","year":"2010","journal-title":"Am. J. Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"17308","DOI":"10.1073\/pnas.2005238117","article-title":"Default-mode network streams for coupling to language and control systems.","volume":"117","author":"Gordon","year":"2020","journal-title":"Proc. Nat. Acad. Sci."},{"key":"B26","article-title":"Despite some popular assertions, a single factor for intelligence, called g, can be measured with IQ tests and does predict success in life.","volume":"1998","author":"Gottfredson","year":"1998","journal-title":"Sci. Am."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/psyp.13032","article-title":"Control networks and hubs.","volume":"55","author":"Gratton","year":"2018","journal-title":"Psychophysiology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.scog.2014.02.001","article-title":"Cognition in schizophrenia: Past, present, and future.","volume":"1","author":"Green","year":"2014","journal-title":"Schizophr. Res. Cogn."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1093\/schbul\/sbu177","article-title":"Patterns of gray matter abnormalities in schizophrenia based on an international mega-analysis.","volume":"41","author":"Gupta","year":"2015","journal-title":"Schizophrenia Bull."},{"key":"B30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s12264-016-0090-1","article-title":"A review of the functional and anatomical default mode network in schizophrenia.","volume":"33","author":"Hu","year":"2017","journal-title":"Neurosci. Bull."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1002\/hbm.24887","article-title":"Disruptions of frontoparietal control network and default mode network linking the metacognitive deficits with clinical symptoms in schizophrenia.","volume":"41","author":"Jia","year":"2020","journal-title":"Human Brain Mapp."},{"key":"B32","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.biopsych.2007.06.017","article-title":"Diffusion tensor imaging of the superior longitudinal fasciculus and working memory in recent-onset schizophrenia.","volume":"63","author":"Karlsgodt","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1038\/mp.2017.170","article-title":"Widespread white matter microstructural differences in schizophrenia across 4322 individuals: Results from the ENIGMA Schizophrenia DTI Working Group.","volume":"23","author":"Kelly","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1002\/hbm.20359","article-title":"Estimating the number of independent components for functional magnetic resonance imaging data.","volume":"28","author":"Li","year":"2007","journal-title":"Human Brain Mapp."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1117\/12.844748","article-title":"Quality control of diffusion weighted images.","volume":"11","author":"Liu","year":"2010","journal-title":"Proc. SPIE Int. Soc. Opt. Eng."},{"key":"B36","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.schres.2013.10.028","article-title":"Stable signatures of schizophrenia in the cortical\u2013subcortical\u2013cerebellar network using fMRI of verbal working memory.","volume":"151","author":"Matsuo","year":"2013","journal-title":"Schizophrenia Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1089\/brain.2015.0408","article-title":"A mapping between structural and functional brain networks.","volume":"6","author":"Meier","year":"2016","journal-title":"Brain Connect."},{"key":"B38","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.schres.2009.06.020","article-title":"Cognitive performance is related to cortical grey matter volumes in early stages of schizophrenia: A population-based study of first-episode psychosis.","volume":"113","author":"Minatogawa-Chang","year":"2009","journal-title":"Schizophrenia Res."},{"key":"B39","first-page":"49","article-title":"Alterations of cerebral white matter structure in psychosis and their clinical correlations: A systematic review of Diffusion Tensor Imaging studies.","volume":"52","author":"Parnanzone","year":"2017","journal-title":"Rivista Di Psichiatria"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00276","article-title":"An introductory review of parallel independent component analysis (p-ICA) and a Guide to Applying p-ICA to genetic data and imaging phenotypes to identify disease-associated biological pathways and systems in common complex disorders.","volume":"6","author":"Pearlson","year":"2015","journal-title":"Front. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1136\/bmj.39227.616447.BE","article-title":"Schizophrenia.","volume":"335","author":"Picchioni","year":"2007","journal-title":"BMJ Br. Med. J."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2013.00176","article-title":"Dysconnectivity in the frontoparietal attention network in schizophrenia.","volume":"2013","author":"Roiser","year":"2013","journal-title":"Front. Psychiatry"},{"key":"B43","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1109\/42.796284","article-title":"Nonrigid registration using free-form deformations: application to breast MR images.","volume":"18","author":"Rueckert","year":"1999","journal-title":"IEEE Trans. Med. Imag."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.neubiorev.2011.12.015","article-title":"Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia.","volume":"36","author":"Shepherd","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/s41583-021-00474-4","article-title":"The default mode network in cognition: A topographical perspective.","volume":"22","author":"Smallwood","year":"2021","journal-title":"Nat. Rev. Neurosci."},{"key":"B46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1002\/hbm.10062","article-title":"Fast robust automated brain extraction.","volume":"17","author":"Smith","year":"2002","journal-title":"Human Brain Mapp."},{"key":"B47","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.neuroimage.2004.07.051","article-title":"Advances in functional and structural MR image analysis and implementation as FSL.","volume":"23","author":"Smith","year":"2004","journal-title":"NeuroImage"},{"key":"B48","doi-asserted-by":"publisher","first-page":"3685","DOI":"10.1093\/cercor\/bhy167","article-title":"Role of the default mode network in cognitive transitions.","volume":"28","author":"Smith","year":"2018","journal-title":"Cerebral Cortex"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00235","article-title":"Combination of Resting State fMRI, DTI, and sMRI data to discriminate schizophrenia by N-way MCCA + jICA.","volume":"7","author":"Sui","year":"2013","journal-title":"Front. Human Neurosci."},{"key":"B50","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.biopsych.2015.02.017","article-title":"In search of multimodal neuroimaging biomarkers of cognitive deficits in schizophrenia.","volume":"78","author":"Sui","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-05432-w","article-title":"Multimodal neuromarkers in schizophrenia via cognition-guided MRI fusion.","volume":"9","author":"Sui","year":"2018","journal-title":"Nat. Commun."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2012.00027","article-title":"A selective review of multimodal fusion methods in schizophrenia.","volume":"6","author":"Sui","year":"2012","journal-title":"Front. Human Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.schres.2013.04.011","article-title":"Schizophrenia and the brain\u2019s control network: Aberrant within- and between-network connectivity of the frontoparietal network in schizophrenia.","volume":"147","author":"Tu","year":"2013","journal-title":"Schizophrenia Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/mp.2015.63","article-title":"Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium.","volume":"21","author":"van Erp","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"B55","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3928\/02793695-20100302-01","article-title":"How neuroplasticity and cognitive reserve protect cognitive functioning.","volume":"48","author":"Vance","year":"2010","journal-title":"J. Psychosoc. Nurs. Ment. Health Serv."},{"key":"B56","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.neuroimage.2008.09.051","article-title":"Joint source based morphometry identifies linked gray and white matter group differences.","volume":"44","author":"Xu","year":"2009","journal-title":"NeuroImage"}],"container-title":["Frontiers in Integrative Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnint.2021.755069\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T07:46:01Z","timestamp":1642664761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnint.2021.755069\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,20]]},"references-count":56,"alternative-id":["10.3389\/fnint.2021.755069"],"URL":"https:\/\/doi.org\/10.3389\/fnint.2021.755069","relation":{},"ISSN":["1662-5145"],"issn-type":[{"type":"electronic","value":"1662-5145"}],"subject":[],"published":{"date-parts":[[2022,1,20]]},"article-number":"755069"}}