{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:12:31Z","timestamp":1788502351949,"version":"build-2803163510"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008062","name":"Fundaci\u00f3n Alicia Koplowitz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Children born with very low birth weight are at increased risk of cognitive difficulties and internalizing symptoms, including anxiety, withdrawal, and depressive features. However, the early neurodevelopmental pathways that connect neonatal brain maturation with emotional outcomes remain incompletely understood. This study examined whether internalizing symptoms at preschool age are associated with cognitive performance in children born with very low birth weight, and whether the interaction between cingulate and amygdala volumes is related to these symptoms directly or through cognition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>This longitudinal cohort included infants born with very low birth weight who were admitted to a neonatal intensive care unit between 2018 and 2021. Participants underwent brain magnetic resonance imaging at term-equivalent age and follow-up assessment at 4 to 6 years. Cognitive performance was evaluated with the Wechsler Preschool and Primary Scale of Intelligence, and internalizing symptoms were assessed with the Child Behavior Checklist. Adjusted linear regression models examined associations between cognition, neonatal regional brain volumes, and internalizing symptom scores. An observed-variable path model tested direct and indirect associations involving cingulate-amygdala interaction and cognition, and receiver operating characteristic analysis evaluated discrimination for clinically relevant internalizing symptoms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ninety-five children were included; mean gestational age was 29.4\u2009\u00b1\u20092.1 weeks and mean birth weight 1191.6\u2009\u00b1\u2009350.8\u2005g. Clinically relevant internalizing symptoms were present in 24\/95 children (25.3%). Lower internalizing T-scores were associated with Higher IQ after adjustment (B\u2009=\u2009\u22120.282;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.020). The cingulate-amygdala interaction was associated with internalizing symptoms (B\u2009=\u2009\u221260.377;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.009). In path analysis, IQ was inversely associated with internalizing symptoms (B\u2009=\u2009\u22120.315;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001), and the indirect effect through IQ was significant (B\u2009=\u2009\u221219.449;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.003). The MRI-based logistic model showed acceptable discrimination (area under the curve, 0.75).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Among children born VLBW, preschool internalizing symptoms were associated with poor cognitive performance and neonatal cingulate-amygdala interaction. These findings support interconnected brain-cognition-behavior pathways after preterm birth and underscore the value of integrated neurodevelopmental follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1880770","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:29:10Z","timestamp":1788499750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cognition, internalizing symptoms and neonatal cingulate-amygdala interaction in children born very low birth weight"],"prefix":"10.3389","volume":"14","author":[{"given":"Carmen","family":"Rodr\u00edguez-Barrios","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Guti\u00e9rrez-Rosa","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Jim\u00e9nez-Luque","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Mar\u00edn-Almagro","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Lubi\u00e1n-Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahram","family":"Jafrasteh","sequence":"additional","affiliation":[{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sim\u00f3n Pedro","family":"Lubi\u00e1n-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Benavente-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Biomedical Research and Innovation Institute of Cadiz (INiBICA), Research Unit, Puerta del Mar University Hospital","place":["Cadiz, Spain"]},{"name":"Department of Child and Mother Health and Radiology, Medical School, University of Cadiz","place":["Cadiz, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1136\/archdischild-2015-309581","article-title":"Early and long-term outcome of infants born extremely preterm","volume":"102","author":"Johnson","year":"2017","journal-title":"Arch Dis Child"},{"key":"B2","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1016\/j.clp.2022.06.001","article-title":"Imaging of premature infants","volume":"49","author":"Locke","year":"2022","journal-title":"Clin Perinatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11R","DOI":"10.1203\/PDR.0b013e318212faa0","article-title":"Preterm birth and childhood psychiatric disorders","volume":"69","author":"Johnson","year":"2011","journal-title":"Pediatr Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3389\/fpsyt.2020.00154","article-title":"What do we know about the preterm behavioral phenotype?","volume":"11","author":"Fitzallen","year":"2020","journal-title":"A Narrative Review. Front Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/DBP.0000000000000898","article-title":"Anxiety and depressive disorders in children born preterm: a meta-analysis","volume":"42","author":"Fitzallen","year":"2021","journal-title":"J Dev Behav Pediatr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1190438","DOI":"10.3389\/fpsyg.2023.1190438","article-title":"High-risk children and social isolation: the importance of family functioning","volume":"14","author":"Vieira","year":"2023","journal-title":"Front Psychol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1002\/imhj.21924","article-title":"Maternal depressive symptoms, poverty, and young motherhood increase the odds of early depressive and anxiety disorders for children born prematurely","volume":"42","author":"Weiss","year":"2021","journal-title":"Infant Ment Health J"},{"key":"B8","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1542\/peds.2008-2816","article-title":"Meta-Analysis of neurobehavioral outcomes in very preterm and\/or very low birth weight children","volume":"124","author":"Aarnoudse-Moens","year":"2009","journal-title":"Pediatrics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"151480","DOI":"10.1016\/j.semperi.2021.151480","article-title":"Cognitive and academic outcomes of children born extremely preterm","volume":"45","author":"Pascoe","year":"2021","journal-title":"Semin Perinatol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"e075630","DOI":"10.1136\/bmj-2023-075630","article-title":"Neurological development in children born moderately or late preterm: national cohort study","volume":"384","author":"Mitha","year":"2024","journal-title":"Br Med J"},{"key":"B11","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/s41390-019-0461-1","article-title":"Altered neonatal white and gray matter microstructure is associated with neurodevelopmental impairments in very preterm infants with high-grade brain injury","volume":"86","author":"Lean","year":"2019","journal-title":"Pediatr Res"},{"key":"B12","doi-asserted-by":"publisher","first-page":"121600","DOI":"10.1016\/j.neuroimage.2025.121600","article-title":"Altered neurobehavioral white matter integrity in preterm children: a confounding-controlled analysis using the adolescent brain and cognitive development (ABCD) study","volume":"323","author":"Li","year":"2025","journal-title":"NeuroImage"},{"key":"B13","author":"Li","year":""},{"key":"B14","first-page":"359","article-title":"Chapter 21 - amygdala function in emotion, cognition, and behavior","volume-title":"The Temporal Lobe","author":"Dom\u00ednguez-Borr\u00e0s","year":"2022"},{"key":"B15","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.neubiorev.2013.01.002","article-title":"Localization of function in anterior cingulate cortex: from psychosurgery to functional neuroimaging","volume":"37","author":"Gasquoine","year":"2013","journal-title":"Neurosci Biobehav Rev"},{"key":"B16","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3389\/fnana.2016.00055","article-title":"Altered amygdala development and fear processing in prematurely born infants","volume":"10","author":"Cismaru","year":"2016","journal-title":"Front Neuroanat"},{"key":"B17","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jaac.2016.11.005","article-title":"Neonatal amygdala functional connectivity at rest in healthy and preterm infants and early internalizing symptoms","volume":"56","author":"Rogers","year":"2017","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","first-page":"fcac009","DOI":"10.1093\/braincomms\/fcac009","article-title":"Neonatal amygdala resting-state functional connectivity and socio-emotional development in very preterm children","volume":"4","author":"Kanel","year":"2022","journal-title":"Brain Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/j.biopsych.2020.06.015","article-title":"Microstructure of the dorsal anterior cingulum bundle in very preterm neonates predicts the preterm behavioral phenotype at 5 years of age","volume":"89","author":"Brenner","year":"2021","journal-title":"Biol Psychiatry"},{"key":"B20","doi-asserted-by":"publisher","first-page":"tgac028","DOI":"10.1093\/texcom\/tgac028","article-title":"Amygdala subnuclei volumes, functional connectivity, and social\u2013emotional outcomes in children born very preterm","volume":"3","author":"Mueller","year":"2022","journal-title":"Cereb Cortex Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e2818","DOI":"10.1002\/brb3.2818","article-title":"Behavioral outcome of very preterm children at 5 years of age: prognostic utility of brain tissue volumes at term-equivalent-age, perinatal, and environmental factors","volume":"13","author":"Liverani","year":"2023","journal-title":"Brain Behav"},{"key":"B22","volume-title":"ASEBA preschool Forms & Profiles","author":"Achenbach","year":"2000"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.3174\/ajnr.A3521","article-title":"New MR imaging assessment tool to define brain abnormalities in very preterm infants at term","volume":"34","author":"Kidokoro","year":"2013","journal-title":"Am J Neuroradiol"},{"key":"B24","volume-title":"Volpe\u2019s Neurology of the Newborn, Sixth edn","author":"Volpe","year":"2018"},{"key":"B25","author":"Jafrasteh","year":"2023"},{"key":"B26","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/s12021-024-09661-x","article-title":"Enhanced spatial fuzzy C-means algorithm for brain tissue segmentation in T1 images","volume":"22","author":"Jafrasteh","year":"2024","journal-title":"Neuroinformatics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"34","DOI":"10.3389\/fnins.2019.00034","article-title":"Desikan-Killiany-Tourville atlas compatible version of M-CRIB neonatal parcellated whole brain atlas: the M-CRIB 2.0","volume":"13","author":"Alexander","year":"2019","journal-title":"Front Neurosci"},{"key":"B28","volume-title":"WPPSI-IV: Escala de Inteligencia de Wechsler Para Preescolar y primaria-IV (Adaptaci\u00f3n Espa\u00f1ola)","author":"Wechsler","year":"2014"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41390-024-03505-9","article-title":"Neurobehavioral outcomes of preterm infants: toward a holistic approach","volume":"97","author":"Camerota","year":"2025","journal-title":"Pediatr Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jpeds.2021.02.005","article-title":"Associations between neonatal magnetic resonance imaging and short- and long-term neurodevelopmental outcomes in a longitudinal cohort of very preterm children","volume":"234","author":"Jansen","year":"2021","journal-title":"J Pediatr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"105076","DOI":"10.1016\/j.earlhumdev.2020.105076","article-title":"Executive function deficits mediate the association between very preterm birth and behavioral problems at school-age","volume":"146","author":"Schnider","year":"2020","journal-title":"Early Hum Dev"},{"key":"B32","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/j.bpsc.2021.10.003","article-title":"The structural connectome and internalizing and externalizing symptoms at 7 and 13 years in individuals born very preterm and full term","volume":"7","author":"Gilchrist","year":"2022","journal-title":"Biol Psychiatry Cogn Neurosci Neuroimaging"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1880770\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:29:11Z","timestamp":1788499751000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1880770\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":32,"alternative-id":["10.3389\/fped.2026.1880770"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1880770","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]},"article-number":"1880770"}}