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However, these associations vary, as youth with better emotion regulation may be more protected from negative parental influence. Yet, it remains unclear how youth\u2019s neural correlates of emotion regulation, particularly in prefrontal regions\u2014such as dorsolateral prefrontal cortex (dlPFC), lateral orbitofrontal cortex (lOFC), and medial orbitofrontal cortex (mOFC)\u2014play a role in these associations. To address this gap, this study used two-wave longitudinal data that spanned 2\u00a0yr from the nationwide Adolescent Brain Cognitive Development study including 7,932 youth (Mage\u2009=\u20099.96\u00a0yr, SD\u2009=\u20097.52; 49% females) and their parents. Results revealed significant longitudinal associations between parents\u2019 and youth\u2019s internalizing symptoms over 2\u00a0yr. Moreover, youth\u2019s dlPFC, lOFC, and mOFC activity to negative emotions moderated these links. Youth with higher activity in these regions showed weaker parent-youth associations in internalizing symptoms over time. This study provides robust evidence that dlPFC, lOFC, and mOFC serve as neurobiological protective factors in the longitudinal links between parents and youth\u2019s internalizing symptoms. Findings inform interventions targeting youth\u2019s neural development in emotion regulation to promote emotional adjustment in families where parents face mental health challenges.<\/jats:p>","DOI":"10.1093\/cercor\/bhaf170","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T17:51:21Z","timestamp":1752601881000},"source":"Crossref","is-referenced-by-count":1,"title":["Prefrontal activity to negative emotions moderates the longitudinal links between parents and youth\u2019s internalizing symptoms"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0687-7391","authenticated-orcid":false,"given":"Zeyi","family":"Shi","sequence":"first","affiliation":[{"name":"School of Psychology and Cognitive Science, East China Normal University , 3663 North Zhongshan Road, Shanghai 200062 ,","place":["China"]},{"name":"School of Education and Social Policy, Northwestern University , 2120 Campus Drive, Evanston, IL 60208 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2869-7845","authenticated-orcid":false,"given":"Beiming","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Education and Social Policy, Northwestern University , 2120 Campus Drive, Evanston, IL 60208 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-724X","authenticated-orcid":false,"given":"Zexi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Human Development and Family Sciences, The University of Texas at Austin , 108 E. 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