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Prior studies have largely focused on young adults regulating simple laboratory stimuli, with few direct comparisons of brain regions that differentiate or mutually implement these strategies. Here, we expanded the typical age range of participants, compared reappraisal and distraction within participants, and used ecologically valid autobiographical memories as regulatory targets. Sixty-two healthy adults aged 35\u201375 years generated cue words for negative and neutral autobiographical memories and were trained to either reappraise, distract, or let their emotions flow naturally in response to cued memories. Strategy-specific contrasts were derived from whole-brain fMRI data using univariate analyses. For reappraisal, relative to flow, we observed activity in bilateral occipital cortex, right cerebellum, and cingulate cortex and primarily left-sided frontal, temporal, and parietal cortices. Distraction, relative to flow, engaged bilateral lateral prefrontal, medial parietal, cingulate, occipital, and retrosplenial regions and left cerebellum. Common areas of activation included midline occipital and posterior cingulate cortices. Direct comparisons yielded strategy differences across multiple cortical areas: distraction engaged paralimbic areas (insula and left parahippocampal gyrus), dorsolateral and ventrolateral PFC, and right inferior frontoparietal cortex, whereas reappraisal engaged dorsomedial PFC, left ventrolateral PFC, anterior temporal cortex, and left posterolateral PFC. In-scanner valence ratings verified the efficacy of the experimental manipulation and revealed a negative impact of age on reappraisal success, which was correlated with greater visual cortical processing. These findings extend knowledge regarding the neural mechanisms of emotion regulation across the adult lifespan for autobiographical events.<\/jats:p>","DOI":"10.1162\/jocn.a.88","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T18:30:46Z","timestamp":1755196246000},"page":"299-318","update-policy":"https:\/\/doi.org\/10.1162\/mitpressjournals.corrections.policy","source":"Crossref","is-referenced-by-count":0,"title":["Regulating Negative Autobiographical Memories: An fMRI Investigation of Reappraisal and Distraction in Middle-aged and Older Adults"],"prefix":"10.1162","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5465-7193","authenticated-orcid":true,"given":"John L.","family":"Graner","sequence":"first","affiliation":[{"name":"Duke University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard","family":"Faul","sequence":"additional","affiliation":[{"name":"Duke University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph M.","family":"Diehl","sequence":"additional","affiliation":[{"name":"Duke University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Duke University"},{"name":"Duke University Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moria J.","family":"Smoski","sequence":"additional","affiliation":[{"name":"Duke University"},{"name":"Duke University Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8253-5417","authenticated-orcid":true,"given":"Kevin S.","family":"LaBar","sequence":"additional","affiliation":[{"name":"Duke University"},{"name":"Duke University Medical Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"281","published-online":{"date-parts":[[2026,2,1]]},"reference":[{"key":"2026030415370245600_bib1","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.neuron.2010.02.005","article-title":"Functional-anatomic fractionation of the brain's default network","volume":"65","author":"Andrews-Hanna","year":"2010","journal-title":"Neuron"},{"key":"2026030415370245600_bib2","doi-asserted-by":"publisher","first-page":"2883","DOI":"10.1016\/j.neuropsychologia.2007.06.015","article-title":"Left ventrolateral prefrontal cortex and the cognitive control of memory","volume":"45","author":"Badre","year":"2007","journal-title":"Neuropsychologia"},{"key":"2026030415370245600_bib3","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1016\/S1053-8119(03)00435-X","article-title":"General multilevel linear modeling for group analysis in fMRI","volume":"20","author":"Beckmann","year":"2003","journal-title":"Neuroimage"},{"key":"2026030415370245600_bib4","volume-title":"Hopkins Verbal Learning Test\u2014Revised professional manual","author":"Brandt","year":"2001"},{"key":"2026030415370245600_bib5","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1016\/j.neuroimage.2010.09.076","article-title":"Multisite reliability of cognitive BOLD data","volume":"54","author":"Brown","year":"2011","journal-title":"Neuroimage"},{"key":"2026030415370245600_bib6","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.1093\/cercor\/bht154","article-title":"Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies","volume":"24","author":"Buhle","year":"2014","journal-title":"Cerebral Cortex"},{"key":"2026030415370245600_bib7","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3389\/fpsyg.2014.00221","article-title":"The common and distinct neural bases of affect labeling and reappraisal in healthy adults","volume":"5","author":"Burklund","year":"2014","journal-title":"Frontiers in Psychology"},{"key":"2026030415370245600_bib8","doi-asserted-by":"publisher","first-page":"330","DOI":"10.3758\/s13415-012-0143-5","article-title":"The precuneus and the insula in self-attributional processes","volume":"13","author":"Cabanis","year":"2013","journal-title":"Cognitive, Affective, & Behavioral Neuroscience"},{"key":"2026030415370245600_bib9","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.tics.2007.02.005","article-title":"Functional neuroimaging of autobiographical memory","volume":"11","author":"Cabeza","year":"2007","journal-title":"Trends in Cognitive Sciences"},{"key":"2026030415370245600_bib10","doi-asserted-by":"publisher","first-page":"20142555","DOI":"10.1098\/rspb.2014.2555","article-title":"Ventrolateral and dorsomedial frontal cortex lesions impair mnemonic context retrieval","volume":"282","author":"Chapados","year":"2015","journal-title":"Proceedings of the Royal Society B: Biological Sciences"},{"key":"2026030415370245600_bib11","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1523\/JNEUROSCI.1534-16.2017","article-title":"Are there multiple kinds of episodic memory? 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