Age differences in what-if thinking from midlife onwards : Prefrontal contribution and implications for emotional health in late life

Article Article scientifique Article Age differences in what-if thinking from midlife onwards : Prefrontal contribution and implications for emotional health in late life eng 2025-10-07 author Galli Riccardo Mattia Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,Department of Neuroscience, University of Geneva, Geneva, Switzerland. 983731 Département de neurosciences fondamentales (NEUFO) author Thams Friederike Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Löwe Bernd Department of Psychosomatic Medicine and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Cheng Bastian Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Thomalla Götz Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Bieder Max Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.,Department of Neurology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Petersen Elina L Hamburg City Health Study, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. author Büchel Christian Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. author Brassen Stefanie 0000-0002-8884-7593 Department of Systems Neuroscience, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. sbrassen@uke.de. 10.1007/s11357-025-01928-8 41057710 2509-2723 https://link.springer.com/10.1007/s11357-025-01928-8 Reduced counterfactual ("What-If") thinking (CFT) in late life is believed to reflect successful adaptation to limited resources for overcoming missed opportunities, thereby preventing feelings of regret. We propose that this adaptation becomes critical from midlife onwards, affects emotional regulation, and is mediated by the preserved functionality of the ventromedial prefrontal cortex (vmPFC). To test this, an epidemiological sample from the Hamburg City Health Study (N = 494), aged 48 to 75, completed a sequential risk-taking task presenting missed opportunities to induce CFT, and was assessed for life satisfaction, depressive symptoms, emotion regulation, and resting-state functional connectivity of the vmPFC. In line with the 'paradox of aging,' our cross-sectional data indicate a positive linear relationship between age and life satisfaction from midlife onward, alongside a negative association between age and depressive symptoms. Crucially, counterfactual thinking (CFT) was also lower in older compared to younger adults; however, reduced CFT in later life was restricted to individuals free of significant depressive symptoms, suggesting that a lack of disengagement from regrets specifically in older age enhances the risk for depression. Mediation models suggest that reduced what-if-thinking improves emotional well-being in late life by facilitating positive reappraisal and depends on preserved vmPFC connectivity with the dorsolateral PFC. Our findings underscore the increasing role of CFT and intra-prefrontal connectivity in emotional adaptation in the second half of life. Equipping middle-aged adults with strategies to address missed opportunities may significantly enhance resilience in aging populations. Counterfactual thinking Depression Emotional resilience Regret Successful aging Dewey 616.8 Deutsche Forschungsgemeinschaft BR 2877/7-1 53 Département de neurosciences fondamentales 21A false https://figshare.com/articles/dataset/behavioral_and_rsfMRI_data_reported_in_Galli_et_al_/28638908 GeroScience 83b98dd8-45b3-431f-b693-be5b7482a1b5 Article (Published version) Public Article_scientifique_from_crossref.pdf 2338459 application/pdf CC BY-4.0 8b9e79847e58b6816345ed221dae2fc7ddbaaa0773ea5fd5ba55a81e4d551fd0 d3c08b54-49b2-42d9-96cb-669ab0dd8912 Supplemental data Public 11357_2025_1928_MOESM1_ESM(1).docx 906806 application/vnd.openxmlformats-officedocument.wordprocessingml.document 476ec01b940488344ea894cb8953597c4ce636da62ee7f49dc229d99b5f17188 Vignette Public 11357_2025_1928_Figa_HTML.jpg 159475 image/png openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Age differences in what-if thinking from midlife onwards : Prefrontal contribution and implications for emotional health in late life	GeroScience			2025	5	7

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