Cortical thickness and resting‐state cardiac function across the lifespan: A cross‐sectional pooled mega‐analysis

Julian Koenig, Birgit Abler, Ingrid Agartz, Torbjörn Åkerstedt, Ole A. Andreassen, Mia Anthony, Karl‐jürgen Bär, Katja Bertsch, Rebecca C. Brown, Romuald Brunner, Luca Carnevali, Hugo D. Critchley, Kathryn R. Cullen, Eco J. C. de Geus, Feliberto Cruz, Isabel Dziobek, Marc D. Ferger, Håkan Fischer, Herta Flor, Michael GaeblerPeter J Gianaros, Melita J. Giummarra, Steven G. Greening, Simon Guendelman, James A. J. Heathers, Sabine C. Herpertz, Mandy X. Hu, Sebastian Jentschke, Michael Kaess, Tobias Kaufmann, Bonnie Klimes‐dougan, Stefan Koelsch, Marlene Krauch, Deniz Kumral, Femke Lamers, Tae‐ho Lee, Mats Lekander, Feng Lin, Martin Lotze, Elena Makovac, Matteo Mancini, Falk Mancke, Kristoffer N. T. Månsson, Stephen B. Manuck, Mara Mather, Frances Meeten, Jungwon Min, Bryon Mueller, Vera Muench, Frauke Nees, Lin Nga, Gustav Nilsonne, Daniela Ordonez Acuna, Berge Osnes, Cristina Ottaviani, Brenda W. J. H. Penninx, Allison Ponzio, Govinda R. Poudel, Janis Reinelt, Ping Ren, Michiko Sakaki, Andy Schumann, Lin Sørensen, Karsten Specht, Joana Straub, Sandra Tamm, Michelle Thai, Julian F. Thayer, Benjamin Ubani, Denise J. van der Mee, Laura S. Velzen, Carlos Ventura‐bort, Arno Villringer, David R. Watson, Luqing Wei, Julia Wendt, Melinda Westlund Schreiner, Lars T. Westlye, Mathias Weymar, Tobias Winkelmann, Guo‐rong Wu, Hyun Joo Yoo, Daniel S. Quintana

Research output: Contribution to JournalArticleAcademicpeer-review


Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting-state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small sample sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega-analysis (N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV; with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.

Original languageEnglish
Article numbere13688
Issue number7
Publication statusPublished - 10 Oct 2020


Tobias Winkelmann, Frauke Nees, and Herta Flor acknowledge the support by Oliver Grimm and Sebastian Pohlack. Michael Kaess, Julian Koenig, and Romuald Brunner acknowledge the help and support of Peter Parzer and Ayaka Ando. Deniz Kumral, Janis Reinelt, Michael Gaebler, and Arno Villringer acknowledge the support by Anahit Babayan and the MBE/LEMON group. Melita J Giummarra was supported by an Australian Research Council Discovery Early Career Researcher Award (DE170100726), and a small project grant from the Monash Biomedical Imaging facility. Mathias Weymar was supported by the German Research Foundation (DFG WE 4801/3‐1). Julian Koenig was supported through a Post‐Doctoral Scholarship provided by the Daimler and Benz Foundation (Ladenburg, Germany) and the Thrasher Research Fund Early Career Award provided by the Thrasher Research Fund (Salt Lake City, UT, USA). Gustav Nilsonne acknowledges help and support by Joe Wexler. All authors contributed significantly and meaningfully to data collection/preparation, to the interpretation of findings, and writing of the paper. Julian Koenig developed the idea for the project, handled the pooling of data, and wrote the first draft of the manuscript. Daniel Quintana and Tobias Kaufmann developed the R‐script for analysis based on consensus with all co‐authors, performed the statistical analyses, and prepared all graphs for publication. All authors extensively revised the manuscript and approved the final version before submission for publication. The authors have no competing financial interests to declare.

FundersFunder number
Anahit Babayan
Monash Biomedical Imaging facility
Thrasher Research Fund
Australian Research CouncilDE170100726
Deutsche ForschungsgemeinschaftWE 4801/3‐1
Daimler und Benz Stiftung


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