The Ups and Downs of Brain Stress: Extending the Triple Network Hypothesis.

Bibliographic Details
Title: The Ups and Downs of Brain Stress: Extending the Triple Network Hypothesis.
Authors: Henze GI; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany; Institute of Psychology, University of Regensburg, Regensburg, Germany. Electronic address: gina-isabelle.henze@charite.de., Giglberger M; Institute of Psychology, University of Regensburg, Regensburg, Germany., Bärtl C; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany; Institute of Psychology, University of Regensburg, Regensburg, Germany., Konzok J; Institute of Psychology, University of Regensburg, Regensburg, Germany., Neidhart M; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany; Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Krause T; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Serin E; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany., Waller L; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany., Peter HL; Institute of Psychology, University of Regensburg, Regensburg, Germany., Kreuzpointner L; Institute of Psychology, University of Regensburg, Regensburg, Germany., Speicher N; Institute of Psychology, University of Regensburg, Regensburg, Germany., Streit F; Hector Institute for Artificial Intelligence in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Germany., Veer IM; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Department of Developmental Psychology, University of Amsterdam, Amsterdam, the Netherlands., Kirsch P; German Center for Mental Health, Partner Site Mannheim-Heidelberg-Ulm, Germany; Department of Clinical Psychology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany., Nichols TE; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom; Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom., Kudielka BM; Institute of Psychology, University of Regensburg, Regensburg, Germany., Wüst S; Institute of Psychology, University of Regensburg, Regensburg, Germany., Erk S; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany., Walter H; Research Division of Mind and Brain, Department of Psychiatry and Psychotherapy at Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; German Center for Mental Health, Partner Site Berlin-Potsdam, Germany.
Source: Biological psychiatry. Cognitive neuroscience and neuroimaging [Biol Psychiatry Cogn Neurosci Neuroimaging] 2026 Sep; Vol. 11 (9), pp. 1141-1156. Date of Electronic Publication: 2025 Aug 22.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Elsevier, Inc Country of Publication: United States NLM ID: 101671285 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2451-9030 (Electronic) Linking ISSN: 24519022 NLM ISO Abbreviation: Biol Psychiatry Cogn Neurosci Neuroimaging Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, NY : Elsevier, Inc., [2016]-
MeSH Terms: Stress, Psychological*/physiopathology , Stress, Psychological*/diagnostic imaging , Nerve Net*/physiopathology , Nerve Net*/diagnostic imaging , Brain*/physiopathology , Default Mode Network*/physiopathology , Default Mode Network*/diagnostic imaging, Hydrocortisone/metabolism ; Heart Rate/physiology ; Humans ; Magnetic Resonance Imaging ; Female ; Male ; Brain Mapping
Abstract: Background: This preregistered functional magnetic resonance imaging study aimed to test and possibly extend the triple network hypothesis of psychosocial stress processing, positing that responses in the salience network (SN) and the default mode network (DMN) dominate at the expense of the central executive network (CEN). Furthermore, we tested the hypothesis that stress-related responses in SN and DMN structures are associated with hormonal, cardiovascular, and affective stress responses, while CEN and DMN structures are associated with task performance. We also examined sex-specific associations between neural and stress-induced cortisol, heart rate, and negative affect responses as well as task performance.
Methods: We reviewed all psychosocial stress studies and conducted a mega-analysis of ScanSTRESS datasets (n = 459; 222 female) with harmonized preprocessing.
Results: Our findings advanced the original hypothesis, revealing activations and deactivations across all 3 networks, related in a complex way to cortisol, heart rate, negative affect, and performance parameters. Additionally, we identified a novel age effect of increasing DMN activation with age, replicated an exposure-time effect of decreasing activation with duration, showed sex-specific patterns, and confirmed the involvement of all networks by task-based connectivity analyses.
Conclusions: Based on our findings we suggest a new, differentiated triple network hypothesis of psychosocial stress processing. Reactivity in SN and DMN structures is associated with hormonal, cardiovascular, and affective stress responses, whereas CEN and DMN structures process the stress-eliciting tasks. Moreover, the age effect may indicate that the ability to downregulate the DMN is reduced with age. Finally, we suggest that the exposure-time effect (decreasing signal within ScanSTRESS) may be a promising resilience biomarker.
(Copyright © 2025 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)
Contributed Indexing: Keywords: Central executive network; Default mode network; Exposure-time effect; Psychosocial stress; Salience network; ScanSTRESS
Substance Nomenclature: WI4X0X7BPJ (Hydrocortisone)
Entry Date(s): Date Created: 20250824 Date Completed: 20260904 Latest Revision: 20260904
Update Code: 20260905
DOI: 10.1016/j.bpsc.2025.08.004
PMID: 40850355
Database: MEDLINE
Description
ISSN:2451-9030
DOI:10.1016/j.bpsc.2025.08.004