Data-Driven Approach to Dynamic Resting State Functional Connectivity in Post-Traumatic Stress Disorder: An ENIGMA-PGC PTSD Study

  • Carissa W Tomas*
  • , Jacklynn M Fitzgerald
  • , C Lexi Baird
  • , Courtney C Haswell
  • , Chadi G Abdallah
  • , Michael Angstadt
  • , Justin T Baker
  • , Hannah Berg
  • , Jennifer U Blackford
  • , Josh Cisler
  • , Andrew S Cotton
  • , Judith K Daniels
  • , Nicholas D Davenport
  • , Richard J Davidson
  • , Terri A deRoon-Cassini
  • , Seth G Disner
  • , Wissam El Hage
  • , Negar Fani
  • , Jessie L Frijling
  • , Evan M Gordon
  • Daniel W Grupe, Xiaofu He, Ryan Herringa, David Hofmann, Ashley A Huggins, Ahmed Hussain, Jonathan Ipser, Neda Jahanshad, Tanja Jovanovic, Milissa L Kaufman, Yoojean Kim, Anthony King, Saskia B J Koch, Sheri Koopowitz, Amit Lazarov, Lauren A M Lebois, Isreal Liberzon, Shmuel Lissek, Antje Manthey, Geoffrey May, Katie A McLaughlin, Laura Nawijn, Steven M Nelson, Yuval Neria, Jack B Nitschke, Bunmi O Olatunji, Miranda Olff, Matthew Peverill, Yann Quidé, Orren Ravid, Kerry Ressler, Marisa Ross, Lauren E Salminen, Kelly Sambrook, Chiahao Shih, Anika Sierk, Scott R Sponheim, Dan J Stein, Jennifer Stevens, Thomas Straube, Benjamin Suarez-Jimenez, Paul M Thompson, Nic J A van der Wee, Steven J A van der Werff, Sanne J H van Rooij, Mirjam van Zuiden, Dick J Veltman, Robert R J M Vermeiren, Henrik Walter, Xin Wang, Hong Xie, Xi Zhu, Sigal Zilcha-Mano, Christine L Larson, Rajendra Morey
*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Using functional magnetic resonance imaging (fMRI), symptoms of posttraumatic stress disorder (PTSD) have been associated with aberrations in brain networks in the absence of a given cognitive demand or task, called resting-state networks. Prior work has focused on disruption in the static functional connectivity (FC) among specific regions constrained by a priori hypotheses. However, dynamic FC, an approach that examines brain network characteristics over time, may provide a more sensitive measure to understand the network properties underlying dysfunction in PTSD. Further, using a data-driven analytic approach may reveal the contribution of other larger network disturbances beyond those revealed by hypothesis-driven examinations of ROIs or canonical networks. Therefore, the current study used group independent components analysis (ICA) and graph theory principles to identify, characterize, and subsequently compare brain network dynamics and recurrent connectivity states in a large sample of trauma exposed individuals (N = 1035) with and without PTSD from the ENIGMA-PGC PTSD workgroup. Neither static FC nor dynamic FC results showed robust differences between groups. There were also no group differences in dwell time or number of transitions of recurrent connectivity states. This multi-cohort sample with heterogenous trauma types and demographic features offers a significantly larger scale approach than prior literature with smaller homogenous trauma cohorts. Heterogeneity of PTSD, especially within diffuse brain networks, may not be captured by evaluating only diagnostic groups, further work should be done to evaluate brain network dynamics with respect to specific symptom profiles and trauma types.

Original languageEnglish
Article numbere70116
Number of pages12
JournalHuman Brain Mapping
Volume46
Issue number11
DOIs
Publication statusPublished - 1 Aug 2025

Bibliographical note

Publisher Copyright:
© 2025 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.

Funding

Funding: Miranda Olff was supported by ZonMw, the Netherlands organization for Health Research and Development (40-00812-98-10041), and by the Academic Medical Center Research Council (110614). Dan J. Stein and Jonathan Ipser were supported by the SAMRC Unit on Risk & Resilience in Mental Disorders. Benjamin Suarez-Jimenez was supported by NIMH K01MH118428 and NIMH R01MH131532. Xi Zhu was supported by NARSAD 27040 and NIH K01MH122774. Yuval Neria was supported by R01MH105355-01A. Rajendra Morey was supported by RO1 MH111671 and VISN6 MIRECC. Jennifer Stevens, Kerry Ressler, and Tanja Jovanovic were supported by MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850. Sanne J. H. van Rooij was supported by Narsad Young Investigator and K01MH121653. Negar Fani was supported by MH101380 and AT011267. Judith K. Daniels was supported by the German Research Foundation DA 1222/4-1 and WA 1539/8-2. Lauren A. M. Lebois was supported by K01MH118467 and the Julia Kasparian Fund for Neuroscience Research. Milissa L. Kaufman was supported by R21MH112956, R01MH119227, McLean Hospital Trauma Scholars Fund, and the Julia Kasaparian Fund for Neuroscience Research. Isreal Liberzon was supported by R01MH113574. Christine L. Larson was supported by R01 MH106574. Nicholas D. Davenport was supported by VA RR&D 1IK2RX000709. Scott R. Sponheim was supported by VA RR&D I01RX000622 and CDMRP W81XWH-08-2-0038. Seth G. Disner was supported by VA RR&D 1K1RX002325 and 1K2RX002922. Thomas Straube and David Hofmann were supported by the German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07). Xin Wang was supported by 1R01MH110483 and 1R21 MH098198. Wissam El Hage was supported by PHRC, Foundation Pierre Deniker and SFR FED4226. Shmuel Lissek and Hannah Berg were supported by NIH 5R01MH107382. Jennifer U. Blackford and Bunmi O. Olatunji were supported by NIMH R21MH106998. Evan M. Gordon was supported by VA CSR&D 1IK2CX001680; VISN17 Center of Excellence Pilot funding. Jack B. Nitschke was supported by the Dana Foundation. Daniel W. Grupe was supported by a National Science Foundation Graduate Research Fellowship. Richard J. Davidson was supported by the National Institute of Mental Health (NIMH) R01-MH043454 and T32-MH018931; and a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30-HD003352). Chadi G. Abdallah was funded by the VA National Center for PTSD. Most importantly, we thank the study participants for their willingness to take part in their respective studies. We thank all current and former members of the respective research sites within the ENIGMA-PGC PTSD Working group who contributed to study organization, recruitment, data collection, and analysis. Carissa W. Tomas would like to extend a special thanks to Dr. Krista Lisdahl and Dr. Han Joo Lee at the University of Wisconsin Milwaukee for their role and guidance and as dissertation committee members for parts of this work. Lauren A. M. Lebois reports unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation (ISSTD), grant support from the National Institute of Mental Health, K01 MH118467, and spousal IP payments from Vanderbilt University for technology licensed to Acadia Pharmaceuticals unrelated to the present work. ISSTD and NIMH were not involved in the analysis or preparation of the manuscript. Milissa L. Kaufman reports unpaid membership on the Scientific Committee for the International Society for the Study of Trauma and Dissociation (ISSTD), grant support from National Institutes of Mental Health (R21MH112956, R01MH119227). ISSTD and NIMH were not involved in the analysis or preparation of the manuscript. Wissam El Hage reports affiliations with Air Liquide, Boehringer Ingelheim, CHUGAI, EISAI, Jazz Pharmaceuticals, Janssen, Lundbeck, Novartis, Otsuka, UCB of which none relate to the current manuscript. Richard J. Davidson is the founder and president of, and serves on the board of directors for, the non‐profit organization Healthy Minds Innovations Inc., not related to the current manuscript. Chadi G. Abdallah has served as a consultant and/or on advisory boards for Douglas Pharmaceutical, Aptinyx, Genentech, Janssen, Psilocybin Labs, Lundbeck, Guidepoint, and FSV7. He also filed a patent for using mTORC1 inhibitors to augment the effects of antidepressants (August 20, 2018). None was involved in the preparation of the current manuscript. The remaining authors have nothing to disclose. Miranda Olff was supported by ZonMw, the Netherlands organization for Health Research and Development (40‐00812‐98‐10041), and by the Academic Medical Center Research Council (110614). Dan J. Stein and Jonathan Ipser were supported by the SAMRC Unit on Risk & Resilience in Mental Disorders. Benjamin Suarez‐Jimenez was supported by NIMH K01MH118428 and NIMH R01MH131532. Xi Zhu was supported by NARSAD 27040 and NIH K01MH122774. Yuval Neria was supported by R01MH105355‐01A. Rajendra Morey was supported by RO1 MH111671 and VISN6 MIRECC. Jennifer Stevens, Kerry Ressler, and Tanja Jovanovic were supported by MH098212; MH071537; M01RR00039; UL1TR000454; HD071982; HD085850. Sanne J. H. van Rooij was supported by Narsad Young Investigator and K01MH121653. Negar Fani was supported by MH101380 and AT011267. Judith K. Daniels was supported by the German Research Foundation DA 1222/4‐1 and WA 1539/8‐2. Lauren A. M. Lebois was supported by K01MH118467 and the Julia Kasparian Fund for Neuroscience Research. Milissa L. Kaufman was supported by R21MH112956, R01MH119227, McLean Hospital Trauma Scholars Fund, and the Julia Kasaparian Fund for Neuroscience Research. Isreal Liberzon was supported by R01MH113574. Christine L. Larson was supported by R01 MH106574. Nicholas D. Davenport was supported by VA RR&D 1IK2RX000709. Scott R. Sponheim was supported by VA RR&D I01RX000622 and CDMRP W81XWH‐08‐2‐0038. Seth G. Disner was supported by VA RR&D 1K1RX002325 and 1K2RX002922. Thomas Straube and David Hofmann were supported by the German Research Society (Deutsche Forschungsgemeinschaft, DFG; SFB/TRR 58: C06, C07). Xin Wang was supported by 1R01MH110483 and 1R21 MH098198. Wissam El Hage was supported by PHRC, Foundation Pierre Deniker and SFR FED4226. Shmuel Lissek and Hannah Berg were supported by NIH 5R01MH107382. Jennifer U. Blackford and Bunmi O. Olatunji were supported by NIMH R21MH106998. Evan M. Gordon was supported by VA CSR&D 1IK2CX001680; VISN17 Center of Excellence Pilot funding. Jack B. Nitschke was supported by the Dana Foundation. Daniel W. Grupe was supported by a National Science Foundation Graduate Research Fellowship. Richard J. Davidson was supported by the National Institute of Mental Health (NIMH) R01‐MH043454 and T32‐MH018931; and a core grant to the Waisman Center from the National Institute of Child Health and Human Development (P30‐HD003352). Chadi G. Abdallah was funded by the VA National Center for PTSD. Funding:

FundersFunder number
University of Wisconsin-Milwaukee
International Society for the Study of Trauma and Dissociation
National Science Foundation
Dana Foundation
National Center for PTSD, U.S. Department of Veterans Affairs
PHRC
ACADIA Pharmaceuticals
Vanderbilt University
ZonMw40‐00812‐98‐10041
VA CSR&D1IK2CX001680
National Alliance for Research on Schizophrenia and Depression27040
Julia Kasparian Fund for Neuroscience ResearchR01MH119227
National Institute of Mental HealthK01 MH118467, R01‐MH043454, T32-MH018931
SAMRC Unit on Risk & Resilience in Mental DisordersR01MH131532, K01MH118428
National Institutes of Mental HealthR21MH112956
Rehabilitation Research and Development Service1IK2RX000709, I01RX000622
National Institute of Child Health and Human DevelopmentP30‐HD003352
Fondation Pierre Deniker pour la Recherche et la Prévention en Santé Mentale5R01MH107382, SFR FED4226, R21MH106998
Deutsche ForschungsgemeinschaftK01MH118467, C06, C07, DA 1222/4‐1, WA 1539/8-2, 1R01MH110483, 1R21 MH098198
Congressionally Directed Medical Research Programs1K2RX002922, W81XWH‐08‐2‐0038, 1K1RX002325
National Institutes of HealthMH101380, UL1TR000454, HD085850, M01RR00039, K01MH121653, K01MH122774, HD071982, MH071537, MH098212, RO1 MH111671, AT011267
Academisch Medisch Centrum110614
Julia Kasaparian Fund for Neuroscience ResearchR01 MH106574, R01MH113574

    Keywords

    • Adult
    • Brain/diagnostic imaging
    • Connectome/methods
    • Female
    • Humans
    • Magnetic Resonance Imaging/methods
    • Male
    • Middle Aged
    • Nerve Net/diagnostic imaging
    • Stress Disorders, Post-Traumatic/physiopathology
    • Young Adult

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