Cecilia A. Hinojosa, Delin Sun, Courtney Russell, C. Lexi Baird, Ahmed Hussain, Mohammad Sendi, Neda Jahanshad, Lauren E. Salminen, M. Olff, Jessie L. Frijling, Dick J. Veltman, Saskia Bj Koch, Laura Nawijn, Mirjam van Zuiden, Li Wang, Ye Zhu, Gen Li, Dan J. Stein, Jonathan Ipser, Sheri-Michelle Koopowitz, Yuval Neria, Xi Zhu, Orren Ravid, Sigal Zilcha-Mano, Amit Lazarov, Benjamin Suarez-Jimenez, Ashley A. Huggins, Kerry Ressler, T Jovanović, Negar Fani, Sven C. Mueller, Anna R. Hudson, Judith K. Daniels, Anika Sierk, Antje Manthey, Henrik Walter, Nic J.A. van der Wee, Steven J.A. Van der Werff, Robert R.J.M. Vermeiren, Ivan Rektor, Pavel Říha, Milissa L. Kaufman, Lauren A.M. Lebois, Justin T. Baker, Anthony King, Israel Liberzon, Mike Angstadt, Nicholas D. Davenport, Seth G. Disner, Scott R. Sponheim, Thomas Straube, David Hofmann, G. Lu, Rongfeng Qi, X Wang, Austin Kunch, Hong Xie, Yann Quidé, Wissam El-Hage, Shmuel Lissek, H. J W ter Berg, Josh Cisler, Marisa Ross, Ryan J. Herringa, Daniel W. Grupe, Jack B. Nitschke, Richard J. Davidson, Christine L. Larson, Terri DeRoon-Cassini, Carissa W. Tomas, Jacklynn M. Fitzgerald, Brandee Feola, Jennifer Urbano-Blackford, B. O. Olatunji, Geoffrey May, Steven M. Nelson, Evan M. Gordon, Chadi G. Abdallah, Ruth A. Lanius, Maria Densmore, Jean Théberge, Richard WJ Neufeld, Lee A. Baugh, Raluca M. Simons, Jeffrey S. Simons, Vincent A. Magnotta, Kelene A. Fercho, Jeremy A. Elman, Matthew Panizzon, Carol E. Franz, Michael J. Lyons, William Kremen, Katie A. McLaughin, Matthew Peverill, Kelly Sambrook, Paul M. Thompson, Jennifer S. Stevens, Rajendra A. Morey, Sanne J.H. van Rooij
OBJECTIVE: Studies investigating resting-state functional connectivity of the amygdala and hippocampus have produced inconsistent findings. The authors' objective was to conduct the largest systematic comparison of alterations in functional connectivity of the amygdala and hippocampus in individuals with posttraumatic stress disorder (PTSD) using a multicohort mega-analysis with uniform processing steps and parameters across all cohorts. METHODS: Resting-state functional MRI data from 1,017 PTSD patients and 1,702 control participants from 32 international sites were centrally preprocessed with HALFpipe and analyzed using the Image-Based Meta- and Mega-Analysis (IBMMA) package for neuroimaging processing. Group-level seed-based whole-brain analyses were completed for the right and left amygdala and hippocampus. Additional correlation analyses were conducted between PTSD norm-severity scores and resting-state functional connectivity (rs-FC). RESULTS: Compared to control participants, individuals with PTSD showed stronger rs-FC between the left amygdala seed and right hippocampus and amygdala and the left and right lingual gyri. Greater PTSD total norm-severity scores were significantly associated with rs-FC between the left amygdala and right hippocampus/amygdala and rs-FC between the right amygdala and left hippocampus/amygdala. CONCLUSIONS: Greater connectivity between subcortical threat centers involved in fear processing, memory, and extinction learning characterizes the resting state in PTSD. Future directions include investigating how different interventions, such as brain stimulation, neurofeedback, and psychotherapy, might modulate the aberrant neural networks in PTSD.