Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder

Amit Etkin, Adi Maron-Katz, Wei Wu, Gregory A. Fonzo, Julia Huemer, Petra E. Vértes, Brian Patenaude, Jonas Richiardi, Madeleine S. Goodkind, Corey J. Keller, Jaime Ramos-Cejudo, Yevgeniya V. Zaiko, Kathy K. Peng, Emmanuel Shpigel, Parker Longwell, Russ T. Toll, Allison Thompson, Sanno Zack, Bryan Gonzalez, Raleigh EdelsteinJingyun Chen, Irene Akingbade, Elizabeth Weiss, Roland Hart, Silas Mann, Kathleen Durkin, Steven H. Baete, Fernando E. Boada, Afia Genfi, Jillian Autea, Jennifer Newman, Desmond J. Oathes, Steven E. Lindley, Duna Abu-Amara, Bruce A. Arnow, Nicolas Crossley, Joachim Hallmayer, Silvia Fossati, Barbara O. Rothbaum, Charles R. Marmar, Edward T. Bullmore, Ruth O’Hara

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.

Original languageEnglish (US)
Article numbereaal3236
JournalScience translational medicine
Issue number486
StatePublished - Apr 3 2019
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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