RT Journal Article SR Electronic T1 Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder JF Science Translational Medicine FD American Association for the Advancement of Science SP eaal3236 DO 10.1126/scitranslmed.aal3236 VO 11 IS 486 A1 Etkin, Amit A1 Maron-Katz, Adi A1 Wu, Wei A1 Fonzo, Gregory A. A1 Huemer, Julia A1 Vértes, Petra E. A1 Patenaude, Brian A1 Richiardi, Jonas A1 Goodkind, Madeleine S. A1 Keller, Corey J. A1 Ramos-Cejudo, Jaime A1 Zaiko, Yevgeniya V. A1 Peng, Kathy K. A1 Shpigel, Emmanuel A1 Longwell, Parker A1 Toll, Russ T. A1 Thompson, Allison A1 Zack, Sanno A1 Gonzalez, Bryan A1 Edelstein, Raleigh A1 Chen, Jingyun A1 Akingbade, Irene A1 Weiss, Elizabeth A1 Hart, Roland A1 Mann, Silas A1 Durkin, Kathleen A1 Baete, Steven H. A1 Boada, Fernando E. A1 Genfi, Afia A1 Autea, Jillian A1 Newman, Jennifer A1 Oathes, Desmond J. A1 Lindley, Steven E. A1 Abu-Amara, Duna A1 Arnow, Bruce A. A1 Crossley, Nicolas A1 Hallmayer, Joachim A1 Fossati, Silvia A1 Rothbaum, Barbara O. A1 Marmar, Charles R. A1 Bullmore, Edward T. A1 O’Hara, Ruth YR 2019 UL http://stm.sciencemag.org/content/11/486/eaal3236.abstract AB Post-traumatic stress disorder (PTSD) is a severe psychiatric illness. Psychotherapy is the only effective treatment for PTSD but only works in a portion of patients. Etkin and colleagues now report a neuroimaging and behavioral signature in a subgroup of PTSD patients who failed to respond to psychotherapy. This signature was associated with impairments in fMRI connectivity in the brain’s ventral attention network and a deficit on a word list learning task. Use of noninvasive brain stimulation in combination with neuroimaging identified a brain location in which network connectivity correlated with the effects of stimulation. This work may help to define a target for future noninvasive brain stimulation approaches for treating patients with PTSD who are refractory to psychotherapy.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.