PT - JOURNAL ARTICLE AU - Etkin, Amit AU - Maron-Katz, Adi AU - Wu, Wei AU - Fonzo, Gregory A. AU - Huemer, Julia AU - Vértes, Petra E. AU - Patenaude, Brian AU - Richiardi, Jonas AU - Goodkind, Madeleine S. AU - Keller, Corey J. AU - Ramos-Cejudo, Jaime AU - Zaiko, Yevgeniya V. AU - Peng, Kathy K. AU - Shpigel, Emmanuel AU - Longwell, Parker AU - Toll, Russ T. AU - Thompson, Allison AU - Zack, Sanno AU - Gonzalez, Bryan AU - Edelstein, Raleigh AU - Chen, Jingyun AU - Akingbade, Irene AU - Weiss, Elizabeth AU - Hart, Roland AU - Mann, Silas AU - Durkin, Kathleen AU - Baete, Steven H. AU - Boada, Fernando E. AU - Genfi, Afia AU - Autea, Jillian AU - Newman, Jennifer AU - Oathes, Desmond J. AU - Lindley, Steven E. AU - Abu-Amara, Duna AU - Arnow, Bruce A. AU - Crossley, Nicolas AU - Hallmayer, Joachim AU - Fossati, Silvia AU - Rothbaum, Barbara O. AU - Marmar, Charles R. AU - Bullmore, Edward T. AU - O’Hara, Ruth TI - Using fMRI connectivity to define a treatment-resistant form of post-traumatic stress disorder AID - 10.1126/scitranslmed.aal3236 DP - 2019 Apr 03 TA - Science Translational Medicine PG - eaal3236 VI - 11 IP - 486 4099 - http://stm.sciencemag.org/content/11/486/eaal3236.short 4100 - http://stm.sciencemag.org/content/11/486/eaal3236.full 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.