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

• Type of Material: Article
• Authors: Amit Etkin, Stanford University; Adi Maron-Katz, Stanford University; Wei Wu, Emory University; Gregory A. Fonzo, Stanford University; Julia Huemer, Stanford University; Petra E. Vertes, University of Cambridge; Brian Patenaude, Stanford University; Jonas Richiardi, Lausanne University Hospital; Madeleine S. Goodkind, New Mexico Veterans Affairs Healthcare System; Barbara Rothbaum, Emory University
• Language: English
• Date: 2019-04-03
• Publisher: American Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
• Final Published Version (URL): http://dx.doi.org/10.1126/scitranslmed.aal3236
• Title of Journal or Parent Work: Science Translational Medicine
• Volume: 11
• Issue: 486
• Grant/Funding Information: G.A.F. was supported by NIMH grant T32 MH019938 and the Office of Academic Affiliations, Advanced Fellowship Program in Mental Illness Research and Treatment, Department of Veterans Affairs.; P.E.V. was supported by the UK Medical Research Council (grant MR/K020706/1) and is a Fellow of MQ: Transforming Mental Health (MQF17_24) and of the Alan Turing Institute funded by EPSRC grant EP/N510129/1.; A.E. and R.O. were also funded by the Sierra-Pacific Mental Illness Research, Education, and Clinical Center of the Palo Alto Veterans Affairs Health Care System.; This work was funded by R01 MH091860 from the National Institute of Mental Health (to A.E.), a grant from the Steven A. and Alexandra M. Cohen Foundation to NYU School of Medicine (to C.R.M.), and funds from Cohen Veterans Bioscience and Ann and Peter Tarlton (to A.E.).; W.W. was funded by the National Key Research and Development Plan of China (grant 2017YFB1002505).
• Keywords: Medicine, Research & Experimental; EPISODIC MEMORY; Science & Technology; BIPOLAR DISORDER; FUNCTIONAL CONNECTIVITY; Life Sciences & Biomedicine; NETWORK CONNECTIVITY; TRANSCRANIAL MAGNETIC STIMULATION; BRAIN CONNECTIVITY; DORSOLATERAL PREFRONTAL CORTEX; Cell Biology; VERBAL MEMORY; DOUBLE-BLIND; Research & Experimental Medicine; DEFAULT-MODE

Abstract

Copyright © 2019 The Authors. 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.